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https://www.readbyqxmd.com/read/28535410/effect-of-enzyme-inhibition-on-perampanel-pharmacokinetics-why-study-design-matters
#1
Barry E Gidal, Rama Maganti, Antonio Laurenza, Haichen Yang, David A Verbel, Edgar Schuck, Jim Ferry
OBJECTIVES: Perampanel, a selective, noncompetitive AMPA receptor antagonist, is indicated as adjunctive therapy for the treatment of partial seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy aged 12years and older. In vitro studies and Phase I trials indicate that perampanel is metabolized almost exclusively by CYP3A, with an elimination half-life (t1/2) averaging approximately 105h. Understanding of pharmacokinetic (PK) interactions-enzyme inhibition or induction-and anticipating their occurrence are important for management of patients with epilepsy...
April 26, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28535154/randomised-controlled-trial-of-early-prophylactic-feeding-vs-standard-care-in-patients-with-head-and-neck-cancer
#2
Teresa E Brown, Merrilyn D Banks, Brett G M Hughes, Charles Y Lin, Lizbeth M Kenny, Judith D Bauer
BACKGROUND: Weight loss remains significant in patients with head and neck cancer, despite prophylactic gastrostomy and intensive dietary counseling. The aim of this study was to improve outcomes utilising an early nutrition intervention. METHODS: Patients with head and neck cancer at a tertiary hospital in Australia referred for prophylactic gastrostomy prior to curative intent treatment were eligible for this single centre randomised controlled trial. Exclusions included severe malnutrition or dysphagia...
May 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28534028/mechanisms-affecting-the-gut-of-preterm-infants-in-enteral-feeding-trials
#3
Nicholas D Embleton, Janet E Berrington, Jon Dorling, Andrew K Ewer, Edmund Juszczak, John A Kirby, Christopher A Lamb, Clare V Lanyon, William McGuire, Christopher S Probert, Stephen P Rushton, Mark D Shirley, Christopher J Stewart, Stephen P Cummings
Large randomized controlled trials (RCTs) in preterm infants offer unique opportunities for mechanistic evaluation of the risk factors leading to serious diseases, as well as the actions of interventions designed to prevent them. Necrotizing enterocolitis (NEC) a serious inflammatory gut condition and late-onset sepsis (LOS) are common feeding and nutrition-related problems that may cause death or serious long-term morbidity and are key outcomes in two current UK National Institutes for Health Research (NIHR) trials...
2017: Frontiers in Nutrition
https://www.readbyqxmd.com/read/28530031/celecoxib-for-osteoarthritis
#4
REVIEW
Livia Puljak, Ana Marin, Davorka Vrdoljak, Filipa Markotic, Ana Utrobicic, Peter Tugwell
BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis and is caused by degeneration of the joint cartilage and growth of new bone, cartilage and connective tissue. It is often associated with major disability and impaired quality of life. There is currently no consensus on the best treatment to improve OA symptoms. Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID). OBJECTIVES: To assess the clinical benefits (pain, function, quality of life) and safety (withdrawals due to adverse effects, serious adverse effects, overall discontinuation rates) of celecoxib in osteoarthritis (OA)...
May 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28527899/egfr-mutation-analysis-for-prospective-patient-selection-in-two-phase-ii-registration-studies-of-osimertinib
#5
Suzanne Jenkins, James Chih-Hsin Yang, Pasi A Jänne, Kenneth S Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A Shepherd
INTRODUCTION: Osimertinib is an oral, CNS active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of EGFR T790M-positive advanced non-small cell lung cancer (NSCLC). Here we evaluate EGFR mutation frequencies in two Phase II studies of osimertinib (AURA extension and AURA2). METHODS: Patients with EGFR mutation-positive advanced NSCLC provided tumor samples following progression on their latest line of therapy for mandatory central T790M testing for study selection criteria...
May 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28527657/clinical-outcomes-and-cost-effectiveness-of-brief-guided-parent-delivered-cognitive-behavioural-therapy-and-solution-focused-brief-therapy-for-treatment-of-childhood-anxiety-disorders-a-randomised-controlled-trial
#6
Cathy Creswell, Mara Violato, Hannah Fairbanks, Elizabeth White, Monika Parkinson, Gemma Abitabile, Alessandro Leidi, Peter J Cooper
BACKGROUND: Half of all lifetime anxiety disorders emerge before age 12 years; however, access to evidence-based psychological therapies for affected children is poor. We aimed to compare the clinical outcomes and cost-effectiveness of two brief psychological treatments for children with anxiety referred to routine child mental health settings. We hypothesised that brief guided parent-delivered cognitive behavioural therapy (CBT) would be associated with better clinical outcomes than solution-focused brief therapy and would be cost-effective...
