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Klaus Griesar, John Bessant, Sabine Bernschneider-Reif
The elephant is in the room-a metaphorical idiom for an obvious problem or risk that nobody wants to discuss. This abstract is not intended to be a summary, to reveal major findings, or unveil conclusions. On the contrary, it is aimed to provoke curiosity as to the question of corporate survival. Is there any recipe to be followed for companies to achieve this? The answer comes neither from the modest and traditional study rooms of philosophers nor the recent fact-based studies from the offices (and well-paid opinions) of business consultants...
March 15, 2018: Angewandte Chemie
Adriano Luís Soares De Souza, Stefan Rudin, Rui Chang, Keith Mitchell, Timothy Crandall, Shuning Huang, Ji-Kyung Choi, Shinji L Okitsu, Danielle L Graham, Blake Tomkinson, Tammy Dellovade
INTRODUCTION: Antigen-specific immunotherapy could provide a targeted approach for the treatment of multiple sclerosis that removes the need for broad-acting immunomodulatory drugs. ATX-MS-1467 is a mixture of four peptides identified as the main immune-dominant disease-associated T-cell epitopes in myelin basic protein (MBP), an autoimmune target for activated autoreactive T cells in multiple sclerosis. Previous animal studies have shown that ATX-MS-1467 treatment prevented the worsening of signs of disease in experimental autoimmune encephalitis (EAE) in the humanized (DR2 × Ob1)F1 mouse in a dose-dependent fashion...
March 14, 2018: Neurology and Therapy
R van Eekelen, R I Tjon-Kon-Fat, P M M Bossuyt, N van Geloven, M J C Eijkemans, A J Bensdorp, F van der Veen, B W Mol, M van Wely
STUDY QUESTION: What is the natural conception rate over the course of 12 months in couples with unexplained or mild male subfertility who are scheduled for fertility treatment and have a predicted unfavourable prognosis for natural conception? SUMMARY ANSWER: The natural conception rate over the course of 12 months in couples who were allocated to treatment was estimated to be 24.5% (95% CI: 20-29%). WHAT IS KNOWN ALREADY: After starting treatment, couples often perceive unsuccessful cycles as evidence of definitive failure even though they are still able to conceive naturally in between and after treatment...
March 12, 2018: Human Reproduction
Z K Smith, A J Thompson, J P Hutcheson, W T Nichols, B J Johnson
Crossbred beef steers (n = 240; 12 pens/treatment; initial BW = 305 ± 17.7 kg) were used in a randomized block design feedlot study to evaluate the influence of coated trenbolone acetate (TBA) and estradiol-17β (E2) implants (Merck Animal Health, Madison, NJ) on gain performance, carcass traits, and sera metabolites. The five treatments were no implant (NI), Revalor-XR on d 0 [200 mg TBA + 20 mg E2 (coated); XR], Revalor-XS on d 0 [200 mg TBA + 40 mg E2 (total): 80 mg TBA + 16 mg E2 (non-coated) and 120 mg TBA + 24 mg E2 (coated); XS], Revalor-200 on d 0 [200 mg TBA + 20 mg E2 (non-coated); E200], or Revalor-200 on d 70 (D200)...
March 9, 2018: Journal of Animal Science
Toni K Choueiri, James Larkin, Mototsugu Oya, Fiona Thistlethwaite, Marcella Martignoni, Paul Nathan, Thomas Powles, David McDermott, Paul B Robbins, David D Chism, Daniel Cho, Michael B Atkins, Michael S Gordon, Sumati Gupta, Hirotsugu Uemura, Yoshihiko Tomita, Anna Compagnoni, Camilla Fowst, Alessandra di Pietro, Brian I Rini
BACKGROUND: The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma...
March 9, 2018: Lancet Oncology
Guiqin Wang, Yuling Zeng, Jifeng Xu, Wengui Liu
We report a new method for calibrating the current gain of 1013 Ω amplifiers in both positive and negative mode used in thermal ionisation mass spectrometry (TIMS). This method uses any isotopic standard or sample to calibrate the gain factor as long as it can produce a stable current signal. It is simpler and more flexible than that recommended by Thermo-Fisher (the manufacture of the TIMS). In these analyses, the gains of five 1013 Ω amplifiers were assessed. The precision of gain factors was better than 100 ppm (2 RSD) in a day, and the long term reproducibility was better than 300 ppm (2 RSD) within 2 - 8 months...
March 9, 2018: Journal of Mass Spectrometry: JMS
Katharine C Pike, Melika Akhbari, Dylan Kneale, Katherine M Harris
BACKGROUND: Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere...
