tbuckley/cabot-search huggingface dataset:
Abstract 17461: Ambiguity of the Self-report Description of Cormack-lehane View Grading in the Prehospital Settings
Authors: Hiromichi Naito, Francis X Guyette, Christian Martin-Gill, Atsunori Nakao, Clifton W Callaway
Journal: Circulation (2016)

Introduction:  Cormack-Lehane (C-L) view is common method for grading difficult endotracheal intubation (ETI). Although until recently, C-L view could not be analyzed by the individuals other than the provider performing ETI. Video laryngoscopy (VL) is a relatively new device primarily to facilitate ETI. VL can also provide recorded data for objective review of the technique.   Hypothesis:  We tested whether C-L view evaluated by prehospital provider (paramedic/nurse) correlates with the true C-L view verified by with VL video recorded data.   Methods:  A retrospective review of the patients transported from Mar 2010 to Oct 2015 by air critical care medical service. The VL used in the study has the ability to display and digitally record the procedure which can be reviewed after the incident. True C-L view was confirmed by medical doctors using VL recorded data. Prehospital provider C-L view was obtained from self-reported medical charts description. We defined prehospital provider C-L view grading of I or II as “easy view” and provider C-L view grading of III or IV as “difficult view”. For the primary outcome, Cohen’s kappa was used to evaluate the reliability of prehospital provider C-L view. For the secondary outcome, characteristics between “easy view” and “difficult view” were compared.   Results:  Results: 236 patients were included in the study. Overall ETI success rate was 93%. True C-L view grades were (I: 159 [67%], II: 72 [31%], III: 4 [2%], IV: 1 [0%]) whereas, prehospital providers graded (I: 129 [55%], II: 80 [34%], III: 24 [10%], IV: 3 [1%]). There was 57% agreement: kappa 0.21 ( p   p  = 0.33), total attempt time for ETI (59±35 s vs 26±27 s, p  p   p     Conclusions:  C-L view grading only had “fair” agreement between prehospital provider and VL video recorded data. Self-reported description of C-L view grading may contain recall bias and observer bias influenced by ETI difficulty besides true C-L view.
TEMPORAL CHANGES IN LEFT ATRIAL FUNCTION IN WOMEN WITH HER2+ BREAST CANCER RECEIVING SEQUENTIAL ANTHRACYCLINES AND TRASTUZUMAB THERAPY
Authors: Jennifer Meloche, Mark Nolan, Eitan Amir, Christine Brezden-Masley, Andrew Yan, Babitha Thampinathan, Anna Woo, Wintersperger Bernd, Paaladinesh Thavendiranathan
Journal: Journal of the American College of Cardiology (2018)
A phase Ib open-label, dose escalation and expansion study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in combination with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer.
Authors: Ulka N. Vaishampayan, Vivek Narayan, David Wise, Joshua Michael Lang, Benjamin H Lowentritt, Begona Mellado, Joan Carles, M Isabel Sáez, Wassim Abida, Mary-Ellen Taplin, Arun Azad, Karrie Wang, Olena Barbash, Geraldine Ferron-Brady, Doug Fecteau, Ahmed Hussein Khaled, Arindam Dhar, Johann S. De Bono
Journal: Journal of Clinical Oncology (2018)

