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https://www.readbyqxmd.com/read/28346823/design-and-monitoring-of-multi-arm-multi-stage-clinical-trials
#1
Pranab Ghosh, Lingyun Liu, P Senchaudhuri, Ping Gao, Cyrus Mehta
Two-arm group sequential designs have been widely used for over 40 years, especially for studies with mortality endpoints. The natural generalization of such designs to trials with multiple treatment arms and a common control (MAMS designs) has, however, been implemented rarely. While the statistical methodology for this extension is clear, the main limitation has been an efficient way to perform the computations. Past efforts were hampered by algorithms that were computationally explosive. With the increasing interest in adaptive designs, platform designs, and other innovative designs that involve multiple comparisons over multiple stages, the importance of MAMS designs is growing rapidly...
March 27, 2017: Biometrics
https://www.readbyqxmd.com/read/28346693/using-a-novel-nqo1-bioactivatable-drug-beta-lapachone-arq761-to-enhance-chemotherapeutic-effects-by-metabolic-modulation-in-pancreatic-cancer
#2
Muhammad Shaalan Beg, Xiumei Huang, Molly A Silvers, David E Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J Deberardinis, Matthew E Merritt, Xian-Jin Xie, Richard Leff, Daniel Laheru, David A Boothman
Novel, tumor-selective therapies are needed to increase the survival rate of pancreatic cancer patients. K-Ras-mutant-driven NAD(P)H:quinone oxidoreductase 1 (NQO1) is over-expressed in pancreatic tumor versus associated normal tissue, while catalase expression is lowered compared to levels in associated normal pancreas tissue. ARQ761 undergoes a robust, futile redox cycle in NQO1+ cancer cells, producing massive hydrogen peroxide (H2 O2 ) levels; normal tissues are spared by low NQO1 and high catalase expression...
March 27, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28343976/prophylactic-cranial-irradiation-versus-observation-in-patients-with-extensive-disease-small-cell-lung-cancer-a-multicentre-randomised-open-label-phase-3-trial
#3
Toshiaki Takahashi, Takeharu Yamanaka, Takashi Seto, Hideyuki Harada, Hiroshi Nokihara, Hideo Saka, Makoto Nishio, Hiroyasu Kaneda, Koichi Takayama, Osamu Ishimoto, Koji Takeda, Hiroshige Yoshioka, Motoko Tachihara, Hiroshi Sakai, Koichi Goto, Nobuyuki Yamamoto
BACKGROUND: Results from a previous phase 3 study suggested that prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs overall survival compared with no prophylactic cranial irradiation in patients with extensive-disease small-cell lung cancer. However, because of the absence of brain imaging before enrolment and variations in chemotherapeutic regimens and irradiation doses, concerns have been raised about these findings. We did a phase 3 trial to reassess the efficacy of prophylactic cranial irradiation in the treatment of extensive-disease small-cell lung cancer...
March 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28343206/-euthanasia-an-attempt-to-organize-issue
#4
Tomasz Kirmes, Mateusz Wilk, Czesław Chowaniec
This article is an attempt to complete and holistically discuss problem of euthanasia, especially its ethical and legal aspects, comparing to Polish law. The subject of euthanasia arouse interest of the society because it touches one of the most important aspects of life, which is the death. Even bigger emotions are aroused amongst physicians. They are forced to put on the line the life as biggest value on the one side and autonomy of human being on the other. It also touches the empathy for suffering. The euthanasia was divided into three forms: active euthanasia, passive euthanasia and assisted suicide...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28338546/a-double-blind-placebo-controlled-pilot-study-of-riluzole-monotherapy-for-acute-bipolar-depression
#5
Lawrence T Park, Marc S Lener, Matthew Hopkins, Nicolas Iadorola, Rodrigo Machado-Vieira, Elizabeth Ballard, Allison Nugent, Carlos A Zarate
BACKGROUND: Glutamatergic system abnormalities are implicated in the pathophysiology and treatment of both major depressive disorder and bipolar depression (BDep). Subsequent to studies demonstrating the rapid and robust antidepressant effects of ketamine, an N-methyl-D-aspartate receptor antagonist, other glutamatergic modulators are now being studied in clinical trials of mood disorders. A previous open-label study found that riluzole, administered in combination with the mood stabilizer lithium, had antidepressant effects...