May 17, 2017: Lancet Psychiatry
https://www.readbyqxmd.com/read/28525389/biological-and-clinical-evidence-for-somatic-mutations-in-brca1-and-brca2-as-predictive-markers-for-olaparib-response-in-high-grade-serous-ovarian-cancers-in-the-maintenance-setting
#7
Brian A Dougherty, Zhongwu Lai, Darren R Hodgson, Maria C M Orr, Matthew Hawryluk, James Sun, Roman Yelensky, Stuart K Spencer, Jane D Robertson, Tony W Ho, Anitra Fielding, Jonathan A Ledermann, J Carl Barrett
To gain a better understanding of the role of somatic mutations in olaparib response, next-generation sequencing (NGS) of BRCA1 and BRCA2 was performed as part of a planned retrospective analysis of tumors from a randomized, double-blind, Phase II trial (Study 19; D0810C00019; NCT00753545) in 265 patients with platinum-sensitive high-grade serous ovarian cancer. BRCA1/2 loss-of-function mutations were found in 55% (114/209) of tumors, were mutually exclusive, and demonstrated high concordance with Sanger-sequenced germline mutations in matched blood samples, confirming the accuracy (97%) of tumor BRCA1/2 NGS testing...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520207/comparison-of-f13a1-gene-mutations-in-73-patients-treated-with-recombinant-fxiii-a2
#8
V Ivaškevičius, A Biswas, M-L Garly, J Oldenburg
INTRODUCTION: Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder usually caused by mutations in the F13A1 gene that produce a severe quantitative (type I) deficiency of the FXIII-A subunit. AIM: To determine the genotypes of patients with severe FXIII-A deficiency treated with recombinant FXIII-A subunit (rFXIII-A2 ) participating in three international efficacy and safety trials. METHODS: We determined the genotypes of 73 patients in total; 32 had already undergone genotype analysis and were known to carry F13A1 mutations that have been previously reported in the literature...
May 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28513635/the-impact-of-dark-chocolate-intake-on-arterial-elasticity-in-individuals-with-hiv-aids-undergoing-art-a-randomized-double-blind-crossover-trial
#9
Andrea Mariana Nunes da Costa Teixeira, Liania Alves Luzia, Suelen Jorge de Souza, Aline de Almeida Petrilli, Patrícia de Moraes Pontilho, Jose Maria Pacheco de Souza, Aluísio Augusto Cotrim Segurado, Priscila Efraim, Camila de Melo Picone, Patrícia Helen de Carvalho Rondo
An increase in the frequency of cardiovascular diseases has been observed in the HIV/AIDS population. Studies involving healthy subjects or subjects with other diseases have shown benefits of chocolate supplementation on endothelial function and vasodilation. We evaluate the impact of chocolate consumption on arterial elasticity in people living with human immunodeficiency virus - PLHIV. A double-blind, crossover trial including 110 PLHIV (19 to 59 years) on antiretroviral therapy - ART for at least 6 months and with a viral load of <500 copies per mL was conducted...
May 17, 2017: Food & Function
https://www.readbyqxmd.com/read/28512453/alterations-in-the-rumen-liquid-particle-and-epithelium-associated-microbiota-of-dairy-cows-during-the-transition-from-a-silage-and-concentrate-based-ration-to-pasture-in-spring
#10
Melanie Schären, Kerstin Kiri, Susanne Riede, Mark Gardener, Ulrich Meyer, Jürgen Hummel, Tim Urich, Gerhard Breves, Sven Dänicke
In spring dairy cows are often gradually transitioned from a silage- and concentrate-based ration (total mixed ration, TMR) to pasture. Rumen microbiota adaptability is a key feature of ruminant survival strategy. However, only little is known on the temporal and spatial microbial alterations involved. This study aims to investigate how the rumen liquid (LAAB), particle (PAAB), and epithelium (EAAB) associated archaea and bacteria are influenced by this nutritional change. A 10-wk trial was performed, including 10 rumen-fistulated dairy cows, equally divided into a pasture- and a confinement- group (PG and CG)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28506538/epitope-specific-immunotherapy-targeting-cd4-positive-t-cells-in-coeliac-disease-two-randomised-double-blind-placebo-controlled-phase-1-studies
#11
Gautam Goel, Tim King, A James Daveson, Jane M Andrews, Janakan Krishnarajah, Richard Krause, Gregor J E Brown, Ronald Fogel, Charles F Barish, Roger Epstein, Timothy P Kinney, Philip B Miner, Jason A Tye-Din, Adam Girardin, Juha Taavela, Alina Popp, John Sidney, Markku Mäki, Kaela E Goldstein, Patrick H Griffin, Suyue Wang, John L Dzuris, Leslie J Williams, Alessandro Sette, Ramnik J Xavier, Ludvig M Sollid, Bana Jabri, Robert P Anderson
BACKGROUND: A gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet...
