tbuckley/cabot-search huggingface dataset:
Home Oxygen in Chronic Obstructive Pulmonary Disease
Authors: Yves Lacasse, Ai-Yui M. Tan, François Maltais, Jerry A. Krishnan
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Two landmark trials conducted more than 35 years ago provided scientific evidence that, under very specific circumstances, long-term oxygen therapy (LTOT) may prolong life. These two trials enrolled 290 patients with chronic obstructive pulmonary disease and severe daytime hypoxemia documented by direct arterial blood gas measurement. From that time, LTOT became a standard of care, and the indications for oxygen therapy expanded to include nocturnal oxygen therapy for isolated nocturnal oxygen desaturation, ambulatory oxygen to correct exercise-induced desaturation, and short-burst oxygen to relieve dyspnea. In most cases, the rationale for broadening the indications for oxygen therapy is that, if hypoxemia exists, correcting it by increasing the FiO2 should help. However, with the exception of LTOT in severely hypoxemic patients with chronic obstructive pulmonary disease, randomized controlled trials of oxygen therapy have failed to demonstrate clinically significant benefits. Also, adherence to LTOT is usually suboptimal. Important areas for future research include improving understanding of the mechanisms of action of supplemental oxygen, the clinical and biochemical predictors of responsiveness to LTOT, the methods for measuring and enhancing adherence to LTOT, and the cost-effectiveness of oxygen therapy. A standardization of terminology to describe the use of supplemental oxygen at home is provided.
SEVERE MITRAL AND LEFT VENTRICULAR CALCIFICATION AS A LATE COMPLICATION OF ANOMALOUS LEFT MAIN CORONARY ARTERY FROM THE PULMONARY ARTERY
Authors: Patrick Proctor, Leah J. Schoel, Satinder Singh, Pankaj Arora, Garima Arora, Marc Cribbs
Journal: Journal of the American College of Cardiology (2018)
Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis
Authors: Shrujal Baxi, Annie Yang, Renee L Gennarelli, Niloufer Khan, Ziwei Wang, Lindsay Boyce, Deborah Korenstein
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. <h3>Design</h3> Systematic review and meta-analysis. <h3>Data sources</h3> Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. <h3>Study selection</h3> Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. <h3>Data extraction</h3> Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. <h3>Results</h3> 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. <h3>Conclusions</h3> Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse events may be common.
Why a middle aged general practitioner sat the MRCP
Authors: Michael Houghton
Journal: BMJ (2004)

They say that there is no fool like an old fool. So you might think that a 49 year old general practitioner (GP) taking the exam for membership of the Royal College of Physicians (MRCP) either has delusions of grandeur or has something missing. Having lived through the adventure and survived, I would disagree.

As a rural GP with an interest in education and assessment, I found myself questioning the ways we teach clinical skills and decision making. I was also becoming increasingly disillusioned about the lack of communication and understanding between primary and secondary care. Was I becoming pompous as well as old? To justify my scepticism, I decided that the first thing I had to do was to make sure I was up to scratch myself.

It seemed logical to use my prolonged study leave to spend a few months in secondary care—so I …
CQC to impose annual fees of at least £550, despite opposition from GPs
Authors: Helen Jaques
Journal: BMJ (2013)

General practices in England will have to pay fees of between £550 and £15 000 to register with the Care Quality Commission from April, despite most GPs who responded to the commission’s consultation opposing the proposed fee schedule.

General practices and other providers of NHS primary care services with one location will have to pay fees of between £550 and £850, depending on their list size, to register with the regulator in 2013-14.

