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https://www.readbyqxmd.com/read/27913695/a-randomized-double-blind-placebo-controlled-trial-of-coenzyme-q10-in-huntington-disease
#1
Andrew McGarry, Michael McDermott, Karl Kieburtz, Elisabeth A de Blieck, Flint Beal, Karen Marder, Christopher Ross, Ira Shoulson, Peter Gilbert, William M Mallonee, Mark Guttman, Joanne Wojcieszek, Rajeev Kumar, Mark S LeDoux, Mary Jenkins, H Diana Rosas, Martha Nance, Kevin Biglan, Peter Como, Richard M Dubinsky, Kathleen M Shannon, Padraig O'Suilleabhain, Kelvin Chou, Francis Walker, Wayne Martin, Vicki L Wheelock, Elizabeth McCusker, Joseph Jankovic, Carlos Singer, Juan Sanchez-Ramos, Burton Scott, Oksana Suchowersky, Stewart A Factor, Donald S Higgins, Eric Molho, Fredy Revilla, John N Caviness, Joseph H Friedman, Joel S Perlmutter, Andrew Feigin, Karen Anderson, Ramon Rodriguez, Nikolaus R McFarland, Russell L Margolis, Eric S Farbman, Lynn A Raymond, Valerie Suski, Sandra Kostyk, Amy Colcher, Lauren Seeberger, Eric Epping, Sherali Esmail, Nancy Diaz, Wai Lun Alan Fung, Alan Diamond, Samuel Frank, Philip Hanna, Neal Hermanowicz, Leon S Dure, Merit Cudkowicz
OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months...
December 2, 2016: Neurology
https://www.readbyqxmd.com/read/27913460/autoimmune-and-other-acquired-neutropenias
#2
Peter E Newburger
This educational review addresses the diagnostic evaluation of patients for autoimmune and other forms of acquired neutropenia, including the futility of deconstructing the overlap of chronic "autoimmune," "benign," and "idiopathic" categories. Isolated neutropenias caused by infection, drugs, and immunologic disorders are also addressed. Discussion of management options emphasizes a conservative approach, with largely supportive care for these mostly benign and self-limited disorders.
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27908942/the-need-for-an-effective-process-to-resolve-conflicts-over-medical-futility-a-case-study-and-analysis
#3
Jocelyn A Olmstead, Michael D Dahnke
The issue of medical futility requires a well-defined process in which both sides of the dispute can be heard and a resolution reached in a fair and ethical manner. Procedural approaches to medical futility cases provide all parties involved with a process-driven framework for resolving these disputes. Medical paternalism or the belief in the absolute rightness of the medical model will not serve to resolve these disputes. Although medical futility is first determined by medicine, in order for the determination to meet legal criteria, it must be subject to review...
December 2016: Critical Care Nurse
https://www.readbyqxmd.com/read/27906720/decisions-regarding-forgoing-life-sustaining-treatments
#4
Gail A Van Norman
PURPOSE OF REVIEW: Decisions to forego life-sustaining treatments are complex, and disagreements between physicians and patients occur. This review discusses recent findings regarding what factors influence physicians and patients or their surrogates in these decisions and considers whether futility arguments regarding life-sustaining treatments should be abandoned. RECENT FINDINGS: Cardiopulmonary resuscitation is one paradigm in the literature for studying end-of-life decision-making...
November 30, 2016: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/27906117/carotid-artery-stenting-versus-no-stenting-assisting-thrombectomy-for-acute-ischaemic-stroke-protocol-for-a-systematic-review-of-randomised-clinical-trials-with-meta-analyses-and-trial-sequential-analyses
#5
Henrik Steglich-Arnholm, Markus Holtmannspötter, Christian Gluud, Derk Wolfgang Krieger
BACKGROUND: In patients with intracranial large vessel arterial occlusion, ipsilateral extracranial carotid artery occlusions or near-occlusions pose a significant hurdle in endovascular management of acute ischaemic stroke. Stenting of the carotid lesion may be beneficial in this situation to provide a stable access for introducing catheters through the carotid lesion into the intracranial vasculature and the target occlusion. Furthermore, carotid stenting may ensure ample blood flow for wash-out of clot material and reperfusion of the ischaemic penumbral tissue...
