tbuckley/cabot-search huggingface dataset:
The president of the GMC
Authors: Leyla Sanai
Journal: BMJ (2006)

Professor Sir Graeme Catto qualified from the University of Aberdeen in 1969. He won a Harkness Fellowship to Harvard University to work in renal medicine. He became dean and vice principal at Aberdeen and then at King9s College London, and pro vice chancellor at the University of London. In the 1990s he was the chief scientist at the Scottish Executive Health Department and chairman of the GMC Education Committee. He has been president of the GMC since 2002, and is also professor of medicine at the University of Aberdeen
The BMJ Debate: BMA and Remedy UK
Authors: Deborah Cohen
Journal: BMJ (2008)

The BMA and Remedy UK have been at odds over who best represents the views of junior doctors. Yet they share many of the same concerns. The <i>BMJ</i>’s <b>Deborah Cohen</b> talks to <b>Ram Moorthy</b>, chairman of the BMA’s Junior Doctors Committee, and <b>Matt Jameson-Evans</b>, one of Remedy’s founders about what happens next
Detection of sensitizing and resistance EGFR mutations from circulating tumor DNA (ctDNA) in blood using multiplexed next-generation sequencing in patients with advanced EGFR-mutant lung adenocarcinoma.
Authors: Sarah B. Goldberg, Azeet Narayan, Nicholas J. Carriero, Roxanne Nemati, Ananth Bommakanti, Anna Wurtz, Daniel J Boffa, Roy H. Decker, Roy S. Herbst, Juliane M. Juergensmeier, Katerina A Politi, Scott N. Gettinger, Abhijit Patel
Journal: Journal of Clinical Oncology (2014)

8093 Background: Analysis of tumor biopsies obtained after the development of acquired resistance (AR) to EGFR tyrosine kinase inhibitors can contribute to the understanding of resistance mechanisms, but requires an invasive procedure and only provides data on a single site of disease at one timepoint. We developed a next-generation sequencing method that employs novel error-suppression techniques to measure tumor-specific mutations in plasma at levels as low as 1 variant in 5,000. Here we report on the detection of sensitizing EGFR mutations and the emergence of the T790M resistance mutation in ctDNA and in tumor specimens. Methods: We collected plasma samples from patients (pts) with advanced EGFR-mutant lung adenocarcinoma. When feasible, serial plasma samples were collected during treatment and repeat tumor biopsies were performed at AR. Plasma was analyzed using error-suppressed deep sequencing to quantify point-mutations and insertions/deletions in multiple genes that are commonly mutated in lung cancer, including EGFR. Results: Plasma samples were obtained from 52 pts with known activating EGFR mutations. Thirty-two pts had serial samples, allowing monitoring of mutant DNA levels and detection of the emergence of new mutations in the plasma. Of the 31 pts who had a repeat biopsy, the T790M mutation was found in 15 (48%) in the tumor at AR. Data for the ctDNA and repeat tumor biopsy results for the first 5 pts tested in this cohort are presented in the Table. Conclusions: Detection of EGFR sensitizing and resistance mutations in ctDNA from the plasma using multiplexed next generation sequencing is feasible and shows a high concordance with results from tumor biopsy. This novel method using plasma may allow for earlier identification of resistance in pts treated with targeted therapy without the need for invasive biopsies. Pt # Source of DNA Sensitizing EGFR mutation EGFR T790M resistance mutation Exon 19 del L858R 1 Lymph node - + - Plasma - + - 2 Lymph node + - + Plasma + - + 3 Pleural fluid + - + Plasma + - + 4 Neck mass - + - Plasma - + - 5 Liver mass + - + Plasma + - -
A scoring system to predict the elevation of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis
Authors: Taiki Furukawa, Yasuhiro Kondoh, Hiroyuki Taniguchi, Mitsuaki Yagi, Toshiaki Matsuda, Tomoki Kimura, Kensuke Kataoka, Takeshi Johkoh, Masahiko Ando, Naozumi Hashimoto, Koji Sakamoto, Yoshinori Hasegawa
Journal: European Respiratory Journal (2018)

