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https://www.readbyqxmd.com/read/28087591/clinical-trials-in-antineutrophil-cytoplasmic-antibody-associated-vasculitis-what-we-have-learnt-so-far-and-what-we-still-have-to-learn
#1
Divi Cornec, Emilie Cornec-Le Gall, Ulrich Specks
The prognosis of the antineutrophil cytoplasmic antibody associated vasculitides (AAV), microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA), has been fundamentally improved over the last five decades by the use of glucocorticoids and immunosuppressants, turning them from consistently fatal diseases into chronic conditions. The long-term course is now largely determined by the frequency of disease flares and by accruing damage caused by disease activity and treatment-related comorbidities...
January 12, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28087265/myocardial-relaxation-is-accelerated-by-fast-stretch-not-reduced-afterload
#2
Charles S Chung, Charles W Hoopes, Kenneth S Campbell
Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction...
January 10, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28079566/retesting-the-hypothesis-of-a-clinical-randomized-controlled-trial-in-a-simulation-environment-to-validate-anesthesia-simulation-in-error-research-the-vaser-study
#3
Alan F Merry, Jacqueline A Hannam, Craig S Webster, Kylie-Ellen Edwards, Jane Torrie, Chris Frampton, Daniel W Wheeler, Arun K Gupta, Ravi P Mahajan, Rachel Evley, Jennifer M Weller
BACKGROUND: Simulation has been used to investigate clinical questions in anesthesia, surgery, and related disciplines, but there are few data demonstrating that results apply to clinical settings. We asked "would results of a simulation-based study justify the same principal conclusions as those of a larger clinical study?" METHODS: We compared results from a randomized controlled trial in a simulated environment involving 80 cases at three centers with those from a randomized controlled trial in a clinical environment involving 1,075 cases...
January 12, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28078996/kinase-inhibitors-in-multitargeted-cancer-therapy
#4
Carla Gentile, Annamaria Martorana, Antonino Lauria, Riccardo Bonsignore
The old-fashioned anticancer approaches, aiming in arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual single-target drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28078991/vegetable-organosulfur-compounds-and-their-health-promoting-effects
#5
Spyridon A Petropoulos, Francesco Di Gioia, Georgia Ntatsi
BACKGROUND: Trends in modern pharmaceutical science show an increase in demand for new drugs and diet supplements derived from natural products, while during the last decades, great research is conducted regarding the natural compounds and their medicinal and bioactive properties. Organosulfur compounds are present in many plants and their bioactive properties have been used in folk and traditional medicine throughout the centuries. Not until recently, modern science confirmed and revealed the chemical compounds that are responsible for these properties, the chemistry involved in their biosynthesis and the main mechanisms of action...
January 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28078982/phytochemicals-a-novel-and-prominent-source-of-anti-cancer-drugs-against-colorectal-cancer
#6
Ravikiran Mahadevappa, Hang Fai Kwok
Colorectal cancer (CRC) is a malignant disease whose incidence and mortality rates are greatly influenced by environmental factors. Under-treatment of CRC such as a poor diagnostic evaluation, less aggressive surgery, less intensive chemotherapy results in metastasizing of the primary tumor cells and recurrence of cancer. Prolonged chemotherapy treatment against cancer is hazardous to the patients, which also limits its use in cancer therapy. Current research in developing a novel anti-cancer agent, direct towards finding a better anti-metastatic and an anti-invasive drug with reduced side effects...
January 12, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28078079/looking-forward-to-new-targeted-treatments-for-chronic-spontaneous-urticaria
#7
REVIEW
Emek Kocatürk, Marcus Maurer, Martin Metz, Clive Grattan
The introduction of omalizumab to the management of chronic spontaneous urticaria (CSU) has markedly improved the therapeutic possibilities for both, patients and physicians dealing with this disabling disease. But there is still a hard core of patients who do not tolerate or benefit from existing therapies and who require effective treatment. Novel approaches include the use of currently available drugs off-licence, investigational drugs currently undergoing clinical trials and exploring the potential for therapies directed at pathophysiological targets in CSU...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/28076854/open-angle-glaucoma-drug-development-pipeline-during-the-last-20-years-1995-2015
#8
André Vicente, Sylvie Prud'homme, Joana Ferreira, Luís Abegão Pinto, Ingeborg Stalmans
OBJECTIVES: To analyse drug development for open-angle glaucoma during the last 20 years. METHODS: Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition "open-angle glaucoma" with the intervention "drug" was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered...