Providers of primary care services with between two and 10 locations will have to pay fees of £1200 to £3000. …
Outcomes of Patients With Hypoplastic Left Heart Syndrome Reaching Adulthood After Fontan Palliation
Authors: William M. Wilson, Anne M. Valente, Edward J. Hickey, Paul Clift, Luke Burchill, Yaso Emmanuel, Patrick Gibson, Matthias Greutmann, Jasmine Grewal, Leeanne E. Grigg, Michelle Gurvitz, Kelsey Hickey, Paul Khairy, John E. Mayer, Eliza Teo, Isabelle Vonder Muhll, S. Lucy Roche, Candice K. Silversides, Rachel M. Wald
Journal: Circulation (2018)
Abstract 13929: Pulmonary Artery Diameter Index Predicts the Complications of Balloon Pulmonary Angioplasty
Authors: Koichi Sugimoto, Kazuhiko Nakazato, Akiomi Yoshihisa, Nobuo Sakamoto, Takayoshi Yamaki, Hiroyuki Kunii, Yasuchika Takeishi
Journal: Circulation (2015)

Backgrounds: Balloon pulmonary angioplasty (BPA) has been an attractive strategy as a new treatment for peripheral type chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA occasionally causes fatal complications such as hemorrhagic pulmonary edema, and asymptomatic mild lung injury detected on computed tomography (CT) image is not rare. Pathogenesis of lung injury after BPA has been considered to be a direct vascular injury due to guide wire or balloon, cytokine release at the time of reperfusion, and vulnerability of peripheral pulmonary vascular wall. However, predictive factors of lung injury have not been established. The pulmonary artery expansion of the central portion is frequently observed in patients with advanced pulmonary hypertension and the pulmonary artery diameter can be measured easily and accurately by CT. Therefore, we focused on the pulmonary artery diameter and investigated the association between complications after BPA. Methods: The subject consisted of 16 CTEPH patients diagnosed by right heart catheterization and pulmonary arteriography who underwent BPA (2 males, 14 females, age 60.5 ± 11 years. Initial hemodynamic indices of study subjects were mean pulmonary artery pressure (mPAP) 48.8±12.8 mmHg, cardiac output (CO) 3.62±1.07 L/min, and pulmonary vascular resistance (PVR) 11.6±8.15 WoodUnits. Patients were divided into two groups: group N (no symptoms or signs of any complications, n=9) and group C (symptoms such as hemoptysis or lung infiltration on CT image without symptoms, n=7). We measured pulmonary artery diameter on CT at the transition from the main trunk to the right pulmonary artery and corrected by body surface area. We defined this as the pulmonary diameter index. Results: CO was lower in group C than in group N, but there was no difference in mPAP, PVR, BNP, and the use of pulmonary vasodilators between two groups. Pulmonary artery diameter index in group C was significantly higher than that in group N (21.95 ± 5.89 vs. 14.22 ± 2.41 mm/m 2 , P&lt;0.01). ROC curve indicated 85.7% sensitivity and 88.9% specificity using cut-off value of 18.0 to predict the complications after BPA. Conclusions: Our study suggested that pulmonary artery diameter index would be a novel predictor of the complications after BPA.
Locum cap will lead to staff shortages and patient safety risks, official assessment warns
Authors: Abi Rimmer
Journal: BMJ (2015)

Capping the fees that locum doctors working for the NHS can be paid could lead to staff shortages and increase risks to patient safety, the bodies proposing the cap have warned in their official assessment of its expected impact.

The cap on locum fees was proposed by Monitor and the NHS Trust Development Authority to limit the amount trusts can pay per hour for a locum doctor.1 In their impact assessment of the …
New HIV strain drives growing Philippines epidemic
Authors: Owen Dyer
Journal: BMJ (2018)

A new, drug resistant subtype of the human immunodeficiency virus (HIV) is responsible for a surge in new cases of AIDS in the Philippines, the country’s leading virologist has said.

Although the number of new HIV cases each year has been declining globally, the Philippines has bucked that trend, and the increase in new cases is accelerating.

Figures released in February by the health department showed 11 103 new cases in 2017, up 20% from the 9264 …
Handwashing campaigns lead to rise in dermatitis in health workers
Authors: Abi Rimmer
Journal: BMJ (2015)

Handwashing campaigns to prevent infections such as meticillin resistant Staphylococcus aureus (MRSA) have led to a more than fourfold rise in the risk of dermatitis among healthcare workers, researchers have found.