Elevated mean pulmonary arterial pressure (MPAP; ≥21 mmHg) is sometimes seen in patients with idiopathic pulmonary fibrosis (IPF) and has an adverse impact upon survival. Although early diagnosis is crucial, there is no established screening tool that uses a combination of noninvasive examinations. We retrospectively analysed IPF patients at initial evaluation from April 2007 to July 2015 and, using logistic regression analysis, created a screening tool to identify elevated MPAP. Internal validation was also assessed for external validity using a bootstrap method. Using right-heart catheterisation (RHC), elevation of MPAP was determined to be present in 55 out of 273 patients. Multivariate models demonstrated that % predicted diffusing capacity of the lung for carbon monoxide ( D LCO ) &lt;50%, ratio of pulmonary artery diameter to aorta diameter (PA/Ao) on computed tomography (CT) ≥0.9 and arterial oxygen tension ( P aO 2 ) &lt;80 Torr were independent predictors. When we assigned a single point to each variable, the prevalence of elevation of MPAP with a score of zero, one, two or three points was 6.7%, 16.0%, 29.1% and 65.4%, respectively. The area under curve (AUC) for the receiver operating characteristic (ROC) curve was good at 0.757 (95% CI 0.682–0.833). A simple clinical scoring system consisting of % predicted D LCO , PA/Ao ratio on CT and P aO 2 can easily predict elevation of MPAP in patients with IPF.
PERFORMANCE AND CHARACTERISTICS OF HOSPITALS PARTICIPATING IN THE AMERICAN COLLEGE OF CARDIOLOGY VOLUNTARY PUBLIC REPORTING PROGRAM
Authors: Karl E. Minges, Jeptha Curtis, Nihar Desai, Yongfei Wang, Frederick A. Masoudi, John Messenger, Sean Hilscher, William Oetgen, Michael Simanowith, Lara Slattery, Gregory Dehmer
Journal: Journal of the American College of Cardiology (2018)
Personalised CFTR pharmacotherapeutic response testing and therapy of cystic fibrosis
Authors: Cormac McCarthy, John J. Brewington, Beth Harkness, John P. Clancy, Bruce C. Trapnell
Journal: European Respiratory Journal (2018)

Cystic fibrosis (CF) is a fatal, multisystem, genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride transporter critical to luminal fluid homeostasis at respiratory airway and other ductal epithelial surfaces. Therapeutic options for some CF patients were transformed by the approval of ivacaftor and lumacaftor/ivacaftor, which are indicated, respectively, for patients heterozygous for a subset of rare class III mutations [1] or homozygous for the common class II mutation Phe508del [2]. Notwithstanding, more than 40% of CF patients do not meet the CFTR mutation-specific inclusion criteria and are excluded from these therapies and, while it is impractical to conduct a clinical trial for each new pharmacotherapy-responsive CFTR mutation identified, an evolution of the drug approval process now permits drug label expansion based on in vitro physiological response testing. Indeed, the development of novel patient cell-based methods such as cultured intestinal organoids [3, 4] or nasal epithelial spheroids [5] permit in vitro testing of targeted CFTR molecular therapies. Here, we report the use of a novel preclinical test in one such patient to demonstrate patient-specific functional correction of CFTR ex vivo followed by initiation of therapy and functional correction in vivo . Further, while adverse respiratory effects have been reported with lumacaftor/ivacaftor therapy [6], a comprehensive description of the treatment adjustment period has not been previously reported, here we provide a detailed account of this phenomenon. Pharmacotherapeutic response testing identified CFTR Ser1159Pro as responsive to cystic fibrosis modulator therapy <http://ow.ly/dvsq30jcBMw>
Excess Mortality in Patients With Type 1 Diabetes Without Albuminuria—Separating the Contribution of Early and Late Risks
Authors: Per-Henrik Groop, Merlin Thomas, Maija Feodoroff, Carol Forsblom, Valma Harjutsalo
Journal: Diabetes Care (2018)