January 12, 2017: Ophthalmic Research
https://www.readbyqxmd.com/read/28076528/the-brief-life-of-norplant%C3%A2-in-brazil-controversies-and-reassemblages-between-science-society-and-state
#9
Ana Cristina de Lima Pimentel, Cláudia Bonan Jannotti, Paula Gaudenzi, Luiz Antonio da Silva Teixeira
Norplant® is the brand name of the world's first registered subdermal hormonal contraceptive implant, developed by the laboratories of the Population Council, an international organisation working in the area of fertility and population growth. The article revisits the trajectory of this contraceptive in Brazil from its arrival through clinical trials to its eventual ban in 1986 by the Brazilian regulatory agency responsible for approving medications at the time. Its circulation generated controversies related to research practices, side effects and political uses of the drug as a birth control method...
January 2017: Ciência & Saúde Coletiva
https://www.readbyqxmd.com/read/28075527/recent-development-of-the-second-and-third-generation-irreversible-egfr-inhibitors
#10
REVIEW
Weiwei Han, Yongli Du
Recent reports suggested that essential directions for new lung cancer, breast carcinoma therapies, as well as the roomier realm of targeted cancer therapies were provided through targeting the epidermal growth factor receptor (EGFR). Patients who carrying non-small cell lung carcinoma (NSCLC) with activating mutations in EGFR initially respond well to the EGFR inhibitors erlotinib and gefitinib, which were located the active site of the EGFR kinase and designed to act as competitive inhibitors of combining with the ATP...
January 11, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28075105/heart-failure-due-to-reduced-ejection-fraction-medical-management
#11
William E Chavey, Robrt V Hogikyan, R Van Harrison, John M Nicklas
Heart failure is an increasingly common condition resulting in high rates of morbidity and mortality. For patients who have heart failure and reduced ejection fraction, randomized clinical trials demonstrate consistent mortality benefit from angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, direct-acting vasodilators, beta blockers, and aldosterone antagonists. Additionally, some data show benefits from two new classes of drugs: angiotensin receptor blocker/neprilysin inhibitor and sinus node modulator...
January 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28073867/the-maimed-martian-credible-intervals-and-bias-against-benefit
#12
David Kault
A sad little story about a maimed Martian astronaut is used to illustrate a method of improving confidence interval (CI) calculations. CIs in medical statistics are currently calculated from the data available in a clinical trial or meta-analysis considered in isolation from all other information available on earth. Likewise, the Martian in the story uses only information available to it, in isolation from further information from earth. However, there is further objective knowledge available to people on earth to improve the Martian's estimate...
January 10, 2017: Evidence-based Medicine
https://www.readbyqxmd.com/read/28071818/safety-profile-of-the-direct-oral-anticoagulants-an-analysis-of-the-who-database-of-adverse-drug-reactions
#13
Luca Monaco, Chiara Biagi, Valentino Conti, Mauro Melis, Monia Donati, Mauro Venegoni, Alberto Vaccheri, Domenico Motola
AIM: Direct oral anticoagulants (DOACs) have shown non-inferiority to warfarin for stroke prevention in non-valvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase...
January 10, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28070712/microdialysis-monitoring-in-clinical-traumatic-brain-injury-and-its-role-in-neuroprotective-drug-development
#14
Eric Peter Thelin, Keri L H Carpenter, Peter J Hutchinson, Adel Helmy
Injuries to the central nervous system continue to be vast contributors to morbidity and mortality; specifically, traumatic brain injury (TBI) is the most common cause of death during the first four decades of life. Several modalities are used to monitor patients suffering from TBI in order to prevent detrimental secondary injuries. The microdialysis (MD) technique, introduced during the 1990s, presents the treating physician with a robust monitoring tool for brain chemistry in addition to conventional intracranial pressure monitoring...
