tbuckley/cabot-search huggingface dataset:
Ultrafine and Fine Particle Number and Surface Area Concentrations and Daily Cause-Specific Mortality in the Ruhr Area, Germany, 2009–2014
Authors: Frauke Hennig, Ulrich Quass, Bryan Hellack, Miriam Küpper, Thomas A. J. Kuhlbusch, Massimo Stafoggia, Barbara Hoffmann
Journal: Environmental Health Perspectives (2018)

Background: Although epidemiologic studies have shown associations between particle mass and daily mortality, evidence on other particle metrics is weak. Objectives: We investigated associations of size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) with cause-specific daily mortality in contrast to PM10. Methods: We used time-series data (March 2009–December 2014) on daily natural, cardiovascular, and respiratory mortality (NM, CVM, RM) of three adjacent cities in the Ruhr Area, Germany. Size-specific PNC (electric mobility diameter of 13.3–750 nm), PSC, and PM10 were measured at an urban background monitoring site. In single- and multipollutant Poisson regression models, we estimated percentage change (95% confidence interval) [% (95% CI)] in mortality per interquartile range (IQR) in exposure at single-day (0–7) and aggregated lags (0–1, 2–3, 4–7), accounting for time trend, temperature, humidity, day of week, holidays, period of seasonal population decrease, and influenza. Results: PNC100–750 and PSC were highly correlated and had similar immediate (lag0–1) and delayed (lag4–7) associations with NM and CVM, for example, 1.12% (95% CI: 0.09, 2.33) and 1.56% (95% CI: 0.22, 2.92) higher NM with IQR increases in PNC100–750 at lag0–1 and lag4–7, respectfully, which were slightly stronger then associations with IQR increases in PM10. Positive associations between PNC and NM were strongest for accumulation mode particles (PNC 100–500 nm), and for larger UFPs (PNC 50–100 nm). Associations between NM and PNC<100 changed little after adjustment for O3 or PM10, but were more sensitive to adjustment for NO2. Conclusion: Size-specific PNC (50–500 nm) and lung-deposited PSC were associated with natural and cardiovascular mortality in the Ruhr Area. Although associations were similar to those estimated for an IQR increase in PM10, particle number size distributions can be linked to emission sources, and thus may be more informative for potential public health interventions. Moreover, PSC could be used as an alternative metric that integrates particle size distribution as well as deposition efficiency. https://doi.org/10.1289/EHP2054
WATCHMAN DEVICE SIZING: IS MULTI-DETECTOR COMPUTED TOMOGRAPHY SUPERIOR TO TRANSESOPHAGEAL ECHOCARDIOGRAPHY?
Authors: Bo Xu, Jorge Betancor, Kimi Sato, Serge Harb, Karim Abdur Rehman, Kunal Patel, Arnav Kumar, Paul Cremer, Wael Jaber, L. Leonardo Rodriguez, Paul Schoenhagen, Oussama Wazni
Journal: Journal of the American College of Cardiology (2018)
Abstract 18390: Changes in Leisure-Time Physical Activity Are Associated With Risk of Incident Atrial Fibrillation - The Atherosclerosis Risk in Communities Study
Authors: Sheila Hegde, Brian Claggett, Tor Biering-Sørenson, Susan Cheng, Amil M Shah, Lin Y Chen, Elsayed Z Soliman, Alvaro Alonso, Scott D Solomon
Journal: Circulation (2016)

Introduction:  Greater leisure-time physical activity (LTPA) is associated with lower risk of cardiovascular disease. However, the association of LTPA, and changes in LTPA over time, with incident atrial fibrillation (AF) in a community-based, non-athletic population is unclear.   Hypothesis:  Persons with persistently poor activity in adult life have higher incident AF relative to those with persistently ideal activity.   Methods:  Among 12,228 participants in the Atherosclerosis Risk in Communities Study who were free of AF at visit 3, self-reported LTPA assessed at visits 1 and 3 were categorized as poor, intermediate, or ideal LTPA using American Heart Association (AHA) criteria. Change in LTPA categories and average LTPA over the 6 year period were related to incident AF with multivariable Cox models.   Results:  The mean age was 60.4 ± 5.7 years. Over a median follow up of 16.7 years, incident AF occurred in 1518 participants. Compared to those with persistently ideal activity over 6 years, participants with persistently poor activity (HR 1.26; CI 1.07, 1.47) and who decreased activity from ideal to poor (HR 1.32; CI 1.07, 1.62) had a higher risk of incident AF after adjusting for age, sex, race, prior coronary disease, prior heart failure, diabetes, systolic blood pressure, and anti-hypertensive medication use. Those who increased activity from poor to ideal (HR 1.12; CI 0.91, 1.37) did not have a significantly different risk of AF compared to those with persistently ideal activity. Age modified the association of LTPA with incident AF such that higher average activity (MET-min/week) was associated with a lower risk of incident AF in younger participants, but this association weakened in older individuals (p interaction for age = 0.007, Figure).   Conclusions:  In younger, middle-aged individuals, maintaining average activity levels over 500 MET-min/week, as recommended by the AHA, is associated with a lower risk of incident AF. This relationship weakens with increasing age.
Seniority payments to end as part of GP contract changes
Authors: Abi Rimmer
Journal: BMJ (2013)