TPS391 Background: Metastatic castrate-resistant prostate cancer (mCRPC) remains an incurable illness as resistance develops after androgen deprivation therapy (ADT) and/or androgen receptor (AR) axis targeted therapies. The bromodomain (BRD) and extraterminal (BET) proteins are critical for transcription. Preclinically, one of these proteins, BRD4, acts in complex with AR to mediate androgen signaling that leads to prostate cell growth and proliferation. GSK525762 is an oral pan-BET inhibitor that suppresses BET dependent activated AR-driven transcription. Combined with androgen production or receptor targeted agents like abiraterone or enzalutamide, GSK525762 may enhance efficacy of or overcome resistance to either agent. Methods: This is a Phase Ib open-label, dose-escalation study to evaluate the safety and efficacy of oral administration of GSK525762 in combination with either abiraterone plus prednisone (Arm A) or enzalutamide (Arm B) in mCRPC patients whose disease has progressed on prior abiraterone or enzalutamide. Patients must have documented prostate cancer progression as assessed by rising PSA or radiographic progression of soft tissue by PCWG3-modified RECIST 1.1 criteria or bone metastasis. Dose escalation is designed to identify safe doses to move into dose expansion. Dose expansion will explore safety and efficacy in patients who failed in first line (L2 population) or after multiple lines of prior therapy (LX population). Primary objectives include defining the safety, tolerability and clinical activity of GSK525762 when combined with products in Arm A or Arm B. Primary clinical activity endpoint is defined as the response rate of subjects achieving a 50% or more reduction from baseline of PSA at 12 weeks or thereafter. Dose escalation will employ a modified Toxicity Probability Interval (mTPI) design. Dose expansion will use a Bayesian adaptive design, which will calculate posterior probability that utility of the dose is clinically significant at interim futility analysis for each dose level. Funding: GSK Clinical trial information: NCT03150056.
How the gut inflames the joints
Authors: David S Pisetsky
Journal: Annals of the Rheumatic Diseases (2018)

A study by Pianta et al published in the Journal of Clinical Investigation provides new evidence that the pathogenesis of rheumatoid arthritis (RA) may involve molecular mimicry, one of the most venerable models for the aetiology of rheumatic disease.1 Molecular mimicry represents the development of cross-reactive B or T cell responses to a component of an infecting agent. As shown in this study, the agent in question may be a commensal in the gut microbiome rather than a bacterium or virus inducing clinical disease.

While a violation of tolerance, molecular mimicry can occur due to the sharing of amino sequences by proteins from pathogen and host. If an immune response during infection goes awry, autoreactivity to the shared sequence can ensue. The most dramatic example of molecular mimicry is acute rheumatic fever (ARF), still a major problem worldwide. The scenario is now classic: within weeks of an infection with group A Streptococcus , usually pharyngitis, an inflammatory syndrome encompassing arthritis strikes a susceptible person. In ARF, the infection is obvious; the culprit bacterial antigen is the M protein.2 

In a novel approach to finding molecular mimics, Pianta et al …
Anti-Inflammatory Therapy With Canakinumab for the Prevention and Management of Diabetes
Authors: Brendan M. Everett, Marc Y. Donath, Aruna D. Pradhan, Tom Thuren, Prem Pais, Jose C. Nicolau, Robert J. Glynn, Peter Libby, Paul M Ridker
Journal: Journal of the American College of Cardiology (2018)
The Value of Early Depth of Response in Predicting Long-Term Outcome in EGFR-Mutant Lung Cancer
Authors: Chee Khoon Lee, Sally Lord, Ian Marschner, Yi Long Wu, Lecia Sequist, Rafael Rosell, Masahiro Fukuoka, Tetsuya Mitsudomi, Rebecca Asher, Lucy Davies, Val Gebski, Richard Gralla, Tony Mok, James Chih-Hsin Yang
Journal: Journal of Thoracic Oncology (2018)
Optimal timing of post-prostatectomy radiotherapy for prostate cancer with high-risk pathologic features: A multi-institutional analysis.
Authors: William L. Hwang, Rahul D. Tendulkar, Andrzej Niemierko, Shree Agrawal, Kevin L. Stephans, Daniel Eidelberg Spratt, Jason W.D. Hearn, Bridget F. Koontz, W. Robert Lee, Jeff M. Michalski, Thomas Michael Pisansky, Stanley L. Liauw, Matthew Abramowitz, Alan Pollack, Drew Moghanaki, Mitchell Anscher, Robert Benjamin Den, Anthony L. Zietman, Andrew J. Stephenson, Jason A Efstathiou
Journal: Journal of Clinical Oncology (2018)

