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https://www.readbyqxmd.com/read/28287348/survival-in-idiopathic-pulmonary-fibrosis-perspectives-from-pulmonary-arterial-hypertension
#1
Toby M Maher, Fred Dejonckheere, Steven D Nathan
Maher has received grants, consulting fees, and speaker fees from GlaxoSmithKline and UCB and grants from Novartis. He has also received consulting fees and speaker fees from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, Lanthio, InterMune International AG (a wholly owned Roche subsidiary since 2014), F. Hoffmann-La Roche, Sanofi-Aventis, and Takeda. Maher is supported by a National Institute for Health Research Clinician Scientist Fellowship (NIHR Ref: CS:-2013-13-017). Dejonckheere is an employee of F...
March 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28287347/predicting-life-expectancy-for-pirfenidone-in-idiopathic-pulmonary-fibrosis
#2
Mark Fisher, Steven D Nathan, Christian Hill, Jade Marshall, Fred Dejonckheere, Per-Olof Thuresson, Toby M Maher
BACKGROUND: Conducting an adequately powered survival study in idiopathic pulmonary fibrosis (IPF) is challenging due to the rare nature of the disease and the need for extended follow-up. Consequently, registration trials of IPF treatments have not been designed to estimate long-term survival. OBJECTIVE: To predict life expectancy for patients with IPF receiving pirfenidone versus best supportive care (BSC) in a population that met the inclusion criteria of patients enrolled in the ASCEND and CAPACITY trials...
March 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28279849/discovery-and-pharmacological-evaluation-of-a-novel-series-of-adamantyl-cyanoguanidines-as-p2x7-receptor-antagonists
#3
James O'Brien-Brown, Alexander Jackson, Tristan A Reekie, Melissa L Barron, Eryn L Werry, Paolo Schiavini, Michelle McDonnell, Lenka Munoz, Shane Wilkinson, Benjamin Noll, Shudong Wang, Michael Kassiou
Here we report adamantyl cyanoguanidine compounds based on hybrids of the adamantyl amide scaffold reported by AstraZeneca and cyanoguanidine scaffold reported by Abbott Laboratories. Compound 27 displayed five-fold greater inhibitory potency than the lead compound 2 in both pore-formation and interleukin-1β release assays, while 35-treated mice displayed an antidepressant phenotype in behavioral studies. This SAR study provides a proof of concept for hybrid compounds, which will help in the further development of P2X7R antagonists...
March 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28270720/rate-of-egfr-mutation-testing-for-patients-with-nonsquamous-non-small-cell-lung-cancer-with-implementation-of-reflex-testing-by-pathologists
#4
P K Cheema, S Raphael, R El-Maraghi, J Li, R McClure, L Zibdawi, A Chan, J C Victor, A Dolley, A Dziarmaga
BACKGROUND: Testing for mutation of the EGFR (epidermal growth factor receptor) gene is a standard of care for patients with advanced nonsquamous non-small-cell lung cancer (nsclc). To improve timely access to EGFR results, a few centres implemented reflex testing, defined as a request for EGFR testing by the pathologist at the time of a nonsquamous nsclc diagnosis. We evaluated the impact of reflex testing on EGFR testing rates. METHODS: A retrospective observational review of the Web-based AstraZeneca Canada EGFR Database from 1 April 2010 to 31 March 2014 found centres within Ontario that had requested EGFR testing through the database and that had implemented reflex testing (with at least 2 years' worth of data, including the pre- and post-implementation period)...
