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https://www.readbyqxmd.com/read/28427153/comparison-between-proton-boron-fusion-therapy-pbft-and-boron-neutron-capture-therapy-bnct-a-monte-carlo-study
#1
Joo-Young Jung, Do-Kun Yoon, Brendan Barraclough, Heui Chang Lee, Tae Suk Suh, Bo Lu
The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426845/her2-specific-chimeric-antigen-receptor-modified-virus-specific-t-cells-for-progressive-glioblastoma-a-phase-1-dose-escalation-trial
#2
Nabil Ahmed, Vita Brawley, Meenakshi Hegde, Kevin Bielamowicz, Mamta Kalra, Daniel Landi, Catherine Robertson, Tara L Gray, Oumar Diouf, Amanda Wakefield, Alexia Ghazi, Claudia Gerken, Zhongzhen Yi, Aidin Ashoori, Meng-Fen Wu, Hao Liu, Cliona Rooney, Gianpietro Dotti, Adrian Gee, Jack Su, Yvonne Kew, David Baskin, Yi Jonathan Zhang, Pamela New, Bambi Grilley, Milica Stojakovic, John Hicks, Suzanne Z Powell, Malcolm K Brenner, Helen E Heslop, Robert Grossman, Winfried S Wels, Stephen Gottschalk
Importance: Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. Objective: To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. Design, Setting, and Participants: In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014...
April 20, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28426675/indicators-of-suboptimal-biologic-therapy-over-time-in-patients-with-ulcerative-colitis-and-crohn-s-disease-in-the-united-states
#3
Haridarshan Patel, Trevor Lissoos, David T Rubin
This study assessed the occurrence of indicators for suboptimal biologic therapy among ulcerative colitis (UC) and Crohn's disease (CD) patients over time in the United States (US). Data from a large US claims database (2005-2013) were used to retrospectively identify patients with diagnosed with either UC or CD who were new biologic users. Indicators of suboptimal biologic therapy included: dose escalation during the maintenance phase, discontinuation of the initial biologic, switch to another biologic within 90 days following the last day of supply of the initial biologic, augmentation with a non-biologic systemic therapy, UC- or CD-related surgery, UC- or CD-related urgent care, and development of fistula (for CD only)...
2017: PloS One
https://www.readbyqxmd.com/read/28426355/income-levels-and-response-to-contingency-management-for-smoking-cessation
#4
Carla López-Núñez, Roberto Secades-Villa, Elsa Peña-Suárez, Sergio Fernández-Artamendi, Sara Weidberg
BACKGROUND: Contingency management (CM) has demonstrated its efficacy in treating many drug addictions, including nicotine. However, one of the most commonly perceived limitations with regard to its dissemination into community settings is whether this protocol could be equally effective for treating patients across different income levels. OBJECTIVE: This study aimed to examine whether individuals' income levels affect treatment success in a cognitive behavioral treatment (CBT) that included a voucher-based CM protocol for smoking cessation...
June 7, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28426137/hydroxyurea-hydroxycarbamide-for-sickle-cell-disease
#5
REVIEW
Sarah J Nevitt, Ashley P Jones, Jo Howard
BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising fetal haemoglobin. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting...
April 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28425767/chronic-total-coronary-occlusion-treatment-results
#6
Martin Kirk Christensen, Phillip Fischer Freeman, Jeppe Groendal Rasmussen, Anton Boel Villadsen, Bent Raungaard, Svend Eggert Jensen, Leif Thuesen
OBJECTIVES: To describe the clinical and procedural coronary chronic total occlusion (CTO) treatment results in a Nordic PCI centre during the implementation of a CTO treatment program. DESIGN: In a retrospective registry study, we assessed; (1) indication for the procedure, (2) Canadian Cardiovascular Society angina pectoris score (CCS)/New York Heart Association (NYHA) heart failure score, (3) lesion complexity and (4) adverse events during hospital stay and three months following the index procedure...