Researchers from the University of Manchester found that healthcare workers’ incidence of dermatitis rose 4.5 times from 1996 to 2012.1 The researchers studied reports …
Learning for Health Improvement: a practical guide for the workplace
Authors: Rachel Hooke
Journal: BMJ (2006)

Lynne Caley

Radcliffe, 2006, £21.95, 144 pages

ISBN 1 846 19027 4

Rating: ★★★/5



There is much talk nowadays about “learning organisations.” Is this just modern jargon, or is there something in it? Is it relevant to doctors, who often feel more affinity with their profession than their trust, particularly at junior level? These doctors and other staff will move on, taking their learning with them to another employer. If we are looking at the benefits to the NHS as a whole, then perhaps that is the organisation in question rather than …
TAK1 restricts spontaneous NLRP3 activation and cell death to control myeloid proliferation
Authors: R.K. Subbarao Malireddi, Prajwal Gurung, Jayadev Mavuluri, Tejasvi Krishna Dasari, Jeffery M. Klco, Hongbo Chi, Thirumala-Devi Kanneganti
Journal: The Journal of Experimental Medicine (2018)

The NOD-like receptor (NLR)-P3 inflammasome is a global sensor of infection and stress. Elevated NLRP3 activation levels are associated with human diseases, but the mechanisms controlling NLRP3 inflammasome activation are largely unknown. Here, we show that TGF-β activated kinase-1 (TAK1) is a central regulator of NLRP3 inflammasome activation and spontaneous cell death. Absence of TAK1 in macrophages induced spontaneous activation of the NLRP3 inflammasome without requiring toll-like receptor (TLR) priming and subsequent activating signals, suggesting a distinctive role for TAK1 in maintaining NLRP3 inflammasome homeostasis. Autocrine tumor necrosis factor (TNF) signaling in the absence of TAK1 induced spontaneous RIPK1-dependent NLRP3 inflammasome activation and cell death. We further showed that TAK1 suppressed homeostatic NF-κB and extracellular signal-related kinase (ERK) activation to limit spontaneous TNF production. Moreover, the spontaneous inflammation resulting from TAK1-deficient macrophages drives myeloid proliferation in mice, and was rescued by RIPK1 deficiency. Overall, these studies identify a critical role for TAK1 in maintaining NLRP3 inflammasome quiescence and preserving cellular homeostasis and survival.
Aspartyl (Asparaginyl) ß hydroxylase (AABH) as a serum bio-marker for prostate cancer to identify prostate cancer, regardless of PSA level.
Authors: Mahmood Moshiri, Kiarash Moshiri, Arsha Moshiri, Hassan Monhemi, Mohammad Hadi Sekhavati
Journal: Journal of Clinical Oncology (2018)

10 Background: Background: Prostate Specific Antigen (PSA) is a molecular marker of prostate cancer (PC). I most countries, standard of care suggests annual PSA testing in all men over 50 years of age; and for men at high risk, the test is recommended from 40 years of age. Due to low Specificity and low sensitivity of the PSA test, a large number of unnecessary biopsies occur every year. This low specificity can be due to the fact that PSA is found in both benign and malignant lesions of Prostate tissue. To date measurement of the percentage of free PSA, have resulted an small improvements in specificity of PSA testing. Thus, the development of a simple blood test to detect prostate cancer that exhibits higher specificity compared to PSA could have the potential of reducing biopsies performed due to false positive screening results and improve the quality of medical care. Methods: We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a prostate cancer biomarker. AABH has been detected by immunohistochemical staining (IHC) in a broad range of cancers including Prostate Adenocarcinoma through out the world. AABH have been detected by IHC in more than 97% of tumor specimens tested (n &gt; 200) while absent in normal and non cancer tissue. We have developed a sandwich ELISA test for the detection of AABH in serum samples. Preliminary results showed an accuracy of 91- 94% for detecting cancer patients from non-cancer patients in different types of Cancer. Here we have utilized this assay to detect AABH levels in the sera of patients diagnosed with Prostate cancer (biopsy proven, pre-treatment samples), compared to non-cancer individuals. Results: AABH was detected above a threshold level of 1.2 ng/mL in 91% of the sera of PC patients (n = 60), in all different stages and grades of Prostate Cancer. All non-cancer individuals (n = 30) had AABH values below the threshold. Further study of direct comparison of AABH to PSA levels (n = 4,000) is underway. Conclusions: Our data suggest that measurement of serum AABH levels may help to detect Prostate Cancer in early stage and potentially reduce the number of prostate biopsies performed due to increased high serum PSA.
Sellu is cleared of medical misconduct
Authors: Clare Dyer
Journal: BMJ (2018)

David Sellu, the surgeon jailed for gross negligence manslaughter who later had his conviction overturned, has been comprehensively cleared of misconduct by a medical practitioners tribunal.

