tbuckley/cabot-search huggingface dataset:
Azithromycin for Acute Exacerbations of Asthma
Authors: Sebastian L. Johnston, Matyas Szigeti, Mary Cross, Christopher Brightling, Rekha Chaudhuri, Timothy Harrison, Adel Mansur, Laura Robison, Zahid Sattar, David Jackson, Patrick Mallia, Ernie Wong, Christopher Corrigan, Bernard Higgins, Philip Ind, Dave Singh, Neil C. Thomson, Deborah Ashby, Anoop Chauhan
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Guidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use. <h3>Objective</h3> To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit. <h3>Design, Setting, and Participants</h3> The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom–based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids. <h3>Interventions</h3> Azithromycin 500 mg daily or matched placebo for 3 days. <h3>Main Outcomes and Measures</h3> The primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of −0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score. <h3>Results</h3> Of 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference, −0.166; 95% CI, −0.670 to 0.337), nor on any day between exacerbation and day 10. No significant between-group differences were observed in quality-of-life questionnaires or lung function between exacerbation and day 10, or in time to 50% reduction in symptom score. <h3>Conclusions and Relevance</h3> In this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01444469
Frequency, clinical features and outcome of monosomy 7 in childhood acute lymphoblastic leukemia (ALL): Results of the EORTC-CLCG study
Authors: N Dastugue, S Suciu, MP Pages, AM Manel, A Fackenrodt, N Philippe, C Bastard, Anne Hagemeijer-Hausman, P Brock, D Leroux, S Raynaud, A Thyss, F Speleman, C D'Hooge, P Boutard, JL Lai, B Nelken, J Otten, E Vilmer
Journal: Blood (1999)
Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia
Authors: N Gökbuget, M Kelsh, V Chia, A Advani, R Bassan, H Dombret, M Doubek, A K Fielding, S Giebel, V Haddad, D Hoelzer, C Holland, N Ifrah, A Katz, T Maniar, G Martinelli, M Morgades, S O'Brien, J-M Ribera, J M Rowe, A Stein, M Topp, M Wadleigh, H Kantarjian
Journal: Blood Cancer Journal (2016)

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.
GMC relaunches language test for overseas doctors, but concerns remain over equivalence
Authors: Anne Gulland
Journal: BMJ (2016)

The General Medical Council has relaunched its test for international medical graduates wishing to work in the UK, with the aim of making it more rigorous and reflective of real life practice. But one of the researchers whose work led the GMC to overhaul the test has warned that the revised examination will still not assess overseas graduates to the same level as UK graduates.

The first students sat the updated Professional and Linguistics Assessment Board (PLAB) test on 7 September. The exam was updated after a review of the exam commissioned by the GMC recommended that candidates should not be able to resit the test several times if they failed.1 The review also recommended that the exam should test candidates on the ethical and professional principles outlined in the GMC’s Good Medical Practice guidance.

Concern had also been expressed that the pass marks for the PLAB test were too low, after …
Add on Interferon-Alpha-2a for the Treatment of HBeAg Negative Hepatitis B Patients Receiving Effective Nucleos(t)ide Therapy: Interim Results of the Prospective Multicentre PADD-On Trial
Authors: M.F. Sprinzl, A. Grambihler, G. Teuber, M. Ebert, S. Zeuzem, J. Lohmeyer, M. Cornberg, F. Tacke, H. Löhr, T. Berg, F. Lammert, E. Schott, R. Heyne, C. Berg, M. Dollinger, A. Pathil-Warth, F. Geisler, U. Spengler, R. Thimme, K. Weigand, U. Alshuth, A. Ehrlich, M. Riedl, J. Kittner, M. Schuchmann, P.R. Galle
Journal: Journal of Hepatology (2016)
Downregulation of tumor suppressor Runx genes in malignant cutaneous melanoma
Authors: S. R. Martinez, C. T. Kuo, A. J. Bilchik, J. Kim, D. L. Morton, D. S. B. Hoon
Journal: Journal of Clinical Oncology (2005)

