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https://www.readbyqxmd.com/read/28817373/cabozantinib-as-salvage-therapy-for-patients-with-tyrosine-kinase-inhibitor-refractory-differentiated-thyroid-cancer-results-of-a-multicenter-phase-ii-international-thyroid-oncology-group-trial
#1
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817366/trajectory-of-dyspnea-and-respiratory-distress-among-patients-in-the-last-month-of-life
#2
Margaret L Campbell, Jason M Kiernan, John Strandmark, Hossein N Yarandi
BACKGROUND: The trajectory of dyspnea has been reported among patients approaching the end of life. However, patients near death have been dropped from longitudinal studies or excluded altogether because of an inability to self-report; proxy estimates have been reported. It is not known whether dyspnea or respiratory distress remains stable, escalates, or abates as patients reach last days. OBJECTIVE: Determine trajectory of dyspnea (self-reported) and respiratory distress (observed) among patients who were approaching death...
August 17, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28817229/performance-equivalency-between-computer-based-and-traditional-pen-and-paper-assessment-a-case-study-in-clinical-anatomy
#3
Bruno Guimarães, José Ribeiro, Bernardo Cruz, André Ferreira, Hélio Alves, Ricardo Cruz-Correia, Maria Dulce Madeira, Maria Amélia Ferreira
The time, material, and staff-consuming nature of anatomy's traditional pen-and-paper assessment system, the increase in the number of students enrolling in medical schools and the ever-escalating workload of academic staff have made the use of computer-based assessment (CBA) an attractive proposition. To understand the impact of such shift in the assessment method, an experimental study evaluating its effect on students' performance was designed. Additionally, students' opinions toward CBA were gathered. Second-year medical students attending a Clinical Anatomy course were randomized by clusters in two groups...
August 17, 2017: Anatomical Sciences Education
https://www.readbyqxmd.com/read/28817190/a-phase-1-and-2-study-of-filanesib-alone-and-in-combination-with-low-dose-dexamethasone-in-relapsed-refractory-multiple-myeloma
#4
Jatin J Shah, Jonathan L Kaufman, Jeffrey A Zonder, Adam D Cohen, William I Bensinger, Brandi W Hilder, Selena A Rush, Duncan H Walker, Brian J Tunquist, Kevin S Litwiler, Mieke Ptaszynski, Robert Z Orlowski, Sagar Lonial
BACKGROUND: Filanesib (ARRY-520) is a highly selective inhibitor of kinesin spindle protein, which has demonstrated preclinical antimyeloma activity. METHODS: This open-label Phase 1/2 study determined the maximum tolerated dose of Filanesib administered on Days 1 and 2 of 14-Day Cycles in patients with multiple myeloma (MM) and included expansion cohorts with and without dexamethasone (40 mg/week). Patients in the dose-escalation (N = 31) and Phase 2 single-agent (N = 32) cohorts had received prior bortezomib as well as prior thalidomide and/or lenalidomide...
August 17, 2017: Cancer
https://www.readbyqxmd.com/read/28816767/allopurinol-medication-adherence-as-a-mediator-of-optimal-outcomes-in-gout-management
#5
Brian W Coburn, Kayli A Bendlin, Harlan Sayles, Jane Meza, Cynthia L Russell, Ted R Mikuls
BACKGROUND: Patient and provider factors, including allopurinol medication adherence, affect gout treatment outcomes. OBJECTIVES: The aim of this study was to examine associations of patient and provider factors with optimal gout management. METHODS: Linking longitudinal health and pharmacy dispensing records to questionnaire data, we assessed patient and provider factors among 612 patients with gout receiving allopurinol during a recent 1-year period...