24 Background: The use of radical prostatectomy (RP) as initial treatment of high-risk/locally-advanced prostate cancer is increasing but patients (pts) with adverse pathologic features such as positive surgical margins or T3 disease have up to 70% recurrence risk. These high-risk pts may be managed with adjuvant radiotherapy (ART) or early salvage radiotherapy (ESRT). The optimal timing of post-operative radiotherapy is unclear. Methods: Individual data from 1566 consecutive pts with pT2N0M0/R1 or pT3N0M0/R0-1 disease who underwent post-prostatectomy ART or ESRT (1987-2013) at 10 academic centers were pooled. Post-irradiation freedom from biochemical failure (FFBF), freedom from distant metastases (FFDM), prostate-cancer specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier and multivariate competing-risks regression (MVA) analyses. Propensity score (PS) matching was used to account for covariates potentially associated with treatment allocation. All outcomes were measured from the date of surgery to address lead time bias. Results: After PS-matching, median follow-up after surgery was 66 vs. 73 months for the ART and ESRT groups, respectively, and baseline characteristics were well-matched. ART was associated with higher FFBF (12-yr: 69% vs. 43%; log-rank P &lt; 0.0001), FFDM (12-yr: 95% vs. 85%; log-rank P = 0.03), PCSS (12-yr: 99% vs. 94%; log-rank P = 0.048), and OS (12-yr: 91% vs. 79%; log-rank P = 0.01). ART, lower Gleason score, lower T-stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on MVA for BF. Sensitivity analysis demonstrated that the decreased risk of BF associated with ART remained significant unless more than 56% of ART pts were cured by surgery alone. This threshold is greater than the estimated 12-yr FFBF of 46% after RP alone as determined by a contemporary nomogram. Conclusions: To the best of our knowledge, this represents the largest multi-institutional study to date comparing ART to ESRT. ART was associated with reduced biochemical recurrence, distant metastases, and death compared to ESRT for high-risk pts, pending prospective validation.
DEVELOPMENT, VALIDATION AND IMPLEMENTATION OF A NOVEL PRE-PROCEDURAL ACCESS SITE COMPLICATION RISK SCORE THAT IMPACTS PHYSICIANS’ UTILIZATION OF ARTERIOTOMY CLOSURE DEVICE AFTER PERIPHERAL VASCULAR INTERVENTION
Authors: Daniel Ortiz, Khawaja Afzal Ammar, Suhail Allaqaband, Tanvir Bajwa, Mark Mewissen
Journal: Journal of the American College of Cardiology (2018)
Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate-to-severe psoriasis: Feasibility study using 18F-fluorodeoxyglucose PET/CT
Authors: Byung-Soo Kim, Won-Ku Lee, Kyoungjune Pak, Junhee Han, Gun-Wook Kim, Hoon-Soo Kim, Hyun-Chang Ko, Moon-Bum Kim, Seong-Jang Kim
Journal: Journal of the American Academy of Dermatology (2018)
Health department sexed up Keogh strike letter, says<i>Independent</i>
Authors: Abi Rimmer
Journal: BMJ (2016)

The Department of Health for England strengthened a letter sent by the medical director of NHS England to the BMA that questioned whether striking doctors would respond in the event of a terrorist attack, the Independent newspaper has claimed.