7531 Background: Frequent genomic alterations of the 6p and 1p chromosomal regions have been demonstrated in cutaneous melanoma and are thought to be sites of candidate tumor suppressor genes. Two transcription factors with proposed tumor suppressor activity, Runx2 and Runx3, map to 6p21 and 1p36 chromosomal loci, respectively. Runx genes play important regulatory roles in tissue development and tumor progression. We hypothesized that Runx2 and Runx3 expression will be altered during melanoma progression. Methods: Eleven established human metastatic melanoma cell lines, a normal melanocyte cell line, and 27 paraffin-embedded lymph node metastases from stage III melanoma patients were assessed. Runx2 and Runx3 mRNA expression was assessed by quantitative real-time RT-PCR. RNA was extracted and purified from cell lines and paraffin-embedded tissues. Runx2 and Runx3 mRNA expression levels were measured relative to a housekeeping gene to ensure RNA integrity and compared to the mRNA levels detected in normal melanocytes. Results: Runx2 and Runx3 were differentially expressed among the 11 melanoma lines and 27 tumor specimens. For both the Runx2 and Runx3 genes, the mean mRNA expression was significantly over 1000-fold decreased in 11 of 11 (100%, p<0.001) lines compared to melanocytes, and in 11 of 11 (100%, p<0.001) lines over 100-fold compared to melanocytes, respectively. Mean mRNA levels of Runx2 and Runx3 in melanoma tumors had a 1.4- and 6-fold decrease, respectively, in expression compared to normal controls (p< 0.01 and p< 0.0001). Conclusions: These preliminary studies are the first report of Runx2 and Runx3 transcription factor downregulation in metastatic melanoma. These two Runx genes are candidate tumor suppressor genes and may play important roles in melanoma tumor development and progression. No significant financial relationships to disclose.
Healthy life expectancy of colorectal cancer survivors.
Authors: I. Soerjomataram, M. Thong, L. V. Poll, M. Ezzati, W. Nusselder
Journal: Journal of Clinical Oncology (2010)

e14007 Background: Life expectancy after colorectal cancer has been increasing. However, the proportion of life that survivors spend in good health has never been assessed. Methods: Using a population-based cancer registry database, life expectancy for colorectal cancer survivors diagnosed in 2000-2006 followed until 2007 was calculated. We used the Sullivan method to calculate healthy life expectancy (HLE) and disability- free life expectancy (DFLE) using self-reported health and functional status from a random sample of colorectal cancer survivors. Results: On average a 50-year old colorectal cancer survivor may enjoy 75%–77% of his/her remaining life in good health or without disability. Survivors with stage I-III have a similar proportion of remaining life in good health ranging from 74%–84%, whereas survivors of stage IV colorectal cancer spent less than half of their remaining life in good health or without disability. Female survivors were disadvantaged in HLE and DFLE as compared to males especially among the oldest old (proportion of males' HLE at age 85: 69% vs. female's: 59%), the lowest socioeconomic class (proportion of males' HLE: 65% vs. females: 55%) and those with one or more comorbidities at time of diagnosis (proportion of males' HLE: 70% vs. females': 63%). There were no difference in HLE and DFLE by treatments (proportion of HLE for patients who had surgery only, surgery with radiotherapy with or without chemotherapy and surgery with chemotherapy was ± 78%) and subsites of colorectal cancer (proportion of HLE for colon or rectal cancer was ± 77%). Conclusions: Most patients with colorectal cancer may expect to spend a large amount of their life in good health and without daily activity limitation. The high proportion of unhealthy years or years with disability among the oldest old and those with advanced cancer suggests the need for better assistance in daily functioning for these groups and better palliative care. No significant financial relationships to disclose.
Addison’s forum helps to support and engage patients
Authors: Katherine G White, Nick Willson, Pippa Sharman, Vick Smith
Journal: BMJ (2016)

As Armstrong observes, social media can allow people with rare conditions to connect and share experiences, especially when unstable health makes travel difficult.1

The combined visitor peak to the Addison’s Disease Self-Help Group (ADSHG) website and forum in one day was 443 (www.addisons.org.uk); by contrast, our largest in-person meeting numbered 180.

