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https://www.readbyqxmd.com/read/29346838/first-in-human-study-to-assess-safety-pharmacokinetics-and-pharmacodynamics-of-bms-962212-a-direct-reversible-small-molecule-factor-xia-inhibitor-in-non-japanese-and-japanese-healthy-subjects
#1
Vidya Perera, Joseph M Luettgen, Zhaoqing Wang, Charles E Frost, Cynthia Yones, Cesare Russo, John Lee, Yue Zhao, Frank P LaCreta, Xuewen Ma, Robert M Knabb, Dietmar Seiffert, Mary DeSouza, Pierre Mugnier, Brenda Cirincione, Takayo Ueno, Robert J A Frost
AIMS: To assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class Factor XIa inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a randomized, placebo-controlled, double-blind, sequential, ascending dose study of 2 hour (Part A) and 5 day (Part B) intravenous (IV) infusions of BMS-962212. Part A used 4 doses (1.5, 4, 10, and 25 mg h-1 ) assigned to BMS-962212 or placebo in a 3:1 ratio per dose. Part B used 4 doses (1, 3, 9, and 20 mg h-1 ) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese subjects (n = 4 active, n = 1 placebo) per dose...
January 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29346837/a-phase-1-randomized-placebo-and-active-controlled-crossover-study-to-determine-the-effect-of-single-dose-ertugliflozin-on-qtc-interval-in-healthy-volunteers
#2
Vaishali Sahasrabudhe, Didier Saur, Kyle Matschke, Steven G Terra, Anne Hickman, Isabelle Huyghe, Haihong Shi, David L Cutler
Ertugliflozin, a selective sodium-glucose cotransporter-2 inhibitor, is being developed for the treatment of type 2 diabetes mellitus. This randomized, 6-sequence, 3-period crossover study assessed the effect of ertugliflozin (100 mg; supratherapeutic dose) vs placebo and moxifloxacin (400 mg; positive control) on the QT interval corrected for heart rate (QTc) in 42 male or female healthy subjects. Triplicate electrocardiograms were performed predose and serially over 48 hours postdose in each treatment period...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346831/postoperative-reduction-of-intraventricular-hemorrhage-volume-single-versus-dual-catheter-drainage
#3
Syed Shahzad Hussain, Asif Raza, Saman Shahid, Hafiz Hamza Asif, Usman Ahmad, Naveed Ashraf
BACKGROUND/AIMS:  The use of single/dual external ventricular drains (EVD) for reducing intraventricular hemorrhage (IVH) is under investigation. A randomized controlled trial was conducted to compare postoperative reduction of IVH volume using single- and dual-catheter drainage in spontaneous IVH patients. We investigated factors that may influence an effective hematoma volume reduction by EVDs. MATERIALS AND METHODS:  The average cerebrospinal fluid (CSF) drainage volumes were analyzed...
January 18, 2018: Journal of Neurological Surgery. Part A, Central European Neurosurgery
https://www.readbyqxmd.com/read/29346734/fluctuation-effects-on-the-brush-structure-of-mixed-brush-nanoparticles-in-solution
#4
Jason P Koski, Amalie L Frischknecht
A potentially attractive way to control nanoparticle assembly is to graft one or more polymers on the nanoparticle, to control the nanoparticle-nanoparticle interactions. When two immiscible polymers are grafted on the nanoparticle, they can microphase separate to form domains at the nanoparticle surface. Here we computationally investigate the phase behavior of such binary mixed brush nanoparticles in solution, across a large and experimentally relevant parameter space. Specifically, we calculate the mean-field phase diagram, assuming uniform grafting of the two polymers, as a function of the nanoparticle size relative to the length of the grafted chains, the grafting density, the enthalpic repulsion between the grafted chains, and the solvent quality...