The newspaper said that it had seen leaked emails showing that a letter sent by Bruce Keogh went through various revisions “to ensure concerns about the possible impact of a major incident during the strike were made as ‘hard-edged’ as possible.”1 It also claimed that the letter’s specific reference to terrorist attacks in Paris “may have been …
Carbon‐Dot‐Decorated TiO<sub>2</sub> Nanotubes toward Photodynamic Therapy Based on Water‐Splitting Mechanism
Authors: Dan Yang, Guixin Yang, Qianqian Sun, Shili Gai, Fei He, Yunlu Dai, Chongna Zhong, Piaoping Yang
Journal: Advanced Healthcare Materials (2018)

Abstract The use of visible light to produce reactive oxygen species (ROS) from renewable water splitting is a highly promising means in photodynamic therapy (PDT). Up to date, diverse inorganic–organic hybrid materials developed as photosensitizers still undergo low therapeutic efficiency and/or poor stability. Herein, a kind of carbon‐nanodot‐decorated TiO 2 nanotubes (CDots/TiO 2 NTs) composite is developed and applied for photodynamic therapy. Upon 650 nm laser light excitation, the emissions with short wavelengths (325–425 nm) from the CDots as a result of upconversion process excite TiO 2 NTs to form electron/hole (e − /h + ) pairs, triggering the reaction with the adsorbed oxidants to produce ROS. Moreover, the CDots deposited on the surface of TiO 2 NTs markedly enhance the light absorption response and narrow the band gap compared with anatase TiO 2 nanoparticles, thereby increasing the photosensitizing efficiency. Besides, the CDots show high chemical catalytic activity for H 2 O 2 decomposition even if no light is needed, which is essential for PDT. The excellent therapeutic performance actuated by 650 nm light is demonstrated by in vitro and in vivo assays. This photosensitizer comprises low‐cost, earth‐abundant, environment‐friendly merits, and especially excellent stability, implying its feasible application in biomedical field.
Essential books for starting out in general practice
Authors: Anna Greenham
Journal: BMJ (2005)

Gone are the days when you could get by with just the “little yellow bible” in your pocket. When you start working as a GP registrar you will be overwhelmed by the variety of cases that walk through your door. Although supervision is available, it is just not possible to ask every time you reach a gap in your knowledge. So, which books do I rely …
PERSISTENT IPSILATERAL FRONTAL AND SUPRAORBITAL FACIAL PAIN IN A PATIENT WITH A LEFT AXILLARY ARTERY INTRA-AORTIC BALLOON PUMP
Authors: Abdallah Sanaani, Srikanth Yandrapalli, Gregg Lanier, William Frishman, Wilbert Aronow, Alan Gass
Journal: Journal of the American College of Cardiology (2018)
Meniscal root tears: a silent epidemic
Authors: Mark E Cinque, Jorge Chahla, Gilbert Moatshe, Scott C Faucett, Aaron J Krych, Robert F LaPrade
Journal: British Journal of Sports Medicine (2018)

Half of adults will experience knee pain at some point during their lives, resulting in approximately 4 million primary care office visits in the USA annually.1 The majority of these visits for knee pain evaluation are due to osteoarthritis (OA).2 As of 2015, it was estimated that 14 million people in the USA have symptomatic knee OA,3 and this number is expected to increase to up to 28 million over the next decade.4 One of the most common factors that can initiate the cascade of knee OA is meniscus tears.5 

Meniscus root tears are a specific type of meniscal injury that have gained attention over the past 5 years and have been reported to account for 10%–21% of all meniscal tears, affecting nearly 100 000 patients annually.6–8 Untreated meniscal root tears have been reported to result in altered joint biomechanics and accelerated articular cartilage degeneration. In this regard, the ‘recently’ recognised pathology of meniscal root tears has been reported to precipitously worsen articular cartilage degeneration (figure 1), cause painful bone oedema and lead to progressive OA (figure 2) if left untreated.9–13 Furthermore, it is important to recognise the association of meniscal injuries leading to subchondral insufficiency and potentially spontaneous osteonecrosis of the knee (SONK). Previously, SONK was a pathology often diagnosed as an ‘idiopathic’ osteonecrosis of the knee prior to the recognition that this pathology was caused by a meniscal tear.9 13–15 However, the pathogenesis of SONK continues to be debated in the literature with many aetiologies, including certain meniscal tears and meniscectomy, reported to be the primary cause of insufficiency fracture development. It was recently reported that the term SONK is a misrepresentation of the aetiology and pathogenesis of the condition, and should be replaced with ‘subchondral insufficiency fractures of the knee’ (SIFK).16 