We established a members-only online discussion forum in 2008. This now …
Comparison of Echocardiographic Indices Used to Predict Fluid Responsiveness in Ventilated Patients
Authors: Philippe Vignon, Xavier Repessé, Emmanuelle Bégot, Julie Léger, Christophe Jacob, Koceila Bouferrache, Michel Slama, Gwenaël Prat, Antoine Vieillard-Baron
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Assessment of fluid responsiveness relies on dynamic echocardiographic parameters that have not yet been compared in large cohorts.To determine the diagnostic accuracy of dynamic parameters used to predict fluid responsiveness in ventilated patients with a circulatory failure of any cause.In this multicenter prospective study, respiratory variations of superior vena cava diameter (∆SVC) measured using transesophageal echocardiography, of inferior vena cava diameter (∆IVC) measured using transthoracic echocardiography, of the maximal Doppler velocity in left ventricular outflow tract (∆VmaxAo) measured using either approach, and pulse pressure variations (∆PP) were recorded with the patient in the semirecumbent position. In each patient, a passive leg raise was performed and an increase of aortic velocity time integral greater than or equal to 10% defined fluid responsiveness.Among 540 patients (379 men; age, 65 ± 13 yr; Simplified Acute Physiological Score II, 59 ± 18; Sequential Organ Failure Assessment, 10 ± 3), 229 exhibited fluid responsiveness (42%). ∆PP, ∆VmaxAo, ∆SVC, and ∆IVC could be measured in 78.5%, 78.0%, 99.6%, and 78.1% of cases, respectively. ∆SVC greater than or equal to 21%, ∆VmaxAo greater than or equal to 10%, and ∆IVC greater than or equal to 8% had a sensitivity of 61% (95% confidence interval, 57-66%), 79% (75-83%), and 55% (50-59%), respectively, and a specificity of 84% (81-87%), 64% (59-69%), and 70% (66-75%), respectively. The area under the receiver operating characteristic curve of ∆SVC was significantly greater than that of ∆IVC (P = 0.02) and ∆PP (P = 0.01).∆VmaxAo had the best sensitivity and ∆SVC the best specificity in predicting fluid responsiveness. ∆SVC had a greater diagnostic accuracy than ∆IVC and ∆PP, but its measurement requires transesophageal echocardiography.
A Randomized, Placebo Controlled, Double Blind Trial of the Effect of Combined Therapy with Deferoxamine and Deferiprone on Myocardial Iron in Thalassaemia Major Using Cardiovascular Magnetic Resonance.
Authors: Mark A. Tanner, Renzo Galanello, Carlo Dessi, Mark A. Westwood, Gillian C. Smith, Mohammed Khan, Sunil V. Nair, J. M. Walker, Dudley J. Pennell
Journal: Blood (2005)
P1353 : A single tablet regimen of ledipasvir/sofosbuvir for 12 weeks in HCV genotype 1 or 4 infected patients with HIV-1 co-infection : The phase 3 ION-4 study
Authors: C. Cooper, S. Naggie, M. Saag, J. Yang, L. Stamm, P. Pang, J. McHutchison, D. Dieterich, M. Sulkowski
Journal: Journal of Hepatology (2015)
Feasibility, phase I, and phase II studies of tandutinib, an oral platelet-derived growth factor receptor-β tyrosine kinase inhibitor, in patients with recurrent glioblastoma
Authors: Tracy T Batchelor, Elizabeth R Gerstner, Xiaobu Ye, Serena Desideri, Daniel G Duda, David Peereboom, Glenn J Lesser, Sajeel Chowdhary, Patrick Y Wen, Stuart Grossman, Jeffrey G Supko
Journal: Neuro-Oncology (2016)

Platelet-derived growth factor (PDGF) signaling is important in gliomagenesis and PDGF receptor-β is expressed on most endothelial cells in glioblastoma specimens.
Bmi-1 regulates stem cell-like properties of gastric cancer cells via modulating miRNAs
Authors: Xiaofeng Wang, Chang Wang, Xiaowei Zhang, Ruixi Hua, Lu Gan, Mingzhu Huang, Liqin Zhao, Sujie Ni, Weijian Guo
Journal: Journal of Hematology & Oncology (2016)

