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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/28816767/allopurinol-medication-adherence-as-a-mediator-of-optimal-outcomes-in-gout-management
#3
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
#4
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
#5
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
#6
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/28814898/reducing-rectal-injury-in-men-receiving-prostate-cancer-radiation-therapy-current-perspectives
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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/28811354/safety-and-efficacy-of-baricitinib-through-128-weeks-in-an-open-label-longterm-extension-study-in-patients-with-rheumatoid-arthritis
#13
Edward C Keystone, Mark C Genovese, Douglas E Schlichting, Inmaculada de la Torre, Scott D Beattie, Terence P Rooney, Peter C Taylor
OBJECTIVE: To assess the safety and efficacy of baricitinib in patients with rheumatoid arthritis (RA) up to 128 weeks in a phase IIb study (NCT01185353). METHODS: After a 24-week blinded period, eligible patients entered an initial 52-week open-label extension (OLE); patients receiving 8 mg once daily (QD) continued with that dose and all others received 4 mg QD. Doses could be escalated to 8 mg QD at 28 or 32 weeks at investigator discretion when ≥ 6 tender and ≥ 6 swollen joints were present...
August 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28810899/chronic-pain-and-opioid-misuse-a-review-of-reviews
#14
REVIEW
Pauline Voon, Mohammad Karamouzian, Thomas Kerr
OBJECTIVE: The crisis of prescription opioid (PO) related harms has focused attention toward identifying and treating high-risk populations. This review aims to synthesize systematic reviews on the epidemiology and clinical management of comorbid chronic pain and PO or other substance misuse. METHODS: A systematic database search was conducted to identify systematic reviews published between 2000 and 2016. Eligible studies were systematic reviews related to chronic non-cancer pain and PO or other substance misuse...
August 15, 2017: Substance Abuse Treatment, Prevention, and Policy
https://www.readbyqxmd.com/read/28810885/intensity-modulated-versus-3-dimensional-conformal-radiotherapy-in-the-definitive-treatment-of-esophageal-cancer-comparison-of-outcomes-and-acute-toxicity
#15
Matthias Felix Haefner, Kristin Lang, Vivek Verma, Stefan Alexander Koerber, Lorenz Uhlmann, Juergen Debus, Florian Sterzing
BACKGROUND: Though the vast majority of seminal trials for locally advanced esophageal cancer (EC) utilized three-dimensional conformal radiotherapy (3DCRT), the advanced and highly conformal technology known as intensity-modulated radiotherapy (IMRT) can decrease doses to critical cardiopulmonary organs. To date, there have been no studies comparing both modalities as part of definitive chemoradiation (dCRT) for EC. Herein, we investigated local control and survival and evaluated clinical factors associated with these endpoints between cohorts...
August 15, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28809608/treatment-of-patients-with-metastatic-cancer-using-a-major-histocompatibility-complex-class-ii-restricted-t-cell-receptor-targeting-the-cancer-germline-antigen-mage-a3
#16
Yong-Chen Lu, Linda L Parker, Tangying Lu, Zhili Zheng, Mary Ann Toomey, Donald E White, Xin Yao, Yong F Li, Paul F Robbins, Steven A Feldman, Pierre van der Bruggen, Christopher A Klebanoff, Stephanie L Goff, Richard M Sherry, Udai S Kammula, James C Yang, Steven A Rosenberg
Purpose Adoptive transfer of genetically modified T cells is being explored as a treatment for patients with metastatic cancer. Most current strategies use genes that encode major histocompatibility complex (MHC) class I-restricted T-cell receptors (TCRs) or chimeric antigen receptors to genetically modify CD8(+) T cells or bulk T cells for treatment. Here, we evaluated the safety and efficacy of an adoptive CD4(+) T-cell therapy using an MHC class II-restricted, HLA-DPB1*0401-restricted TCR that recognized the cancer germline antigen, MAGE-A3 (melanoma-associated antigen-A3)...
August 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28809446/deferasirox-for-managing-iron-overload-in-people-with-thalassaemia
#17
REVIEW
Claudia Bollig, Lisa K Schell, Gerta Rücker, Roman Allert, Edith Motschall, Charlotte M Niemeyer, Dirk Bassler, Joerg J Meerpohl
BACKGROUND: Thalassaemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusions. Iron chelation therapy is needed to prevent long-term complications.Both deferoxamine and deferiprone are effective; however, a review of the effectiveness and safety of the newer oral chelator deferasirox in people with thalassaemia is needed. OBJECTIVES: To assess the effectiveness and safety of oral deferasirox in people with thalassaemia and iron overload...
August 15, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28808818/first-in-human-study-of-the-epichaperome-inhibitor-pu-h71-clinical-results-and-metabolic-profile
#18
Giovanna Speranza, Larry Anderson, Alice P Chen, Khanh Do, Michelle Eugeni, Marcie Weil, Larry Rubinstein, Eva Majerova, Jerry Collins, Yvonne Horneffer, Lamin Juwara, Jennifer Zlott, Rachel Bishop, Barbara A Conley, Howard Streicher, Joseph Tomaszewski, James H Doroshow, Shivaani Kummar
Background Molecular chaperone targeting has shown promise as a therapeutic approach in human cancers of various histologies and genetic backgrounds. The purine-scaffold inhibitor PU-H71 (NSC 750424), selective for Hsp90 in epichaperome networks, has demonstrated antitumor activity in multiple preclinical cancer models. The present study was a first in-human trial of PU-H71 aimed at establishing its safety and tolerability and characterizing its pharmacokinetic (PK) profile on a weekly administration schedule in human subjects with solid tumors refractory to standard treatments...
August 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28807656/opportunities-for-model-based-precision-dosing-in-the-treatment-of-sickle-cell-anemia
#19
Min Dong, Tomoyuki Mizuno, Alexander A Vinks
Hydroxyurea is the primary pharmacotherapy to prevent complications of sickle cell anemia (SCA). Accumulated clinical experience across multiple age ranges has suggested that the use of an individualized maximum tolerated dose (MTD) will achieve optimal benefit of hydroxyurea treatment. However, the current empirical and trial-and-error approach for dose escalation often results in a lengthy titration process and is not strictly implemented in many clinics. Opportunities exist for pharmacokinetics model-based precision dosing of hydroxyurea to quickly achieve individual MTD...
August 9, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28806209/refractory-intracranial-hypertension-the-role-of-decompressive-craniectomy
#20
Martin Smith
Raised intracranial pressure (ICP) is associated with worse outcomes after acute brain injury, and clinical guidelines advocate early treatment of intracranial hypertension. ICP-lowering therapies are usually administered in a stepwise manner, starting with safer first-line interventions, while reserving higher-risk options for patients with intractable intracranial hypertension. Decompressive craniectomy is a surgical procedure in which part of the skull is removed and the underlying dura opened to reduce brain swelling-related raised ICP; it can be performed as a primary or secondary procedure...
August 10, 2017: Anesthesia and Analgesia
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