Figure 1 
Sagittal (A) and …
Low genomic diversity of Legionella pneumophila within clinical specimens
Authors: S. David, M. Mentasti, J. Parkhill, V.J. Chalker
Journal: Clinical Microbiology and Infection (2018)

Legionella pneumophila is the leading cause of Legionnaires' disease, a severe form of pneumonia acquired from environmental sources. Investigations of both sporadic cases and outbreaks rely mostly on analysis of a single to a few colony pick(s) isolated from each patient. However, because of the lack of data describing diversity within single patients, the optimal number of picks is unknown. Here, we investigated diversity within individual patients using sequence-based typing (SBT) and whole-genome sequencing (WGS).Ten isolates of L. pneumophila were obtained from each of ten epidemiologically unrelated patients. SBT and WGS were undertaken, and single-nucleotide polymorphisms (SNPs) were identified between isolates from the same patient.The same sequence type (ST) was obtained for each set of ten isolates. Using genomic analysis, zero SNPs were identified between isolates from seven patients, a maximum of one SNP was found between isolates from two patients, and a maximum of two SNPs was found amongst isolates from one patient. Assuming that the full within-host diversity has been captured with ten isolates, statistical analyses showed that, on average, analysis of one isolate would yield a 70% chance of capturing all observed genotypes, and seven isolates would yield a 90% chance.SBT and WGS analyses of multiple colony picks obtained from ten patients showed no, or very low, within-host genomic diversity in L. pneumophila, suggesting that analysis of one colony pick per patient will often be sufficient to obtain reliable typing data to aid investigation of cases of Legionnaires' disease.
Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) with a novel radiopaque (RO) drug eluting bead (DEB).
Authors: Riccardo Lencioni, Tatiana Fraud, Mehul Doshi, Shree Venkat, Ana Echenique, Govindarajan Narayanan
Journal: Journal of Clinical Oncology (2018)

366 Background: Preclinical studies have suggested that RO beads may offer advantages over standard microspheres used for TACE of HCC. The ability to image bead distribution during the procedure is expected to improve the coverage of the tumor minimizing off-target delivery. We conducted a retrospective analysis of efficacy and safety of RO DEB-TACE in patients with HCC. Methods: Forty-eight patients (38 males and 10 females, median age 64 years) with nodular, noninvasive HCC unsuitable for curative treatments, Child-Pugh A (n = 29) or B (n = 19) liver functional status, and ECOG PS 0-1 received DEB-TACE with injection of 2-4 ml of 70-150-micron RO microspheres (LC Bead LUMI; BTG-Biocompatibles) loaded with 37.5 mg/ml doxorubicin. Thirty-seven of 48 patients (77%) had unilobar disease and 11 of 48 (23%) bilobar tumors. The baseline sum tumor diameter was 5.3±2.6 cm (range, 1.2-14.5 cm). The primary endpoint was tumor response by mRECIST. Secondary endpoints were time to progression (TTP), overall survival (OS), and safety. Results: The number of treatments was 1 in 28 patients (58%), 2 in 16 (33%), and 3 in 4 (8%). The mean doxorubicin dose per treatment was 43.9±34.4mg (range, 3.3-150 mg). Best response was CR, PR, SD, and PD in 32, 10, 4 and 2 patients, respectively, for an objective response rate (ORR) of 87.5%. Median TTP was 8.5 months (95% CI, 6.7-not reached). Median OS was not reached in Child class A patients; in class B patients it was 19.5 months (95% CI, 6.0-not reached). There was one treatment-emergent grade 5 AE unrelated to treatment. Grade 3/4 AEs included pain (n = 4), fatigue (n = 2), and fever (n = 1). Grade 3/4 laboratory abnormalities were thrombocytopenia (n = 9), leukopenia (n = 3), elevation of transaminases (n = 3) or bilirubin (n = 3), and anemia (n = 2). Conclusions: In this first clinical study, treatment with RO DEB-TACE resulted in a high ORR and was well tolerated. The encouraging efficacy signal requires confirmation with long-term survival data.
Clinical trials in allergen immunotherapy: current concepts and future needs
Authors: O. Pfaar, M. Alvaro, V. Cardona, E. Hamelmann, R. Mösges, J. Kleine‐Tebbe
Journal: Allergy (2018)