December 1, 2016: Systematic Reviews
https://www.readbyqxmd.com/read/27901352/the-social-amplification-of-haze-related-risks-on-the-internet
#6
Mark Chong, Murphy Choy
This study explores the implications of the digital network society for public health communication and management through an empirical study on communication related to the transboundary haze crisis in Singapore. Using the Social Amplification of Risk Framework (SARF), the authors applied sentiment and thematic analysis on haze-related posts on an online discussion forum (HardwareZone) and a social networking site (Facebook), and to haze-related articles in The Straits Times (a newspaper). The study shows that the medium matters in social amplification of risk: Facebook had an effect on the amplification of emotions, while HardwareZone and The Straits Times did not...
November 30, 2016: Health Communication
https://www.readbyqxmd.com/read/27896320/influences-of-do-not-resuscitate-order-prohibition-on-cpr-outcomes
#7
Umut Gulacti, Ugur Lok
OBJECTIVES: The aim of the study is to determine factors affecting the return of spontaneous circulation (ROSC) ratios, neurological outcomes at discharge, the ratio of living patients discharged from the hospital and due to Do not attempt resuscitation (DNAR) prohibition. MATERIAL AND METHODS: This is a retrospective observational study conducted on patients of cardiopulmonary resuscitation (CPR) performed in emergency department (ED) and intensive care units between February 2010 and February 2012...
June 2016: Turkish Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27894931/the-unique-status-of-first-in-human-studies-strengthening-the-social-value-requirement
#8
Michelle G J L Habets, Johannes J M van Delden, Annelien L Bredenoord
For clinical research to be ethical, risks need to be balanced by anticipated benefits. This is challenging for first-in-human (FIH) studies as participants are not expected to benefit directly, and risks are potentially high. We argue that this differentiates FIH studies from other clinical trials to the extent that they should be given unique status in international research ethics guidelines. As there is a general positive attitude regarding the benefits of science, it is important to establish a more systematic method to assess anticipated social value to safeguard participants not only from enrolling in risky, but also in futile trials...
November 25, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27894766/risk-and-relevance-of-open-lung-biopsy-in-pediatric-ecmo-patients-the-dutch-experience
#9
Robert Jan Houmes, Chantal A Ten Kate, Enno D Wildschut, Rob M Verdijk, René M H Wijnen, Ivo de Blaauw, Dick Tibboel, Arno F van Heijst
BACKGROUND: Open lung biopsy can help differentiate between reversible and irreversible lung disease and may guide therapy. To assess the risk-benefit ratio of this procedure in pediatric extracorporeal membrane oxygenation (ECMO) patients, we reviewed data of all patients who underwent an open lung biopsy during ECMO in one of the two pediatric ECMO centers in a nationwide study in the Netherlands. RESULTS: In nineteen neonatal and six pediatric patients (0-15...
November 14, 2016: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/27891574/termination-of-pre-hospital-resuscitation-by-anaesthesiologists-causes-and-consequences-a-retrospective-study
#10
S Mikkelsen, H M Lossius, L G Binderup, C Schaffalitzky de Muckadell, P Toft, A T Lassen
AIM: Differentiating between a newly deceased patient and the lifeless patient in whom immediate resuscitation is required may be facilitated by a pre-hospital anaesthesiologist. The purpose of our study was to investigate to what extent and why the pre-hospital anaesthesiologist pronounced life extinct in situations where an emergency medical technician (EMT) would have been required to resuscitate. METHODS: All lifeless patients seen pre-hospitally by the anaesthesiologist-manned Mobile Emergency Care Unit in Odense, Denmark, from 2010 to 2014 were retrospectively studied...