January 9, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28068987/effects-of-acetyl-dl-leucine-on-cerebellar-ataxia-alcat-trial-study-protocol-for-a-multicenter-multinational-randomized-double-blind-placebo-controlled-crossover-phase-iii-trial
#15
Katharina Feil, Christine Adrion, Julian Teufel, Sylvia Bösch, Jens Claassen, Ilaria Giordano, Holger Hengel, Heike Jacobi, Thomas Klockgether, Thomas Klopstock, Wolfgang Nachbauer, Ludger Schöls, Claudia Stendel, Ellen Uslar, Bart van de Warrenburg, Ingrid Berger, Ivonne Naumann, Otmar Bayer, Hans-Helge Müller, Ulrich Mansmann, Michael Strupp
BACKGROUND: Cerebellar ataxia (CA) is a frequent and often disabling condition that impairs motor functioning and impacts on quality of life (QoL). No medication has yet been proven effective for the symptomatic or even causative treatment of hereditary or non-hereditary, non-acquired CA. So far, the only treatment recommendation is physiotherapy. Therefore, new therapeutic options are needed. Based on three observational studies, the primary objective of the acetyl-DL-leucine on ataxia (ALCAT) trial is to examine the efficacy and tolerability of a symptomatic therapy with acetyl-DL-leucine compared to placebo on motor function measured by the Scale for the Assessment and Rating of Ataxia (SARA) in patients with CA...
January 10, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28068669/kinetically-e-selective-macrocyclic-ring-closing-metathesis
#16
Xiao Shen, Thach T Nguyen, Ming Joo Koh, Dongmin Xu, Alexander W H Speed, Richard R Schrock, Amir H Hoveyda
Macrocyclic compounds are central to the development of new drugs, but preparing them can be challenging because of the energy barrier that must be surmounted in order to bring together and fuse the two ends of an acyclic precursor such as an alkene (also known as an olefin). To this end, the catalytic process known as ring-closing metathesis (RCM) has allowed access to countless biologically active macrocyclic organic molecules, even for large-scale production. Stereoselectivity is often critical in such cases: the potency of a macrocyclic compound can depend on the stereochemistry of its alkene; alternatively, one isomer of the compound can be subjected to stereoselective modification (such as dihydroxylation)...
January 9, 2017: Nature
https://www.readbyqxmd.com/read/28067079/mglu5-negative-allosteric-modulators-a-patent-review-2013-2016
#17
Kyle A Emmitte
The pursuit of small molecule mGlu5 NAMs as treatments for a variety of psychiatric and neurodegenerative disorders has developed into a mature field. In addition to extensive preclinical studies, multiple compounds have advanced into clinical trials with the most advanced studies occurring in patients with FXS, PD-LID, and MDD. Areas covered: This review begins with an update of the clinical activity with mGlu5 NAMs, and then moves into a summary of patent applications filed since 2013. The summaries are organized into three separate sections: (1) inventions centered on improvements to existing clinical compounds; (2) new small molecules that maintain the prototypical disubstituted alkyne chemotype found in many mGlu5 NAM compounds; and (3) new small molecules that are not from a disubstituted alkyne chemotype...
January 8, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28066534/chagas-disease-research-and-development-is-there-light-at-the-end-of-the-tunnel
#18
REVIEW
Eric Chatelain
Chagas disease, or American trypanosomiasis, is the result of infection by the parasite Trypanosoma cruzi. It is endemic in Latin America, and spreading around the globe due to human migration. Although it was first identified more than a century ago, only two old drugs are available for treatment and a lot of questions related to the disease progression, its pathologies, and not to mention the assessment of treatment efficacy, are subject to debate and remain to be answered. Indeed, the current status of evidence and data available does not allow any absolute statement related to treatment needs and outcome for Chagas patients to be made...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28066096/pain-on-propofol-injection-causes-and-remedies
#19
REVIEW
Kalindi Anil Desousa
Pain on propofol injection (POPI) is a minor problem that all anesthetists face every day. Introduction of several new formulations and hundreds of clinical trials have failed to find its remedy with just one intervention in all patients. This article highlights the causes of POPI and interventions that are used to eliminate this pain in current practice. Relevant articles from Medline and Embase databases were searched and included in this descriptive review with the following conclusions: (1) POPI is due to irritation of venous adventitia leading to release of mediators such as kininogen from kinin cascade...
November 2016: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28064554/evaluating-bempedoic-acid-for-the-treatment-of-hyperlipidaemia
#20
Peter Penson, Mary McGowan, Maciej Banach
Despite the effectiveness of statins in the treatment of lipid disorders, residual risk still exists, and hitherto studies where additional drugs were added to statin therapy have been mainly negative or the outcomes were very modest. Therefore there is still a need for new and effective oral agents in the combination therapy of lipid disorders. Areas Covered: The review covers the current state of knowledge on the mechanism of action of bempedoic acid (ETC-1002) and results from recent clinical studies. Expert Opinion: ETC-1002 is a novel oral lipid-lowering therapy...
January 9, 2017: Expert Opinion on Investigational Drugs
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