The General Medical Council alleged that he failed to provide good clinical care to James Hughes, the patient whose death had been at the centre of the criminal case against him.1 But after a six week hearing in which the tribunal took extensive evidence from many witnesses, many of them staff and clinicians working at the private hospital where Hughes had died, not one of the allegations against Sellu was found proved.

The result means in effect that charges that were found proved to the higher criminal standard (beyond reasonable doubt) by a crown court jury did not even reach the lower standard of proof applying in the tribunal (on the balance of probabilities).

The outcome will fuel concern, already widespread, about the use of the criminal law to pin the blame for a patient’s death on a single individual working in a complex system where multiple factors are at play.

> The outcome will …
Abstract P6-07-05: Interactions between adipocyte stem cells and normal or tumoral mammary epithelial cells. Potantial role of <i>BRCA</i> status and estrogen pathway
Authors: M-A Benderra, M Zaoui, M Atlan, N Ferrand, JA Denis, M Leban, F Lamari, AK Larsen, M Sabbah, J Gligorov
Journal: Cancer Research (2018)

Abstract Prophylactic mastectomies are more and more frequent. As a result, breast reconstruction is also more frequent and mammary lipofilling often used to improve the aesthetic results. Contradictory cliniacal data have been published concerning the risk of breast cancer after using this technique. It is possible that Adipose-Derived Stem / Stromal Cells (ADSC or ASC), present in the lipofilling may interact with normal or tumoral epithelial mammary cells. In this context, we studied the effect of conditioned media of human ASC on different tumor breast lines (MCF7, T47D, ZR75-1, SKBR3, SUM159). The ASCs were extracted from non-cancer patients with identical body mass index (BRCA1 and BRCA2 mutated or wild-type). We observed that the conditioned media of ASC induced the proliferation of luminal, Her2 and basal-like tumor breast lines. This proliferative effect is more important when ASCs are differentiated and the BRCA mutation status has no impact on it. Finally, we have demonstrated an estrogen signaling within the ASCs which is set up during their differentiation. Differentiated ASCs express ERα and produce 17β-estradiol (E2). This estrogenic pathway seems to be established independently of the BRCA mutational status. The proliferative effect on luminal mammary lines induced by conditioned media of ASC could pass through this estrogenic signaling, but remains to be confirmed. These data highlight the fact that adipose-derived stem cells in mammary lipofilling should only be used after a cancer has been eliminated, as there are still some uncertainties concerning their implication on carcinogenesis. Citation Format: Benderra M-A, Zaoui M, Atlan M, Ferrand N, Denis JA, Leban M, Lamari F, Larsen AK, Sabbah M, Gligorov J. Interactions between adipocyte stem cells and normal or tumoral mammary epithelial cells. Potantial role of BRCA status and estrogen pathway [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-07-05.
Outcomes for advanced HER2-positive gastroesophageal cancer by anatomical location: Experience from the Princess Margaret Cancer Centre.
Authors: Charles Henry Lim, Daniel Yokom, Di Maria Jiang, Lucy Xiaolu Ma, Peiran Sun, Hao-Wen Sim, Akina Natori, Bryan Anthony Chan, Stephanie Moignard, Jennifer J. Knox, Eric Xueyu Chen, Geoffrey Liu, Carol Jane Swallow, Gail Elizabeth Darling, Savtaj Singh Brar, Sara Hafezi-Bakhtiari, James Conner, Elena Elimova, Raymond Woo-Jun Jang
Journal: Journal of Clinical Oncology (2018)