Abstract Allergen immunotherapy (AIT) is a safe, effective treatment for allergic rhinoconjunctivitis and allergic asthma. However, AIT's clinical effect is still contested—primarily due to heterogeneity in clinical trial designs, study populations, therapeutic formulations, and efficacy criteria. After discussing current concepts and unmet needs, an international panel of experts made several recommendations: (i) explore and validate definitions for (clinical) responders in AIT trials; (ii) use of well‐documented, standardized provocation tests prior to inclusion of subjects with relevant diseases in AIT trials; (iii) monitoring neo‐sensitizations and occurrence of new allergy in extended AIT trials, and exclusion of polyallergic participants; (iv) validation of allergen exposure chambers with regard to natural exposure; (v) in studies of seasonal allergies, focus on peak exposure but also consider organizing two parallel, geographically distinct but otherwise identical trials; (vi) discuss adaptive trial designs with the regulatory authorities; (vii) use e‐health and m‐health technologies to capture more information on individual exposure to allergens; (viii) initiate research on potential psychological, biochemical, immune, neural, and even genomic markers of the placebo response; (ix) identify trial designs and primary endpoints that will give children with allergies easier, faster access to AIT formulations; and (x) promote and apply standardized methods for reporting systemic and local adverse events. The latest technologies and trial designs may provide novel, ethical ways of reducing bias and heterogeneity in AIT clinical trials. There is scope for physicians, patient organizations, companies, and regulators to improve clinical trials in AIT and, ultimately, to provide patients with better treatments.
ASSESSMENT OF TRANSIENT ISCHEMIC DILATATION IN THE SETTING OF AN OTHERWISE NORMAL MYOCARDIAL PERFUSION SCAN WITH CORONARY ANGIOGRAPHY IN PATIENTS OF THE U.S. DEPARTMENT OF VETERANS AFFAIRS
Authors: Andrew Chen, Moarij Qazi, Dalia Hawwass, Farzad Majidi
Journal: Journal of the American College of Cardiology (2018)
DEM modeling of high shear wet granulation of a simple system
Authors: Saurabh Sarkar, Bodhisattwa Chaudhuri
Journal: Asian Journal of Pharmaceutical Sciences (2018)

High shear wet granulation (HSWG) is one of the most poorly understood processes with known difficulties in optimization and scale up. The purpose of the current study is to develop a DEM model which can be applied under dynamic process conditions with high predictive capacity to improve process insight. The DEM model is used to predict agglomeration as a function of impeller speed and liquid addition rate in a high shear wet granulator. The DEM model tracks dynamic formation and breakage of liquid bridges between particles as liquid binder in the system is added, and corrects for the change in material properties as a function of the binder content.
Diploma in Geriatric Medicine (DGM)
Authors: Denise Stevens
Journal: BMJ (2005)

The diploma is aimed at general practitioners wanting to demonstrate competence in geriatric medicine. It is also a useful qualification for clinical assistants and other non-career grade posts in geriatric medicine.

May/June 1998. I had previously gained three years' experience as a registrar in geriatric and general medicine. After a career break for family reasons, I had just started a part time clinical assistant post in geriatric medicine.

I had already passed MRCP in 1988, so ostensibly it didn't make sense to pursue what initially …