OBJECTIVE The current study investigated whether the risk of mortality in patients with type 1 diabetes without any signs of albuminuria is different than in the general population and matched control subjects without diabetes. RESEARCH DESIGN AND METHODS We studied a nationwide, population-based Finnish register of 10,737 patients diagnosed with type 1 diabetes during 1980–2005 and followed for 10 years and 2,544 adults with long-standing diabetes drawn from the Finnish Diabetic Nephropathy Study (FinnDiane). Mortality was compared with the general Finnish population and 6,655 control subjects without diabetes. RESULTS The standardized mortality ratio (SMR) was increased during the first 10 years after the diagnosis (2.58 [95% CI 2.07–3.18], P &amp;lt; 0.001). Mortality in adults with long-standing diabetes, but without albuminuria, was no different from that of the general population (1.02 [0.84–1.22], P = 0.83). However, it was higher compared with that of control subjects without diabetes (1.33 [1.06–1.66], P = 0.01). Excess mortality was largely due to acute diabetes complications and ischemic heart disease, which remained more than fourfold higher (mortality rate ratio 4.34 [2.49–7.57]) in adults with type 1 diabetes than in control subjects without diabetes, despite the absence of albuminuria. By contrast, deaths due to alcohol and drugs were reduced in adults with type 1 diabetes (P = 0.007), especially in men. CONCLUSIONS Excess mortality in type 1 diabetes is the result of its complications. Acute complications drive an increased SMR in the first years. In individuals who remain free of albuminuria, mortality due to ischemic heart disease is still four times higher, and acute complications also occur.
Abstract P016: Physical Activity as Key Risk Factors for Incident Dementiain a Thai Population: Health Checks Ubon Ratchathani (HCUR) Study
Authors: Parinya Chamnan, Prasert Boongird, Somsak Laptikultham, Wannee Nitiyanont, Wichai Aekplakorn
Journal: Circulation (2018)

Introduction: There is little evidence to describe risk factors for dementia in a Thai general population. Hypothesis: This study was aimed to examine factors associated with the risk of developing dementia in a Thai general population in Ubon Ratchathani. Methods: Data on 761,935 men and women participating in the Health Check Ubon Ratchathani (HCUR) Project in 2006-7 were merged with diagnostic information from hospital’s electronic medical records in the following 5 years (2006-2012). Using a retrospective cohort study design, we examined the incidence of physician-diagnosed dementia over 5 years. Factors independently associated with the risk of developing dementia were examined using multivariate cox proportional hazard regression. Results: Over a total time at risk of 4,407,201 person-years, 519 individuals developed dementia, the incidence rate of dementia was 0.12 (95%CI 0.11-0.13) per 1,000 person-years. Factors independently associated with the risk of developing dementia in multivariate cox regression included increasing age, diabetes and lack of physical exercise. The risk of dementia rose by 9% for every one year of age older (Hazard ratio (HR) of 1.09 (1.08-1.09), p&lt;0.001). Diabetes increased the risk of dementia by almost 2 times (HR 1.67 (1.26-2.23), p&lt;0.05). Compared to no physical exercise, regular physical exercise of 3-5 days/week and &gt;5 days/week reduced the risk of dementia by 36% and 57% (HR 0.64 (0.52-0.78) and 0.43 (0.28-0.67) respectively). These associations remained significant after controlling for sex, hypertension, systolic blood pressure, smoking, body mass index, waist circumference, high salt diet and alcohol drinking. Discussion: In this Thai general population, the incidence of dementia was modest and its independent risk factors included increasing age, diabetes and lack of physical exercise. Regular physical exercise may counter balance aging process, the main drive of dementia. The more physical exercise you do, the lower risk of dementia.
Holistic Needs Assessment in Brain Cancer Patients: A Systematic Review of Available Tools
Authors: Janyne Afseth, Lis Neubeck, Thanos Karatzias, Robin Grant
Journal: Neuro-Oncology (2018)

