tbuckley/cabot-search huggingface dataset:
Guidelines for the diagnosis and management of asthma: a look at the key differences between BTS/SIGN and NICE
Authors: John White, James Y Paton, Robert Niven, Hilary Pinnock
Journal: Thorax (2018)

The British Thoracic Society (BTS) first produced a guideline on asthma and its management in 1990. The first collaborative guideline with the Scottish Intercollegiate Guideline Network (SIGN) using evidence-based medicine methodology was published in 2003.1 It has since become a mainstay of asthma management across the UK and beyond with updates published regularly every 18–24 months. The latest BTS/SIGN guideline for the management of asthma was published in 2016.2 Both BTS and SIGN are committed to continuing updates with the next update planned for publication in 2019.

Following publication of National Institute for Health and Care Excellence (NICE) guidelines for diagnosis and monitoring, and for management of chronic asthma,3–5 there are now two if not three national guidelines, for England at least, with some (apparently) striking differences. This statement considers the similarities and differences to assist clinical colleagues in the care of people with asthma.

The evidence base considered by the BTS/SIGN and NICE guideline development groups is broadly the same for each guideline, but the methodology used to produce recommendations is significantly different:



These different processes have resulted in some discrepancies in recommendations made by BTS/SIGN and NICE. This article seeks to provide some context to these differences in key areas:



The BTS/SIGN guideline also provides recommendations …
COMPARE analysis of the NCI-60 cancer cell lines reveals a pharmacological interplay between farnesyltransferase and tubulin deacetylase.
Authors: Jun Zhou, Adam I. Marcus, Susan L. Holbeck, Paraskevi Giannakakou
Journal: Cancer Research (2005)

27  The COMPARE algorithm provides an instrumental platform for correlating drug sensitivities and/or molecular targets among the 60 human cancer cell lines of the National Cancer Institute (NCI-60). In this study, the level of tubulin acetylation in the NCI-60 cell lines is examined by quantitative western blotting and used as a seed for COMPARE analysis against the gene expression database generated from microarray data. This analysis generates a list of genes that correlate with tubulin acetylation. One such gene with a strong negative correlation is farnesyltransferase (FTase), such that cell lines with high levels of tubulin acetylation have low FTase gene expression. We have also examined the protein levels of FTase in all 60 cell lines, which confirm the negative correlation between FTase and tubulin acetylation. In addition, western blotting and immunofluorescence studies reveal that inhibition of FTase activity in cancer cells dramatically enhances the level of tubulin acetylation. Interestingly, co-immunoprecipitation experiments demonstrate that FTase interacts with the tubulin deacetylase HDAC6, providing evidence that these two enzymes are biologically linked. Lastly, we show that FTase inhibitors suppress HDAC6 activity in a cell-free tubulin deacetylation assay. These data indicate a pharmacological interplay between FTase and HDAC6. Additional mechanistic studies investigating the molecular nature of FTase interaction with HDAC6 are currently under investigation in our laboratory.
Pre-injury variables and risk of sport concussion
Authors: Sandhya Mylabathula, Lynda Mainwaring, Michael Hutchison, Doug Richards, Paul Comper
Journal: British Journal of Sports Medicine (2017)

Objective The study examined whether cognitive functioning, history of concussion (HOC), and sex predicted risk of sport concussion. Design Retrospective study design. Predictive models were used to determine the predictive ability of each variable. Setting Canadian University. Participants 708 data observations from 701 varsity athletes (41.2% female), representing 14 sports. Assessment of risk factors Two measures of cognitive functioning (mean reaction time and throughput [speed and accuracy]) were assessed using the Automated Neuropsychological Assessment Metrics testing battery. Categorical and continuous measures of HOC, and sex, were examined. Outcome measures Occurrence of concussion after baseline testing. Main results HOC was a significant predictor for both sexes. For every previous concussion, the odds of sustaining another concussion increased by 1.5 (95% Confidence Interval [CI]: 1.1, 2.1 [females]; 1.2, 1.9 [males]). Females with a HOC had twice the odds of sustaining another concussion than those without a HOC (CI: 1.1, 4.0). For males, the odds were three times (CI: 1.7, 5.6). Cognitive functioning and sex were not meaningful predictors. Conclusions This study supports previous findings that HOC is a risk factor and suggests that pre-injury cognitive functioning is not a risk factor for sport concussion. Assessing HOC in all athletes prior to their competitive season provides information regarding their risk of future sport concussion. Thus, it is important for clinicians to record HOC, and to encourage athletes to report concussions to ensure an accurate HOC record. Pre-injury cognitive screening of athletes is not recommended for assessing risk of future concussion. Competing interests Sandhya Mylabathula, Lynda Mainwaring, and Michael Hutchison None. Doug Richards is the Medical Director at the MacIntosh Sports Medicine Clinic at the University of Toronto Paul Comper is a clinical neuropsychologist consultant with the NHLPA and a member of the Concussion Working Group, but neither were related to the current research
Prognostic Impact of Pregnancy on Long-Term Outcome in Acute Leukemias Patients
Authors: Vera V. Troitskaya, Elena N. Parovichnikova, Andrey N. Sokolov, Alina Kokhno, Zalina T. Fidarova, Olga A. Gavrilina, Anna A. Sidorova, Gennadii M. Galstian, Larisa A. Kuzmina, Mikhail Yu. Drokov, Sergei Makhinya, Oleg Latishkevich, Alexandra Zvereva, Anton Olenev, Olga Korobitsyna, Alexandr Korobkin, Elena Kirillova, Sergei M. Kulikov, Valery G. Savchenko
Journal: Blood (2017)
Postmenopausal Hormone-Replacement Therapy
Authors: JoAnn E. Manson, Kathryn A. Martin
Journal: New England Journal of Medicine (2001)