B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) plays an important role in regulating stemness in some kinds of cancer. However, the mechanisms remain unclear. This study was to investigate whether and how Bmi-1 regulates stemness of gastric cancer.We firstly explored the role of Bmi-1 in regulating stem cell-like features in gastric cancer. Secondly, we screened out its downstream miRNAs and clarified whether these miRNAs are involved in the regulation of stemness. Finally, we investigated the mechanisms how Bmi-1 regulates miRNAs.Bmi-1 positively regulates stem cell-like properties of gastric cancer and upregulates miR-21 and miR-34a. There was a positive correlation between Bmi-1 and miR-21 expression in gastric cancer tissues. MiR-21 mediated the function of Bmi-1 in regulating stem cell-like properties, while miR-34a negatively regulates stem cell-like characteristics via downregulating Bmi-1. Bmi-1 binds to PTEN promoter and directly inhibits PTEN and thereafter activates AKT. Bmi-1 also regulates p53 and PTEN via miR-21. Bmi-1 activated NF-kB via AKT and enhanced the binding of NF-kB to the promoter of miR-21 and miR-34a and increased their expression.Bmi-1 positively regulates stem cell-like properties via upregulating miR-21, and miR-34a negatively regulates stem cell-like characteristics by negative feedback regulation of Bmi-1 in gastric cancer. Bmi-1 upregulates miR-21 and miR-34a by activating AKT-NF-kB pathway.
Use of Recombinant Thrombomodulin for Thrombotic Microangiopathy after Hematopoietic Stem Cell Transplantation Ameliorate Disease Severity
Authors: Hideaki Fujiwara, Yoshinobu Maeda, Yasuhisa Sando, Makoto Nakamura, Katsuma Tani, Takanori Ishikawa, Hisakazu Nishimori, Ken-Ichi Matsuoka, Nobuharu Fujii, Eisei Kondo, Mitsune Tanimoto
Journal: Blood (2014)
Self-Reported Quality of Life in Patients Treated with Covered Transjugular Intrahepatic Portosystemic Shunt (TIPS) versus Endoscopic + B-Blocker Treatment for Secondary Prevention of Gastro-Oesophageal Variceal Bleeding
Authors: J. Harki, I.L. Holster, S. Polinder, A. Moelker, H. van Buuren, E.J. Kuipers, E.T.T.L. Tjwa
Journal: Journal of Hepatology (2016)
A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis
Authors: Carsten Speckmann, Sam Doerken, Alessandro Aiuti, Michael H. Albert, Waleed Al-Herz, Luis M. Allende, Alessia Scarselli, Tadej Avcin, Ruy Perez-Becker, Caterina Cancrini, Andrew Cant, Silvia Di Cesare, Andrea Finocchi, Alain Fischer, H. Bobby Gaspar, Sujal Ghosh, Andrew Gennery, Kimberly Gilmour, Luis I. González-Granado, Monica Martinez-Gallo, Sophie Hambleton, Fabian Hauck, Manfred Hoenig, Despina Moshous, Benedicte Neven, Tim Niehues, Luigi Notarangelo, Capucine Picard, Nikolaus Rieber, Ansgar Schulz, Klaus Schwarz, Markus G. Seidel, Pere Soler-Palacin, Polina Stepensky, Brigitte Strahm, Thomas Vraetz, Klaus Warnatz, Christine Winterhalter, Austen Worth, Sebastian Fuchs, Annette Uhlmann, Stephan Ehl
Journal: Journal of Allergy and Clinical Immunology (2016)
P0888 : Effect of baseline factors on response to the fixed-dose combination of daclatasvir (DCV), asunaprevir (ASV) and beclabuvir (BCV), with or without ribavirin (RBV), in patients with HCV genotype 1 infection and cirrhosis
Authors: C. Hezode, R. Herring, P.J. Pockros, A. Sheikh, J. Vierling, S. Lee, A. Thompson, R. Bhore, E.A. Hughes, E.S. Swenson, P.D. Yin
Journal: Journal of Hepatology (2015)
Phenotypic and Genetic Discordance in Monozygotic Twins with Sickle Anemia and ð-Thalassemia.
Authors: Maxwell P. Westerman, Arnold Pizzey, Herbert J. Meiselman, Narla Mohandas, Gregory J. Kato, Mark Gladwin, Laurel Mendelsohn, Jan Dumanski, John B Porter
Journal: Blood (2009)
RPL5 Is a Candidate Tumor Suppressor on 1p22.1 in Multiple Myeloma of Which the Expression Is Linked to Bortezomib Response
Authors: Isabel JF Hofman, Mark van Duin, George Mulligan, Ellen Geerdens, Emanuela Garelli, Cecilia Mancini, Heidi Lemmens, Michel Delforge, Peter Vandenberghe, Iwona Wlodarska, Anna Aspesi, Lucienne Michaux, Pieter Sonneveld, Kim De Keersmaecker
Journal: Blood (2015)
Cover Image: Life-threatening complications of jellyfish <i>Chrysaora pacifica</i> stings in a 5-year-old child
Authors: Y. Ikawa, N. Fujita, Y. Yachi, N. Inoue, A. Kato, M. Kuroda, A. Yachie
Journal: British Journal of Dermatology (2016)