April 20, 2017: Scandinavian Cardiovascular Journal: SCJ
https://www.readbyqxmd.com/read/28424963/pharmacokinetics-and-safety-of-carfilzomib-in-patients-with-relapsed-multiple-myeloma-and-end-stage-renal-disease-esrd-an-open-label-single-arm-phase-i-study
#7
Hang Quach, Darrell White, Andrew Spencer, P Joy Ho, Divaya Bhutani, Mike White, Sandeep Inamdar, Chris Morris, Ying Ou, Martin Gyger
PURPOSE: The pharmacokinetics (PK) of carfilzomib have been previously studied in multiple myeloma patients with varying degrees of renal impairment (normal, mild, moderate, severe, and end-stage renal disease [ESRD]) at doses of 15 and 20 mg/m(2). This study evaluated carfilzomib PK at higher doses of 27 and 56 mg/m(2) in normal renal function and ESRD patients. METHODS: Patients received carfilzomib on two consecutive days/week for 3 weeks every 28-day cycle: 20 mg/m(2) (cycle 1 day 1-2), escalated to 27 mg/m(2) on cycle 1 day 8; if tolerated, 56 mg/m(2) starting cycle 2 day 1...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28424962/phase-i-dose-escalation-study-of-milciclib-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#8
Sandrine Aspeslagh, Kunwar Shailubhai, Rastilav Bahleda, Anas Gazzah, Andréa Varga, Antoine Hollebecque, Christophe Massard, Anna Spreafico, Michele Reni, Jean-Charles Soria
BACKGROUND: This phase I trial evaluated the safety and tolerability of milciclib, an inhibitor of multiple cyclin-dependent kinases and tropomycin receptor kinase A, in combination with gemcitabine in patients with refractory solid tumors. DESIGN: Sixteen patients were enrolled and treated with milciclib at three dose levels (45 mg/m(2)/day, n = 3; 60 mg/m(2)/day, n = 3; and 80 mg/m(2)/day, n = 10) with a fixed dose of gemcitabine (1000 mg/m(2)/day). Milciclib was administered orally once daily for 7 days on/7 days off in a 4-week cycle, and gemcitabine was administered intravenously on days 1, 8 and 15 in a 4-week cycle...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28424891/a-phase-i-dose-escalation-study-of-selumetinib-in-combination-with-erlotinib-or-temsirolimus-in-patients-with-advanced-solid-tumors
#9
Jeffrey R Infante, Roger B Cohen, Kevin B Kim, Howard A Burris, Gregory Curt, Ugochi Emeribe, Delyth Clemett, Helen K Tomkinson, Patricia M LoRusso
Background Combinations of molecularly targeted agents may provide optimal anti-tumor activity and improve clinical outcomes for patients with advanced cancers. Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which is constitutively activated in many cancers. We investigated the safety, tolerability, and pharmacokinetics (PK) of selumetinib in combination with molecularly targeted drugs erlotinib or temsirolimus in patients with advanced solid tumors...
April 19, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28424876/extent-of-surgical-resection-and-adjuvant-temozolomide-improves-survival-in-pediatric-gbm-a-single-center-experience
#10
Subhash Gupta, Supriya Mallick, Rony Benson, K P Haresh, Pramod Kumar Julka, Goura Kishor Rath
BACKGROUND: Pediatric glioblastoma (pGBM) is an uncommon entity. The importance of concurrent and adjuvant temozolomide is not known in this subset of patients. METHODS: We retrospectively analyzed our database between 2000 and 2015. All patients were treated with maximally safe surgical resection. This was followed by a uniform treatment schedule of post-operative radiation with concurrent daily temozolomide at 75 mg/m(2). Radiation dose was 60 Gy in 30 fractions planned by 3-dimensional conformal radiotherapy...