August 14, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28816160/the-impact-of-cardiac-radiation-dosimetry-on-survival-after-radiation-therapy-for-non-small-cell-lung-cancer
#6
S Vivekanandan, D B Landau, N Counsell, D R Warren, A Khwanda, S D Rosen, E Parsons, Y Ngai, L Farrelly, L Hughes, M A Hawkins, J D Fenwick
PURPOSE: The heart receives high radiation doses during radiation therapy of advanced-stage lung cancer. We have explored associations between overall survival, cardiac radiation doses, and electrocardiographic (ECG) changes in patients treated in IDEAL-CRT, a trial of isotoxically escalated concurrent chemoradiation delivering tumor doses of 63 to 73 Gy. METHODS AND MATERIALS: Dosimetric and survival data were analyzed for 78 patients. The whole heart, pericardium, AV node, and walls of left and right atria (LA/RA-Wall) and ventricles (LV/RV-Wall) were outlined on radiation therapy planning scans, and differential dose-volume histograms (dDVHs) were calculated...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28816150/phase-1-study-of-ipilimumab-combined-with-whole-brain-radiation-therapy-or-radiosurgery-for-melanoma-patients-with-brain-metastases
#7
Noelle L Williams, Evan J Wuthrick, Hyun Kim, Joshua D Palmer, Shivank Garg, Harriet Eldredge-Hindy, Constantine Daskalakis, Kendra J Feeney, Michael J Mastrangelo, Lyndon J Kim, Takami Sato, Kari L Kendra, Thomas Olencki, David A Liebner, Christopher J Farrell, James J Evans, Kevin D Judy, David W Andrews, Adam P Dicker, Maria Werner-Wasik, Wenyin Shi
PURPOSE: We performed a phase 1 study to determine the maximum tolerable dose and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) in patients with brain metastases from melanoma. METHODS AND MATERIALS: Based on the intracranial disease burden, patients underwent WBRT (arm A) or SRS (arm B). The ipilimumab starting dose was 3 mg/kg every 3 weeks, starting on day 3 of WBRT or 2 days after SRS. The ipilimumab dose was escalated to 10 mg/kg using a 2-stage, 3+3 design...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28816142/vorinostat-and-concurrent-stereotactic-radiosurgery-for-non-small-cell-lung-cancer-brain-metastases-a-phase-1-dose-escalation-trial
#8
Clara Y H Choi, Heather A Wakelee, Joel W Neal, Mary C Pinder-Schenck, Hsiang-Hsuan Michael Yu, Steven D Chang, John R Adler, Leslie A Modlin, Griffith R Harsh, Scott G Soltys
PURPOSE: To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates. MATERIALS AND METHODS: In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28815736/the-diagnosis-and-management-of-contact-lens-related-microbial-keratitis
#9
REVIEW
Nicole Carnt, Chameen Samarawickrama, Andrew White, Fiona Stapleton
Contact lens-associated microbial keratitis poses a diagnostic dilemma for optometrists on two fronts. The distinction between sterile inflammation and microbial infection is often blurred. In addition, there is a requirement with nearly 50 per cent of the Australian and New Zealand optometric profession being therapeutically endorsed, to distinguish between cases of infection that can be managed in the community verses those that require escalation to public hospitals that have access to laboratory diagnostic tools and advanced imaging techniques, such as in vivo confocal microscopy...