131 Background: The landmark ToGA trial established trastuzumab (T) based therapy as the standard of care for advanced HER2+ gastric and gastroesophageal junction cancer. However, outcomes for T based therapy for HER2+ esophageal cancer have not been well characterized. Methods: We conducted a retrospective analysis of patients (pts) with HER2+ gastroesophageal cancer receiving T based therapy at our institution from 2011-2016. Distal esophagus ( &lt; 35 cm) and Siewert type I/II tumours were defined as esophageal (E). Siewert type III and stomach tumours were defined as gastric (G). Trained abstractors collected pt demographics and treatment details. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of first T treatment. Chi-square tests, t-tests and Cox proportional hazards models were applied where appropriate. Results: We identified 87 pts with advanced HER2+ disease. 62% (n = 54) had de novo metastatic (M1) disease. 57 patients were treated with T based therapy, with median age 57 years (IQR 48-67), 91% baseline performance status 0-1, 19% female, and 7% Asian. 63% (n = 36) had E and 37% (n = 21) had G primary tumours. 67% (n = 38) presented with M1 disease. 33% (n = 19) underwent surgery with curative intent and received T based therapy at recurrence. Baseline characteristics were balanced between the E and G groups. Survival data were available for 51 patients. The E and G groups did not have significant differences in PFS (median 9.5 vs. 9.1 months, HR 0.89 (95% CI 0.44-1.80), p = 0.74) or in OS (median 15.8 vs. 14.2 months, HR 0.88 (95% CI 0.42-1.82), p = 0.73). 63% (n = 36) were treated with subsequent systemic therapy after progression on T, with 23 receiving one line, 9 receiving two lines and 4 receiving three additional lines of treatment. The number subsequent therapies received was similar between E and G groups. Conclusions: Although patients with distal esophagus tumours were not included in the ToGA trial, our analysis suggests that patients with E and G tumours had similar outcomes. Our contemporary cohort had comparable survival outcomes relative to patients receiving T in the ToGA trial (median PFS = 6.7 months, median OS = 13.8 months).
ABNORMAL DIASTOLOGY PREDICTS LONG TERM FUNCTIONAL OUTCOME AND RE-HOSPITALIZATION IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Juan Mundisugih, Antony S. Walton, Stephen J. Duffy, Dion Stub, Roxanne Johnston, Samantha Holland, David M. Kaye, Shane Nanayakkara
Journal: Journal of the American College of Cardiology (2018)
Abstract PD5-02: Not presented
Authors: AL Guerrero-Zotano, TP Stricker, KE Hutchinson, DG Stover, L Formisano, K-M Lee, LJ Schwarz, JM Giltnane, VM Jansen, J Gavila, A Perez-Fidalgo, A Lluch, A Llombart, MA Bayar, S Michiels, F André, M Arnedos, A Ruiz, CL Arteaga
Journal: Cancer Research (2018)

Abstract This abstract was not presented at the symposium.
I want a career in general practice in the United Kingdom. I have passed part 1 of the PLAB test and I'm coming to the United Kingdom for part 2 this year. What is the job situation in UK general practice?
Authors: Rodger Charlton
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
Erratum: β-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex (Nature Genetics (1995) 11 266-273))
Authors: C. G. Bonneman, R. Modi, S. Noguchi, Y. Mizuno, M. Yoshida, E. Gussoni, E. N. McNalley, D. J. Duggan, C. Angelini, E. P. Hoffman, E. Ozawa, L. M. Kunkel
Journal: Nature Genetics (1996)
Just 43% of FY2 doctors move straight into specialty training
Authors: Ingrid Torjesen
Journal: BMJ (2018)

Taking a break between the foundation programme and specialty training is now the norm, with fewer than half of juniors now going straight into specialty training.1

The latest UK Foundation Programme career destinations report, which is based on a survey of foundation year 2 (FY2) doctors in 2017, showed that the trend to take a break between finishing foundation training and starting a specialty post is growing.

In 2017 the proportion of FY2s who immediately took up a specialty post was 42.6%, down from 50.4% in 2016, and 71.3% in 2011, when the survey was first conducted.

However, …