A diagnosis of brain cancer affects nearly 10 000 adults per year in the United Kingdom and has a devastating impact. This is due to the poor prognosis as well as a significant symptom burden, which often includes neurocognitive deficits. It is essential, therefore, to have a comprehensive way to determine the needs of these patients. Holistic Needs Assessment (HNA) is widely used for other cancers, and is recommended for brain cancers. The aim of this study was to identify brain specific patient reported outcome measures and investigate the potential of these for HNA. We searched four databases (Medline, CINAHL, BNI and Psychinfo), with no date limits, for studies published in English, and identified 1004 studies. After review, eight studies fulfilled our inclusion criteria; these reported the development of tools developed for a brain cancer population for use in a clinical setting and assessed more than one domain of need. COSMIN criteria, which have been developed through consultation with 57 experts, were used to assess the psychometric properties and they were also assessed against criteria for HNA. The studies which were included, reported the development of four tools. Two tools were developed as symptom assessment tools; the MD Anderson Symptom Inventory – Brain Tumor Module (MDASI-BT); and the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Brain Symptom Index (NFbrSI-24), which both demonstrated evidence of good or fair psychometric properties but would need further development to be used in HNA. The Supportive Care Needs Survey 34 plus brain subscale (SCNS34-BS) and Brain Patient Concern Inventory (PCI) were developed as HNA tools but lacked psychometric testing. While some progress has been made in the development of tools, the results indicate that no tools are adequate without further development for HNA assessment in brain cancer.
Immune response to antigen adsorbed to aluminum hydroxide particles: Effects of co-adsorption of ALF or ALFQ adjuvant to the aluminum-antigen complex
Authors: Zoltan Beck, Oscar B. Torres, Gary R. Matyas, David E. Lanar, Carl R. Alving
Journal: Journal of Controlled Release (2018)

Aluminum salts have been used as vaccine adjuvants for >50 years, and they are currently present in at least 146 licensed vaccines worldwide. In this study we examined whether adsorption of Army Liposome Formulation (ALF) to an aluminum salt that already has an antigen adsorbed to it might result in improved immune potency of the aluminum-adsorbed antigen. ALF is composed of a family of anionic liposome-based adjuvants, in which the liposomes contain synthetic phospholipids having dimyristoyl fatty acyl groups, cholesterol and monophosphoryl lipid A (MPLA). For certain candidate vaccines, ALF has been added to aluminum hydroxide (AH) gel as a second adjuvant to form ALFA. Here we show that different methods of preparation of ALF changed the physical structures of both ALF and ALFA. Liposomes containing the saponin QS21 (ALFQ) have also been mixed with AH to form ALFQA as an effective combination. In this study, we first adsorbed one of two different antigens to AH, either tetanus toxoid conjugated to 34 copies of a hapten (MorHap), which has been used in a candidate heroin vaccine, or gp140 protein derived from the envelope protein of HIV-1. We then co-adsorbed ALF or ALFQ to the AH to form ALFA or ALFQA. In each case, the immune potency of the antigen adsorbed to AH was greatly increased by co-adsorbing either ALF or ALFQ to the AH. Based on IgG subtype and cytokine analysis by ELISPOT, ALFA induced predominately a Th2-type response and ALFQ and ALFQA each induced more balanced Th1/Th2 responses.
Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02)
Authors: M. Tahara, N. Kiyota, T. Yokota, Y. Hasegawa, K. Muro, S. Takahashi, T. Onoe, A. Homma, J. Taguchi, M. Suzuki, K. Minato, K. Yane, S. Ueda, H. Hara, K. Saijo, T. Yamanaka
Journal: Annals of Oncology (2018)

The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN.Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients.Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia.The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population.UMIN000010507.
Professor John Savill, vice principal and head of the College of Medicine and Veterinary Medicine, University of Edinburgh
Authors: Hannah Peters
Journal: BMJ (2008)

“I started medical school in 1975 as an 18 year old undergraduate at Oxford. The great thing about Oxford was that I was exposed to research and I learnt how to write and think about scientific issues. I would like to see more students have the chance to do an intercalated BSc, which offers exposure to research. I think it would be wonderful if one day medicine was a six year course, with a year of science in the middle, especially now postgraduate training is going to be shorter. I now work in academic medicine. While medical school prepared me for research, I was still not exposed to how wonderful a career in academic medicine could be. I did not realise that professors did the kind of things that professors do.

