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Yong-Li Zhong, Nobuyoshi Yasuda, Hongming Li, Mark McLaughlin, David Tschaen
This article reviews antiviral therapies that have been approved for human use during the last decade, with a focus on the process chemistry that enabled access to these important drugs. In particular, process chemistry highlights from the practical syntheses of the HCV drugs sofosbuvir (Gilead), grazoprevir (Merck), and elbasvir (Merck), the HIV therapy darunavir (Tibotec) and the influenza treatment peramivir (BioCryst) are presented.
December 2016: Topics in Current Chemistry (Journal)
Aditya H Gaur, Hilda Kizito, Wasana Prasitsueubsai, Natella Rakhmanina, Mohammed Rassool, Rana Chakraborty, Jagmohan Batra, Pope Kosalaraksa, Wicharn Luesomboon, Danielle Porter, Yongwu Shao, Michael Myers, Lillian Ting, Devi SenGupta, Erin Quirk, Martin S Rhee
BACKGROUND: The prodrug tenofovir alafenamide is associated with improved renal and bone safety compared with tenofovir disoproxil fumarate. We aimed to assess safety, pharmacokinetics, and efficacy of this single-tablet, fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-infected, treatment-naive adolescents. METHODS: We did a 48 week, single-arm, open-label trial in treatment-naive adolescents with HIV from ten hospital clinics in South Africa, Thailand, Uganda, and the USA...
December 2016: Lancet HIV
Marius M Hoeper, Vallerie V McLaughlin, Joan Albert Barberá, Adaani E Frost, Hossein-Ardeschir Ghofrani, Andrew J Peacock, Gérald Simonneau, Stephan Rosenkranz, Ronald J Oudiz, R James White, Karen L Miller, Jonathan Langley, Julia H N Harris, Christiana Blair, Lewis J Rubin, Jean-Luc Vachiery
BACKGROUND: In treatment-naive patients with pulmonary arterial hypertension, initial combination therapy with ambrisentan and tadalafil reduces the risk of clinical failure events compared with monotherapy. We did this secondary analysis to further investigate the effect of combination therapy on survival. METHODS: We analysed survival data from the modified intention-to-treat population of the Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) trial...
October 10, 2016: Lancet Respiratory Medicine
Zobair M Younossi, Haesuk Park, Douglas Dieterich, Sammy Saab, Aijaz Ahmed, Stuart C Gordon
BACKGROUND: New direct-acting antiviral (DAA) therapy has dramatically increased cure rates for patients infected with hepatitis C virus (HCV), but has also substantially raised treatment costs. AIM: The aim of this analysis was to evaluate the therapeutic benefit and net costs (i.e. efficiency frontier) and the quality-adjusted cost of care associated with the evolution of treatment regimens for patients with HCV genotype 1 in the United States. DESIGN: A decision-analytic Markov model...
October 2016: Medicine (Baltimore)
Dennis C Liotta, George R Painter
The HIV/AIDS epidemic, which was first reported on in 1981, progressed in just 10 years to a disease afflicting 10 million people worldwide including 1 million in the US. In 1987, AZT was approved for treating HIV/AIDS. Unfortunately, its clinical usefullness was severly limited by associated toxicities and the emergence of resistance. Three other drugs that were approved in the early 1990s suffered from similar liabilities. In 1990, the Liotta group at Emory University developed a highly diastereoselective synthesis of racemic 3'-thia-2',3'-dideoxycytidine and 3'-thia-2',3'-5-fluorodideoxycytidine and demonstrated that these compounds exhibited excellent anti-HIV activity with no apparent cytotoxicity...
October 5, 2016: Accounts of Chemical Research
Andrew Jack
No abstract text is available yet for this article.
September 8, 2016: BMJ: British Medical Journal
Pradyot Bhattacharya, Nahid Ali
Visceral leishmaniasis (VL) is one of the severest forms of parasite borne diseases worldwide with a mortality rate second only to malaria. Treatment of VL patients with currently available chemotherapeutic agents poses problems of large scale failure, toxicity, prolonged hospitalization time, high treatment cost and drug resistance. However, most of these problems can be overcome by the use of liposomal formulations of Amphotericin B (L-AmB). Of the two L-AmBs currently available in Indian market, AmBisome is imported and FUNGISOME is indigenous...
September 2016: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
Kathleen Squires, Cissy Kityo, Sally Hodder, Margaret Johnson, Evgeny Voronin, Debbie Hagins, Anchalee Avihingsanon, Ellen Koenig, Shuping Jiang, Kirsten White, Andrew Cheng, Javier Szwarcberg, Huyen Cao
BACKGROUND: Women are under-represented in HIV antiretroviral therapy (ART) studies. Guidelines for selection of ART as initial therapy in patients with HIV-1 infection do not contain sex-specific treatment. We aimed to assess the safety and efficacy of the single tablet integrase inhibitor regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate compared with a boosted protease inhibitor regimen of ritonavir-boosted atazanavir with emtricitabine and tenofovir disoproxil fumarate...
September 2016: Lancet HIV
Arpita Patel, Luiz F Gil, Arthur Castellano, Gileade Freitas, Daniel Navarro, Ana P Peredo, Nick Tovar, Paulo Coelho
This study was designed to compare the combined effect of two different drilling techniques (conventional expansion and one-step) and four different implant geometries in a beagle dog model. The nondecalcified bone-implant samples underwent histologic/metric analysis at 2 and 6 weeks. Morphologic analysis showed similarities between different drilling technique groups and implant geometries. Histomorphometric parameters, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO) were analyzed, and no statistical difference between drilling groups and/or implant geometry was found...