February 2017: Current Oncology
https://www.readbyqxmd.com/read/28259610/vandetanib-plus-gemcitabine-versus-placebo-plus-gemcitabine-in-locally-advanced-or-metastatic-pancreatic-carcinoma-vip-a-prospective-randomised-double-blind-multicentre-phase-2-trial
#5
Gary Middleton, Daniel H Palmer, William Greenhalf, Paula Ghaneh, Richard Jackson, Trevor Cox, Anthony Evans, Victoria E Shaw, Jonathan Wadsley, Juan W Valle, David Propper, Harpreet Wasan, Stephen Falk, David Cunningham, Fareeda Coxon, Paul Ross, Srinivasan Madhusudan, Nick Wadd, Pippa Corrie, Tamas Hickish, Eithne Costello, Fiona Campbell, Charlotte Rawcliffe, John P Neoptolemos
BACKGROUND: Erlotinib is an EGFR tyrosine kinase inhibitor that has shown a significant but only marginally improved median overall survival when combined with gemcitabine in patients with locally advanced and metastatic pancreatic cancer. Vandetanib is a novel tyrosine kinase inhibitor of VEGFR2, RET, and EGFR, all of which are in involved in the pathogenesis of pancreatic cancer. We investigated the clinical efficacy of vandetanib when used in combination with gemcitabine in patients with advanced pancreatic cancer...
March 1, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28238711/efficacy-and-safety-of-ticagrelor-versus-aspirin-in-acute-stroke-or-transient-ischaemic-attack-of-atherosclerotic-origin-a-subgroup-analysis-of-socrates-a-randomised-double-blind-controlled-trial
#6
Pierre Amarenco, Gregory W Albers, Hans Denison, J Donald Easton, Scott R Evans, Peter Held, Michael D Hill, Jenny Jonasson, Scott E Kasner, Per Ladenvall, Kazuo Minematsu, Carlos A Molina, Yongjun Wang, K S Lawrence Wong, S Claiborne Johnston
BACKGROUND: Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial...
February 23, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28236271/glucagon-like-peptide-1-receptor-agonist-treatment-attributes-important-to-injection-experienced-patients-with-type-2-diabetes-mellitus-a-preference-study-in-germany-and-the-united-kingdom
#7
Lei Qin, Stephanie Chen, Emuella Flood, Alka Shaunik, Beverly Romero, Marie de la Cruz, Cynthia Alvarez, Susan Grandy
INTRODUCTION: This study assessed the relative importance of treatment-related attributes in influencing patient preferences for glucagon-like peptide-1 receptor agonists (GLP-1RAs) among injection-experienced type 2 diabetes mellitus (T2DM) patients in Germany and the United Kingdom. METHODS: T2DM patients experienced with injecting once-weekly (QW) exenatide or once-daily (QD) liraglutide completed an online discrete-choice experiment (DCE) survey. Patients chose between hypothetical blinded treatment profiles reflecting attributes of GLP-1RAs...
February 24, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28230450/characteristics-and-medication-use-of-psoriasis-patients-who-may-or-may-not-qualify-for-randomized-controlled-trials
#8
William Malatestinic, Beth Nordstrom, Jashin J Wu, Orin Goldblum, Kathleen Solotkin, Chen-Yen Lin, Kristin Kistler, Kathy Fraeman, Joseph Johnston, Lcdr Lesley Hawley, Nicholas Sicignano, Andre Araujo
BACKGROUND: Clinical trials impose exclusion criteria that may limit the generalizability of results. OBJECTIVES: To (a) determine the percentage of real-world patients who would qualify for psoriasis randomized controlled trials; (b) ascertain differences between moderate-to-severe psoriasis patients who would be eligible, ineligible, or potentially eligible for clinical trials; and (c) compare their biologic treatment patterns. METHODS: Moderate-to-severe psoriasis patients were identified from the U...
March 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28230449/real-world-glycemic-control-from-glp-1ra-therapy-with-and-without-concurrent-insulin-in-patients-with-type-2-diabetes
#9
Mukul Singhal, Sudhir Unni, Marisa Schauerhamer, Hiep Nguyen, Jeff Hurd, Carrie McAdam-Marx
BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended as add-on therapy in patients with uncontrolled type 2 diabetes (T2D), with no specific guidance as to timing versus insulin. Furthermore, real-world data assessing GLP-1RA outcomes with or without concurrent insulin therapy are lacking. OBJECTIVE: To identify glycemic response with GLP-1RAs by insulin use in patients with T2D at 1-year follow-up to inform decisions regarding GLP-1RA use with or without insulin...
