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https://www.readbyqxmd.com/read/29346478/differentiation-syndrome-associated-with-enasidenib-a-selective-inhibitor-of-mutant-isocitrate-dehydrogenase-2-analysis-of-a-phase-1-2-study
#1
Amir T Fathi, Courtney D DiNardo, Irina Kline, Laurie Kenvin, Ira Gupta, Eyal C Attar, Eytan M Stein, Stephane de Botton
Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity...
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29346247/concurrent-versus-sequential-intrapleural-instillation-of-tissue-plasminogen-activator-and-deoxyribonuclease-for-pleural-infection
#2
Fayez Kheir, George Cheng, Estefania Rivera, Alejandro Folch, Erik Folch, Fernandez-Bussy Sebastian, Colleen Keyes, Mihir Parikh, Colleen Channick, Alex Chee, Adnan Majid
BACKGROUND: Treatment of pleural infection with instillation of sequential intrapleural tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) twice daily for a total of 6 doses has been shown to decrease surgical referral and improve radiographic imaging. This labor-intensive regimen was empirically chosen. Thus, it remains unclear whether the 2 drugs can be administered immediately one after the other (concurrent administration) instead of instilling them separately with a 1-hour to 2-hour interval in between (sequential administration)...
January 16, 2018: Journal of Bronchology & Interventional Pulmonology
https://www.readbyqxmd.com/read/29345855/increased-estradiol-in-hepatitis-e-virus-infected-pregnant-women-promote-viral-replication
#3
Chenchen Yang, Wenhai Yu, Yanhong Bi, Feiyan Long, Yunlong Li, Daqiao Wei, Xianhui Hao, Jianwen Situ, Yongqin Zhao, Fen Huang
Hepatitis E virus (HEV) infection causes subclinical diseases, leading to high mortality (> 25%) in pregnant women. HEV replication is aggressively escalated in pregnant women, especially in the third trimester of pregnancy. Estrogen plays an important role in pregnancy. However, the pathogenesis of HEV in pregnant women or immunosuppressive pregnant women (such as HIV-infected, or organ-transplanted pregnant women) remains unclear. We investigated the role of estradiol in HEV infection in a cell culture system...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29345517/pet-adapted-therapy-for-advanced-hodgkin-lymphoma-systematic-review
#4
Irina Amitai, Ronit Gurion, Liat Vidal, Eldad J Dann, Pia Raanani, Anat Gafter-Gvili
INTRODUCTION: Positron emission tomography-computed tomography (PET-CT) performed after two chemotherapy cycles (PET-2) has become an accepted prognostic tool in Hodgkin lymphoma (HL). We evaluated the effect of PET-adapted strategy on outcome in advanced stage HL. METHODS: In August 2017, we searched electronic databases, conference proceedings and ongoing trials. We included all studies in which treatment modification for advanced HL was performed based on the results of the interim PET scan...
January 18, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29344926/the-mexican-drug-war-and-early-life-health-the-impact-of-violent-crime-on-birth-outcomes
#5
Ryan Brown
This study examines the relationship between exposure to violent crime in utero and birth weight using longitudinal data from a household survey conducted in Mexico. Controlling for selective migration and fertility, the results suggest that early gestational exposure to the recent escalation of the Mexican Drug War is associated with a substantial decrease in birth weight. This association is especially pronounced among children born to mothers of low socioeconomic status and among children born to mothers who score poorly on a mental health index...
January 17, 2018: Demography
https://www.readbyqxmd.com/read/29344836/boost-irradiation-integrated-to-whole-brain-radiotherapy-in-the-management-of-brain-metastases
#6
Ágnes Dobi, Emese Fodor, Anikó Maráz, Zsófia Együd, Adrienne Cserháti, László Tiszlavicz, Zita Reisz, Pál Barzó, Zoltán Varga, Katalin Hideghéty
Our retrospective analysis aimed to evaluate the clinical value of dose intensification schemes: WBRT and consecutive, delayed, or simultaneous integrated boost (SIB) in brain metastasis (BM) management. Clinical data and overall survival (OS) of 468 patients with BM from various primaries treated with 10 × 3 Gy WBRT (n = 195), WBRT+ 10 × 2 Gy boost (n = 125), or simultaneously 15 × 2.2 Gy WBRT+0.7 Gy boost (n = 148) during a 6-year period were statistically analysed. Significant difference in OS could be detected with additional boost to WBRT (3...