March 23, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28331014/reducing-futile-attempts-at-resuscitation
#6
John Launer
No abstract text is available yet for this article.
April 2017: Postgraduate Medical Journal
https://www.readbyqxmd.com/read/28328527/on-the-conditional-power-in-survival-time-analysis-considering-cure-fractions
#7
Andreas Kuehnapfel, Fabian Schwarzenberger, Markus Scholz
Conditional power of survival endpoints at interim analyses can support decisions on continuing a trial or stopping it for futility. When a cure fraction becomes apparent, conditional power cannot be calculated accurately using simple survival models, e.g. the exponential model. Non-mixture models consider such cure fractions. In this paper, we derive conditional power functions for non-mixture models, namely the non-mixture exponential, the non-mixture Weibull, and the non-mixture Gamma models. Formulae were implemented in the R package CP...
March 17, 2017: International Journal of Biostatistics
https://www.readbyqxmd.com/read/28327257/determining-the-mechanism-for-low-sludge-yields-in-the-cannibal%C3%A2-solids-reduction-system
#8
Steven W Van Ginkel Joseph Miceli Bi-O Kim Ziming Yang Michelle Young Andrew Marcus And Bruce E Rittmann
Extracellular polymeric substances (EPS) and solids concentrations in samples from the Interchange Bioreactor (IBR) andreturn activated sludge (RAS) from Cannibal® plants having low and high sludge yields were analyzed to understand the mechanisms behind low sludge production. Low sludge yields correlated to more EPS degradation, higher concentrations of iron, and reducing conditions in the IBR. In the low-yield plants, iron was reduced when the RAS passed through the anaerobic and reducing conditions of the IBR, and this led to more EPS solubilization and degradation...
March 16, 2017: Water Environment Research: a Research Publication of the Water Environment Federation
https://www.readbyqxmd.com/read/28326805/a-retrospective-analysis-of-care-in-patients-with-dementia-hospitalized-at-a-tertiary-medical-center
#9
Riddhi Patira, Huaqing Zhao, Ausim Azizi
BACKGROUND: Hospitalization is an opportunity to address various aspects related to management of dementia, including the goals of care to avoid futile care. We studied the prevalence of these factors when patients with dementia are hospitalized. DESIGN: One hundred and thirty-one charts of patients with dementia admitted to a single university-based hospital were retrospectively reviewed. Data were collected and analyzed for age, gender, the severity of dementia, co-morbidities, co-existing vascular dementia, reversible causes of dementia, mental status scores, medications, consultations, procedures, complications, availability of advance directives, decision-maker, code status, and goals of care discussion...
March 22, 2017: Aging & Mental Health
https://www.readbyqxmd.com/read/28325843/a-biochemical-framework-for-eif4e-dependent-mrna-export-and-nuclear-re-cycling-of-the-export-machinery
#10
Laurent Volpon, Biljana Culjkovic-Kraljacic, Hye Seon Sohn, Alexis Blanchett-Cohen, Michael J Osborne, Katherine L B Borden
The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ~50 nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end...
