tbuckley/cabot-search huggingface dataset:
Postmenopausal Women With a “Normal” BMI Might Be Overweight or Even Obese
Authors: Rita Rubin
Journal: JAMA (2018)

t's been 20 years since the federal government, on the advice of an expert panel convened by the National Heart, Lung, and Blood Institute (NHLBI), lowered the body mass index (BMI) cutoff point for overweight, a move skeptics worried would spur Americans struggling to slim down to throw in the towel.Soon after the guidelines were published, though, researchers began suggesting that the cutoff-the lowest BMI at which people are classified as overweightstill wasn't low enough for at least 1 segment of the population: postmenopausal women.Misclassifying overweight postmenopausal women as normal weight means they could miss out on treatments that could reduce their risk of obesityrelated health problems, particularly cardiovascular disease.Body mass index is an estimate of body fat based on weight relative to height.Before the NHLBI expert panel recommended lowering the cutoff point for overweight to 25 for all adults, it had been 27.8 in men and 27.3 in women.The panel also recommended 30 as the cutoff point for obesity.Those moves brought the US definition of overweight and obesity in line with that of the World Health Organization (WHO).According to the NHLBI expert panel's final report, epidemiological studies showed that a BMI of 25 up to 30 was associated with a modest increase in mortality, while a BMI of 30 or more was asso-ciated with death rates 50% to 100% higher than among people with a BMI of 20 up to 25.When the federal government
Management standards for doctors must be supported by profession, says Keogh
Authors: Matthew Limb
Journal: BMJ (2015)

Standards of leadership and management set for doctors must be taken up and supported by the medical profession, said the national medical director for NHS England, Bruce Keogh. 

Keogh, together with leaders of the Royal College of Surgeons and the General Medical Council, has said that the standards, produced by the Faculty of Medical Leadership and Management,1 should be more widely adopted.

Keogh said, “Standards are really only as good as their implementation. So we must ensure they are integrated into the mainstream, day to day business of the NHS.” Medical leadership in the NHS was “more important and necessary” than ever before, and the new standards would “impact on the care we offer …
P071 Autoantibodies against serum amyloid a reduce il-6 release from peripheral blood mononuclear cells
Authors: T Kuret, K Lakota, P Mali, S Cucnik, S Praprotnik, M Tomšic, S Sodin-Šemrl
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Serum amyloid A (SAA) is a sensitive inflammatory marker rapidly increased during the acute phase, followed by a steady decline to physiological levels during resolution. While resolution and SAA reduction have been documented, the exact mechanism remains elusive. Although antibodies against SAA (anti-SAA) have been previously identified in healthy blood donors (HBDs) in smaller, preliminary studies, their potential function is still unclear.<sup>1,2</sup> <h3>Objectives</h3> To detect anti-SAA and anti-SAA1α in the sera of 300 HBDs using ELISA, characterise their subclasses and avidity. Additionally, we aimed to evaluate their presence in intravenous immunoglobulin (IVIG) and potential effects on released IL-6 from SAA-treated peripheral blood mononuclear cells (PBMCs). <h3>Methods</h3> An <i>in-house</i> ELISA was adapted from Rosenau and Schur<sup>1</sup> and developed<sup>2</sup> for detection of anti-SAA and anti-SAA1α. Both antibody fractions were isolated from IVIG using MicroLink Protein Coupling Kit (Thermo Scientific). PBMCs were purified from 5 HBDs by density gradient centrifugation and stimulated with SAA or SAA1α (1.5 µg/ml) in the presence/absence of anti-SAA and anti-SAA1α for 5 hours, 37°C. IL-6 concentration was measured in supernatants by ELISA (Invitrogen). <h3>Results</h3> The median (IQR) absorbance in HBDs was 0.655 (0.262–1.293) for anti-SAA and 0.493 (0.284–0.713) for anti-SAA1α. Both anti-SAA and anti-SAA1α reached peak levels between 41–50 years and diminished with age, with women exhibiting significantly higher levels than men. Good positive correlation was observed between anti-SAA and anti-SAA1α. Both antibodies were prevalently of the IgG subclass, with heterogeneous to high avidity and were detected also in IVIG. Stimulation of PBMCs with SAA significantly induced IL-6 release (mean ±SD) (389.5±184.4 pg/ml) with levels decreasing significantly upon addition of 4.5 (131.4±44.4 pg/ml) or 9.0 µg/ml (118.1±57.4 pg/ml) anti-SAA. A similar trend was also found for SAA1α and anti-SAA1α. <h3>Conclusions</h3> Anti-SAA could play a physiological role in down-regulating proinflammatory activity of SAA and could represent an attractive, novel therapeutic option for patients with chronic inflammatory diseases. <h3>References</h3> . Rosenau BJ, Schur PH. Antibody to serum amyloid A. J Autoimmun2004;23:179–82. . Lakota K, Thallinger GG, Cucnik S, Bozic B, Mrak-Poljsak K, Ambrozic A, et al. Could antibodies against serum amyloid a function as physiological regulators in humans?Autoimmunity2011;44:149–58. <h3>Acknowledgements</h3> The authors would like to acknowledge funding from the Slovenian Research Agency (ARRS) for the National Research Program P3-0314. <h3>Disclosure of interest</h3> None declared
Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis
Authors: Sarah R. Kingsbury, Puvan Tharmanathan, Ada Keding, Sarah J. Ronaldson, Andrew Grainger, Richard J. Wakefield, Catherine Arundel, Fraser Birrell, Michael Doherty, Tonia Vincent, Fiona E. Watt, Krysia Dziedzic, Terence W. O'Neill, Nigel K. Arden, David L. Scott, John Dickson, Toby Garrood, Michael Green, Ajit Menon, Tom Sheeran, David Torgerson, Philip G. Conaghan
Journal: Annals of Internal Medicine (2018)