September 2016: International Journal of Periodontics & Restorative Dentistry
Michael Gilead, Chelsea Boccagno, Melanie Silverman, Ran R Hassin, Jochen Weber, Kevin N Ochsner
Can taking the perspective of other people modify our own affective responses to stimuli? To address this question, we examined the neurobiological mechanisms supporting the ability to take another person's perspective and thereby emotionally experience the world as they would. We measured participants' neural activity as they attempted to predict the emotional responses of two individuals that differed in terms of their proneness to experience negative affect. Results showed that behavioral and neural signatures of negative affect (amygdala activity and a distributed multivoxel pattern reflecting affective negativity) simulated the presumed affective state of the target person...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
(no author information available yet)
No abstract text is available yet for this article.
August 9, 2016: Nature Biotechnology
Michael Gilead, Nira Liberman, Anat Maril
How does our brain allow us comprehend abstract/symbolic descriptions of human action? Whereas past research suggested that processing action language relies on sensorimotor brain regions, recent work suggests that sensorimotor activation depends on participants' task goals, such that focusing on abstract (vs. concrete) aspects of an action activates "default mode network" (rather than sensorimotor) regions. Following a Piagetian framework, we hypothesized that for actions acquired at an age wherein abstract/symbolic cognition is fully-developed, even when participants focus on the concrete aspects of an action, they should retrieve abstract-symbolic mental representations...
November 1, 2016: NeuroImage
Genevieve M Halpenny
Turing Pharmaceuticals raised the price of Daraprim 5,500%, illustrating how the absence of competition in the sale of low-volume, low-price drugs can lead to price gouging. For patented medicines, society allows supracompetitive pricing to incentivize innovation. However, Gilead's decision to sell Sovaldi for $84,000 per course of treatment raised the question whether society must accept any price set by the patent holder. Unfortunately, these incidents illustrate a broader trend in which pharmaceutical prices are greater in the United States than abroad, placing the United States at the top in per capita expenditures on pharmaceuticals...
June 9, 2016: ACS Medicinal Chemistry Letters
Calvin Q Pan, Zhongping Duan, Erhei Dai, Shuqin Zhang, Guorong Han, Yuming Wang, Huaihong Zhang, Huaibin Zou, Baoshen Zhu, Wenjing Zhao, Hongxiu Jiang
BACKGROUND: Few data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV). METHODS: In this trial, we included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28...
June 16, 2016: New England Journal of Medicine
Tehillah S Menes, Orit Golan, Gilead Vainer, Hedva Lerman, Schlomo Schneebaum, Joseph Klausner, Einat Even-Sapir
BACKGROUND: Assessment of residual disease after neoadjuvant therapy for breast cancer is an ongoing challenge of breast imaging. This study evaluates the accuracy of a novel dedicated system for molecular breast imaging (MBI) composed of the new generation of cadmium zinc telluride detectors in assessing residual disease after neoadjuvant therapy in patients with breast cancer. PATIENTS AND METHODS: Clinical data, imaging, surgical, and pathological findings of 51 women with breast cancer undergoing neoadjuvant therapy were recorded...
May 14, 2016: Clinical Breast Cancer
Mark Ratner
No abstract text is available yet for this article.
June 9, 2016: Nature Biotechnology
Michael Jacobs, Alison Rodger, David J Bell, Sanjay Bhagani, Ian Cropley, Ana Filipe, Robert J Gifford, Susan Hopkins, Joseph Hughes, Farrah Jabeen, Ingolfur Johannessen, Drosos Karageorgopoulos, Angie Lackenby, Rebecca Lester, Rebecca S N Liu, Alisdair MacConnachie, Tabitha Mahungu, Daniel Martin, Neal Marshall, Stephen Mepham, Richard Orton, Massimo Palmarini, Monika Patel, Colin Perry, S Erica Peters, Duncan Porter, David Ritchie, Neil D Ritchie, R Andrew Seaton, Vattipally B Sreenu, Kate Templeton, Simon Warren, Gavin S Wilkie, Maria Zambon, Robin Gopal, Emma C Thomson
BACKGROUND: There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2). METHODS: A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood...
July 30, 2016: Lancet
Burak Erem, Ramon Martinez Orellana, Damon E Hyde, Jurriaan M Peters, Frank H Duffy, Petr Stovicek, Simon K Warfield, Rob S MacLeod, Gilead Tadmor, Dana H Brooks
This paper addresses the challenge of extracting meaningful information from measured bioelectric signals generated by complex, large scale physiological systems such as the brain or the heart. We focus on a combination of the well-known Laplacian eigenmaps machine learning approach with dynamical systems ideas to analyze emergent dynamic behaviors. The method reconstructs the abstract dynamical system phase-space geometry of the embedded measurements and tracks changes in physiological conditions or activities through changes in that geometry...
April 2016: Physical Review. E
(no author information available yet)
No abstract text is available yet for this article.
May 6, 2016: Nature Biotechnology
Malena Cohen-Cymberknoh, Noa Gilead, Silvia Gartner, Sandra Rovira, Hannah Blau, Huda Mussaffi, Joseph Rivlin, Michal Gur, Michal Shteinberg, Lea Bentur, Galit Livnat, Micha Aviram, Elie Picard, Ariel Tenenbaum, Shoshana Armoni, Oded Breuer, David Shoseyov, Eitan Kerem
: Eradication of Pseudomonas aeruginosa (PA) is critical in cystic fibrosis (CF) patients. OBJECTIVES: To determine eradication success rate of newly acquired PA and to identify characteristics associated with eradication failure. METHODS: In an observational study, data from patients with newly acquired PA infection from 2007 to 2013 were collected. Clinical variables were compared in patients with and without successful eradication for ≥1year...
April 30, 2016: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
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