January 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29346679/risk-stratification-in-takotsubo-syndrome-a-role-of-mitral-annular-plane-systolic-excursion
#5
Ibrahim El-Battrawy, Uzair Ansari, Siegfried Lang, Christian Fastner, Xiaobo Zhou, Martin Borggrefe, Ibrahim Akin
Aims: Takotsubo syndrome (TTS) patients have a higher mortality rate than the general population. Our study was conducted to determine the short- and long-term outcome of TTS patients associated with a significantly compromised mitral annular plane systolic excursion (MAPSE) on hospital admission. Methods and results: Our institutional database constituted a collective of 53 patients diagnosed with TTS between 2003 and 2016. The patients were classified into two groups based on the MAPSE, with those presenting with a MAPSE <1 cm on admission categorized into one group (n = 20, 38%) and those presenting with MAPSE ≥1 cm (n = 33, 62%) categorized into another group...
January 15, 2018: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/29346644/genome-wide-analysis-of-disease-progression-in-age-related-macular-degeneration
#6
Qi Yan, Ying Ding, Yi Liu, Tao Sun, Lars G Fritsche, Traci Clemons, Rinki Ratnapriya, Michael L Klein, Richard J Cook, Yu Liu, Ruzong Fan, Lai Wei, Gonçalo R Abecasis, Anand Swaroop, Emily Y Chew, Daniel E Weeks, Wei Chen
Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related Macular Degeneration (AMD), one of the first batch and most successful examples of genome-wide association study (GWAS). However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization [CNV] or geographic atrophy [GA]). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2,721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study...
January 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29346597/exenatide-increases-il-1ra-concentration-and-induces-nrf-2-keap-1-regulated-anti-oxidant-enzymes-relevance-to-%C3%AE-cell-function
#7
Paresh Dandona, Husam Ghanim, Sanaa Abuaysheh, Kelly Green, Sandeep Dhindsa, Antoine Makdissi, Manav Batra, Nitesh D Kuhadiya, Ajay Chaudhuri
Purpose: We have previously demonstrated anti-inflammatory and antioxidant effects of exenatide. We have now hypothesized that exenatide also increases the plasma concentration of IL-1RA, an endogenous anti-inflammatory protein and modulates the Nrf-2-Keap-1-ARE system to induce key antioxidant enzymes to suppress inflammatory and oxidative stress. Methods: Twenty four obese type 2 diabetic patients on combined oral and insulin therapy were randomized to receive either exenatide 10μg or placebo b...
January 15, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29346581/melatonin-attenuates-lung-ischaemia-reperfusion-injury-via-inhibition-of-oxidative-stress-and-inflammation
#8
Ming-Liang Wang, Chun-Hua Wei, Wen-Dong Wang, Jia-Shun Wang, Jun Zhang, Jian-Jun Wang
OBJECTIVES: Lung ischaemia-reperfusion injury is a complex pathophysiological process due to the production of reactive oxygen species and the generation of inflammatory reaction. We investigated the protective effects and the corresponding mechanism of melatonin (MT), a potent free-radical scavenger, on lung injury induced by ischaemia-reperfusion in a mouse model. METHODS: Adult male C57BL/6J mice (n = 30) were randomly and equally allocated into 5 groups: sham controls, IR, IR + 10 mg/kg MT, IR + 20 mg/kg MT and IR + 30 mg/kg MT...
January 15, 2018: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29346579/web-based-cognitive-behavior-therapy-for-chronic-pain-patients-with-aberrant-drug-related-behavior-outcomes-from-a-randomized-controlled-trial
#9
Honoria Guarino, Chunki Fong, Lisa A Marsch, Michelle C Acosta, Cassandra Syckes, Sarah K Moore, Ricardo A Cruciani, Russell K Portenoy, Dennis C Turk, Andrew Rosenblum
Objective: There is high unmet need for effective behavioral treatments for chronic pain patients at risk for or with demonstrated histories of opioid misuse. Despite growing evidence supporting technology-based delivery of self-management interventions for chronic pain, very few such programs target co-occurring chronic pain and aberrant drug-related behavior. This randomized controlled trial evaluated the effectiveness of a novel, web-based self-management intervention, grounded in cognitive behavior therapy, for chronic pain patients with aberrant drug-related behavior...