Seniority pay for GPs in England will be abolished in 2020 as part of a government drive to remove pay progression in the public sector.

Under the 2014-15 GP contract, agreed last week by the BMA’s General Practitioners Committee and NHS Employers, seniority payments for GPs will cease on 31 March 2020.

The Department of Health said that seniority payments, which are on average around £6000 a year and based on a GP’s length of service, will be reinvested …
Professor Andy Adam, president of the Royal College of Radiologists
Authors: Nana Seiwaa Opare
Journal: BMJ (2008)

There is no doubt that the housemen of my day worked extremely hard. My first few years after qualification are a blur of non-stop work. But, and I hope my memories are not distorted by the usual propensity to remember only the good things and forget pain, we saw medicine as much more than a job and did not expect the same lifestyle as our contemporaries in other professions. Nowadays, training is more structured but I am not entirely sure whether all of the changes we have seen in the past 30 years have been beneficial—at least for patients. I regret the demise of the medical and surgical “firm,” with its clear lines of accountability and excellent continuity of patient …
Assessment of inflammation and damage by MRI in established RA patients with Methotrexate inadequate response receiving Golimumab: Results of the GO-FORWARD trial
Authors: P.G. Conaghan, P. Emery, Mikkel Østergaard, E.C. Keystone, M.C. Genovese, L. Klareskog, W. Xu, E.C. Hsia, M.U. Rahman
Journal: Annals of the Rheumatic Diseases (2011)
Managing latent tuberculosis infection and tuberculosis in children
Authors: I. Carvalho, D. Goletti, S. Manga, D.R. Silva, D. Manissero, G. Migliori
Journal: Pulmonology (2018)

Tuberculosis (TB) is a major cause of childhood morbidity and mortality worldwide. The aim of this review is to describe the management of the child with TB and latent tuberculosis infection (LTBI). To develop this article, a working group reviewed relevant epidemiological and other scientific studies and established practices in conducting LBTI and TB in children. The article describes how to manage the child with LTBI, considering transmission and infectiousness of tuberculosis, contact screening and prioritization of contacts and recommendations on treatment of children with LTBI and how to manage the child with TB considering the susceptibility of children to developing tuberculosis, epidemiology and classification of tuberculosis in children, diagnosis and treatment.
Diploma in tropical medicine in practice (Malawi)
Authors: Kate Woods
Journal: BMJ (2008)

Anyone with an interest in tropical medicine and infectious diseases or who is planning to work or carry out research in a low resource setting (particularly within Africa) and wants a safe and informative taster. It is also an ideal tag-on to the diploma in tropical medicine and hygiene (DTM&H) for those who have completed this and want to see some real patients.

May-June 2006, as a senior house officer, immediately after having completed the DTM&H in Liverpool. The course also runs in September-October each year and any level of experience is accepted. The minimum qualification for taking the course is a medical degree.

As a consolidation of my learning on the DTM&H and to gain some first hand experience of the realities of working in a …
Self-indicating, fully active pharmaceutical ingredients nanoparticles (FAPIN) for multimodal imaging guided trimodality cancer therapy
Authors: Xiangdong Xue, Yee Huang, Xinshuai Wang, Zhongling Wang, Randy P. Carney, Xiaocen Li, Ye Yuan, Yixuan He, Tzu-yin Lin, Yuanpei Li
Journal: Biomaterials (2018)
Abstract ES9-1: Androgen Receptor in breast cancer. When might it serve as a suitable target?
Authors: JK Richer
Journal: Cancer Research (2018)