In Psoriasis: Diagnosis and Management systemic agents are discussed concisely with therapeutic approaches outlined according to the European guidelines.Several biologics are discussed, including those used only for psoriatic arthritis.One of the most fascinating areas is the development of new treatments, a topic that is handled well in Psoriasis: Diagnosis and Management, with a good up-to-date summary of other treatments including new biologics, oral agents and topical treatments in development.However, for those looking for more detail in this area, 'The Research Pipeline' chapters in Advances in Psoriasis cover treatments in development, including new topical agents: janus kinase (JAK) inhibitors, phosphodiesterase 4 inhibitors and new combination treatments.Given the nature of the topic, these advances are necessarily out of date.It would be interesting to know more about any agents that may soon be available; however, the chapter was written early in the production of the book (the latest online references are from 2011).The subsequent chapter features new oral drugs, including apremilast, and fumaric acid esters (not used in the U.S.) and other agents, trials of which have now ceased.It is unclear which have progressed or are likely to make it into clinical practice.
The economic effects of supporting tuberculosis-affected households in Peru
Authors: Tom Wingfield, Marco A. Tovar, Doug Huff, Delia Boccia, Rosario Montoya, Eric Ramos, James J. Lewis, Robert H. Gilman, Carlton A. Evans
Journal: European Respiratory Journal (2016)

The End TB Strategy mandates that no tuberculosis (TB)-affected households face catastrophic costs due to TB. However, evidence is limited to evaluate socioeconomic support to achieve this change in policy and practice. The objective of the present study was to investigate the economic effects of a TB-specific socioeconomic intervention. The setting was 32 shantytown communities in Peru. The participants were from households of consecutive TB patients throughout TB treatment administered by the national TB programme. The intervention consisted of social support through household visits and community meetings, and economic support through cash transfers conditional upon TB screening in household contacts, adhering to TB treatment/chemoprophylaxis and engaging with social support. Data were collected to assess TB-affected household costs. Patient interviews were conducted at treatment initiation and then monthly for 6 months. From February 2014 to June 2015, 312 households were recruited, of which 135 were randomised to receive the intervention. Cash transfer total value averaged US$173 (3.5% of TB-affected households' average annual income) and mitigated 20% of households' TB-related costs. Households randomised to receive the intervention were less likely to incur catastrophic costs (30% (95% CI 22–38%) versus 42% (95% CI 34–51%)). The mitigation impact was higher among poorer households. The TB-specific socioeconomic intervention reduced catastrophic costs and was accessible to poorer households. Socioeconomic support and mitigating catastrophic costs are integral to the End TB strategy, and our findings inform implementation of these new policies.
Daclatasvir and Sofosbuvir Therapy for Patients with Decompensated Cirrhosis or Post-Liver Transplant HCV Recurrence and Advanced Fibrosis or Cirrhosis: United States Multicentretreatment Protocol
Authors: R. Brown, M. Fried, R.K. Reddy, C.S. Pico, S. Khemichian, J. Darling, A.A. Napoli, B. Anduze-Faris, P. Kwo
Journal: Journal of Hepatology (2016)
Quality of Life and Outcomes in Multiple Myeloma Patients
Authors: Shilpa Paul, Samith T. Kochuparambil, Carrie A Thompson, Tait D. Shanafelt, Francis K Buadi, Martha Q. Lacy, Morie A Gertz, Angela Dispenzieri, David Dingli, Prashant Kapoor, Suzanne R Hayman, Lisa Hwa, Jane K Case, S. Vincent Rajkumar, Shaji Kumar
Journal: Blood (2014)
Association Between the Hepato-Adrenal Syndrome and Features of Cirrhotic Cardiomyopathy
Authors: E. Theocharidou, S. Anastasiadis, T. Vasiliadis, F. Adamidou, A. Fotoglidis, E. Pagourelias, V. Vassilikos, M. Kouskoura, A. Markopoulou, A. Balaska, A. Slavakis, A. Notopoulos, A. Karagiannis, O. Giouleme
Journal: Journal of Hepatology (2016)
Pooled RCTs: After ischemic stroke or TIA, aspirin for secondary prevention reduced early recurrence and severity
Authors: Mark J. Alberts
Journal: Annals of Internal Medicine (2016)

Source Citation Rothwell PM, Algra A, Chen Z, et al. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. Lancet. 2016;May 18 [Epub ahead of print]. 27209146