November 27, 2016: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/27890638/aberrant-base-excision-repair-pathway-of-oxidatively-damaged-dna-implications-for-degenerative-diseases
#11
Ibtissam Talhaoui, Bakhyt T Matkarimov, Thierry Tchenio, Dmitry O Zharkov, Murat K Saparbaev
In cellular organisms composition of DNA is constrained to only four nucleobases A, G, T and C, except for minor DNA base modifications such as methylation which serves for defence against foreign DNA or gene expression regulation. Interestingly, this severe evolutionary constraint among other things demands DNA repair systems to discriminate between regular and modified bases. DNA glycosylases specifically recognize and excise damaged bases among vast majority of regular bases in the base excision repair (BER) pathway...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27886777/characteristics-of-patients-who-are-not-resuscitated-in-out-of-hospital-cardiac-arrests-and-opportunities-to-improve-community-response-to-cardiac-arrest
#12
S Rajagopal, C R Kaye, R Lall, C D Deakin, S Gates, H Pocock, T Quinn, N Rees, M Smyth, G D Perkins
AIM: This study explores why resuscitation is withheld when emergency medical staff arrive at the scene of a cardiac arrest and identifies modifiable factors associated with this decision. METHODS: This is a secondary analysis of unselected patients who sustained an out of hospital cardiac arrest attended by ambulance vehicles participating in a randomized controlled trial of a mechanical chest compression device (PARAMEDIC trial). Patients were categorized as 'non-resuscitation' patients if there was a do-not-attempt-cardiopulmonary-resuscitation (DNACPR) order, signs unequivocally associated with death or resuscitation was deemed futile (15min had elapsed since collapse with no bystander-CPR and asystole recorded on EMS arrival)...
December 2016: Resuscitation
https://www.readbyqxmd.com/read/27883873/doctors
#13
Gaya Sritharan, Amber C Mills, Michele R Levinson, Anthea L Gellie
Objectives The aims of the present study were to investigate doctors' attitudes regarding the discussion and writing of not for resuscitation (NFR) orders and to identify potential barriers to the completion of these orders.Methods A questionnaire-based convenience study was undertaken at a tertiary hospital. Likert scales and open-ended questions were directed to issues surrounding the discussion, timing, understanding and writing of NFR orders, including legal and personal considerations.Results Doctors thought the presence of an NFR order both should and does alter care delivered by nursing staff, particularly delivery of pain relief, nursing observations and contacting the medical emergency team...
November 25, 2016: Australian Health Review: a Publication of the Australian Hospital Association
https://www.readbyqxmd.com/read/27872182/an-ompr-envz-two-component-system-ortholog-regulates-phase-variation-osmotic-tolerance-motility-and-virulence-in-acinetobacter-baumannii-strain-ab5075
#14
Kyle A Tipton, Philip N Rather
: Recently, a novel phase-variable colony opacity phenotype was discovered in Acinetobacter baumannii strain AB5075, where colonies interconvert between opaque and translucent variants. Opaque colonies become mottled/sectored after 24 hours of growth due to translucent variants arising within the colony. This easily distinguishable opaque colony phenotype was used to screen for random transposon insertions that increased the frequency of sectoring at a time point when wild-type colonies were uniformly opaque...
November 21, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27871490/predictive-models-for-mortality-after-ruptured-aortic-aneurysm-repair-do-not-predict-futility-and-are-not-useful-for-clinical-decision-making
#15
Patrick C Thompson, Ronald L Dalman, E John Harris, Venita Chandra, Jason T Lee, Matthew W Mell
OBJECTIVE: The clinical decision-making utility of scoring algorithms for predicting mortality after ruptured abdominal aortic aneurysms (rAAAs) remains unknown. We sought to determine the clinical utility of the algorithms compared with our clinical decision making and outcomes for management of rAAA during a 10-year period. METHODS: Patients admitted with a diagnosis rAAA at a large university hospital were identified from 2005 to 2014. The Glasgow Aneurysm Score, Hardman Index, Vancouver Score, Edinburgh Ruptured Aneurysm Score, University of Washington Ruptured Aneurysm Score, Vascular Study Group of New England rAAA Risk Score, and the Artificial Neural Network Score were analyzed for accuracy in predicting mortality...