Synovitis is believed to play a role in producing symptoms in persons with hand osteoarthritis, but data on slow-acting anti-inflammatory treatments are sparse.To determine the effectiveness of hydroxychloroquine versus placebo as an analgesic treatment of hand osteoarthritis.Randomized, double-blind, placebo-controlled clinical trial with 12-month follow-up. (ISRCTN registry number: ISRCTN91859104).13 primary and secondary care centers in England.Of 316 patients screened, 248 participants (82% women; mean age, 62.7 years) with symptomatic (pain ≥4 on a 0- to 10-point visual analogue scale) and radiographic hand osteoarthritis were randomly assigned and 210 (84.7%) completed the 6-month primary end point.Hydroxychloroquine (200 to 400 mg) or placebo (1:1) for 12 months with ongoing usual care.The primary end point was average hand pain during the previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months. Secondary end points included self-reported pain and function, grip strength, quality of life, radiographic structural change, and adverse events. Baseline ultrasonography was done.At 6 months, mean hand pain was 5.49 points in the placebo group and 5.66 points in the hydroxychloroquine group, with a treatment difference of -0.16 point (95% CI, -0.73 to 0.40 point) (P = 0.57). Results were robust to adjustments for adherence, missing data, and use of rescue medication. No significant treatment differences existed at 3, 6, or 12 months for any secondary outcomes. The percentage of participants with at least 1 joint with synovitis was 94% (134 of 143) on grayscale ultrasonography and 59% on power Doppler. Baseline structural damage or synovitis did not affect treatment response. Fifteen serious adverse events were reported (7 in the hydroxychloroquine group [3 defined as possibly related] and 8 in the placebo group).Hydroxychloroquine dosage restrictions may have reduced efficacy.Hydroxychloroquine was no more effective than placebo for pain relief in patients with moderate to severe hand pain and radiographic osteoarthritis.Arthritis Research UK.
Coaching and Mentoring in Health and Social Care: the essentials of practice for professionals and organisations
Authors: Rachel Hooke
Journal: BMJ (2006)

Julia Foster-Turner

Radcliffe, 2005, £21.95, 152 pages

ISBN 1 85775 549 9

Rating: ★★★★/5



Coaching1 and mentoring2 are becoming more common and accepted in the NHS, even for doctors. Some might dismiss these concepts as too “fluffy,” but there is evidence that they can have a positive effect on workers' performance and morale.