January 17, 2018: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29343563/robotic-crabs-reveal-that-female-fiddler-crabs-are-sensitive-to-changes-in-male-display-rate
#7
Sophie L Mowles, Michael D Jennions, Patricia R Y Backwell
Males often produce dynamic, repetitive courtship displays that can be demanding to perform and might advertise male quality to females. A key feature of demanding displays is that they can change in intensity: escalating as a male increases his signalling effort, but de-escalating as a signaller becomes fatigued. Here, we investigated whether female fiddler crabs, Uca mjoebergi, are sensitive to changes in male courtship wave rate. We performed playback experiments using robotic male crabs that had the same mean wave rate, but either escalated, de-escalated or remained constant...
January 2018: Biology Letters
https://www.readbyqxmd.com/read/29343509/efficacy-and-safety-of-tregalizumab-in-patients-with-rheumatoid-arthritis-and-an-inadequate-response-to-methotrexate-results-of-a-phase-iib-randomised-placebo-controlled-trial
#8
Ronald F van Vollenhoven, Edward Clark Keystone, Vibeke Strand, Cesar Pacheco-Tena, Jiří Vencovský, Frank Behrens, Arthur Racewicz, Daniela Zipp, Faiza Rharbaoui, Ralf Wolter, Luise Knierim, Rainer Schmeidl, Xuefei Zhou, Silke Aigner, Benjamin Dälken, Andrea Wartenberg-Demand
OBJECTIVE: To evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). METHODS: 321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment...
January 17, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29343176/on-understanding-the-nature-of-interpersonal-conflict-between-coaches-and-athletes
#9
Svenja Wachsmuth, Sophia Jowett, Chris G Harwood
Conflict is a part of coach-athlete relationships and should be carefully considered as it can have effects on the quality of coaching and the level of performance. Despite its practical relevance, there is a dearth of research around coach-athlete conflict. Therefore, the current study aimed to explore the characteristics and topics of conflict, as well as coaches and athletes' emotional, cognitive and behavioural experiences during conflict. A total of 22 independent coaches and athletes participated in semi-structured interviews evolving around the nature of interpersonal conflict...
January 18, 2018: Journal of Sports Sciences
https://www.readbyqxmd.com/read/29341985/dexmedetomidine-as-single-continuous-sedative-during-noninvasive-ventilation-typical-usage-hemodynamic-effects-and-withdrawal
#10
Brittany L Shutes, Samantha W Gee, Cheryl L Sargel, Kelsey A Fink, Joseph D Tobias
OBJECTIVES: Dexmedetomidine use in pediatric critical care is increasing. Its prolonged effects as a single continuous agent for sedation are not well described. The aim of the current study was to describe prolonged dexmedetomidine therapy without other continuous sedation, specifically the hemodynamic effects, discontinuation strategies, and risk factors for withdrawal. DESIGN: Retrospective chart review. SETTING: Large, single-center, quaternary care pediatric academic institution...
January 16, 2018: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/29341844/empiric-antibiotics-for-sepsis
#11
Sara A Buckman, Isaiah R Turnbull, John E Mazuski
BACKGROUND: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Early recognition and treatment are the cornerstones of management. METHODS: Review of the English-language literature. RESULTS: For both sepsis and septic shock "antimicrobials [should be] be initiated as soon as possible and within one hour" (Surviving Sepsis Campaign). The risk of progression from severe sepsis to septic shock increases 8% for each hour before antibiotics are started...
January 17, 2018: Surgical Infections
https://www.readbyqxmd.com/read/29341836/a-cohort-study-of-patient-reported-outcomes-and-healthcare-utilization-in-acute-myeloid-leukemia-patients-receiving-active-cancer-therapy-in-the-last-six-months-of-life
#12
Jared R Lowe, Yinxi Yu, Steven Wolf, Greg Samsa, Thomas W LeBlanc
BACKGROUND: Evidence about the unique palliative care needs of patients with acute myeloid leukemia (AML) is limited. Improving the care of these patients will require a better understanding of their unmet needs, including symptom burden at the end of life, and patterns of healthcare utilization. OBJECTIVE: To describe AML patients' experiences in the last six months of life regarding symptom burden, blood product utilization, and use of palliative care services...