May 11, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28506408/genetics-of-medullary-thyroid-cancer-an-overview
#12
REVIEW
Giacomo Accardo, Giovanni Conzo, Daniela Esposito, Claudio Gambardella, Marco Mazzella, Filomena Castaldo, Carlo Di Donna, Andrea Polistena, Nicola Avenia, Vittorio Colantuoni, Dario Giugliano, Daniela Pasquali
Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved...
May 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28500488/-analysis-of-intrusion-errors-in-free-recall
#13
H F A Diesfeldt
Extra-list intrusion errors during five trials of the eight-word list-learning task of the Amsterdam Dementia Screening Test (ADST) were investigated in 823 consecutive psychogeriatric patients (87.1% suffering from major neurocognitive disorder). Almost half of the participants (45.9%) produced one or more intrusion errors on the verbal recall test. Correct responses were lower when subjects made intrusion errors, but learning slopes did not differ between subjects who committed intrusion errors and those who did not so...
May 12, 2017: Tijdschrift Voor Gerontologie en Geriatrie
https://www.readbyqxmd.com/read/28499583/histotype-tailored-neoadjuvant-chemotherapy-versus-standard-chemotherapy-in-patients-with-high-risk-soft-tissue-sarcomas-isg-sts-1001-an-international-open-label-randomised-controlled-phase-3-multicentre-trial
#14
Alessandro Gronchi, Stefano Ferrari, Vittorio Quagliuolo, Javier Martin Broto, Antonio Lopez Pousa, Giovanni Grignani, Umberto Basso, Jean-Yves Blay, Oscar Tendero, Robert Diaz Beveridge, Virginia Ferraresi, Iwona Lugowska, Domenico Franco Merlo, Valeria Fontana, Emanuela Marchesi, Davide Maria Donati, Elena Palassini, Emanuela Palmerini, Rita De Sanctis, Carlo Morosi, Silvia Stacchiotti, Silvia Bagué, Jean Michelle Coindre, Angelo Paolo Dei Tos, Piero Picci, Paolo Bruzzi, Paolo Giovanni Casali
BACKGROUND: Previous trials from our group suggested an overall survival benefit with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised high-risk soft-tissue sarcoma of the extremities or trunk wall, and no difference in overall survival benefit between three cycles versus five cycles of the same neoadjuvant regimen. We aimed to show the superiority of the neoadjuvant administration of histotype-tailored regimen to standard chemotherapy. METHODS: For this international, open-label, randomised, controlled, phase 3, multicentre trial, patients were enrolled from 32 hospitals in Italy, Spain, France, and Poland...
May 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28494788/comprehensive-analysis-of-treatment-response-phenotypes-in-rheumatoid-arthritis-for-pharmacogenetic-studies
#15
Kristopher A Standish, C Chris Huang, Mark E Curran, Nicholas J Schork
BACKGROUND: An individual patient's response to a particular drug is influenced by multiple factors, which may include genetic predisposition. Pharmacogenetic studies attempt to discover and estimate the contributions of genetic variants to the variability in response to a drug treatment. The task of identifying the genetic contribution is often complicated by response phenotypes that are based on imprecise or subjective clinical observations. Because the success of a pharmacogenetic study depends on the analysis of a heritable phenotype, it is important to identify phenotypes with a significant heritable component to ensure reliable and reproducible results in subsequent genetic association studies...