This book is aimed at anyone involved in coaching or mentoring in a public sector organisation. It is relevant to those on the receiving end, those delivering it, and …
Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial
Authors: Hans Gelderblom, Claire Cropet, Christine Chevreau, Richard Boyle, Martin Tattersall, Silvia Stacchiotti, Antoine Italiano, Sophie Piperno-Neumann, Axel Le Cesne, Virginia Ferraresi, Nicolas Penel, Florence Duffaud, Philippe Cassier, Maud Toulmonde, Paolo Casali, Sophie Taieb, Séverine Guillemaut, Séverine Metzger, David Pérol, Jean-Yves Blay
Journal: The Lancet Oncology (2018)
Pensions bill will “entrench unfairness” claims BMA
Authors: Caroline White
Journal: BMJ (2012)

Health unions have dubbed the Public Service Pensions Bill, published last week, “unfair” and accused the government of “steamrollering” it through despite widespread opposition.

The government forecasts that the legislation will save the tax payer £65bn over the next 50 years and almost halve the cost of pensions in the public sector.

As a result of the bill, most public sector workers will have to work for longer and stump up more for their pensions. …
Diffusion-Weighted Imaging Shows a False-Negative Finding for Bone Marrow Involvement on 18F-FDG PET/MRI in a Patient With Malignant Lymphoma After Blood Transfusion
Authors: Feibi Zeng, Munenobu Nogami, Taiichiro Shirai, Yoh Zen, Takamichi Murakami
Journal: Clinical Nuclear Medicine (2018)

Iron overload is a major complication in blood transfusion procedures. This report presents a case of malignant lymphoma, in which the findings of bone marrow involvement were discordant between F-FDG PET imaging studies and MRI with diffusion-weighted imaging studies. In this case, the PET imaging studies were positive for malignant lymphoma, whereas the MRI studies were negative. Iron deposition in the reticuloendothelial system due to posttransfusion iron overload was considered to be the cause of the decrease in signal intensity on diffusion-weighted imaging, resulting in a false-negative finding on MRI.
P022 Checkpoint inhibitors activate store-operated CA2+ entry and ERK1/2 signalling and promote TH17 differentiation
Authors: B Zapp, P Lehmkuhl, H Schulze-Koops, A Skapenko
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Anti-tumour therapy with immune checkpoint inhibitors for programmed-death 1 receptor (PD1), such as nivolumab is often accompanied by immune-related adverse events (irAE). The cellular and molecular mechanisms underlying this phenomenon are not defined yet. Interaction of PD-1 with its ligand (PD-L1) mediates potent inhibitory signals to hinder proliferation and effector function of T cells. Interruption of PD1:PD-L1 interaction by nivolumab during anti-tumour therapy might therefore amplify T cell receptor (TCR) signalling and facilitate the development of a pro-inflammatory autoimmune response. <h3>Objectives</h3> To investigate the impact of PD1 inhibition on intracellular signalling mechanisms down-stream of the TCR such as calcium (Ca<sup>2+</sup>) influx and activation of mitogen-activated protein kinases (MAPK) pathway and to assess the effect of PD1 inhibition on T cell effector function by evaluating the cytokine profile of the nivolumab-treated T cells. <h3>Methods</h3> CD4 memory T cells were stimulated with anti-CD3 and anti-CD28 in the presence of nivolumab for 24 hour. Afterwards intracellular Ca<sup>2+</sup> influx in response to ionomycin was assessed by flow cytometry following loading the cells with Fluo-8. Expression of proteins involved in store-operated Ca<sup>2+</sup> entry (SOCE), stromal activation molecule (STIM) 1, an activator of Ca<sup>2+</sup> release-activated Ca<sup>2+</sup> (CRAC) channels, and Orai1, a component of CRAC channels was determined by TaqMan real-time PCR. Phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2) in response to anti-CD3/28 was determined by intracellular flow cytometry. The cytokine profile of nivolumab-treated cells was assessed after four-day culture by intracellular flow cytometry. <h3>Results</h3> Treatment of CD4 T cells with nivolumab led to a pronounced increase of the ionomycin-mediated Ca<sup>2+</sup> influx. At the same time expression of SOCE proteins, STIM1 and Orai1, was significantly up regulated in the nivolumab-treated cells. Phosphorylation of Erk1/2 in response to short anti-CD3/CD28 restimulation was almost twice as high in CD4 T cells cultured with as without nivolumab. Finally nivolumab-treated cells contained higher frequencies of IL-17-producing T cells (Th17 cells). <h3>Conclusions</h3> Interruption of PD1:PD-L1 interaction by nivolumab activate SOCE and promotes Erk1/2 activation. Both T cell signalling pathways are essential for a proper mounting an immune response. Their deregulation might therefore precede an abnormal T cell response as shown for example by increased Th17 cell frequency and facilitate the onset of autoimmune phenomena such as irAE. <h3>Acknowledgements</h3> This work was supported by DFG grants SK59/09–1 and Schu1683/10–1, and by BMBF Project Arthromark 01EC1401B. <h3>Disclosure of interest</h3> None declared
Genetic Fate Mapping Defines the Vascular Potential of Endocardial Cells in the Adult Heart
Authors: Juan Tang, Hui Zhang, Lingjuan He, Xiuzhen Huang, Yan Li, Wenjuan Pu, Wei Yu, Libo Zhang, Dongqing Cai, Kathy O. Lui, Bin Zhou
Journal: Circulation Research (2018)