Abstract In the last decade it has become clear that androgen receptors (AR) are present in the normal breast and are even more widely expressed in breast cancer than estrogen or progesterone receptors (ER or PR). The majority of estrogen receptor positive (ER+) breast cancers and a subset of triple negative breast cancer (TNBC) express AR. AR has long served as an effective therapeutic target In prostate cancer and potent drugs have been developed that either bind to AR or inhibit enzymes involved in androgen synthesis. In women, the primary source of androgens is the adrenal gland. Fat cells convert androgens to estrogens via the enzyme aromatase, the target of aromatase inhibitors. The relative abundance of the various steroid hormone receptors and context can affect the behavior of the receptors. Indeed, the role of AR differs in the three main subtypes of breast cancer (ER+, HER2+ and TNBC) and can change with treatment or disease progression. For instance, ER+ primary breast cancers can increase expression of AR following treatment with anti-estrogens such as tamoxifen or aromatase inhibitors, such that recurrent disease (having been deprived of estrogen), is rendered more dependent on androgens and AR. In some TNBC, AR can substitute for ER to some degree, and such tumors are slower growing and therefore less responsive to chemotherapy and often overexpress HER2. These types of tumors may therefore be responsive to concurrent treatment with anti-androgen combined with chemotherapy or HER2 targeting agents, much as we do for ER+/HER2+ tumors. This lecture will summarize impactful preclinical studies and summarize results of recent and ongoing clinical trials targeting AR in breast cancer. Citation Format: Richer JK. Androgen Receptor in breast cancer. When might it serve as a suitable target? [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 ES9-1.
HDL PARTICLE CONCENTRATION IS NOT ASSOCIATED WITH RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS FOLLOWING ACUTE CORONARY SYNDROMES
Authors: Taufiq Salahuddin, John Kittleson, Jean Claude Tardif, Prediman Shah, Anders Olsson, Stephen Nicholls, John J.V. McMurray, Eran Leitersdorf, Lawrence Leiter, Philip Barter, Christie Ballantyne, Gregory Schwartz
Journal: Journal of the American College of Cardiology (2018)
Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial
Authors: Jin Kyun Park, Yun Jong Lee, Kichul Shin, You-Jung Ha, Eun Young Lee, Yeong Wook Song, Yunhee Choi, Kevin L Winthrop, Eun Bong Lee
Journal: Annals of the Rheumatic Diseases (2018)

To determine whether a 2-week methotrexate (MTX) discontinuation after vaccination improves the efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis (RA).In this prospective randomised parallel-group multicentre study, patients with RA on stable dose of MTX were randomly assigned at a ratio of 1:1 to continue MTX or to hold MTX for 2 weeks after 2016-2017 quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B-Yamagata and B-Victoria. The primary outcome was frequency of satisfactory vaccine response, defined as greater than or equal to fourfold increase of haemagglutination inhibition (HI) antibody titre at 4 weeks after vaccination against ≥2 of four vaccine strains. Secondary endpoints included seroprotection (ie, HI titre ≥1:40) rate, fold change in antibody titres.The modified intention-to-treat population included 156 patients in the MTX-continue group and 160 patients in the MTX-hold group. More patients in MTX-hold group achieved satisfactory vaccine response than the MTX-continue group (75.5% vs 54.5%, p<0.001). Seroprotection rate was higher in the MTX-hold group than the MTX-continue group for all four antigens (H1N1: difference 10.7%, 95% CI 2.0% to 19.3%; H3N2: difference 15.9%, 95% CI 5.9% to 26.0%; B-Yamagata: difference13.7%, 95% CI 5.2% to 22.4%; B-Victoria: difference 14.7%, 95% CI 4.5% to 25.0%). The MTX-hold group showed higher fold increase in their antibody titres against all four influenza antigens (all p<0.05). Change in disease activity was similar between groups.A temporary MTX discontinuation for 2 weeks after vaccination improves the immunogenicity of seasonal influenza vaccination in patients with RA without increasing RA disease activity.NCT02897011.
Long-term outcomes of stereotactic body radiotherapy for low- and intermediate-risk prostate adenocarcinoma: A multi-institutional consortium study.
Authors: Amar Upadhyaya Kishan, Alan J. Katz, Constantine Mantz, Fang-I Chu, Limor Appelbaum, Andrew Loblaw, Patrick Cheung, Irving D. Kaplan, Donald B. Fuller, Huong T. Pham, Robert Meier, Mark K. Buyyounouski, Narek Shaverdian, Audrey Dang, Ye Yuan, Hilary Bagshaw, Nicolas Prionas, Patrick Kupelian, Michael L. Steinberg, Christopher R. King
Journal: Journal of Clinical Oncology (2018)