May 12, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28493891/antibody-to-hsv-gd-peptide-induced-by-vaccination-does-not-protect-against-hsv-2-infection-in-hsv-2-seronegative-women
#16
Peter B Gilbert, Jean-Louis Excler, Georgia D Tomaras, Lindsay N Carpp, Barton F Haynes, Hua-Xin Liao, David C Montefiori, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Jaranit Kaewkungwal, Gustavo H Kijak, Sodsai Tovanabutra, Donald P Francis, Carter Lee, Faruk Sinangil, Phillip W Berman, Nakorn Premsri, Prayura Kunasol, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Rhoda Morrow, Lawrence Corey, Jerome H Kim
BACKGROUND: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence...
2017: PloS One
https://www.readbyqxmd.com/read/28492226/circulating-tumour-dna-sequence-analysis-as-an-alternative-to-multiple-myeloma-bone-marrow-aspirates
#17
Olena Kis, Rayan Kaedbey, Signy Chow, Arnavaz Danesh, Mark Dowar, Tiantian Li, Zhihua Li, Jessica Liu, Mark Mansour, Esther Masih-Khan, Tong Zhang, Scott V Bratman, Amit M Oza, Suzanne Kamel-Reid, Suzanne Trudel, Trevor J Pugh
The requirement for bone-marrow aspirates for genomic profiling of multiple myeloma poses an obstacle to enrolment and retention of patients in clinical trials. We evaluated whether circulating cell-free DNA (cfDNA) analysis is comparable to molecular profiling of myeloma using bone-marrow tumour cells. We report here a hybrid-capture-based Liquid Biopsy Sequencing (LB-Seq) method used to sequence all protein-coding exons of KRAS, NRAS, BRAF, EGFR and PIK3CA in 64 cfDNA specimens from 53 myeloma patients to >20,000 × median coverage...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28490940/systemic-therapy-in-the-curative-treatment-of-head-and-neck-squamous-cell-cancer-cancer-care-ontario-clinical-practice-guideline
#18
E Winquist, C Agbassi, B M Meyers, J Yoo, K K W Chan
OBJECTIVE: The aim of the present work was to make recommendations about the use of systemically administered drugs in combination or in sequence with radiation (rt) or surgery, or both, for cure or organ preservation, or both, in patients with locally advanced nonmetastatic (stages iii-ivb) squamous cell carcinoma of the head and neck (lascchn). METHODS: The Meta-analysis of Chemotherapy in Head and Neck Cancer (mach-nc) reports have, de facto, guided practice since 2000, and so we searched the literature for systematic reviews published from January 2000 to February 2015 in reference to five research questions...
April 2017: Current Oncology
https://www.readbyqxmd.com/read/28490871/home-noninvasive-positive-pressure-ventilation-with-built-in-software-in-stable-hypercapnic-copd-a-short-term-prospective-multicenter-randomized-controlled-trial
#19
Luqian Zhou, Xiaoying Li, Lili Guan, Jianhua Chen, Bingpeng Guo, Weiliang Wu, Yating Huo, Ziqing Zhou, Zhenyu Liang, Yuqi Zhou, Jie Tan, Xin Chen, Yuanlin Song, Rongchang Chen
BACKGROUND: The benefits of noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic COPD are controversial. It is presumed that methodology and appropriate use of NIV ventilator might be crucial for the outcomes. With the new built-in software, the performance of NIV can be monitored at home, which can guarantee the compliance and appropriate use. This study investigated effects of home use of NIV in hypercapnia in COPD patients using the NIV ventilator with built-in software for monitoring...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28488912/a-high-level-of-estrogen-stimulated-proteins-selects-breast-cancer-patients-treated-with-adjuvant-endocrine-therapy-with-good-prognosis
#20
Katrine L H Weischenfeldt, Tove Kirkegaard, Birgitte B Rasmussen, Anita Giobbie-Hurder, Maj-Britt Jensen, Bent Ejlertsen, Anne E Lykkesfeldt
BACKGROUND: Adjuvant endocrine therapy has significantly improved survival of estrogen receptor α (ER)-positive breast cancer patients, but around 20% relapse within 10 years. High expression of ER-stimulated proteins like progesterone receptor (PR), Bcl-2 and insulin-like growth factor receptor I (IGF-IR) is a marker for estrogen-driven cell growth. Therefore, patients with high tumor levels of these proteins may have particularly good prognosis following adjuvant endocrine therapy...
May 10, 2017: Acta Oncologica
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