“I had a fantastic time at Oxford because term was only eight weeks long. I …
Selective tumour necrosis factor receptor-1 inhibition in acute lung injury: a new hope or a false dawn?
Authors: Pratik Sinha, Lorraine B Ware
Journal: Thorax (2018)

A complex myriad of aetiologies and pathologies coalesce within the clinical syndrome of acute respiratory distress syndrome (ARDS) often obfuscating our understanding of the disorder. Amidst the complexity, acute lung inflammation stands out as the fundamental unifying pathophysiology underlying ARDS. A better understanding of the mechanisms driving inflammation in the lung and the ensuing response from the innate immune system, endothelial and epithelial barriers are key to developing disease-modifying drugs in ARDS. Targeted inhibition of proinflammatory molecules such as tumour necrosis factor (TNF)-α would seem a logical and fruitful line of investigation for disease-modifying intervention in ARDS.

As suggested by its name, TNF-α was first described as a mediator in abrogating malignant proliferation of cancerous cells.1 Since then, TNF-α has also been identified as a key cytokine in modulating inflammation. TNF-α is mainly produced by macrophages and monocytes, but it is released by most cells, including endothelial cells, epithelial cells and most other leucocytes. A pleiotropic cytokine, TNF-α has a wide range of biological activities. TNF-α has been implicated as a chemoattractant for neutrophils and eosinophils, as a mediator of apoptosis and a major stimulant of other proinflammatory cytokine release.2

In ARDS, elevated levels of TNF-α are found in both plasma and bronchioalveolar lavage (BAL).3 4 In the lungs, TNF-α expression directly leads to increased endothelial permeability5 6 and downregulates epithelial sodium channel expression leading to impaired alveolar fluid clearance.7 Aside from ARDS, TNF-α is also a critical mediator in other inflammatory conditions such as rheumatoid arthritis, psoriasis and Crohn’s disease. Moreover, in these diseases, inhibitors of TNF-α are now in widespread therapeutic use, setting a precedent for their use in ARDS.

As a ligand, TNF-α binds to two members of TNF-receptor superfamily: TNF-receptor 1 (TNFR1) and TNF-receptor 2 (TNFR2). TNFR1 is a transmembrane receptor with …
Re: Low-Dose Radioactive Iodine Ablation Is Sufficient in Patients With Small Papillary Thyroid Cancer Having Minor Extrathyroidal Extension and Central Lymph Node Metastasis (T3 N1a)
Authors: Arnoldo Piccardo, Luca Giovanella
Journal: Clinical Nuclear Medicine (2018)

Department of Nuclear Medicine and Competence Center for Thyroid Diseases, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. Conflicts of interest and sources of funding: none declared.
How to apply successfully for an ST1 training post in cardiothoracic surgery
Authors: Philip J McElnay, Joseph George, Joshil Lodhia, Daniel Moffat, Akshay Patel, Shubhra Sinha, Charlene Tennyson, Michael Gooseman, Sion Barnard
Journal: BMJ (2014)

Phil McElnay and colleagues explain how best to approach the new ST1 applications for cardiothoracic surgery
BMA rejects call for pay to be frozen again next year
Authors: Matthew Limb
Journal: BMJ (2013)

Doctors’ leaders have rejected a call by NHS employers for a pay freeze next year, saying that incomes have been eroding and that a “fair” increase is needed.

The BMA has urged the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) to recommend to ministers a pay rise at least in line with inflation for 2014-15.

Responding to NHS Employers’ claim that a pay rise was unaffordable and unnecessary,1 the BMA said that, although it fully recognised the economic pressure facing the NHS, the decline in the real value of doctors’ contracts had now reached a “critical point.” The BMA’s chairman of council, Mark Porter, said, “When faced with an unprecedented funding squeeze, inadequate staffing levels, and rising patient demand, it is no surprise that morale among doctors is low, and yet they continue to work as hard as ever on behalf of their patients. It is only fair that they do not face a further cut in pay.”

The BMA and NHS Employers submitted evidence to the DDRB on Friday …
Associations Between Treatment Restrictions, Patient-Reported Treatment Burden and Adherence to Tyrosine-Kinase Inhibitor Therapy Among Chronic Myeloid Leukemia Patients in the United States and Europe
Authors: Shaloo Gupta, Amir Goren, Timothy W Victor, Jonathan Chapnick, Stephanie Hawthorne, Ishan Hirji, Eduardo Olavarría, Alyson B Moadel, Colleen Lemoine, Catherine Davis
Journal: Blood (2011)