Rationale: Endocardium is the major source of coronary endothelial cells (ECs) in the fetal and neonatal hearts. It remains unclear whether endocardium in the adult stage is also the main origin of neovascularization after cardiac injury. Objective: To define the vascular potential of adult endocardium in homeostasis and after cardiac injuries by fate-mapping studies. Methods and Results: We generate an inducible adult endocardial Cre line ( Npr3 [natriuretic peptide receptor C]- CreER ) and show that Npr3-CreER efficiently and specifically labels endocardial cells but not coronary blood vessels in the adult heart. The adult endocardial cells do not contribute to any vascular ECs during cardiac homeostasis. To examine the formation of blood vessels from endocardium after injury, we generate 4 cardiac injury models with Npr3-CreER mice: myocardial infarction, myocardial ischemia–reperfusion, cryoinjury, and transverse aortic constriction. Lineage tracing experiments show that adult endocardium minimally contributes to coronary ECs after myocardial infarction. In the myocardial ischemia–reperfusion, cryoinjury, or transverse aortic constriction models, adult endocardial cells do not give rise to any vascular ECs, and they remain on the inner surface of myocardium that connects with lumen circulation. In the myocardial infarction model, very few endocardial cells are trapped in the infarct zone of myocardium shortly after ligation of coronary artery, indicating the involvement of endocardial entrapment during blood vessels formation. When these adult endocardial cells are relocated and trapped in the infarcted myocardium by transplantation or myocardial constriction model, very few endocardial cells survive and gain vascular EC properties, and their contribution to neovascularization in the injured myocardium remains minimal. Conclusions: Unlike its fetal or neonatal counterpart, adult endocardium naturally generates minimal, if any, coronary arteries or vascular ECs during cardiac homeostasis or after injuries.
Does Extracorporeal Membrane Oxygenation Improve Survival in Pediatric Acute Respiratory Failure?
Authors: Ryan P. Barbaro, Yuejia Xu, Santiago Borasino, Edward J. Truemper, R. Scott Watson, Ravi R. Thiagarajan, David Wypij, Martha A. Q. Curley
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Extracorporeal membrane oxygenation (ECMO) has supported gas exchange in children with severe respiratory failure for more than 40 years, without ECMO efficacy studies.Objectives: To compare the mortality and functional status of children with severe acute respiratory failure supported with and without ECMO.Methods: This cohort study compared ECMO-supported children to pair-matched non–ECMO-supported control subjects with severe acute respiratory distress syndrome (ARDS). Both individual case matching and propensity score matching were used. The study sample was selected from children enrolled in the cluster-randomized RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) clinical trial. Detailed demographic and daily physiologic data were used to match patients. The primary endpoint was in-hospital mortality. Secondary outcomes included hospital-free days, ventilator-free days, and change in functional status at hospital discharge.Measurements and Main Results: Of 2,449 children in the RESTORE trial, 879 (35.9%) non–ECMO-supported patients with severe ARDS were eligible to match to 61 (2.5%) ECMO-supported children. When individual case matching was used (60 matched pairs), the in-hospital mortality rate at 90 days was 25% (15 of 60) for both the ECMO-supported and non–ECMO-supported children (P > 0.99). With propensity score matching (61 matched pairs), the ECMO-supported in-hospital mortality rate was 15 of 61 (25%), and the non–ECMO-supported hospital mortality rate was 18 of 61 (30%) (P = 0.70). There was no difference between ECMO-supported and non–ECMO-supported patients in any secondary outcomes.Conclusions: In children with severe ARDS, our results do not demonstrate that ECMO-supported children have superior outcomes compared with non–ECMO-supported children. Definitive answers will require a rigorous multisite randomized controlled trial.
Basic skills in gastrointestinal endoscopy
Authors: Sreedhari Thayalasekaran
Journal: BMJ (2011)