December 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/27870712/a-phase-2-randomized-open-label-study-of-irosustat-versus-megestrol-acetate-in-advanced-endometrial-cancer
#16
Patricia Pautier, Ignace Vergote, Florence Joly, Bohuslav Melichar, Elzbieta Kutarska, Geoffrey Hall, Anna Lisyanskaya, Nicholas Reed, Ana Oaknin, Valerijus Ostapenko, Zanete Zvirbule, Eric Chetaille, Agnès Geniaux, Muhammad Shoaib, John A Green
OBJECTIVE: Advanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer. METHODS: This was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor-positive endometrial cancer...
November 17, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27863566/molecular-imaging-and-precision-medicine-in-lung-cancer
#17
REVIEW
Katherine A Zukotynski, Victor H Gerbaudo
Precision medicine allows tailoring of preventive or therapeutic interventions to avoid the expense and toxicity of futile treatment given to those who will not respond. Lung cancer is a heterogeneous disease functionally and morphologically. PET is a sensitive molecular imaging technique with a major role in the precision medicine algorithm of patients with lung cancer. It contributes to the precision medicine of lung neoplasia by interrogating tumor heterogeneity throughout the body. It provides anatomofunctional insight during diagnosis, staging, and restaging of the disease...
January 2017: PET Clinics
https://www.readbyqxmd.com/read/27863419/tsc-loss-distorts-dna-replication-programme-and-sensitises-cells-to-genotoxic-stress
#18
Govind M Pai, Alexandra Zielinski, Dennis Koalick, Kristin Ludwig, Zhao-Qi Wang, Kerstin Borgmann, Helmut Pospiech, Ignacio Rubio
Tuberous Sclerosis (TSC) is characterized by exorbitant mTORC1 signalling and manifests as non-malignant, apoptosis-prone neoplasia. Previous reports have shown that TSC-/- cells are highly susceptible to mild, innocuous doses of genotoxic stress, which drive TSC-/- cells into apoptotic death. It has been argued that this hypersensitivity to stress derives from a metabolic/energetic shortfall in TSC-/- cells, but how metabolic dysregulation affects the DNA damage response and cell cycle alterations in TSC-/- cells exposed to genotoxic stress is not understood...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27858564/preparing-for-value-based-payment-a-stepwise-approach-for-cancer-centers
#19
Kerin B Adelson, Salimah Velji, Kavita Patel, Basit Chaudhry, Catherine Lyons, Rogerio Lilenbaum
Most cancer centers are ill-equipped to pursue value-based payment (VBP) because of limited information on their population's cost of care. Herein, we outline the stepwise approach used by Smilow Cancer Hospital at Yale-New Haven in our pursuit of better value care. First, we addressed institutional barriers. A move toward value required demonstration to Yale-New Haven Health System leadership that OCM would improve patient care, fund new infrastructure, and provide the opportunity to gain experience with VBP without a major threat to the financial stability of the health system...
October 2016: Journal of Oncology Practice
https://www.readbyqxmd.com/read/27856525/microvilli-morphology-can-affect-efflux-active-p-glycoprotein-in-confluent-mdckii-nki_hmdr1-and-caco-2-cell-monolayers
#20
Zhou Meng, Sylvain Le Marchand, Deep Agnani, Matt Szapacs, Harma Ellens, Joe Bentz
From fits of drug transport kinetics across confluent MDCKII-hMDR1-NKI and Caco-2 cell monolayers we estimated the levels of efflux active P-glycoprotein (P-gp) in these two cell lines (companion paper, Meng at el., 2016a). In the present work, we compared the efflux active P-gp number to the total P-gp level, using LC/MSMS, and showed that in Caco-2 cells total P-gp is about 10-fold greater than efflux active P-gp, while in MDCKII-hMDR1-NKI cells these values are within 2-fold. We further visualized the microvilli in MDCKII-hMDR1-NKI and Caco-2 cells using three-dimensional structured illumination super-resolution microscopy and found that the microvilli in Caco-2 cells are taller and more densely packed than those in MDCK-NKI-hMDR1 cells...
November 16, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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