April 19, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28424801/problem-based-review-immune-mediated-complications-of-checkpoint-inhibitors-for-the-acute-physician
#11
Philip Webb, Terry W Rice, Tim Cooksley
Immunotherapy with 'checkpoint-inhibitors' has significantly improved outcomes for patients with a range of malignancies. However, significant immune-mediated toxicities of these therapies are well-described. These immune-mediated toxicities can affect virtually all organ systems and are potentially fatal. The timing of onset of the adverse effects is dependent on the organ system affected and can occur after completion of the treatment. The increasing utilisation of 'checkpoint-inhibitors' means that Acute Physicians are likely to see a number of immune-mediated complications presenting to the AMU...
2017: Acute Medicine
https://www.readbyqxmd.com/read/28423962/the-utility-of-fecal-calprotectin-in-predicting-the-need-for-escalation-of-therapy-in-inflammatory-bowel-disease
#12
Lukasz Kwapisz, Jamie Gregor, Nilesh Chande, Brian Yan, Terry Ponich, Mahmoud Mosli
BACKGROUND AND AIMS: Fecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. It has proven to be an effective tool in initial screening as well monitoring response to therapy. The aim of this study is to examine the utility of fecal calprotectin both as a predictor for the escalation of therapy in established inflammatory bowel disease and as a predictor of de novo diagnosis. METHODS: Patients with signs and symptoms concerning for inflammatory bowel disease presenting to outpatient clinics were recruited to provide fecal calprotectin stool samples prior to endoscopic evaluation...
April 20, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28423367/imatinib-dose-escalation-versus-sunitinib-as-a-second-line-treatment-against-advanced-gastrointestinal-stromal-tumors-a-nationwide-population-based-cohort-study
#13
Jun-Te Hsu, Puo-Hsien Le, Chang-Fu Kuo, Meng-Jiun Chiou, Chia-Jung Kuo, Tsung-Hsing Chen, Chun-Jung Lin, Jen-Shi Chen, Huang-Pin Yu, Chun-Nan Yeh, Yi-Yin Jan, Ta-Sen Yeh
BACKGROUND: Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference between these two treatment strategies or the role of surgery. RESULTS: This study recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups 1, 2, and 3, respectively...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421991/patterns-in-use-and-costs-of-conventional-and-biologic-disease-modifying-anti-rheumatic-drugs-in-australia
#14
Ellen Donges, Christine Staatz, Helen Benham, Paul Kubler, Samantha A Hollingworth
OBJECTIVES: The aim of this study was to characterise the use and costs of subsidising conventional disease-modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs in Australia from 2004-2014 through pharmaceutical benefits schemes. METHODS: Dispensing and expenditure data on conventional and biologic DMARDs were extracted from Medicare Australia and temporal trends were analysed. Medicine use was standardised in terms of the defined daily dose (DDD) per 1,000 population per day (DDD/1,000 population/day)...
April 18, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28421383/pharmacokinetics-safety-and-tolerability-of-single-and-multiple-doses-of-guanfacine-extended-release-formulation-in-healthy-japanese-and-caucasian-male-adults
#15
Yumiko Matsuo, Masafumi Okita, James Ermer, Toshihiro Wajima
BACKGROUND AND OBJECTIVE: Guanfacine extended-release (guanfacine XR) could be a useful treatment option for children and adolescent patients with attention-deficit/hyperactivity disorder (ADHD). As an initial step in the development in Japan, the pharmacokinetics, safety and tolerability were assessed in healthy Japanese and non-Hispanic Caucasian adults. METHODS: A Phase 1, double-blind, randomized, placebo-controlled, single- and multiple-oral dose escalation study of guanfacine XR was conducted...
