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https://www.readbyqxmd.com/read/28636538/phase-i-dose-escalation-study-of-the-c-met-tyrosine-kinase-inhibitor-sar125844-in-asian-patients-with-advanced-solid-tumors-including-patients-with-met-amplified-gastric-cancer
#1
Kohei Shitara, Tae Min Kim, Tomoya Yokota, Masahiro Goto, Taroh Satoh, Jin-Hee Ahn, Hyo Song Kim, Sylvie Assadourian, Corinne Gomez, Marzia Harnois, Satoshi Hamauchi, Toshihiro Kudo, Toshihido Doi, Yung-Jue Bang
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636294/-selective-therapeutic-de-escalation-in-early-stage-breast-cancer
#2
Aikaterini Liapi, Apostolos Sarivalasis, Wendy Jeanneret Sozzi, Loïc Lelièvre, Khalil Zaman
The survival of patients with breast cancer has improved considerably thanks to adjuvant radiotherapy and systemic treatments. Due to the potential adverse events associated with these treatments, a de-escalation effort was undertaken concerning surgery and more recently the adjuvant treatments. Conservative breast surgery and the avoidance of axillary dissection were possible for the majority of the patients without detrimental effect on survival. New radiotherapy techniques and the consideration of cancer biology allowed to better protect the peripheral organs and even to avoid treatment in certain low-risk patients...
May 17, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28635362/costs-and-effectiveness-of-fingolimod-versus-alemtuzumab-in-the-treatment-of-highly-active-relapsing-remitting-multiple-sclerosis-in-the-uk-retreatment-discount-and-disutility
#3
Stephen M Montgomery, Jeanette Kusel, Richard Nicholas, Nicholas Adlard
OBJECTIVE: Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod or may be considered for alemtuzumab. Previous economic modelling used Markov models; applying one alternative technique, discrete event simulation (DES) modelling, allows retreatment and long-term adverse events (AEs) to be included in the analysis. METHODS: A DES was adapted to model relapse-triggered retreatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous one year Markov cycles...
June 21, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28634283/phase-ib-study-of-utomilumab-pf-05082566-a-4-1bb-cd137-agonist-in-combination-with-pembrolizumab-mk-3475-in-patients-with-advanced-solid-tumors
#4
Anthony W Tolcher, Mario Sznol, Siwen Hu-Lieskovan, Kyriakos P Papadopoulos, Amita Patnaik, Drew Rasco, Donna Di Gravio, Bo Huang, Dhiraj Gambhire, Ying Chen, Aron Thall, Nuzhat Pathan, Emmett V Schmidt, Laura Q M Chow
Purpose:  This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors. <p>Experimental Design:  Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event-continual reassessment method...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28633561/regulation-of-energy-homeostasis-after-gastric-bypass-surgery
#5
Martin L Yarmush, Matthew D'Alessandro, Nima Saeidi
The obesity epidemic continues to escalate each year in the United States more than anywhere else in the world. The existing pharmaceutical and other nonsurgical treatments for morbid obesity produce suboptimal physiologic outcomes compared with those of Roux-en-Y gastric bypass (RYGB) surgery. RYGB has been the gold standard of bariatric surgery because the beneficial long-term outcomes, which include sustainable weight loss and type 2 diabetes mellitus (T2DM) resolution, are far superior to those obtained with other bariatric surgeries...
June 21, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/28633362/human-papillomavirus-related-oropharyngeal-cancer
#6
M Taberna, M Mena, M A Pavón, L Alemany, M L Gillison, R Mesía
High-risk (HR) human papillomavirus (HPV) is now recognised as the principal cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in some parts of the world.The primary risk factor for developing HPV-related OPSCC is oral HPV-infection and the majority of oral HPV-infections are acquired by oral sex. Progression into a OPSCC includes persistent infection with evasion of immune response in the microenvironment, the activation of viral early genes (E6, E7) in basal epithelial cells, the deregulation of cell cycle and the accumulation of chromosomal instability...
June 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28632196/drug-hypersensitivity-and-desensitizations-mechanisms-and-new-approaches
#7
REVIEW
Leticia de Las Vecillas Sánchez, Leila A Alenazy, Marlene Garcia-Neuer, Mariana C Castells
Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS)...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28631197/prioritizing-future-research-on-allopurinol-and-febuxostat-for-the-management-of-gout-value-of-information-analysis
#8
Eric Jutkowitz, Fernando Alarid-Escudero, Hyon K Choi, Karen M Kuntz, Hawre Jalal
OBJECTIVES: The aim of this study was to quantify the value of conducting additional research and reducing uncertainty regarding the cost effectiveness of allopurinol and febuxostat for the management of gout. METHODS: We used a previously developed Markov model that evaluated the cost effectiveness of nine urate-lowering strategies: no treatment, allopurinol-only fixed dose (300 mg), allopurinol-only dose escalation (up to 800 mg), febuxostat-only fixed dose (80 mg), febuxostat-only dose escalation (up to 120 mg), allopurinol-febuxostat sequential therapy fixed dose, allopurinol-febuxostat sequential therapy dose escalation, febuxostat-allopurinol sequential therapy fixed dose, and febuxostat-allopurinol sequential therapy dose escalation...