March 8, 2018: Cochrane Database of Systematic Reviews
Christine M Durand, Mary G Bowring, Diane M Brown, Michael A Chattergoon, Guido Massaccesi, Nichole Bair, Russell Wesson, Ashraf Reyad, Fizza F Naqvi, Darin Ostrander, Jeremy Sugarman, Dorry L Segev, Mark Sulkowski, Niraj M Desai
Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource. Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R- transplantation)...
March 6, 2018: Annals of Internal Medicine
Irina A Tikhonova, Nicola Huxley, Tristan Snowsill, Louise Crathorne, Jo Varley-Campbell, Mark Napier, Martin Hoyle
BACKGROUND: Combination therapies with cetuximab (Erbitux® ; Merck Serono UK Ltd) and panitumumab (Vectibix® ; Amgen UK Ltd) are shown to be less effective in adults with metastatic colorectal cancer who have mutations in exons 2, 3 and 4 of KRAS and NRAS oncogenes from the rat sarcoma (RAS) family. OBJECTIVE: The objective of the study was to estimate the cost effectiveness of these drugs in patients with previously untreated RAS wild-type (i.e. non-mutated) metastatic colorectal cancer, not eligible for liver resection at baseline, from the UK National Health Service and Personal Social Services perspective...
March 1, 2018: PharmacoEconomics
Shu-Yu Lin, Teng-Kuang Yeh, Jen-Shin Song, Ming-Shiu Hung, Ming-Fu Cheng, Fang-Yu Liao, An-Shiou Li, Shu-Ying Cheng, Li-Mei Lin, Chun-Hsien Chiu, Mine-Hsine Wu, Yi-Jyun Lin, Wenchi Hsiao, Manwu Sun, Yi-Hsin Wang, Chin-Hsiang Huang, Ya-Chu Tang, Hsin-Huei Chang, Zih-Ting Huang, Yu-Sheng Chao, Chuan Shih, Shiow-Lin Pan, Su-Ying Wu, Ching-Chuan Kuo, Shau-Hua Ueng
Indoleamine 2,3-dioxygenase is a heme-containing enzyme implicated in the down regulation of the anti-tumor immune response, and considered a promising anti-cancer drug target. Several pharmaceutical companies, including Pfizer, Merck, and Bristol-Myers Squibb, are known to be in pursuit of IDO inhibitors, and Incyte recently reported good results in the phase II clinical trial of the IDO inhibitor Epacadostat. In previous work, we developed a series of IDO inhibitors based on a sulfonylhydrazide core structure, and explored how they could serve as potent IDO inhibitors with good drug profiles...
February 12, 2018: Bioorganic Chemistry
D Valerio, A Luddi, V De Leo, D Labella, S Longobardi, P Piomboni
STUDY QUESTION: Are cohesins SA1/SA2 and the NAD-dependent deacetylase SIRT1 involved in telomere homeostasis of cumulus cells and thus eligible as biomarkers of follicular physiology and ovarian aging? SUMMARY ANSWER: SA1/SA2 cohesins and SIRT1 are associated with telomere length in cumulus cells and may be eligible biomarkers of follicular physiology and ovarian aging. WHAT IS KNOWN ALREADY: In somatic cells, cohesins SA1/SA2 mediate sister chromatid cohesion at the telomere termini (for SA1) and along chromatid arms (for SA2)...
February 22, 2018: Human Reproduction
Anthony Markham
Ertugliflozin (Steglatro™) is an orally active sodium glucose co-transporter type 2 inhibitor being developed by Merck and Pfizer as a treatment for type 2 diabetes mellitus (T2DM). Ertugliflozin as monotherapy and in combination with various other antidiabetic drugs was associated with improvements in glycaemic control and secondary outcome measures in the VERTIS phase III clinical trial program. Ertugliflozin and fixed-dose combinations of ertugliflozin and metformin (Segluromet™) and ertugliflozin and sitagliptin (Steglujan™) have recently been approved by the US FDA as an adjunct to diet and exercise to improve glycaemic control in adults with T2DM...
February 23, 2018: Drugs
(no author information available yet)
No abstract text is available yet for this article.
February 23, 2018: BMJ: British Medical Journal
Mauricio Sauerbrey, Lindsay J Rakers, Frank O Richards
The Onchocerciasis Elimination Program for the Americas (OEPA) is a regional initiative and international partnership that has made considerable progress toward its goal since it was launched in 1993. Its strategy is based on mass drug administration of ivermectin (Mectizan, donated by MSD, also known as Merck & Co., Inc., Kenilworth, NJ, USA), twice or four times per year, with at least 85% coverage of eligible populations. From 1989 to 2016, 11 741 276 ivermectin treatments have been given in the Americas, eliminating transmission in 11 of 13 foci...