August 16, 2017: Clinical & Experimental Optometry: Journal of the Australian Optometrical Association
https://www.readbyqxmd.com/read/28814898/reducing-rectal-injury-in-men-receiving-prostate-cancer-radiation-therapy-current-perspectives
#10
REVIEW
Nicholas A Serrano, Noah S Kalman, Mitchell S Anscher
Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28814858/spotlight-on-glycopyrronium-formoterol-fumarate-inhalation-aerosol-in-the-management-of-copd-design-development-and-place-in-therapy
#11
REVIEW
Santosh Dhungana, Gerard J Criner
Long-acting bronchodilators are the mainstay of the treatment of COPD. With the advent of several combination inhalers with long-acting antimuscarinic agents (LAMAs) and long-acting beta agonists (LABAs), the choice of therapy in the treatment of COPD has been ever expanding. With the focus of COPD management shifting from FEV1-based treatment escalation to symptoms and risk-based treatment, we are seeing a paradigm shift in COPD treatment with early introduction of LAMA-LABA combination as a single inhaler...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28814857/when-is-dual-bronchodilation-indicated-in-copd
#12
REVIEW
Mike Thomas, David Mg Halpin, Marc Miravitlles
Inhaled bronchodilator medications are central to the management of COPD and are frequently given on a regular basis to prevent or reduce symptoms. While short-acting bronchodilators are a treatment option for people with relatively few COPD symptoms and at low risk of exacerbations, for the majority of patients with significant breathlessness at the time of diagnosis, long-acting bronchodilators may be required. Dual bronchodilation with a long-acting β2-agonist and long-acting muscarinic antagonist may be more effective treatment for some of these patients, with the aim of improving symptoms...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28814674/rilonacept-maintains-long-term-inflammatory-remission-in-patients-with-deficiency-of-the-il-1-receptor-antagonist
#13
Megha Garg, Adriana A de Jesus, Dawn Chapelle, Paul Dancey, Ronit Herzog, Rafael Rivas-Chacon, Theresa L Wampler Muskardin, Ann Reed, James C Reynolds, Raphaela Goldbach-Mansky, Gina A Montealegre Sanchez
BACKGROUND: Deficiency of IL-1 receptor antagonist (DIRA) is a rare autoinflammatory disease that presents with life-threatening systemic inflammation, aseptic multifocal osteomyelitis, and pustulosis responsive to IL-1-blocking treatment. This study was performed (a) to investigate rilonacept, a long-acting IL-1 inhibitor, in maintaining anakinra-induced inflammatory remission in DIRA patients, (b) to determine doses needed to maintain remission, and (c) to evaluate the safety and pharmacokinetics of rilonacept in young children (<12 years)...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814664/pulmonary-arterial-hypertension-treatment-with-carvedilol-for-heart-failure-a-randomized-controlled-trial
#14
Samar Farha, Didem Saygin, Margaret M Park, Hoi I Cheong, Kewal Asosingh, Suzy Aa Comhair, Olivia R Stephens, Emir C Roach, Jacqueline Sharp, Kristin B Highland, Frank P DiFilippo, Donald R Neumann, W H Wilson Tang, Serpil C Erzurum
BACKGROUND: Right-sided heart failure is the leading cause of death in pulmonary arterial hypertension (PAH). Similar to left heart failure, sympathetic overactivation and β-adrenoreceptor (βAR) abnormalities are found in PAH. Based on successful therapy of left heart failure with β-blockade, the safety and benefits of the nonselective β-blocker/vasodilator carvedilol were evaluated in PAH. METHODS: PAH Treatment with Carvedilol for Heart Failure (PAHTCH) is a single-center, double-blind, randomized, controlled trial...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814591/spleno-renal-artery-transposition-in-a-solitary-functioning-kidney-for-treatment-resistant-hypertension-and-acute-kidney-injury
#15
Subash Somalanka, Fiona E Harris, Eric Chemla, Rebecca Jo Suckling, Pauline A Swift
Renal Artery Stenosis (RAS) is an important cause of treatment-resistant hypertension. Uncontrolled hypertension with RAS can cause progressive chronic kidney disease (CKD) leading to end-stage kidney disease. Therapeutic revascularisation can be helpful in appropriate circumstances where pharmaceutical intervention has failed and significant renovascular disease contributes to resistant hypertension. We present an interesting case of a Caucasian male with peripheral vasculopathy, abdominal aortic aneurysm (AAA), single functioning kidney and ostial RAS caused by stent struts from an endovascular AAA stent graft...