January 17, 2018: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/29341491/clinical-outcomes-of-carbon-ion-radiotherapy-with-concurrent-chemotherapy-for-locally-advanced-uterine-cervical-adenocarcinoma-in-a-phase-1-2-clinical-trial-protocol-1001
#13
Noriyuki Okonogi, Masaru Wakatsuki, Shingo Kato, Kumiko Karasawa, Hiroki Kiyohara, Shintaro Shiba, Daijiro Kobayashi, Takashi Nakano, Tadashi Kamada, Makio Shozu
We conducted a phase 1/2 study to evaluate the efficacy and safety of carbon ion radiotherapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma. Thirty-three patients were enrolled between April 2010 and March 2014. Treatment consisted of C-ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2 . In the phase 1 component, the total dose was escalated from 68.0 Gy (relative biological effectiveness [RBE]) to 74.4 Gy (RBE) to determine the maximum tolerated dose of C-ion RT...
January 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29340015/apatinib-alone-or-combined-with-radiotherapy-in-metastatic-prostate-cancer-results-from-a-pilot-multicenter-study
#14
Feng Zhao, Wei Tian, Ming Zeng, Jianling Xia, Honglin Hu, Xinbao Hao, Liangfu Han, Hao Liu, Yangke He, Xueqiang Zhu, Liang Liang, Rui Ao, Min Wei, Lili Deng, Yuquan Wei
Background: To study safety and efficacy of apatinib in combination of radiotherapy in patients with symptomatic bony disease prostate cancer(SBPC), based on the potential synergistic antitumor activity between apatinib and Radiation Therapy (RT). Patients and methods: In phase I dose escalation part, 18 patients received apatinib dose at 250 mg every other day, 250 mg daily and 500 mg daily. In phase II part, the 250 mg daily cohorts were expanded to 20 patients in combination of RT (6 Gy/fraction, 5 fraction in total), one patient lost followed up and excluded the study, comparing with RT alone cohort with 10 patients, ratio of RT to RT + apatinib was 1 to 2...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339097/safety-and-preliminary-efficacy-of-venetoclax-with-decitabine-or-azacitidine-in-elderly-patients-with-previously-untreated-acute-myeloid-leukaemia-a-non-randomised-open-label-phase-1b-study
#15
Courtney D DiNardo, Keith W Pratz, Anthony Letai, Brian A Jonas, Andrew H Wei, Michael Thirman, Martha Arellano, Mark G Frattini, Hagop Kantarjian, Relja Popovic, Brenda Chyla, Tu Xu, Martin Dunbar, Suresh K Agarwal, Rod Humerickhouse, Mack Mabry, Jalaja Potluri, Marina Konopleva, Daniel A Pollyea
BACKGROUND: Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study...
January 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29338663/cultural-competency-in-dementia-care-an-african-american-case-study
#16
Jennie Leeder Clark, Sarah Phoenix, Ann Choryan Bilbrey, Terese McManis, Kristel Anne Escal, Rohini Arulanantham, Tiana Sisay, Rita Ghatak
Age is the greatest risk factor for Alzheimer's disease, the most common cause of dementia. The older population in the United States is growing, and within this demographic ethnic and racial diversity is also on the rise. This article introduces Stanford Health Care's Memory Support Program (MSP) as a model for culturally competent dementia care that spans inpatient and outpatient settings. The case study of an African American patient and family dealing with an Alzheimer's disease diagnosis and comorbid conditions is presented and explored to illustrate the MSP model...
December 26, 2017: Clinical Gerontologist
https://www.readbyqxmd.com/read/29338536/p2y12-receptor-inhibitors-an-evolution-in-drug-design-to-prevent-arterial-thrombosis
#17
Danny Kupka, Dirk Sibbing
P2Y12 inhibitors are a critical component of dual antiplatelet therapy (DAPT) - a combination of a P2Y12 receptor inhibitor and aspirin - which is the superior strategy to prevent arterial thrombosis in patients with acute coronary syndromes (ACS) and undergoing stent implantation. Areas covered: Basic science articles, clinical studies, and reviews from 1992-2017 were searched using Pubmed library to collet impactful literature. After an introduction to the purinergic receptor biology, this review summarizes current knowledge on P2Y12 receptor inhibitors including their specific pharmacodynamic as well as pharmacokinetic and drug interaction features...