April 18, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28421162/r-ideal-a-framework-for-systematic-clinical-evaluation-of-technical-innovations-in-radiation-oncology
#16
Helena M Verkooijen, Linda G W Kerkmeijer, Clifton D Fuller, Robbert Huddart, Corinne Faivre-Finn, Marcel Verheij, Stella Mook, Arjun Sahgal, Emma Hall, Chris Schultz
The pace of innovation in radiation oncology is high and the window of opportunity for evaluation narrow. Financial incentives, industry pressure, and patients' demand for high-tech treatments have led to widespread implementation of innovations before, or even without, robust evidence of improved outcomes has been generated. The standard phase I-IV framework for drug evaluation is not the most efficient and desirable framework for assessment of technological innovations. In order to provide a standard assessment methodology for clinical evaluation of innovations in radiotherapy, we adapted the surgical IDEAL framework to fit the radiation oncology setting...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28421005/autoimmune-aspects-of-neurodegenerative-and-psychiatric-diseases-a-template-for-innovative-therapy
#17
REVIEW
Peter de Haan, Hans C Klein, Bert A 't Hart
Neurodegenerative and psychiatric diseases (NPDs) are today's most important group of diseases, surpassing both atherosclerotic cardiovascular disease and cancer in morbidity incidence. Although NPDs have a dramatic impact on our society because of their high incidence, mortality, and severe debilitating character, remarkably few effective interventions have become available. The current treatments, if available, comprise the lifelong intake of general immunosuppressants to delay disease progression or neurotransmitter antagonists/agonists to dampen undesired behaviors...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28420761/in-situ-measurements-of-tensile-forces-in-the-tibialis-anterior-tendon-of-the-rat-in-concentric-isometric-and-resisted-co-contractions
#18
Martin Schmoll, Ewald Unger, Hazel Sutherland, Michael Haller, Manfred Bijak, Hermann Lanmüller, Jonathan C Jarvis
Tensile-force transmitted by the tibialis anterior (TA) tendon of 11 anesthetized adult male Wistar rats (body-mass: 360.6 ± 66.3 g) was measured in-situ within the intact biomechanical system of the hind-limb using a novel miniature in-line load-cell. The aim was to demonstrate the dependence of the loading-profile experienced by the muscle, on stimulation-frequency and the resistance to shortening in a group of control-animals. Data from these acute-experiments shows the type of loading achievable by means of implantable electrical stimulators activating agonists or agonist/antagonist groups of muscles during programmed resistance-training in freely moving healthy subjects...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28420720/a-phase-i-study-of-abc294640-a-first-in-class-sphingosine-kinase-2-inhibitor-in-patients-with-advanced-solid-tumors
#19
Carolyn D Britten, Melanie B Thomas, Elizabeth Garrett-Mayer, Steven H Chin, Keisuke Shirai, Besim Ogretmen, Tricia A Bentz, Alan Brisendine, Kate Anderton, Susan L Cusack, Lynn W Maines, Yan Zhuang, Charles D Smith
Purpose:  Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating the mitogenic and pro-inflammatory lipid sphingosine 1-phosphate (S1P). This phase I study investigated the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of ABC294640, a first-in-class orally-available inhibitor of SK2.  <p>Experimental Design:  Escalating doses of ABC294640 were administered orally to patients with advanced solid tumors in sequential cohorts at the following dose levels: 250 mg qd, 250 mg bid, 500 mg bid and 750 mg bid, continuously in cycles of 28 days...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28420454/genetic-and-environmental-influences-on-the-codevelopment-among-borderline-personality-disorder-traits-major-depression-symptoms-and-substance-use-disorder-symptoms-from-adolescence-to-young-adulthood
#20
Marina A Bornovalova, Brad Verhulst, Troy Webber, Matt McGue, William G Iacono, Brian M Hicks
Although borderline personality disorder (BPD) traits decline from adolescence to adulthood, comorbid psychopathology such as symptoms of major depressive disorder (MDD), alcohol use disorder (AUD), and drug use disorders (DUDs) likely disrupt this normative decline. Using a longitudinal sample of female twins (N = 1,763), we examined if levels of BPD traits were correlated with changes in MDD, AUD, and DUD symptoms from ages 14 to 24. A parallel process biometric latent growth model examined the contributions of genetic and environmental factors to the relationships between developmental components of these phenotypes...
April 19, 2017: Development and Psychopathology
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