tbuckley/cabot-search huggingface dataset:
Irish Songs and Ballads
Authors: Kieran Walsh
Journal: BMJ (2006)

A Saudi man underwent repeated percutaneous aspiration of a pleural effusion before a pleural biopsy showed hydatid disease. Subsequent investigations confirmed hydatid disease in the pleura and liver. The patient underwent surgical evacuation and irrigation of the pleural cavity followed by medical treatment for the liver cyst with albendazole, with complete recovery and disappearance of the liver cyst.
P114 Ionising radiation inhibits inflammation in patients with musculoskeletal diseases: radon treatment vs low-dose radiation therapy
Authors: K Shreder, A Cucu, D Kraft, S Lehrian, J Kondol, G Klein, B Frey, U Gaipl, C Fournier
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common musculoskeletal diseases (MSD) that affect the joints. Reduced mobility and quality of life are the consequences of the cartilage and bone tissue destruction and the chronic inflammation process, caused by release of bone destruction markers and inflammatory factors including adipokines in the joint. Besides medications, an additional pain relief is achieved by the treatment of patients with low-dose ionising radiation, either as local low-dose radiation therapy (LDRT) or whole-body exposure to radon in radon baths or galleries. <h3>Objectives</h3> In the previous work we showed the decrease of serum levels of visfatin and serum carboxy-terminal collagen crosslinks of type-I collagen (CTX-I) in patients treated in radon baths.<sup>1</sup> In the present study, we analysed serum samples of patients with MSD, who had been treated locally with photon radiation (LDRT). In addition, we analysed differentiation and activity of osteoclasts that were differentiated <i>in vitro</i> from patient-derived monocytes. <h3>Methods</h3> Serum samples were collected from patients before and after treatment. Levels of visfatin and CTX-I were measured by ELISA. Monocytes were isolated from blood samples of patients and cultivated with M-CSF and RANKL on bone slices for 2 weeks. Osteoclasts were defined as TRAP and F-actin positive cells. TRAP activity was measured in the cell supernatants using TRAP Staining Kit. <h3>Results</h3> In the serum of patients treated with LDRT, a trend to reduced concentration of CTX-I was observed directly after the therapy. Further, osteoclasts, differentiated<i> in vitro</i> from LDRT patient-derived monocytes, showed reduced TRAP activity. <h3>Conclusions</h3> The observations made in this study so far substantiate that the radiation-induced decrease of CTX-I levels could be one main factor that is related to the attenuation of inflammation and to the decrease of disease activity in the patients with MSD. This hypothesis is endorsed by the observed reduced differentiation and activity of <i>in vitro</i> cultivated patient-derived osteoclasts. <h3>Reference</h3> . Cucu Shreder, et al. Front. Immunol2017;8:882. <h3>Acknowledgements</h3> This work was supported by the German Federal Ministry of Education and Research (grant no. 02NUK017A and 02NUK017G, GREWIS), by Landesamt für Gesundheit und Lebensmittelsicherheit Bayern, and by Bayrisches Staatsbad Bad Steben GmbH. <h3>Disclosure of interest</h3> None declared
Day-and-Night Closed-Loop Insulin Delivery in a Broad Population of Pregnant Women With Type 1 Diabetes: A Randomized Controlled Crossover Trial
Authors: Zoe A. Stewart, Malgorzata E. Wilinska, Sara Hartnell, Leanne K. O’Neil, Gerry Rayman, Eleanor M. Scott, Katharine Barnard, Conor Farrington, Roman Hovorka, Helen R. Murphy
Journal: Diabetes Care (2018)