March 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28218045/the-significance-of-trk-receptors-in-pancreatic-cancer
#10
Matthew D Johnson, Brandon Stone, Bryan J Thibodeau, Andrew M Baschnagel, Sandra Galoforo, Laura E Fortier, Billie Ketelsen, Samreen Ahmed, Zakiya Kelley, Alaa Hana, Thomas G Wilson, John M Robertson, Robert P Jury, George D Wilson
This study investigated the Trk receptor family as a therapeutic target in pancreatic ductal adenocarcinoma and assessed their prognostic significance. Global gene expression analysis was investigated in prospectively collected pancreatic ductal adenocarcinomas that had either undergone neoadjuvant chemoradiation or were treated by surgery. PANC-1 and MIA-PaCa-2 cell lines were investigated to establish whether fractionated radiation altered expression of four neuroendocrine genes and whether this resulted in subsequent changes in radiosensitivity...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28212954/evaluation-of-copd-treatments-a-multicriteria-decision-analysis-of-aclidinium-and-tiotropium-in-the-united-states
#11
Kevin Marsh, Erica Zaiser, Panagiotis Orfanos, Suzanne Salverda, Teresa Wilcox, Shawn Sun, Shailja Dixit
BACKGROUND: Comparisons of the use of aclidinium bromide and tiotropium bromide for the treatment of chronic obstructive pulmonary disease often concentrate on key end points (exacerbations) at the expense of other benefits and risks. Multicriteria decision analysis (MCDA) can help overcome this by using stakeholder preferences to combine multiple end points into an overall value estimate. OBJECTIVES: To evaluate the use of aclidinium bromide twice daily via Pressair™ (AstraZeneca Pharmaceuticals LP, Wilmington, DE) and of tiotropium once daily via HandiHaler(®) (Boehringer Ingelheim Pharmaceuticals, Inc...
January 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28210986/the-role-of-the-pharmacist-in-managing-type-2-diabetes-with-glucagon-like-peptide-1-receptor-agonists-as-add-on-therapy
#12
REVIEW
Jerry Meece
The prevalence and associated clinical burden of type 2 diabetes (T2D) is increasing in the USA and other countries. As a consequence, the role of the pharmacist in managing T2D is expanding, and it is becoming increasingly important for pharmacists to have a complete understanding of the disease course and treatment options. Pharmacists have a key role in the use of injectable therapies, including incretin-based treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This article discusses the role of the pharmacist in the management of patients with T2D, particularly with respect to the use of GLP-1RAs to achieve glycemic control...
February 16, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28195073/effects-of-budesonide-on-the-lung-functions-inflammation-and-apoptosis-in-a-saline-lavage-model-of-acute-lung-injury
#13
D Mokra, P Kosutova, S Balentova, M Adamkov, P Mikolka, J Mokry, M Antosova, A Calkovska
Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28146658/radiation-with-or-without-antiandrogen-therapy-in-recurrent-prostate-cancer
#14
RANDOMIZED CONTROLLED TRIAL
William U Shipley, Wendy Seiferheld, Himanshu R Lukka, Pierre P Major, Niall M Heney, David J Grignon, Oliver Sartor, Maltibehn P Patel, Jean-Paul Bahary, Anthony L Zietman, Thomas M Pisansky, Kenneth L Zeitzer, Colleen A F Lawton, Felix Y Feng, Richard D Lovett, Alexander G Balogh, Luis Souhami, Seth A Rosenthal, Kevin J Kerlin, James J Dignam, Stephanie L Pugh, Howard M Sandler
Background Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. Methods In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0...
February 2, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28138853/sodium-glucose-co-transporter-2-sglt2-inhibitors-comparing-trial-and-real-world-use-study-protocol
#15
Andrew McGovern, Michael Feher, Neil Munro, Simon de Lusignan
BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors (gliflozins) are the newest class of medication available to treat type 2 diabetes (T2DM). Recent findings from the first complete cardiovascular safety trial in SGLT2 inhibitors, the Empagliflozin, Cardiovascular Outcomes, and Mortality in type 2 diabetes (EMPA-REG OUTCOMES) trial, demonstrated reduced cardiovascular outcomes in people with high cardiovascular risk. How to apply these findings to clinical practice remains unclear, with questions remaining on who will reap this cardiovascular benefit...