August 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28814476/phase-i-trial-of-the-androgen-receptor-modulator-cr1447-in-breast-cancer
#16
Martin Zweifel, Beat Thuerlimann, Salome Riniker, Patrik Weder, Roger von Moos, Olivia Pagani, Martin Bigler, Karin M Rothgiesser, Christiane Pilop, Hanne Hawle, Peter Brauchli, Coya Tapia, Wolfgang Schoenfeld, Cristiana Sessa
CR 1447 (4-hydroxytestosterone, 4-OHT) binds to the androgen receptor and has antiproliferative activity in both ER-positive and ER-negative/AR-positive breast cancer cells in pre-clinical studies. The objective of this first-in man trial was to evaluate safety and to determine the dose of CR1447, administered as an ointment, for Phase II. Escalating doses (100, 200, 400 mg) of CR1447 were administered topically on a daily basis to patients with ER-positive/AR-positive/HER2-negative advanced breast cancer pretreated with several lines of therapy...
August 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28813610/poloxamer-decorated-polymer-nanoparticles-for-lung-surfactant-compatibility
#17
Moritz Beck-Broichsitter, Adam Bohr, Christian Arnold Ruge
Lung-delivered polymer nanoparticles provoked dysfunction of the essential lung surfactant system. A steric shielding of the nanoparticle surface with poloxamers could minimize the unwanted interference of polymer nanoparticles with the biophysical function of lung surfactant. The extent of poly(styrene) and poly(lactide) nanoparticle-induced lung surfactant inhibition could be related to the type and content of the applied poloxamer. Escalations of the adsorbed coating layer thickness (>3 nm) as well as concentration (brush- rather than mushroom-like conformation of poly(ethylene glycol), chain-to-chain distance of <5 nm) on the colloidal surface were capable of circumventing bioadverse effects...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28813063/tuning-mass-transport-in-magnetic-nanoparticle-filled-viscoelastic-hydrogels-using-low-frequency-rotating-magnetic-fields
#18
Shahab Boroun, Faïçal Larachi
This study investigates the response of magnetic nanoparticles (MNPs), dispersed in a viscoelastic hydrogel, to an external rotating magnetic field (RMF) for the purpose of developing a new class of magneto-responsive materials with tunable mass transport properties. Ferrogels were prepared by chemical cross-linking and polymerization of acrylamide in colloidal dispersions of thermally blocked MNPs of cobalt ferrite. Magnetization measurements of ferrogels in a swollen state revealed a transitional state from ferromagnetism to superparamagnetism through the shrinkage of hysteresis loops and the reduction of remanent magnetization...
August 16, 2017: Soft Matter
https://www.readbyqxmd.com/read/28812595/compulsive-like-sufentanil-vapor-self-administration-in-the-rat
#19
Janaina Cm Vendruscolo, Brendan J Tunstall, Stephanie A Carmack, Brooke E Schmeichel, Emily G Lowery-Gionta, Maury Cole, Olivier George, Sophia Vandewater, Michael Taffe, George F Koob, Leandro F Vendruscolo
Opioid misuse is at historically high levels in the United States, with inhalation (ie, smoking, and vaping) being one of the most common routes of consumption. We developed and validated a novel preclinical model of opioid self-administration by inhalation that does not require surgery and reliably produces somatic and motivational signs of dependence. Rats were trained to perform an operant response (nosepoke) to receive 10 s of vaporized sufentanil, a potent opioid, in 2 h daily sessions. Rats readily and concentration-dependently self-administered vaporized sufentanil...
August 16, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28812229/economics-and-cost-effectiveness-of-multiple-sclerosis-therapies-in-the-usa
#20
REVIEW
Daniel M Hartung
Multiple sclerosis (MS) is a disabling, chronic disease that imposes a significant economic burden on patients and the US healthcare system. The largest cost component for individuals with MS are prescription drugs, specifically disease-modifying therapies (DMTs). Despite an increase in the number and diversity of DMTs over the past 10 years, acquisition costs for all DMTs have escalated dramatically at rates substantially higher than medical inflation. Currently, costs for most DMTs exceed $70,000 a year. Recent cost-effectiveness studies suggest the cost for nearly all DMTs exceeds generally accepted thresholds for what is considered a good value in the USA, even after factoring expected rebates...
August 15, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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