January 17, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29338496/repeated-lipopolysaccharide-exposure-modifies-immune-and-sickness-behaviour-response-in-an-animal-model-of-chronic-inflammation
#18
Ksenia Musaelyan, Steven Aldridge, Andrea Du Preez, Martin Egeland, Patricia A Zunszain, Carmine M Pariante, Sandrine Thuret, Cathy Fernandes
Repeated lipopolysaccharide exposure is often used in longitudinal preclinical models of depression. However, the potential phenotypic differences from acute depression-mimicking effects are rarely described. This study compared chronic lipopolysaccharide administration of doses previously used in depression research to a new mode of escalating dose injections. Adult male BALB/c mice ( n=8/group) were injected intraperitoneally with either a single 0.83 mg/kg dose, a repeated 0.1 mg/kg lipopolysaccharide dose or a dose which escalated weekly from 0...
January 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29338080/phase-1-trial-evaluating-cisplatin-gemcitabine-and-veliparib-in-2-patient-cohorts-germline-brca-mutation-carriers-and-wild-type-brca-pancreatic-ductal-adenocarcinoma
#19
Eileen M O'Reilly, Jonathan W Lee, Maeve A Lowery, Marinela Capanu, Zsofia K Stadler, Malcolm J Moore, Neesha Dhani, Hedy L Kindler, Hayley Estrella, Hannah Maynard, Talia Golan, Amiel Segal, Erin E Salo-Mullen, Kenneth H Yu, Andrew S Epstein, Michal Segal, Robin Brenner, Richard K Do, Alice P Chen, Laura H Tang, David P Kelsen
BACKGROUND: A phase 1 trial was used to evaluate a combination of cisplatin, gemcitabine, and escalating doses of veliparib in patients with untreated advanced pancreatic ductal adenocarcinoma (PDAC) in 2 cohorts: a germline BRCA1/2-mutated (BRCA+) cohort and a wild-type BRCA (BRCA-) cohort. The aims were to determine the safety, dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase 2 dose (RP2D) of veliparib combined with cisplatin and gemcitabine and to assess the antitumor efficacy (Response Evaluation Criteria in Solid Tumors, version 1...
January 16, 2018: Cancer
https://www.readbyqxmd.com/read/29338000/progression-of-the-first-stage-of-spontaneous-labour-a-prospective-cohort-study-in-two-sub-saharan-african-countries
#20
Olufemi T Oladapo, Joao Paulo Souza, Bukola Fawole, Kidza Mugerwa, Gleici Perdoná, Domingos Alves, Hayala Souza, Rodrigo Reis, Livia Oliveira-Ciabati, Alexandre Maiorano, Adesina Akintan, Francis E Alu, Lawal Oyeneyin, Amos Adebayo, Josaphat Byamugisha, Miriam Nakalembe, Hadiza A Idris, Ola Okike, Fernando Althabe, Vanora Hundley, France Donnay, Robert Pattinson, Harshadkumar C Sanghvi, Jen E Jardine, Özge Tunçalp, Joshua P Vogel, Mary Ellen Stanton, Meghan Bohren, Jun Zhang, Tina Lavender, Jerker Liljestrand, Petra Ten Hoope-Bender, Matthews Mathai, Rajiv Bahl, A Metin Gülmezoglu
BACKGROUND: Escalation in the global rates of labour interventions, particularly cesarean section and oxytocin augmentation, has renewed interest in a better understanding of natural labour progression. Methodological advancements in statistical and computational techniques addressing the limitations of pioneer studies have led to novel findings and triggered a re-evaluation of current labour practices. As part of the World Health Organization's Better Outcomes in Labour Difficulty (BOLD) project, which aimed to develop a new labour monitoring-to-action tool, we examined the patterns of labour progression as depicted by cervical dilatation over time in a cohort of women in Nigeria and Uganda who gave birth vaginally following a spontaneous labour onset...
January 2018: PLoS Medicine
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