January 13, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29346573/the-addition-of-bevacizumab-to-oxaliplatin-based-chemotherapy-impact-upon-hepatic-sinusoidal-injury-and-thrombocytopenia
#10
Michael J Overman, Renata Ferrarotto, Kanwal Raghav, Binsah George, Wei Qiao, Karime K Machado, Leonard B Saltz, Thibault Mazard, J N Vauthey, Paulo M Hoff, Brian Hobbs, Evelyn M Loyer, Scott Kopetz
Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI), portal hypertension, and splenic sequestration of platelets. Evidence suggests that bevacizumab may protect against HSI. Methods: Two cohorts of metastatic colorectal cancer (CRC) were analyzed: a nonrandomized exploratory cohort of 184 patients treated at a single institution from 2003 to 2010 and a confirmatory cohort of 200 patients from a multi-institutional randomized trial (NO16966)...
January 15, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29346559/predicting-plant-biomass-accumulation-from-image-derived-parameters
#11
Dijun Chen, Rongli Shi, Jean-Michel Pape, Kerstin Neumann, Daniel Arend, Andreas Graner, Ming Chen, Christian Klukas
Background: Image-based high-throughput phenotyping technologies have been rapidly developed in plant science recently and they provide a great potential to gain more valuable information than traditionally destructive methods. Predicting plant biomass is regarded as a key purpose for plant breeders and ecologist. However, it is a great challenge to find a predictive biomass model across experiments. Results: In the present study, we constructed four predictive models to examine the quantitative relationship between image-based features and plant biomass accumulation...
January 16, 2018: GigaScience
https://www.readbyqxmd.com/read/29346531/doppler-assessment-of-aortic-stenosis-a-25-operator-study-demonstrating-why-reading-the-peak-velocity-is-superior-to-velocity-time-integral
#12
Stefania Sacchi, Niti M Dhutia, Matthew J Shun-Shin, Massoud Zolgharni, Nilesh Sutaria, Darrel P Francis, Graham D Cole
Aims: Measurements with superior reproducibility are useful clinically and research purposes. Previous reproducibility studies of Doppler assessment of aortic stenosis (AS) have compared only a pair of observers and have not explored the mechanism by which disagreement between operators occurs. Using custom-designed software which stored operators' traces, we investigated the reproducibility of peak and velocity time integral (VTI) measurements across a much larger group of operators and explored the mechanisms by which disagreement arose...
January 15, 2018: European Heart Journal Cardiovascular Imaging
https://www.readbyqxmd.com/read/29346524/-effects-of-a-primary-care-based-multifactorial-intervention-on-physical-and-cognitive-function-in-frail-elderly-individuals-a-randomized-controlled-trial
#13
Laura Romera-Liebana, Francesc Orfila, Josep Maria Segura, Jordi Real, Maria Lluïsa Fabra, Mercedes Möller, Santiago Lancho, Anna Ramirez, Nuria Marti, Montserrat Cullell, Nuria Bastida, Dolors Martinez, Maria Giné, Patricia Cendrós, Anna Bistuer, Elena Perez, Maria Assumpta Fabregat, Gonçal Foz
Background: Detecting and managing frailty at early stages can prevent disability and other adverse outcomes. The study aim was to evaluate whether a multifactorial intervention program could modify physical and cognitive frailty parameters in elderly individuals. Methods: We conducted a multicenter, randomized, single-blind, parallel-group trial in community-living pre-frail/frail elderly individuals in Barcelona. A total of 352 patients, aged ≥65 years old with positive frailty screening, was randomized into two groups to receive a 12-week multidisciplinary intervention or usual care, with concealed allocation...
January 16, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29346507/activity-and-safety-of-afatinib-in-a-window-pre-operative-eortc-study-in-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-scchn
#14
J P Machiels, P Bossi, J Menis, M Lia, C Fortpied, Y Liu, R Lhommel, M Lemort, S Schmitz, S Canevari, L De Cecco, M Guzzo, R Bianchi, P Quattrone, F Crippa, T Duprez, Y Lalami, M Quiriny, N de Saint Aubain, P M Clement, R Coropciuc, E Hauben, L F Licitra
Background: To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5:1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29346499/repeatability-and-agreement-of-visual-acuity-using-the-etdrs-number-chart-landolt-c-chart-or-etdrs-alphabet-chart-in-eyes-with-or-without-sight-threatening-diseases
#15
Voraporn Chaikitmongkol, Onnisa Nanegrungsunk, Direk Patikulsila, Paisan Ruamviboonsuk, Neil M Bressler
Importance: The Early Treatment Diabetic Retinopathy Study (ETDRS) alphabet chart is not feasible for measuring best-corrected visual acuity (BCVA) for individuals who are unfamiliar with the Roman alphabet. The ETDRS Landolt C chart is an alternative, but it may not reflect true BCVA among those with confusion between left and right. The ETDRS number chart might overcome these limitations, but little is known regarding its reliability. Objective: To evaluate repeatability and agreement of BCVA using the ETDRS number chart or Landolt C chart compared with ETDRS alphabet charts in healthy and diseased eyes...