March 21, 2017: RNA
https://www.readbyqxmd.com/read/28325569/transcatheter-aortic-valve-implantation-in-patients-with-advanced-chronic-kidney-disease
#11
Federico Conrotto, Stefano Salizzoni, Alessandro Andreis, Fabrizio D'Ascenzo, Augusto D'Onofrio, Marco Agrifoglio, Alaide Chieffo, Antonio Colombo, Filippo Rapetto, Francesco Santini, Giuseppe Tarantini, Davide Gabbieri, Carlo Savini, Sebastiano Immè, Flavio Ribichini, Orazio Valsecchi, Marco Aiello, Giovanni Lixi, Alessandro Iadanza, Esmeralda Pompei, Miroslava Stolcova, Diego Ornaghi, Alessandro Minati, Mauro Cassese, Gian Luca Martinelli, Pierluigi Sbarra, Andrea Agostinelli, Andrea Audo, Andrea Pieroni, Rosario Fiorilli, Gino Gerosa, Mauro Rinaldi, Fiorenzo Gaita
Advanced chronic kidney disease (CKD) is associated with poor outcomes in patients who underwent surgical aortic valve replacement, whereas its prognostic role in transcatheter aortic valve implantation (TAVI) remains unclear. This study aimed to investigate outcomes in patients with advanced CKD who underwent TAVI. A total of 1,904 consecutive patients who underwent balloon-expandable TAVI in 33 centers between 2007 and 2012 were enrolled in the Italian Transcatheter Balloon-Expandable Valve Implantation Registry...
February 10, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28322154/mechanisms-and-drug-targets-for-pancreatic-cancer-chemoprevention
#12
Deepanshi Dhar, Komal Raina, Rajesh Agarwal
Pancreatic cancer management remains a major challenge to society. Poor prognosis results in dismal survival rates and quality of life for pancreatic cancer patients post chemo/radiation therapies. Although progress has been made in drug development for chemotherapeutics targeting pancreatic cancer, accompanying issues of resistance to these drugs renders the treatment futile. Emerging area of cancer chemoprevention is gaining importance with natural/dietary compounds serving as novel agents with strong anticancer properties; these are pleiotropic agents targeting multiple pathways with minimal toxicities in the surrounding normal tissue...
March 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28320960/glass-transition-imminent-resistance-is-futile
#13
Vassiliy Lubchenko
No abstract text is available yet for this article.
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320259/levosimendan-for-hemodynamic-support-after-cardiac-surgery
#14
Giovanni Landoni, Vladimir V Lomivorotov, Gabriele Alvaro, Rosetta Lobreglio, Antonio Pisano, Fabio Guarracino, Maria G Calabrò, Evgeny V Grigoryev, Valery V Likhvantsev, Marcello F Salgado-Filho, Alessandro Bianchi, Vadim V Pasyuga, Massimo Baiocchi, Federico Pappalardo, Fabrizio Monaco, Vladimir A Boboshko, Marat N Abubakirov, Bruno Amantea, Rosalba Lembo, Luca Brazzi, Luigi Verniero, Pietro Bertini, Anna M Scandroglio, Tiziana Bove, Alessandro Belletti, Maria G Michienzi, Dmitriy L Shukevich, Tatiana S Zabelina, Rinaldo Bellomo, Alberto Zangrillo
Background Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0...
March 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28319243/association-of-antioxidant-supplement-use-and-dementia-in-the-prevention-of-alzheimer-s-disease-by-vitamin-e-and-selenium-trial-preadvise
#15
Richard J Kryscio, Erin L Abner, Allison Caban-Holt, Mark Lovell, Phyllis Goodman, Amy K Darke, Monica Yee, John Crowley, Frederick A Schmitt
Importance: Oxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia. Objective: To determine if antioxidant supplements (vitamin E or selenium) used alone or in combination can prevent dementia in asymptomatic older men. Design, Setting, and Participants: The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADViSE) trial began as a double-blind randomized clinical trial in May 2002, which transformed into a cohort study from September 2009 to May 2015...
March 20, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28317537/diversity-in-the-botryosphaeriales-looking-back-looking-forward
#16
REVIEW
Bernard Slippers, Pedro Willem Crous, Fahimeh Jami, Johannes Zacharias Groenewald, Michael John Wingfield
The Botryosphaeriales are amongst the most widespread, common and important fungal pathogens of woody plants. Many are also known to exist as endophytes in healthy plant tissues. This special issue highlights a number of key themes in the study of this group of fungi. In particular, there have been dramatic taxonomic changes over the past decade; from one family to nine (including two in this special issue) and from 10 to 33 genera known from culture. It is also clear from many studies that neither morphology nor single locus sequence data are sufficient to define taxa...