June 19, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28630876/a-dosimetric-comparison-of-dose-escalation-with-simultaneous-integrated-boost-for-locally-advanced-non-small-cell-lung-cancer
#9
Wenjuan Yang, Biao Zeng, Yanfang Qiu, Jianfeng Tan, Shilei Xu, Yilong Cai, Yujuan Zhou, Zhigang Liu, Junming Luo, Hui Wang
BACKGROUND: Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-small-cell lung cancer (NSCLC). We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) in locally advanced NSCLC. METHODS: We enrolled twenty patients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60 Gy to the planning tumor volume (PTV)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28630629/the-cedar-study-a-longitudinal-study-of-the-clinical-effects-of-conventional-dmards-and-biologic-dmards-in-australian-rheumatology-practice
#10
Lynden Roberts, Kathleen Tymms, Julien de Jager, Geoffrey Littlejohn, Hedley Griffiths, Dave Nicholls, Paul Bird, Jennifer Young, Julie Hill, Jane Zochling
OBJECTIVES: To observe the choices of conventional disease modifying antirheumatic drugs (cDMARDs) and biologic DMARDs (bDMARDs) in the management of rheumatoid arthritis (RA) in Australian routine clinical practice, to assess treatment survival and determine the effect of cDMARDs/bDMARDs on disease activity. METHODS: Routinely collected, deidentified clinical data was sourced from 20 Australian rheumatology practices. RA patients aged ≥18 years, who had received cDMARDs/bDMARDs and a recorded subsequent visit, were included...
2017: International Journal of Rheumatology
https://www.readbyqxmd.com/read/28630239/an-unusual-case-of-escherichia-coli-o157-h7-infection-with-pseudomembranous-colitis-like-lesions-associated-with-haemolytic-uraemic-syndrome-and-neurological-sequelae
#11
James Kennedy, Lauren Simmonds, Robert Orme, Warren Doherty
A 75-year-old man was admitted with abdominal pain and fresh rectal bleeding. Significantly, he had no risk factors for Clostridium difficile infection. An abdominal CT demonstrated colonic thickening, and flexible sigmoidoscopy identified pseudomembranous colitis-like lesions. After initial treatment as C. difficile colitis, a stool sample revealed Escherichia coli O157:H7 infection. Antibiotic therapy was stopped due to the risk of lysis-mediated toxin release, but unfortunately, the patient continued to deteriorate...
June 18, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28630187/cumulative-effect-of-an-antimicrobial-stewardship-and-rapid-diagnostic-testing-bundle-on-early-streamlining-of-antimicrobial-therapy-in-gram-negative-bloodstream-infections
#12
P B Bookstaver, E B Nimmich, T J Smith, J A Justo, J Kohn, K L Hammer, C Troficanto, H A Albrecht, M N Al-Hasan
OBJECTIVES: The use of rapid diagnostic tests (RDT) enhances antimicrobial stewardship programs (ASP) interventions in optimization of antimicrobial therapy. This quasi-experimental cohort study evaluates the combined impact of an ASP/RDT bundle on appropriateness of empirical antimicrobial therapy (EAT) and time to de-escalation of broad-spectrum agents (BSAA) in gram-negative bloodstream infections (GNBSI). METHODS: ASP/RDT bundle consisted of a system-wide GNBSI treatment guidelines, prospective stewardship monitoring, and sequential introduction of two RDTs, Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) and FilmArray® Blood Culture Identification (BCID) panel...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630047/update-on-anti-tumor-necrosis-factor-agents-and-other-new-drugs-for-inflammatory-bowel-disease
#13
REVIEW
Benjamin L Cohen, David B Sachar
The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs...
June 19, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28629442/treatment-patterns-healthcare-resource-utilization-and-costs-following-first-line-antidepressant-treatment-in-major-depressive-disorder-a-retrospective-us-claims-database-analysis
#14
Geneviève Gauthier, Annie Guérin, Maryia Zhdanava, William Jacobson, George Nomikos, Elizabeth Merikle, Clément François, Vanessa Perez
BACKGROUND: Although the symptoms of major depressive disorder (MDD) are often manageable with pharmacotherapy, response to first-line antidepressant treatment is often less than optimal. This study describes long-term treatment patterns in MDD patients in the United States and quantifies the economic burden associated with different treatment patterns following first-line antidepressant therapy. METHODS: MDD patients starting first-line antidepressant monotherapy and having continuous enrollment ≥12 months before and ≥24 months following the index date (i...