March 1, 2018: International Health
Stergios J Moschos, Ryan J Sullivan, Wen-Jen Hwu, Ramesh K Ramanathan, Alex A Adjei, Peter C Fong, Ronnie Shapira-Frommer, Hussein A Tawbi, Joseph Rubino, Thomas S Rush, Da Zhang, Nathan R Miselis, Ahmed A Samatar, Patrick Chun, Eric H Rubin, James Schiller, Brian J Long, Priya Dayananth, Donna Carr, Paul Kirschmeier, W Robert Bishop, Yongqi Deng, Alan Cooper, Gerald W Shipps, Blanca Homet Moreno, Lidia Robert, Antoni Ribas, Keith T Flaherty
BACKGROUND: Constitutive activation of ERK1/2 occurs in various cancers, and its reactivation is a well-described resistance mechanism to MAPK inhibitors. ERK inhibitors may overcome the limitations of MAPK inhibitor blockade. The dual mechanism inhibitor SCH772984 has shown promising preclinical activity across various BRAFV600/RAS-mutant cancer cell lines and human cancer xenografts. METHODS: We have developed an orally bioavailable ERK inhibitor, MK-8353; conducted preclinical studies to demonstrate activity, pharmacodynamic endpoints, dosing, and schedule; completed a study in healthy volunteers (P07652); and subsequently performed a phase I clinical trial in patients with advanced solid tumors (MK-8353-001)...
February 22, 2018: JCI Insight
Barbara Casassus
No abstract text is available yet for this article.
February 16, 2018: BMJ: British Medical Journal
Bijal Shah-Manek, William Wong, Arliene Ravelo, Marco DiBonaventura
BACKGROUND: The increasing prevalence of cancer coupled with approvals of new drugs and technologies used in therapy have brought increased scrutiny to the cost and value of treatments in oncology. To address the rising concern about oncology drug costs, several organizations have developed value frameworks to help assess the value of oncology regimens. The objective of this study was to assess oncologists' perceptions, awareness, and knowledge of all oncology value frameworks in the United States and to understand oncologists' perceptions of affordability in the context of National Comprehensive Cancer Network (NCCN) Evidence Blocks...
February 16, 2018: Journal of Managed Care & Specialty Pharmacy
(no author information available yet)
In the UK, there are twelve disease-modifying drugs licensed for various forms of multiple sclerosis (MS), of which three are oral therapies. An oral formulation of cladribine (Mavenclad - Merck Serono Europe Limited) was recently licensed by the European Medicines Agency (EMA) for the treatment of adult patients with highly active relapsing MS.1,2 It is claimed to be "an innovatively simple approach" for treating this form of MS and "the only disease modifying therapy that can deliver and sustain 4 years of disease control with a maximum of 20 days oral treatment in the first 2 years...
February 2018: Drug and Therapeutics Bulletin
Mathilde Bahuaud, Constance Beaudouin-Bazire, Marine Husson, Anna Molto, Odile Launay, Frédéric Batteux, Maxime Dougados
OBJECTIVES: Patients with rheumatoid arthritis (RA) are at an increased risk of Pneumococcal infections. Immunogenicity and persistence of a prime-boost revaccination strategy using 13-valent/23-valent anti-pneumococcal vaccines was evaluated in patients with RA treated by Methotrexate (MTX) and anti-TNF. METHOD: Twenty-four patients with RA received one dose of PCV13 (Prevenar13ࣨ; Pfizer) followed two months later by one dose of PPV23 (Pneumovax®, Merck). Concentrations of IgG specific for 7 serotypes common to both vaccines and 3 uncommon serotypes, included only in the PPV23 were measured by ELISA and Opsonophagocytic Assay (OPA) at baseline and after 4, 12 and 24 months post-vaccine...
February 12, 2018: Human Vaccines & Immunotherapeutics
Eileen Wilson, Cong Zhu, Susan Galea, Ann Marko, Veronica Victoria Urdaneta, Walter Straus
BACKGROUND: The Centers for Disease Control and Prevention (CDC) coordinates the Vaccines For Children (VFC) program, which provides free vaccines to qualified children in the US. In 2009, the CDC issued Vaccine Storage Requirements, which were later replaced (2012) with an interim guidance and toolkit for vaccine storage and handling. The guidance called for use of Digital Data Loggers (DDL) to monitor vaccine storage temperatures. We describe a change in frequency of Incorrect Product Storage Reports (IPSRs) following issuance of the 2009 CDC guidance...
February 8, 2018: Vaccine
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