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.Patient 1 is a 52-year-old woman at average risk for breast cancer and osteoporosis who is having menopause-related hot flashes and disturbed sleep. Patient 2 is a 58-year-old woman with osteopenia whose mother had breast cancer. Patient 3 is a 65-year-old woman with a history of coronary revascularization and documented osteoporosis. Each wants to know whether hormone-replacement therapy is right for her.The Clinical ProblemOverviewOne of the most complex and difficult health care decisions that women face is whether to use postmenopausal hormone-replacement therapy. The average woman in the United States lives nearly 30 years after menopause, . . .
Annals Graphic Medicine - Back to Work
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2018)

Web Exclusives2 January 2018Annals Graphic Medicine - Back to WorkFREEGrace E. Farris, MDGrace E. Farris, MDFrom Mount Sinai School of Medicine, New York, New York. (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G17-0013 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Dr. Farris recalls the trying moments of being "Doctor Mom." Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Mount Sinai School of Medicine, New York, New York. (G.E.F.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G17-0013.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Icahn School of Medicine at Mount Sinai and chief of hospital medicine at Mount Sinai West hospital in New York, New York. You can view her work on Instagram (www.instagram.com/gracefarriscomics).Corresponding Author: Grace E. Farris, MD, Mount Sinai West, Department of Medicine, 1000 Tenth Avenue, New York, NY 10019; e-mail, Grace.[email protected]org.Author Contributions: Conception and design: G.E. Farris.Drafting of the article: G.E. Farris.Critical revision for important intellectual content: G.E. Farris.Final approval of the article: G.E. Farris.Written and illustrated by Grace E. Farris, MD. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 2 January 2018Volume 168, Issue 1Page: W1-W6 ePublished: 2 January 2018 Issue Published: 2 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 19209: Wide Qrs and Rbbb Morphology Are Associated With Worse Prognosis in Aortic Stenosis
Authors: Edgard A Prihadi, Melissa Leung, E M Vollema, Arnold Ng, Nina Ajmone Marsan, Jeroen J Bax, Victoria Delgado
Journal: Circulation (2016)

Background: The prevalence and prognostic importance of QRS morphology and duration have not been previously documented in a population comprising all grades of aortic stenosis (AS) patients. Purpo...
Abstract 14080: Post-Transcriptional Regulation of Cardiac Protein Expression in Hypertrophy
Authors: Edward Lau, Quan Cao, Dominic C Ng, Brian J Bleakley, Maggie P Lam, Peipei Ping
Journal: Circulation (2016)

Introduction:  Whether gene expression is predominantly regulated by transcriptional or post-transcriptional processes is often debated. Pathological cardiac hypertrophy is associated with the dysregulation of protein homeostasis, but how this may affect the cardiac protein expression profile has not been examined.   Hypothesis:  We hypothesize that the rates of protein turnover contribute to cardiac hypertrophy by acting as a post-transcriptional regulation of cardiac protein expression profile.   Methods:  We integrated stable isotope mass spectrometry, computational modeling and a systems genetics model to generate a large dataset on protein dynamics in six inbred mouse strains showing contrasting susceptibilities to cardiac hypertrophy. To identify candidate disease markers, we performed regression modeling of proteome parameters over phenotypic responses. A meta-analysis on existing transcriptomics datasets was performed to compare implicated disease genes from transcript and protein data.   Results:  We analyzed the turnover and abundance of 3,228 proteins in cardiac hypertrophy, encompassing 201 cellular pathways. The data were acquired from 1,404 mass spectrometry experiments. The data shows evidence that functionally-related proteins are co-regulated in turnover, with the turnover rate of glycolytic enzymes positively correlated with the severity of hypertrophy (r > 0.58), whereas the turnover of fatty acid oxidation pathways is negatively correlated (r    Conclusions:  We demonstrate that protein dynamics information provides independent and complementary insights into the regulation of gene expression in the diseased heart, and can avail in-depth elucidation of disease drivers and mechanisms.
Abstract 12208: Mode of Death in Heart Failure With Preserved Ejection Fraction: A Systematic Review
Authors: Ravi B Patel, Muthiah Vaduganathan, Alexander Michel, Sanjiv J Shah, Michele Senni, Mihai Gheorghiade, Javed Butler
Journal: Circulation (2016)