January 30, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28138556/myocardial-micrornas-associated-with-reverse-remodeling-in-human-heart-failure
#16
Carmen C Sucharov, David P Kao, J David Port, Anis Karimpour-Fard, Robert A Quaife, Wayne Minobe, Karin Nunley, Brian D Lowes, Edward M Gilbert, Michael R Bristow
BACKGROUND: In dilated cardiomyopathies (DCMs) changes in expression of protein-coding genes are associated with reverse remodeling, and these changes can be regulated by microRNAs (miRs). We tested the general hypothesis that dynamic changes in myocardial miR expression are predictive of β-blocker-associated reverse remodeling. METHODS: Forty-three idiopathic DCM patients (mean left ventricular ejection fraction 0.24 ± 0.09) were treated with β-blockers. Serial ventriculography and endomyocardial biopsies were performed at baseline, and after 3 and 12 months of treatment...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28122786/determination-of-incubational-binding-in-in-vitro-microsomal-and-hepatocyte-metabolic-stability-incubations-a-comparison-of-methods
#17
Sofia Chen, Luna Prieto Garcia, Fredrik H Bergstrom, Par Nordell, Ken Grime
Fraction of drug unbound in an in vitro intrinsic clearance (CLint) incubation, fuinc, is an important parameter in the pursuit of accurate clearance predictions and is often predicted using algorithms based on drug lipophilicity measures. Analysis of AstraZeneca's database suggests that simple lipophilicity alone is a relatively poor predictor. Fuinc is typically measured using equilibrium dialysis binding assays but can be measured directly in CLint assays using multiple concentrations of hepatocytes or microsomal protein...
January 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28110919/effect-of-topical-anesthesia-on-pain-from-needle-insertion-and-injection-and-its-relationship-with-anxiety-in-patients-awaiting-apical-surgery-a%C3%A2-randomized-double-blind-clinical-trial
#18
Sin-Yeon Cho, Euiseong Kim, Sung-Ho Park, Byoung-Duck Roh, Chan-Young Lee, Seung-Jong Lee, Il-Young Jung
INTRODUCTION: We aimed to simultaneously investigate the effects of topical anesthesia on needle insertion and injection pain in the labial mucosa of the maxillary central incisors of patients awaiting apical surgery and to assess the relationship between patients' anxiety and pain scores. METHODS: Forty-four patients scheduled for apical surgery of the maxillary anterior incisor or canine were included, and all completed the Modified Dental Anxiety Scale (MDAS) questionnaire...
March 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28106796/preparative-scale-resolution-of-enantiomers-enables-accelerated-drug-discovery-and-development
#19
Hanna Leek, Shalini Andersson
The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agro-chemistry and biotechnology. In drug discovery and development, the enantiomers of a chiral drug depict unique chemical and pharmacological behaviors in a chiral environment, such as the human body, in which the stereochemistry of the chiral drugs determines their pharmacokinetic, pharmacodynamic and toxicological properties. We present a number of challenging case studies of up-to-kilogram separations of racemic or enriched isomer mixtures using preparative liquid chromatography and super critical fluid chromatography to generate individual enantiomers that have enabled the development of new candidate drugs within AstraZeneca...
January 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28078541/glucagon-like-peptide-1-receptor-agonist-glp-1ra-therapy-adherence-for-patients-with-type-2-diabetes-in-a-medicare-population
#20
Hiep Nguyen, Robert Dufour, Amanda Caldwell-Tarr
INTRODUCTION: Anti-diabetes medication regimen adherence is a clinical challenge in elderly patients with type 2 diabetes (T2D) and other comorbidities associated with aging. Glucagon-like peptide-1 receptor agonists (GLP-1RA) therapies such as exenatide once weekly (QW), exenatide twice daily (BID), and liraglutide once daily (QD) are an increasingly used class of drugs with proven efficacy and tolerability. Real-world evidence on adherence to GLP-1RAs in elderly or disabled patients is limited...
January 11, 2017: Advances in Therapy
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