OBJECTIVE Despite advances in technology, optimal glucose control remains elusive and neonatal complications remain ubiquitous in type 1 diabetes (T1D) pregnancy. Our aim was to examine the safety, efficacy, and longer-term feasibility of day-and-night closed-loop insulin delivery. RESEARCH DESIGN AND METHODS We recruited 16 pregnant women (mean [SD]: age 32.8 [5.0] years, T1D duration 19.4 [10.2] years, HbA1c 8.0% [1.1], and BMI 26.6 [4.4] kg/m2) to an open-label, randomized, crossover trial. Participants completed 28 days of closed-loop and sensor-augmented pump (SAP) insulin delivery separated by a washout period. Afterward, participants could continue to use the closed-loop system up to 6 weeks postpartum. The primary end point was the proportion of time with glucose levels within the target range (63–140 mg/dL). RESULTS The proportion of time with glucose levels within target was comparable during closed-loop and SAP insulin delivery (62.3 vs. 60.1% [95% CI −4.1 to 8.3]; P = 0.47). Mean glucose and time spent hyperglycemic &amp;gt;140 mg/dL also did not differ (131.4 vs. 131.4 mg/dL [P = 0.85] and 36.6 vs. 36.1% [P = 0.86], respectively). During closed-loop, fewer hypoglycemic episodes occurred (median 8 [range 1–17] vs. 12.5 [1–53] over 28 days; P = 0.04) and less time at &amp;lt;63 mg/dL (1.6 vs. 2.7%; P = 0.02). Hypoglycemia &amp;lt;50 mg/dL (0.24 vs. 0.47%; P = 0.03) and low blood glucose index (1.0 vs. 1.4; P = 0.01) were lower. Less nocturnal hypoglycemia (2300–0700 h) during closed-loop therapy (1.1 vs. 2.7%; P = 0.008) and a trend toward higher overnight time in target (67.7 vs. 60.6%; P = 0.06) were found. CONCLUSIONS Closed-loop insulin delivery was associated with comparable glucose control and significantly less hypoglycemia than SAP therapy. Larger, longer-duration multicenter trials are now indicated to determine clinical efficacy of closed-loop insulin delivery in T1D pregnancy and the impact on neonatal outcomes.
Mandatory shadowing for foundation doctors set to continue in 2013
Authors: Helen Jaques
Journal: BMJ (2013)

All medical graduates appointed to foundation year 1 roles this summer will be required to complete at least four days of shadowing before they take up their posts in August 2013.

In 2012, Health Education England (HEE) introduced a period of paid shadowing for medical graduates to help them become familiar with their working environment before taking up foundation training posts.1 Almost all trusts implemented shadowing last …
Zonal differences in PD-1 expression in centre of tumour versus periphery in microsatellite stable and unstable colorectal cancer.
Authors: Grainne O'Kane, Mark Lynch, Simon Hooper, John Aird, C. Muldoon, Niall Mulligan, Chrsitine Loscher, David J. Gallagher
Journal: Journal of Clinical Oncology (2015)

3574 Background: Colorectal cancers that show evidence of microsatellite instability (MSI-H) are marked by a high tumour infiltrating lymphocyte population (TiL) which is thought to be prognostic. Programmed Death-1(PD-1) is a negative regulator of the immune system and targeting the interaction with its ligand PD-L1 offers a potential therapeutic target in many malignancies. We aimed to characterize CD8 and PD-1 expression in both the tumour centre and tumour periphery of microsatellite stable (MSS) and unstable colorectal cancers. Methods: Paraffin-embedded tumour blocks were cut at 5um, prepared and stained using specific antibodies for CD8 and PD-1. The tumour periphery was defined as the area within a 400x high power field (HPF) from the outline of the tumor. The tumour centre was defined as the area at least one 400x HPF apart from the tumour outline toward the centre of the tumour. Images were taken at 40x, 100x, 200x and 400x. Positive cells were averaged across 3 high power fields and classified as high or low positivity. Results: Forty-two specimens have been analysed to date including 28 MSI-H and 13 MSS tumours. Sixty-eight percent of MSI-H specimens were stage II and 69% of MSS were stage III. In the MSI-H group, a high CD8 count in the tumour centre and tumour periphery correlated with earlier tumour size and stage. PD-1 positivity was seen in 61% of MSI-H tumour centres compared to no positivity in the tumour centres of MSS specimens. The periphery of both MSS and MSI-H specimens showed significant PD1 expression with 71% and 85% of samples showing positivity respectively. There was no association between high or low densities of staining and stage. Conclusions: Zonal differences exist in the expression of CD8 and PD-1 in microsatellite stable and unstable tumours. A high proportion of MSI-H tumours show PD-1 activity in the centre of the tumour despite an improved prognosis. Further profiling of other T cell populations may help to further understand this expression which may act as a biomarker or provide a therapeutic target.
Sequencing Pancreatic Juice: Squeezing the Most Out of Surveillance
Authors: Matthew B. Lipner, Jen Jen Yeh
Journal: Clinical Cancer Research (2018)

Next-generation sequencing of pancreatic juice can detect and quantify tumor-promoting mutations, supporting imaging and cytology findings to predict the degree of dysplasia in patients at high risk for pancreatic cancer. Future studies are needed to optimize this approach and determine how it best fits into clinical practice. Clin Cancer Res; 24(12); 2713-5. ©2018 AACRSee related article by Suenaga et al., p. 2963.
ASSESSMENT OF PROXIMAL LEFT ANTERIOR DESCENDING ARTERY SIZE BY INTRAVASCULAR ULTRASOUND FOR OPTIMAL STENT SIZING
Authors: Evan Shlofmitz, Mitsuaki Matsumura, Gary Mintz, Cheolmin Lee, Masaru Ishida, Akiko Fujino, Rafal Wolny, Yuqi Fan, Masahiro Hoshino, Eisuke Usui, Yoshihisa Kanaji, Tadashi Murai, Taishi Yonetsu, Ziad Ali, Gregg Stone, Jeffrey Moses, Tsunekazu Kakuta, Akiko Maehara
Journal: Journal of the American College of Cardiology (2018)
4-Step Protocol for Disparities in STEMI Care and Outcomes in Women
Authors: Chetan P. Huded, Michael Johnson, Kathleen Kravitz, Venu Menon, Mouin Abdallah, Travis C. Gullett, Scott Hantz, Stephen G. Ellis, Seth R. Podolsky, Stephen W. Meldon, Damon M. Kralovic, Deborah Brosovich, Elizabeth Smith, Samir R. Kapadia, Umesh N. Khot
Journal: Journal of the American College of Cardiology (2018)

Women with ST-segment elevation myocardial infarction (STEMI) receive suboptimal care and have worse outcomes than men. Whether strategies to reduce STEMI care variability impact disparities in the care and outcomes of women with STEMI is unknown. The study assessed the care and outcomes of men versus women with STEMI before and after implementation of a comprehensive STEMI protocol. On July 15, 2014, the authors implemented: 1) emergency department catheterization lab activation; 2) STEMI Safe Handoff Checklist; 3) immediate transfer to an immediately available catheterization lab; and 4) radial first approach to percutaneous coronary intervention (PCI). The authors prospectively studied consecutive patients with STEMI and assessed guideline-directed medical therapy (GDMT) before PCI, median door-to-balloon time (D2BT), in-hospital adverse events, and 30-day mortality stratified by sex before (January 1, 2011 to July 14, 2014; control group) and after (July 15, 2014 to December 31, 2016) implementation of the STEMI protocol. Of 1,272 participants (68% men, 32% women), women were older with more comorbidities than men. In the control group, women had less GDMT (77% vs. 69%; p = 0.019) and longer D2BT (median 104 min; [interquartile range (IQR): 79 to 133] min vs. 112 [IQR: 85 to 147] min; p = 0.023). Women had more in-hospital stroke, vascular complications, bleeding, transfusion, and death. In the comprehensive 4-step STEMI protocol, sex disparities in GDMT (84% vs. 80%; p = 0.32), D2BT (89 [IQR: 68 to 106] min vs. 91 [IQR: 68 to 114] min; p = 0.15), and in-hospital adverse events resolved. The absolute sex difference in 30-day mortality decreased from the control group (6.1% higher in women; p = 0.002) to the comprehensive 4-step STEMI protocol (3.2% higher in women; p = 0.090). A systems-based approach to STEMI care reduces sex disparities and improves STEMI care and outcomes in women.
My burning issues for 2018: increasing costs and training non-doctors
Authors: John Sandford-Smith
Journal: BMJ (2018)

As an elderly retired ophthalmologist, my burning issues1 were emphasised by your short article about the $1m (£0.7m; €0.8m) once only injection for inherited retinal disease.2

My first issue is the ever increasing cost of healthcare. When will our leaders admit that, in trying to keep us elderly people healthy, the cuckoo has become too big for the nest and …
RSK Regulates PFK-2 Activity to Promote Metabolic Rewiring in Melanoma
Authors: Thibault Houles, Simon-Pierre Gravel, Geneviève Lavoie, Sejeong Shin, Mathilde Savall, Antoine Méant, Benoit Grondin, Louis Gaboury, Sang-Oh Yoon, Julie St-Pierre, Philippe P. Roux
Journal: Cancer Research (2018)

Metabolic reprogramming is a hallmark of cancer that includes increased glucose uptake and accelerated aerobic glycolysis. This phenotype is required to fulfill anabolic demands associated with aberrant cell proliferation and is often mediated by oncogenic drivers such as activated BRAF. In this study, we show that the MAPK-activated p90 ribosomal S6 kinase (RSK) is necessary to maintain glycolytic metabolism in BRAF-mutated melanoma cells. RSK directly phosphorylated the regulatory domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), an enzyme that catalyzes the synthesis of fructose-2,6-bisphosphate during glycolysis. Inhibition of RSK reduced PFKFB2 activity and glycolytic flux in melanoma cells, suggesting an important role for RSK in BRAF-mediated metabolic rewiring. Consistent with this, expression of a phosphorylation-deficient mutant of PFKFB2 decreased aerobic glycolysis and reduced the growth of melanoma in mice. Together, these results indicate that RSK-mediated phosphorylation of PFKFB2 plays a key role in the metabolism and growth of BRAF-mutated melanomas.Significance: RSK promotes glycolytic metabolism and the growth of BRAF-mutated melanoma by driving phosphorylation of an important glycolytic enzyme. Cancer Res; 78(9); 2191-204. ©2018 AACR.
Metal Concentrations in e-Cigarette Liquid and Aerosol Samples: The Contribution of Metallic Coils
Authors: Pablo Olmedo, Walter Goessler, Stefan Tanda, Maria Grau-Perez, Stephanie Jarmul, Angela Aherrera, Rui Chen, Markus Hilpert, Joanna E. Cohen, Ana Navas-Acien, Ana M. Rule
Journal: Environmental Health Perspectives (2018)

Background: Electronic cigarettes (e-cigarettes) generate an aerosol by heating a solution (e-liquid) with a metallic coil. Whether metals are transferred from the coil to the aerosol is unknown. Objective: Our goal was to investigate the transfer of metals from the heating coil to the e-liquid in the e-cigarette tank and the generated aerosol. Methods: We sampled 56 e-cigarette devices from daily e-cigarette users and obtained samples from the refilling dispenser, aerosol, and remaining e-liquid in the tank. Aerosol liquid was collected via deposition of aerosol droplets in a series of conical pipette tips. Metals were reported as mass fractions (μg/kg) in liquids and converted to mass concentrations (mg/m3) for aerosols. Results: Median metal concentrations (μg/kg) were higher in samples from the aerosol and tank vs. the dispenser (all p<0.001): 16.3 and 31.2 vs. 10.9 for Al; 8.38 and 55.4 vs. <0.5 for Cr; 68.4 and 233 vs. 2.03 for Ni; 14.8 and 40.2 vs. 0.476 for Pb; and 515 and 426 vs. 13.1 for Zn. Mn, Fe, Cu, Sb, and Sn were detectable in most samples. Cd was detected in 0.0, 30.4, and 55.1% of the dispenser, aerosol, and tank samples respectively. Arsenic was detected in 10.7% of dispenser samples (median 26.7μg/kg) and these concentrations were similar in aerosol and tank samples. Aerosol mass concentrations (mg/m3) for the detected metals spanned several orders of magnitude and exceeded current health-based limits in close to 50% or more of the samples for Cr, Mn, Ni, and Pb. Conclusions: Our findings indicate that e-cigarettes are a potential source of exposure to toxic metals (Cr, Ni, and Pb), and to metals that are toxic when inhaled (Mn and Zn). Markedly higher concentrations in the aerosol and tank samples versus the dispenser demonstrate that coil contact induced e-liquid contamination. https://doi.org/10.1289/EHP2175
CCGs try to block expansion of Babylon’s GP at Hand service
Authors: Gareth Iacobucci
Journal: BMJ (2018)

A fresh row has broken out over the rollout of the GP at Hand digital primary care service, after the company behind the scheme said that it was being blocked from expanding by “vested interests” regarding the NHS.

GP at Hand, a partnership between the Lillie Road Medical Centre in west London and the technology company Babylon, offers a mixture of “virtual” GP consultations by smartphone and face to face appointments.

In response to its popularity with young patients GP at Hand has asked the Hammersmith and Fulham clinical commissioning group (CCG)—which holds the practice’s contract—for permission to subcontract the service to four additional sites in north and east London that currently have vacant space in their premises. This would enable it to provide services and register new patients at the four sites.

Islington, Enfield, Barnet, and …
Funding innovation in neglected diseases
Authors: Gavin Yamey, Amie Batson, Peter H Kilmarx, Marcel Yotebieng
Journal: BMJ (2018)

Neglected diseases are those with insufficient markets to attract investment from the drug industry.They primarily affect populations living in low income countries and include malaria, tuberculosis, and diarrhoeal diseases.Public and philanthropic funding is required to develop new health technologies to control these diseases.While funding from public-private partnerships helped to bring 37 new treatments for neglected diseases to market between 2000 and 2011, this represented just 4% of all new therapeutic products registered during this period.As neglected diseases cause about 11% of the global burden of disease, there is clearly a "persistent insufficiency" in research and development (R&D). 1 Except for a one-off injection of funding for Ebola and other African viral haemorrhagic fevers, funding for product development for neglected diseases has shown a downward trend since 2009. 2 How can this trend be reversed?Strategies to mobilise funding should engage governments from high, low, and middle income countries, philanthropic foundations, and the private sector.We propose five interconnected approaches.
Differential effects of secukinumab vs. ustekinumab for treatment of psoriasis on quality of life, work productivity and activity impairment: a structural equation modelling analysis
Authors: D.E. Stull, C.E.M. Griffiths, I. Gilloteau, Y. Zhao, A. Guana, A.Y. Finlay, B. Sherif, K. Houghton, L. Puig
Journal: British Journal of Dermatology (2018)