January 18, 2018: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29346473/treatment-for-alcohol-dependence-in-primary-care-compared-to-outpatient-specialist-treatment-a-randomized-controlled-trial
#16
Sara Wallhed Finn, Anders Hammarberg, Sven Andreasson
Aim: To investigate if treatment for alcohol dependence in primary care is as effective as specialist addiction care. Method: Randomized controlled non-inferiority trial, between groups parallel design, not blinded. The non-inferiority limit was set to 50 grams of alcohol per week. About 288 adults fulfilling ICD-10 criteria for alcohol dependence were randomized to treatment in primary care (men n = 82, women n = 62) or specialist care (men n = 77, women n = 67)...
January 16, 2018: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/29346446/osteopontin-opn-as-a-csf-and-blood-biomarker-for-multiple-sclerosis-a-systematic-review-and-meta-analysis
#17
Elmira Agah, Arshia Zardoui, Amene Saghazadeh, Mona Ahmadi, Abbas Tafakhori, Nima Rezaei
Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016...
2018: PloS One
https://www.readbyqxmd.com/read/29346408/long-lasting-insecticidal-bed-nets-ownership-access-and-use-in-a-high-malaria-transmission-setting-before-and-after-a-mass-distribution-campaign-in-uganda
#18
Humphrey Wanzira, Thomas Eganyu, Ronald Mulebeke, Fred Bukenya, Dorothy Echodu, Yeka Adoke
INTRODUCTION: Uganda is conducting a second mass LLIN distribution campaign and Katakwi district recently received LLINs as part of this activity. This study was conducted to measure the success of the campaign in this setting, an area of high transmission, with the objectives to estimate LLIN ownership, access and use pre and post campaign implementation. METHODS: Two identical cross sectional surveys, based on the Malaria Indicator Survey methodology, were conducted in three sub-counties in this district (Kapujan, Magoro and Toroma), six months apart, one before and another after the mass distribution campaign...
2018: PloS One
https://www.readbyqxmd.com/read/29346406/shea-vitellaria-paradoxa-gaertn-c-f-fruit-yield-assessment-and-management-by-farm-households-in-the-atacora-district-of-benin
#19
Koutchoukalo Aleza, Grace B Villamor, Benjamin Kofi Nyarko, Kperkouma Wala, Koffi Akpagana
Vitellaria paradoxa (Gaertn C. F.), or shea tree, remains one of the most valuable trees for farmers in the Atacora district of northern Benin, where rural communities depend on shea products for both food and income. To optimize productivity and management of shea agroforestry systems, or "parklands," accurate and up-to-date data are needed. For this purpose, we monitored120 fruiting shea trees for two years under three land-use scenarios and different soil groups in Atacora, coupled with a farm household survey to elicit information on decision making and management practices...
2018: PloS One
https://www.readbyqxmd.com/read/29346385/combined-effectiveness-of-anthelmintic-chemotherapy-and-wash-among-hiv-infected-adults
#20
Arianna R Means, Lisette van Lieshout, Eric Brienen, Krista Yuhas, James P Hughes, Paul Ndungu, Benson Singa, Judd L Walson
INTRODUCTION: Current global helminth control guidelines focus on regular deworming of targeted populations for morbidity control. However, water, sanitation, and hygiene (WASH) interventions may also be important for reducing helminth transmission. We evaluated the impact of different potential helminth protective packages on infection prevalence, including repeated treatment with albendazole and praziquantel with and without WASH access. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cohort study nested within a randomized trial of empiric deworming of HIV-infected adults in Kenya...
January 2018: PLoS Neglected Tropical Diseases
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