84 Background: While a growing body of evidence supports the use of stereotactic body radiotherapy (SBRT) for the treatment of low- and intermediate-risk prostate adenocarcinoma (PCa), some trepidation exists regarding its long-term efficacy and safety. Methods: Men with low- and intermediate-risk PCa, as defined per the National Comprehensive Cancer Network guidelines, who were enrolled on various institutional phase II trials of SBRT between 2000-2012 were included in a multi-institutional consortium. Biochemical relapse (BCR) was defined as PSA &gt; “nadir +2” or initiation of androgen deprivation therapy (ADT). Toxicity data were scored according to the CTCAE v 3.0 or Radiation Therapy Oncology Group scoring systems. Results: A total of 1644 men were eligible for analysis, with a median followup of 7.2 years. 297 patients (18.1%) had at least 9 years of followup. Fractionation schemes ranged from 33.50-40 Gy in 4-5 fractions. 892 patients had low-risk disease and 752 had intermediate-risk disease. 59 patients (3.6%) received short-term ADT. 100 patients (6.0%) experienced BCR, and 7 (0.4%) experienced distant metastases. No patients died of PCa. By Kaplan-Meier analysis, 5- and 10-year BCR-free survival rates were 98% and 94% in the low-risk group and 96% and 90% in the intermediate-risk group (p &lt; 0.05 by log-rank test). 5- and 10-year overall survival rates were 93% and 86% in the low-risk group and 95% and 91% in the intermediate-risk group (p &gt; 0.05 by log-rank test). Five patients (0.3%) experienced grade 3 acute genitourinary (GU) toxicities, including urinary retention, hematuria, and frequency. 30 (2%) experienced grade 3 late GU toxicity, including urinary strictures, hematuria, and retention. One late grade 4 GU toxicity (hemorrhagic urethritis) and one late grade 4 gastrointestinal toxicity (fistula-in-ano) were seen. Conclusions: To the best of our knowledge, this is the largest analysis of long-term outcomes following SBRT for PCa. The results indicate that SBRT has an efficacy and toxicity profile that compares favorably to more widespread forms of treatment, such as conventionally-fractionated external beam radiotherapy and brachytherapy.
Two thirds of LETBs have conditions imposed on their authorisation
Authors: Helen Jaques
Journal: BMJ (2013)

Nine of the 13 local education and training boards (LETBs) set to take responsibility for medical training and education in England from 1 April have had conditions imposed on their authorisation.

LETBs, which will take over postgraduate deaneries’ roles in the education and training of the healthcare and public health workforce, have had to undergo an authorisation process testing their capabilities.

Only four of the 13 LETBs planned for England met all 96 …
What sort of things should I consider when looking for a locum job?
Authors: Adam Harrison
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.
Junior contract will ensure fair weekend pay for part time trainees, says BMA
Authors: Abi Rimmer
Journal: BMJ (2016)

The proposed new contract for junior doctors in England is being changed to ensure that trainees who work less than full time (LTFT) receive a fair level of pay for working at the weekend, the BMA has said.

The chair of the BMA’s Junior Doctors Committee, Johann Malawana, said that the Department of Health and NHS Employers had confirmed on Thursday 2 June that changes would be made to the proposed contract in regard to LTFT trainees. Writing on Facebook on Saturday 4 June, Malawana said, “On Thursday the DH/NHSE side were able to confirm a few modifications as to the intent with LTFT trainees. Particularly in regard to pro rating the weekend supplement for LTFT.”

A BMA spokesperson confirmed that the government had agreed to respond to concerns that the association had raised over LTFT pay. “The …
A career in epidemiology
Authors: Shah Ebrahim
Journal: BMJ (2005)

The cytokine IL-1β plays a central role in inflammatory responses that are initiated by microbial challenges, as well as in those that are due to endogenous processes (often called sterile inflammation). IL-1β secretion that occurs independently of microbial stimulation is typically associated with the presence of endogenous alarmins, such as extracellular ATP (an indicator of cytopathic damage). In this study, we show that IL-2–activated human invariant NKT (iNKT) cells stimulate the secretion of IL-1β protein by human peripheral blood monocytes in a manner that requires neither the presence of microbial compounds nor signaling through the extracellular ATP receptor P2X<sub>7</sub>. Monocyte IL-1β production was specifically induced by iNKT cells, because similarly activated polyclonal autologous T cells did not have this effect. Secretion of IL-1β protein occurred rapidly (within 3–4 h) and required cell contact between the iNKT cells and monocytes. Similar to IL-1β production induced by TLR stimulation, the iNKT-induced pathway appeared to entail a two-step process involving NF-κB signaling and <i>IL1B</i> gene transcription, as well as assembly of the NLRP3 inflammasome and activation of caspase-1. However, in contrast to the classical inflammasome-mediated pathway of IL-1β production, activation of monocytes via P2X<sub>7</sub> was dispensable for iNKT-induced IL-1β secretion, and potassium efflux was not required. Moreover, the iNKT-induced effect involved caspase-8 activity, yet it induced little monocyte death. These results suggest that IL-2–activated human iNKT cells induce monocytes to produce IL-1β through a distinctive pathway that does not require the presence of microbial danger signals or alarmins associated with cytopathic damage.
Increase UK training places to stop NHS being “held to ransom” by locums, says report
Authors: Abi Rimmer
Journal: BMJ (2015)

The number of medical training places in the UK should be increased to stop the NHS being “held to ransom” by locums, a report has said.

The report by Civitas, the institute for the study of civil society, said that increasing the number of UK trained doctors would help to fill persistent vacancies in less desirable specialties and more remote locations.1 “Such an increase of trained personnel could also ensure that the …
Action on substance misuse in older people is “imperative,” says college
Authors: Jacqui Thornton
Journal: BMJ (2018)

The UK needs to train more psychiatrists specialising in addictions and in old age to treat the “unparalleled” rise in number of baby boomers (people born between 1946 and 1964) seeking help for substance misuse, a new report from the Royal College of Psychiatrists has said.

Deaths related to poisoning by drugs in older people in England and Wales have more than doubled over the past decade, the report said.1 The annual number of alcohol specific deaths in people aged …
Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer
Authors: J. Cortes, J. Perez-Garcia, C. Levy, P. Gómez Pardo, H. Bourgeois, S. Spazzapan, N. Martínez-Jañez, T.-C. Chao, M. Espié, J.M. Nabholtz, X. Gonzàlez Farré, V. Beliakouski, J. Román García, E. Holgado, M. Campone
Journal: Annals of Oncology (2018)
Skeletal metastases in advanced pancreatic ductal adenocarcinoma (PDAC): A retrospective analysis.
Authors: Akshjot Puri, John Chang, Tomislav Dragovich, Patricia Lucente, Madappa N. Kundranda
Journal: Journal of Clinical Oncology (2018)

245 Background: Skeletal metastasis (SM) in advanced PDAC is an infrequent occurrence and has been previously reported to be &lt; 2.5%. However; pathological fractures in these patients can result in intractable pain, immobilization and a significant deterioration in quality of life. Methods: A retrospective analysis was conducted of patients (pts) with advanced PDAC receiving palliative chemotherapy. Data collection included age, gender, ECOG, sites of disease, and overall survival (OS). Statistical analysis included Kaplan Meier survival analysis. Results: The 135 pts included had a median age of 65.8 years (range: 53.7–91.3); 5 (31.2%) were women and 11 (68.7%) had an ECOG performance status of 0 or 1. A majority of patients received combination therapy that was either gemcitabine or 5-flurouracil based. Sixteen pts (11.8%) had skeletal metastasis with the primary tumor located in the pancreatic body/tail (11 pts - 68.7%).The sites of SM included thoracic vertebrae (8), lumbar vertebrae (5), pelvis (5), ribs (4), sacrum (4), scapula (3), acetabulum (2), cervical vertebrae (2), femoral head (2), sternum (1) and humerus head (1). A majority of the lesions were osteolytic (62.5%) with a median time of diagnosis of SM from initial diagnosis being 1.25 months (range 0-33). Bone pain was observed as the initial symptom in 5 pts (32%), 1 pt (6.2%) had a pathological fracture. The mOS for patients with SM was 6.5 months (range 0-38) when compared to 8 months (range 0-147) without SM.The mOS for pts treated with gemcitabine based regimen was 5.75 months (range 2.5-14), and patients who received multiple lines of therapy including gemcitabine and 5-FU based regimens was 15 months (range 5-38). Survival from onset of skeletal metastases ranged from 0-14 months (mOS: 4 months). Conclusions: More effective systemic therapies which improve mOS are likely to result in increased incidence of SM. The most common sites observed were the thoracic and lumbar vertebrae and pathological fractures in these sites can be catastrophic. Therefore careful evaluation of skeletal signs and symptoms, early detection and intervention will be important to prevent morbidity and mortality from pathological fractures.