Introduction: Despite its tremendous clinical and economic impact, remarkably little is known about the specific modes of death (MOD) in patients with heart failure with preserved ejection fraction (HFpEF). Methods: We conducted a systematic review of published HFpEF clinical trials and epidemiological studies from January 1 st , 1985 to December 31 st , 2015 using the PubMed and EMBASE databases. Two independent investigators manually screened 1,608 articles in duplicate, selected studies, and extracted relevant data. The systematic search yielded 8 major randomized controlled trials and 24 epidemiological studies that reported MOD data. Results: Definitions of cardiovascular (CV), sudden, heart failure (HF), and non-CV deaths in HFpEF trials were similar to those used in contemporary trials of HF with reduced ejection fraction (HFrEF). CV causes accounted for ~60-70% of total deaths in HFpEF clinical trials (Figure), while this proportion was more variable (14-83%) in epidemiological studies. Only 4 (50%) trials and 5 (20.8%) epidemiological studies reported data on sudden death (SD). SD accounted for ~40% of the CV deaths in clinical trials, but only 20-28% in epidemiological studies. Proportions of HF deaths were consistent across clinical trials (20-30% of CV deaths) but varied in epidemiological studies (17-60%). Cancer was the most frequently reported non-CV MOD (~30-40% of non-CV deaths), followed by infection/sepsis, which accounted for a quarter of non-CV deaths. Conclusions: Cause-specific mortality is infrequently reported, informed by &lt;1,000 events (in trials) and &lt;500 events (in epidemiological studies), and when it is, event definitions are directly applied from HFrEF studies. The definition of SD is non-specific and suboptimal in the majority of studies; therefore, it is unclear whether these truly represent arrhythmic deaths. Reporting and definitions of MOD must be standardized and tailored to the HFpEF population.
Identification of Functional Determinants of Response and Resistance to CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy of Chronic Lymphocytic Leukemia
Authors: Joseph A Fraietta, Simon F Lacey, Elena Orlando, Julian Pruteanu, Mercy Gohil, Yan Wang, Alina Boesteanu, Roddy OConnor, David E Ambrose, Wei-Ting Hwang, Nicholas Wilcox, Felipe Bedoya, Corin Dorfmeier, Fang Chen, Harit Parakandi, Minnal Gupta, Edward Pequignot, F. Brad Johnson, Irina Kulikovskaya, Li Liu, Stefan M Lundh, Jun Xu, Megan M Davis, Regina M Young, Bruce L Levine, Don L. Siegel, Alexander Huang, E. John Wherry, Jing Zhou, Patrick Paczkowski, Sean Mackay, Jennifer Brogdon, Hans Bitter, David L Porter, Carl H June, J. Joseph Melenhorst
Journal: Blood (2017)
Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications
Authors: Angelika Behrens, Anton Kreuzmayr, Hendrik Manner, Herbert Koop, Albrecht Lorenz, Claus Schaefer, Mathais Plauth, Jens-Uwe Jetschmann, Christian von Tirpitz, Marcus Ewald, Michael Sackmann, Wanja Renner, Martin Krüger, Dieter Schwab, Werner Hoffmann, Olaf Engelke, Oliver Pech, Frank Kullmann, Sonja Pampuch, Berthold Lenfers, Uwe Weickert, Dieter Schilling, Stephan Boehm, Susanne Beckebaum, Vito Cicinnati, Joachim F Erckenbrecht, Franz Ludwig Dumoulin, Claus Benz, Thomas Rabenstein, Georg Haltern, Martin Balsliemke, Christian de Mas, Gerhard Kleber, Christian Pehl, Christoph Vogt, Ralf Kiesslich, Wolfgang Fischbach, Irmtraut Koop, Jens Kuehne, Matthias Breidert, Nils Lennart Sass, Andrea May, Christian Friedrich, Ronni Veitt, Rainer Porschen, Mark Ellrichmann, Alexander Arlt, Wolfgang Schmitt, Markus Dollhopf, Werner Schmidbaur, Axel Dignass, Volker Schmitz, J Labenz, Gernot Kaiser, Alexander Krannich, Nico Barteska, Christian Ell
Journal: Gut (2018)

Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size.Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre.A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis.This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients.DRKS00007768; Pre-results.
Cord Blood Regulatory T Cells for Prevention of Graft Versus Host Disease
Authors: Joshua Kellner, Stefan O. Ciurea, Amanda L. Olson, Yago Nieto, Borje S Andersson, Joseph David Khoury, Richard E. Champlin, Stefan Nierkens, Jaap Jan Boelens, Bruce Blazar, Simrit Parmar
Journal: Blood (2017)
Macrolides, mucoactive drugs and adherence for the management of bronchiectasis
Authors: James D. Chalmers, Eva Polverino
Journal: European Respiratory Journal (2018)

We thank W-J. Guan and colleagues for their comments on the European Respiratory Society (ERS) guidelines for bronchiectasis [1]. We agree these are an important landmark for the field, and hope that clinicians, health professionals, patients and researchers will use the guidelines to improve the quality of care for bronchiectasis patients and to use the gaps identified to stimulate further research [1, 2]. Only evidence-based recommendations were included in the @ERStalk bronchiectasis guidelines <http://ow.ly/Vecb30g1gJy>
Indian government promises independent review of medical regulation reform bill
Authors: Sanjeet Bagcchi
Journal: BMJ (2018)

Doctors on strike in India were told to return to work on 2 January, after the government agreed to refer for independent review a new bill that aims to reform medical education and regulation.

Nearly 29 000 doctors are reported to have refused to see patients in private hospitals in protest at the National Medical Commission Bill, which was introduced to the Indian parliament on 29 December. In November around 270 000 doctors across India took to the streets to protest against the proposed bill.1

The Indian Medical Association, which called for the strike, condemned the bill as “anti-people and anti-patient.”

But the IMA called off the strike after the government agreed to …
Highly flexible, wearable, and disposable cardiac biosensors for remote and ambulatory monitoring
Authors: Stephen P. Lee, Grace Ha, Don E. Wright, Yinji Ma, Ellora Sen-Gupta, Natalie R. Haubrich, Paul C. Branche, Weihua Li, Gilbert L. Huppert, Matthew Johnson, Hakan B. Mutlu, Kan Li, Nirav Sheth, John A. Wright, Yonggang Huang, Moussa Mansour, John A. Rogers, Roozbeh Ghaffari
Journal: npj Digital Medicine (2018)

Contemporary cardiac and heart rate monitoring devices capture physiological signals using optical and electrode-based sensors. However, these devices generally lack the form factor and mechanical flexibility necessary for use in ambulatory and home environments. Here, we report an ultrathin (~1 mm average thickness) and highly flexible wearable cardiac sensor (WiSP) designed to be minimal in cost (disposable), light weight (1.2 g), water resistant, and capable of wireless energy harvesting. Theoretical analyses of system-level bending mechanics show the advantages of WiSP's flexible electronics, soft encapsulation layers and bioadhesives, enabling intimate skin coupling. A clinical feasibility study conducted in atrial fibrillation patients demonstrates that the WiSP device effectively measures cardiac signals matching the Holter monitor, and is more comfortable. WiSP's physical attributes and performance results demonstrate its utility for monitoring cardiac signals during daily activity, exertion and sleep, with implications for home-based care.
Distribution of therapeutic proteins into thoracic lymph after intravenous administration is protein size-dependent and primarily occurs within the liver and mesentery
Authors: Preeti Yadav, Victoria M. McLeod, Cameron J. Nowell, Laura I. Selby, Angus P.R. Johnston, Lisa M. Kaminskas, Natalie L. Trevaskis
Journal: Journal of Controlled Release (2018)
Lymphoma Patients Treated without Anthracyclines Have Negligible Risk of Cardiotoxicity: A Nationwide Cohort Study
Authors: J Baech, SM Hansen, PE Lund, C. Torp-Pedersen, HE Johnsen, P. Søgaard, P. de Nully Brown, Henrik Frederiksen, J. Jørgensen, J. Starklint, P. Josefsson, CB Poulsen, TC El-Galaly
Journal: Blood (2017)
A randomised clinical trial of feedback on inhaler adherence and technique in patients with severe uncontrolled asthma
Authors: Imran Sulaiman, Garrett Greene, Elaine MacHale, Jansen Seheult, Matshediso Mokoka, Shona D'Arcy, Terence Taylor, Desmond M. Murphy, Eoin Hunt, Stephen J. Lane, Gregory B. Diette, J. Mark FitzGerald, Fiona Boland, Aoife Sartini Bhreathnach, Breda Cushen, Richard B. Reilly, Frank Doyle, Richard W. Costello
Journal: European Respiratory Journal (2018)

In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence.Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis.The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% versus 63%; 95% CI 2.8%-17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%).Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy.