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Chaevia Clendinen, Yapei Zhang, Rebecca N Warburton, Donald W Light
BACKGROUND: Nearly all of the 500,000 new cases of cervical cancer and 270,000 deaths occur in middle or lower income countries. Yet the two most prevalent HPV vaccines are unaffordable to most. Even prices to Gavi, the Vaccine Alliance, are unaffordable to graduating countries, once they lose Gavi subsidies. Merck and Glaxosmithkline (GSK) claim their prices to Gavi equal their manufacturing costs; but these costs remain undisclosed. We undertook this investigation to estimate those costs...
October 19, 2016: Vaccine
Alema Galijatovic-Idrizbegovic, Judith E Miller, Wendy D Cornell, James A Butler, Gordon K Wollenberg, Frank D Sistare, Joseph J DeGeorge
Chronic (>3 months) preclinical toxicology studies are conducted to support the safe conduct of clinical trials exceeding 3 months in duration. We have conducted a review of 32 chronic toxicology studies in non-rodents (22 studies in dogs and 10 in non-human primates) and 27 chronic toxicology studies in rats dosed with Merck compounds to determine the frequency at which additional target organ toxicities are observed in chronic toxicology studies as compared to subchronic studies of 3 months in duration...
October 18, 2016: Regulatory Toxicology and Pharmacology: RTP
Marie-Charlotte Desseroit, Florent Tixier, Wolfgang Andreas Weber, Barry Alan Siegel, Catherine Cheze Le Rest, Dimitris Visvikis, Mathieu Hatt
PURPOSE: The main purpose of this study was to assess the reliability of shape and heterogeneity features in both PET and low-dose CT components of PET/CT. A secondary objective was to investigate the impact of image quantization. MATERIAL AND METHODS: A HIPAA-compliant secondary analysis of deidentified prospectively acquired PET/CT test-retest datasets of 74 patients from multi-center Merck and ACRIN trials was performed. Metabolically active volumes were automatically delineated on PET with Fuzzy Locally Adaptive Bayesian (FLAB) algorithm...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
T Hertz, M G Logan, M Rolland, C A Magaret, C Rademeyer, A Fiore-Gartland, P T Edlefsen, A DeCamp, H Ahmed, N Ngandu, B B Larsen, N Frahm, J Marais, R Thebus, D Geraghty, J Hural, L Corey, J Kublin, G Gray, M J McElrath, J I Mullins, P B Gilbert, C Williamson
INTRODUCTION: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. MATERIALS AND METHODS: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients...
October 15, 2016: Vaccine
Corey J Langer, Shirish M Gadgeel, Hossein Borghaei, Vassiliki A Papadimitrakopoulou, Amita Patnaik, Steven F Powell, Ryan D Gentzler, Renato G Martins, James P Stevenson, Shadia I Jalal, Amit Panwalkar, James Chih-Hsin Yang, Matthew Gubens, Lecia V Sequist, Mark M Awad, Joseph Fiore, Yang Ge, Harry Raftopoulos, Leena Gandhi
BACKGROUND: Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer (NSCLC) setting. The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy. We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC...
October 10, 2016: Lancet Oncology
Satoshi Okusu, Kazuki Hirano, Yoshimasa Yasuda, Junki Tanaka, Etsuko Tokunaga, Haruhiko Fukaya, Norio Shibata
Efavirenz is manufactured worldwide, and its asymmetric synthesis requires a complex organometallic approach, while an organocatalytic approach is far less efficient. The first highly enantioselective approach is disclosed for the synthesis of Efavirenz under nonmetal organocatalysis with up to 93% ee for the Merck intermediate and 91% ee for the Lonsa intermediate using novel alkynyl cinchona catalysts.
October 14, 2016: Organic Letters
Jin-Hee Park, Yong-Chul Kim
The P2X7 receptor (P2X7R) is a unique subtype among the family of seven purinergic P2X receptors, which are ATP-gated non-selective cation channels. P2X7R has been reported to have pathological roles in various diseases, including autoimmune diseases such as arthritis and inflammatory bowel disease, neurodegenerative diseases, chronic pain, mood disorders and cancers. Therefore, many pharmaceutical companies have endeavored to develop a clinical candidate targeting P2X7R. Areas covered: This review provides a summary of various patents on chemicals and biologics and their clinical use published between 2010 and 2015...