April 2017: Fungal Biology
https://www.readbyqxmd.com/read/28315947/impact-of-18-f-fdg-pet-ct-on-surgical-management-in-patients-with-advanced-melanoma-an-outcome-based-analysis
#17
Andrea Forschner, Susann-Cathrin Olthof, Brigitte Gückel, Peter Martus, Werner Vach, Christian la Fougère, Konstantin Nikolaou, Ulrike Keim, Thomas Kurt Eigentler, Claus Garbe, Christina Pfannenberg
PURPOSE: To evaluate the influence of (18)F-FDG-PET/CT on clinical decision making and outcome in advanced melanoma patients planned for radical metastasectomy. METHODS AND MATERIALS: A cohort of 333 patients with mainly stage III/IV melanoma having a PET/CT for clinical reasons was prospectively enrolled in our oncologic PET/CT registry between 2013 and 2015. Referring physicians completed questionnaires regarding their intended management for each patient before and after PET/CT...
March 18, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28302424/external-validation-of-the-universal-termination-of-resuscitation-rule-for-out-of-hospital-cardiac-arrest-in-british-columbia
#18
Brian Grunau, John Taylor, Frank X Scheuermeyer, Robert Stenstrom, William Dick, Takahisa Kawano, David Barbic, Ian Drennan, Jim Christenson
STUDY OBJECTIVE: The Universal Termination of Resuscitation Rule (TOR Rule) was developed to identify out-of-hospital cardiac arrests eligible for field termination of resuscitation, avoiding futile transportation to the hospital. The validity of the rule in emergency medical services (EMS) systems that do not routinely transport out-of-hospital cardiac arrest patients to the hospital is unknown. We seek to validate the TOR Rule in British Columbia. METHODS: This study included consecutive, nontraumatic, adult, out-of-hospital cardiac arrests treated by EMS in British Columbia from April 2011 to September 2015...
March 14, 2017: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/28301350/a-phase-ii-study-of-ganetespib-as-second-line-or-third-line-therapy-for-metastatic-pancreatic-cancer
#19
Dana B Cardin, Ramya Thota, Laura W Goff, Jordan D Berlin, Clyde M Jones, Gregory D Ayers, Jennifer G Whisenant, Emily Chan
OBJECTIVES: Heat shock protein 90 regulates multiple signaling proteins involved in key pathways of pancreatic cancer pathogenesis. Ganetespib binds to heat shock protein 90 and interferes with its binding to client proteins thus leading to inactivation and degradation of the signaling proteins that promote cancer progression. This phase II study was designed to evaluate the efficacy of ganetespib in patients with refractory metastatic pancreatic cancer (rMPC). METHODS: Patients with rMPC received 175 mg/m ganetespib intravenously once weekly for 3 weeks in 4-week cycles...
March 15, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28299156/fifty-shades-of-african-lightness-a-bio-psychosocial-review-of-the-global-phenomenon-of-skin-lightening-practices
#20
REVIEW
Meagan Jacobs, Susan Levine, Kate Abney, Lester Davids
Skin-lightening is an aesthetic practice of global concern. By adopting a biopsycho-social approach, we consider the interplay between the biological, psychological and social factors that underpin the circulation and consumption of skin lighteners in South Africa. This paper reflects on biological aspects of skin lightening, interpersonal relationships, individual beliefs and expectations about the maintenance of health and well being that informs cosmetic practices. The paper seeks to examine claims made by historians (Thomas) and political philosophers and activists (Biko) that colonialism and apartheid in South Africa historically reinforced the use of skin lightening products in the country...
December 31, 2016: Journal of Public Health in Africa
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