June 19, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28628868/an-overview-on-exploration-and-environmental-impact-of-unconventional-gas-sources-and-treatment-options-for-produced-water
#15
REVIEW
Tânia L S Silva, Sergio Morales-Torres, Sérgio Castro-Silva, José L Figueiredo, Adrián M T Silva
Rising global energy demands associated to unbalanced allocation of water resources highlight the importance of water management solutions for the gas industry. Advanced drilling, completion and stimulation techniques for gas extraction, allow more economical access to unconventional gas reserves. This stimulated a shale gas revolution, besides tight gas and coalbed methane, also causing escalating water handling challenges in order to avoid a major impact on the environment. Hydraulic fracturing allied to horizontal drilling is gaining higher relevance in the exploration of unconventional gas reserves, but a large amount of wastewater (known as "produced water") is generated...
June 16, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28628679/safety-and-efficacy-of-escalating-doses-of-ingenol-mebutate-for-field-treatment-of-actinic-keratosis-on-the-full-face-full-balding-scalp-or-chest
#16
C William Hanke, Brian Berman, Neil Swanson, David M Pariser, Jonathan S Weiss, Michael Bukhalo, Torsten Skov, John Villumsen, Daniel Siegel
<p>Background: Actinic keratosis (AK) can affect large skin areas. Ingenol mebutate (IngMeb) gel (0.015% and 0.05%) is approved for topical treatment of AK in a single contiguous area of ~25 cm2.</p> <p>Objective: The study sought to determine the maximum tolerated dose (MTD), efficacy, and tolerability of IngMeb applied to AK on a contiguous area less than equal to 250 cm2.</p> <p>Methods: Part 1 determined the MTD of IngMeb at 7 concentrations for 2 or 3 days. Part 2 assessed efficacy and tolerability at the MTD and one dose lower for 2 or 3 days vs vehicle...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28627952/clinical-efficacy-of-piperacillin-tazobactam-in-the-treatment-of-complicated-skin-and-soft-tissue-infections
#17
Kohei Takimoto, Qianzhi Wang, Daisuke Suzuki, Mitsuya Katayama, Yoshiro Hayashi
Introduction Complicated skin and soft tissue infections (cSSTIs) are skin and soft tissue infections (SSTIs) that involve deep soft tissue. cSSTIs often require surgical intervention and/or hospitalization. cSSTIs are associated with significant mortality and morbidity, and carry a significant burden on health care systems. Piperacillin/tazobactam has been regarded as a standard treatment for cSSTIs because of its antibiotic spectrum, safety and clinical efficacy. Several antibiotics, as compared to piperacillin/tazobactam, have been evaluated in the treatment of cSSTIs...
June 19, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28624695/first-in-human-phase-i-study-of-oral-s49076-a-unique-met-axl-fgfr-inhibitor-in-advanced-solid-tumours
#18
Jordi Rodon, Sophie Postel-Vinay, Antoine Hollebecque, Paolo Nuciforo, Analia Azaro, Valérie Cattan, Lucie Marfai, Isabelle Sudey, Karl Brendel, Audrey Delmas, Stéphanie Malasse, Jean-Charles Soria
BACKGROUND AND OBJECTIVES: S49076 is a novel ATP-competitive tyrosine kinase inhibitor of MET, AXL and FGFR with a unique selectivity profile. A phase I open-label study was undertaken to establish the tolerability profile and determine the recommended dose (RD) and administration schedule. MATERIALS AND METHODS: Patients with advanced solid tumours received S49076 orally once-daily (qd) or twice-daily (bid) in continuous 21-day cycles at escalating doses guided by a 3 + 3 design and followed by an expansion phase at the RD...
June 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28624586/modeling-the-development-of-drug-addiction-in-male-and-female-animals
#19
REVIEW
Wendy J Lynch
An increasing emphasis has been placed on the development and use of animal models of addiction that capture defining features of human drug addiction, including escalation/binge drug use, enhanced motivation for the drug, preference for the drug over other reward options, use despite negative consequences, and enhanced drug-seeking/relapse vulnerability. The need to examine behavior in both males and females has also become apparent given evidence demonstrating that the addiction process occurs differently in males and females...
June 14, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28623085/variability-of-treatment-planning-of-seed-implantation-a-japanese-multicenter-simulation-study
#20
Hiromichi Ishiyama, Masahiro Nakano, Kazuhito Toya, Ryuichi Kota, Koyo Kikuchi, Takahiro Yamaguchi, Naoaki Kono, Shogo Kawakami, Yuki Tsutsumi, Tomoki Tanaka, Takahisa Eriguchi, Saiji Ohga, Toshihiro Yamaguchi, Yoshiaki Takakawa, Masashi Morita, Norihisa Katayama, Toshio Ohashi, Manabu Aoki, Atsunori Yorozu, Siro Saito
PURPOSE: This multicenter study was conducted to evaluate the current variability of treatment planning of seed implantation in Japanese centers and the feasibility of two virtual trials. METHODS AND MATERIALS: Two types of contour data were sent to 12 radiation oncologists with a request letter that asked them to make treatment plans on the data in the same manner as in their own practice. Five of the 12 radiation oncologists were asked to participate in the two virtual trials in which the D90 (dose to the hottest 90% of prostate volume) was 1) required to be set at just 180 Gy and 2) increased as much as possible without violating other limitations...
June 13, 2017: Brachytherapy
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