October 10, 2016: Expert Opinion on Therapeutic Patents
Martin Reck, Delvys Rodríguez-Abreu, Andrew G Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Melanie A Leiby, Gregory M Lubiniecki, Yue Shentu, Reshma Rangwala, Julie R Brahmer
Background Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). Methods In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy...
October 8, 2016: New England Journal of Medicine
F Belva, M Bonduelle, M Roelants, D Michielsen, A Van Steirteghem, G Verheyen, H Tournaye
STUDY QUESTION: What is the semen quality of young adult men who were conceived 18-22 years ago by ICSI for male infertility? SUMMARY ANSWER: In this cohort of 54 young adult ICSI men, median sperm concentration, total sperm count and total motile sperm count were significantly lower than in spontaneously conceived peers. WHAT IS KNOWN ALREADY: The oldest ICSI offspring cohort worldwide has recently reached adulthood. Hence, their reproductive health can now be investigated...
October 5, 2016: Human Reproduction
Alina Lelic, Chris P Verschoor, Vivian W C Lau, Robin Parsons, Carole Evelegh, Dawn M Bowdish, Jonathan L Bramson, Mark B Loeb
BACKGROUND:  Little is known about the immunogenicity of live-attenuated Oka/Merck varicella zoster vaccine (VZV) vaccine in frail nursing homes residents nor about immune phenotypes associated with a response. METHODS:  A cohort of 190 frail nursing home residents between the ages of 80 and 102 years and a cohort of 50 community dwelling seniors, ages 60 to 75 years, a comparison group, were vaccinated with the VZV vaccine. IFN-γ ELISpot assay was measured prior to and six-weeks following vaccination...
October 5, 2016: Journal of Infectious Diseases
Jaimini Cegla, Ben Jones, James Howard, Richard Kay, Colin S Creaser, Stephen R Bloom, Tricia Tan
BACKGROUND: One of the main challenges in the measurement of glucagon is the premise that it is unstable in human plasma. Traditionally, protease inhibitors have been used to prevent its degradation, however, their use is controversial. Here we investigated the optimal method of sample collection for glucagon, with measurement by liquid chromatography tandem mass spectrometry (LC-MS/MS) and two commercially available immunoassays. METHODS: Blood from healthy fasting volunteers (n=10) was processed under a variety of pre-analytical condition including collection in EDTA vs lithium heparin tubes and the addition of aprotinin and/or a DPPIV inhibitor...
October 4, 2016: Annals of Clinical Biochemistry
Gin S Malhi, Yulisha Byrow, Frederick Cassidy, Andrea Cipriani, Koen Demyttenaere, Mark A Frye, Michael Gitlin, Sidney H Kennedy, Terence A Ketter, Raymond W Lam, Rupert McShane, Alex J Mitchell, Michael J Ostacher, Sakina J Rizvi, Michael E Thase, Mauricio Tohen
SUMMARY: The appeal of ketamine - in promptly ameliorating depressive symptoms even in those with non-response - has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives - derived from evidence and clinical experience - and to consider strategies for future investigations...
May 2016: BJPsych Open
Brigitta G Baumert, Monika E Hegi, Martin J van den Bent, Andreas von Deimling, Thierry Gorlia, Khê Hoang-Xuan, Alba A Brandes, Guy Kantor, Martin J B Taphoorn, Mohamed Ben Hassel, Christian Hartmann, Gail Ryan, David Capper, Johan M Kros, Sebastian Kurscheid, Wolfgang Wick, Roelien Enting, Michele Reni, Brian Thiessen, Frederic Dhermain, Jacoline E Bromberg, Loic Feuvret, Jaap C Reijneveld, Olivier Chinot, Johanna M M Gijtenbeek, John P Rossiter, Nicolas Dif, Carmen Balana, Jose Bravo-Marques, Paul M Clement, Christine Marosi, Tzahala Tzuk-Shina, Robert A Nordal, Jeremy Rees, Denis Lacombe, Warren P Mason, Roger Stupp
BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration...