The basic skills in gastrointestinal endoscopy course covers the theoretical and practical aspects of upper gastrointestinal endoscopy and is approved and accredited by the Joint Advisory Group on Gastrointestinal Endoscopy (JAG). It is held in various locations across the country; the JAG Endoscopy Training System website gives specific locations and dates (www.jets.nhs.uk). I attended the course at the Mersey School of Endoscopy, which is one of the three national endoscopy training centres in England. 

The course aims to provide trainees with the skills to perform upper gastrointestinal endoscopy safely. The first two days were spent at the Royal Liverpool Hospital. The third day consisted of hands-on training, with half the delegates at the Royal Liverpool Hospital and the other half at Aintree Hospital. The faculty consisted of three consultants, one nurse endoscopist, and one healthcare assistant.

It is for anyone …
Abstract 12921: Role of Transesophageal Echocardiogram in Affecting Treatment in Older Adults Undergoing Evaluation for Transient Ischemic Attack or Stroke
Authors: Ryan C Van Woerkom, Megan L Davis, Austin J LaBanc, Maria F Coakley, Stephen J Lester, M'hamed Temkit, Bart M Demaerschalk, Susan Wilansky
Journal: Circulation (2015)

Background: As the United States medical system transitions to value-based reimbursement, interested parties will increase scrutiny in testing that may not alter management or outcomes. We investigated whether transesophageal echocardiography (TEE) provokes treatment alteration across age strata in hospitalized patients undergoing a TIA/stroke work-up. Methods: Consecutive patients admitted to the Mayo Clinic Arizona healthcare system between 1/1/2010 and 2/9/2015 were evaluated. A total of 832 patients were identified of which 314 were excluded primarily due to the fact that the TEE was performed as an outpatient. Therefore, 518 subjects (mean age = 68.2 +/- 14.1 y, 42.5% female) were included. A change in treatment was defined a priori as: anticoagulation (AC) initiated for atrial fibrillation found on TEE only (i.e. not identified on telemetry), complex proximal aortic arch plaque, left atrial or left atrial appendage thrombus, intracardiac mass, intracardiac shunt (atrial septal defect (ASD)/ patent foramen ovale (PFO)) ; PFO closure; cardiac mass removal; valve replacement for endocarditis; antibiotics for endocarditis. Results: See Tables A &amp; B Conclusion: TEE in the evaluation of hospitalized patients with TIA/stroke resulted in a change in treatment in approximately 7% of patients regardless of age. Many of the decisions to change treatment were judgment-based and therefore adoption of the routine use of TEE in all patients with TIA/stroke is dependent on institutional practice standards.