September 26, 2016: Lancet Oncology
Jaap C Reijneveld, Martin J B Taphoorn, Corneel Coens, Jacoline E C Bromberg, Warren P Mason, Khê Hoang-Xuan, Gail Ryan, Mohamed Ben Hassel, Roelien H Enting, Alba A Brandes, Antje Wick, Olivier Chinot, Michele Reni, Guy Kantor, Brian Thiessen, Martin Klein, Eugenie Verger, Christian Borchers, Peter Hau, Michael Back, Anja Smits, Vassilis Golfinopoulos, Thierry Gorlia, Andrew Bottomley, Roger Stupp, Brigitta G Baumert
BACKGROUND: Temozolomide chemotherapy versus radiotherapy in patients with a high-risk low-grade glioma has been shown to have no significant effect on progression-free survival. If these treatments have a different effect on health-related quality of life (HRQOL), it might affect the choice of therapy. We postulated that temozolomide compromises HRQOL and global cognitive functioning to a lesser extent than does radiotherapy. METHODS: We did a prospective, phase 3, randomised controlled trial at 78 medical centres and large hospitals in 19 countries...
September 26, 2016: Lancet Oncology
Asher Mullard
No abstract text is available yet for this article.
September 29, 2016: Nature Reviews. Drug Discovery
Reshma Shinde, Xiting Cao, Smita Kothari
BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements are key therapeutic targets for biomarker-driven treatment with an EGFR or ALK tyrosine kinase inhibitor (TKI) in patients with metastatic non-small cell lung cancer (NSCLC). To appropriately guide treatment decisions, since 2011, the National Comprehensive Cancer Network and the American Society of Clinical Oncology therefore recommend EGFR and ALK analysis in tumor samples obtained at the time of diagnosis in patients with non-squamous NSCLC...
October 2016: Journal of Managed Care & Specialty Pharmacy
Helena Hognert, Helena Kopp Kallner, Sharon Cameron, Christina Nyrelli, Izabella Jawad, Rebecca Heller, Annette Aronsson, Ingela Lindh, Lina Benson, Kristina Gemzell-Danielsson
STUDY QUESTION: Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? SUMMARY ANSWER: A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. WHAT IS ALREADY KNOWN: The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods...
September 22, 2016: Human Reproduction
B Lawrenz, F Beligotti, N Engelmann, D Gates, H M Fatemi
STUDY QUESTION: Does hormonal stimulation with corifollitropin alpha (CFA) only, mimicking a step down protocol, result in lower incidence of progesterone elevation on the day of hCGtrigger as compared to sustained stimulation with recombinant FSH (rFSH)? SUMMARY ANSWER: The current findings support the concept that sustained FSH stimulus contributes to premature progesterone elevation in stimulated IVF cycles. WHAT IS KNOWN ALREADY: Serum progesterone rise during the follicular phase of ovarian stimulation for IVF treatment seems to be related to a poorer reproductive outcome...
September 12, 2016: Human Reproduction
Anne E Cowan, Sarah J Clark, Jennifer L Gordon, Karin Bok, Angela K Shen
BACKGROUND: Vaccine purchasing groups (VPGs) may help reduce the upfront cost of vaccines. The objective of this study was to describe key business practices of VPGs in the United States. METHODS: Semi-structured, qualitative telephone interviews were conducted with representatives from 11 VPGs, based on a sampling frame of 53 VPGs. Interviews were transcribed and summarized by topic. RESULTS: Characteristics of the 11 VPGs interviewed reflect the broader VPG population: 64% national vs 36% regional; 8% charge a membership fee; membership ranging from 40 to over 300,000 sites...
September 30, 2016: Vaccine
Cormac Sheridan
No abstract text is available yet for this article.
September 8, 2016: Nature Biotechnology
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