LOW ADHERENCE TO DISCHARGE MEDICATIONS PREDICTS RISK OF CARDIAC EVENTS MIDTERM AFTER CARDIAC SURGERY: A PILOT STUDY AMONG PREDOMINANTLY BLACK INNER-CITY PATIENTS
Authors: Phyllis Supino, Ofek Hai, Sriya Avadhani, Ridita Nizam, Daniel Beckles, Jeffrey Borer, SUNY Downstate
Journal: Journal of the American College of Cardiology (2018)
Indian doctors are recruited to fill emergency medicine gaps
Authors: Abi Rimmer
Journal: BMJ (2014)

Health Education England (HEE) and the College of Emergency Medicine are recruiting around 50 doctors from India to work in accident and emergency departments in England. 

The Telegraph reported that HEE was currently considering applications and that the shortlisted candidates would undergo interviews by Skype video link this week.1

HEE told BMJ Careers that the programme was a result of poor recruitment into emergency medicine. In 2013 and 2014 less than half of the places in higher training for this specialty were filled. And last year a review published by the College of Emergency Medicine found that emergency departments in England were spending an average of £600 000 a year on locums, equating to around £120m a year …
THE AMERICAN COLLEGE OF CARDIOLOGY: TRANSCATHETER AORTIC VALVE REPLACEMENT RISK CALCULATOR ACCURATELY PREDICTS HEART FAILURE READMISSIONS AND QUALITY OF LIFE OUTCOMES
Authors: Thammi Ramanan, Abhishek Sawant, Aishwarya Bhardwaj, Rose Hansen, Everett Sinibaldi, Michael Pham, Charl Khalil, Ashutosh Sharma, Abhinav Kumar, Vijay Iyer
Journal: Journal of the American College of Cardiology (2018)
SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors
Authors: Leila Dardaei, Hui Qin Wang, Manrose Singh, Paul Fordjour, Katherine X Shaw, Satoshi Yoda, Grainne Kerr, Kristine Yu, Jinsheng Liang, Yichen Cao, Yan Chen, Michael S Lawrence, Adam Langenbucher, Justin F Gainor, Luc Friboulet, Ibiayi Dagogo-Jack, David T Myers, Emma Labrot, David Ruddy, Melissa Parks, Dana Lee, Richard H DiCecca, Susan Moody, Huaixiang Hao, Morvarid Mohseni, Matthew LaMarche, Juliet Williams, Keith Hoffmaster, Giordano Caponigro, Alice T Shaw, Aaron N Hata, Cyril H Benes, Fang Li, Jeffrey A Engelman
Journal: Nature Medicine (2018)
THE SAFETY AND TOLERABILITY OF MULTIPLE DOSE ADMINISTRATION OF CSL112, AN INTRAVENOUS FORMULATION OF PLASMA-DERIVED APOA-I, AMONG SUBJECTS WITH MODERATE RENAL IMPAIRMENT AFTER ACUTE MYOCARDIAL INFARCTION
Authors: C. Michael Gibson, Megan Yee, Yazan Daaboul, Serge Korjian, Ali Poyan Mehr, Mathieu Kerneis, Pierluigi Tricoci, John Alexander, John Kastelein, Roxana Mehran, Christoph Bode, Basil Lewis, Ravindra Mehta, Danielle Duffy, John Feaster, Majdi Halabi, Dominick Angiolillo, Daniel Duerschmied, Ton Oude Ophius, Bela Merkely
Journal: Journal of the American College of Cardiology (2018)