The appearance and lifelong, chronic nature of psoriasis result in considerable burden to patients, such as sleep impairment, depressive symptoms, negative self-esteem and reduced work productivity.To examine direct and indirect (mediated) effects of secukinumab vs. ustekinumab on quality of life, work productivity and activity impairment based on psoriasis severity and symptoms.Analyses were based on data from the CLEAR study. Structural equation modelling examined the effects of secukinumab vs. ustekinumab on the Dermatology Life Quality Index (DLQI) and on the Work Productivity and Activity Impairment (WPAI) questionnaire using Psoriasis Area and Severity Index (PASI) severity and symptoms (pain, itching and scaling) as potential mediators. Analyses were conducted primarily for patients achieving a PASI 90 response (90% or greater reduction in PASI from baseline) at week 16 (repeated at week 52) and for PASI 50, 75 and 100.Results at weeks 16 and 52 showed that the effect of treatment on change in DLQI score was mediated by the PASI 90 response and by improvements in itching, pain, and scaling. Achieving any PASI response as early as week 16 directly resulted in significantly better WPAI scores. At week 52, both PASI response and improvement in scaling directly resulted in significantly better WPAI scores. Pain, itching and scaling were correlated (r = 0·51-0·68); improvement in any of these had a significant effect (directly or indirectly) on WPAI. All results favoured secukinumab over ustekinumab.The results underscore the important role of both PASI response and reduction in symptoms on improvements in health-related quality of life and work and daily activity in favour of secukinumab vs. ustekinumab.
使用生物疗法治疗银屑病的持续 PASI、DLQI 及 EQ‐5D 结果:基于瑞典国家银屑病登记的十年真实数据
Authors: F. Hjalte, K.S. Carlsson, M. Schmitt‐Egenolf
Journal: British Journal of Dermatology (2018)

轻症患者通常使用局部治疗(外用),中度到重度患者则需要全身治疗(内用),包括使用生物制剂。PsoReg 是于 2006 年成立的瑞典国家银屑病登记协会,旨在监测生物制剂的长期疗效及安全性。PsoReg 记录患者的银屑病皮损面积和严重度指数 (PASI),PASI 是一种在特定时间衡量患者银屑病的严重度及分布面积的方法,便于医生确定症状是恶化还是好转。PsoReg 还会记录患者的健康相关生活质量 (HRQoL),以考量此类疾病如何影响患者的日常活动及情绪健康。该研究使用了 583 位患者的数据,旨在了解转用生物疗法(之前未使用过生物制剂)对患者 PASI 及 HRQoL 的影响。研究分析了在转用生物疗法后第 3–5 个月、第 6–11 个月的 PASI 值和 HRQoL 值,且在转用生物疗法后的 1–9 年间至少需要再分析一次。数据表明,在转用生物疗法后 3–5 个月相关分数明显提高,且在整个观察期,这种情况持续。通过该研究的结果,对于通过其他类型的治疗疗效不佳的患者,临床医生可以开始或者继续给其使用生物疗法。
Evaluation of the in Vitro Penetration of Fluticasone Propionate (FP) from Azelastine Hydrochloride–Fluticasone Propionate Nasal Spray (MP-AzeFlu) & Fluticasone Propionate Nasal Spray through Epiairway™606 Tissues Using Vertical Diffusion Cells
Authors: William E. Berger, Alex D'Addio, Robert Allara, Bindu Upadhyay, Arkady Koltun, Ferdinand Kopietz, Joachim Maus
Journal: Journal of Allergy and Clinical Immunology (2018)
Workload warnings risk becoming “self fulfilling prophecy,” NHS chief tells GPs
Authors: Tom Moberly
Journal: BMJ (2014)

Warnings over the rising workload in general practice risk becoming a “self fulfilling prophecy,” if they deter doctors from becoming GPs, the chief executive of the NHS has warned GPs.

Speaking at the annual conference of the Royal College of General Practitioners (RCGP) in Liverpool last week, Simon Stevens said that “a conundrum” was facing leaders of the profession. “There’s a balancing act to be struck here,” he said. “Quite rightly, you are telling it as it is in general practice, as a wake-up call for those who need to work with you to respond.

“But the danger is that that wake-up call sounds like a proposition to young doctors [they] want to steer clear of general practice. So how to have that honest conversation without it also becoming a self fulfilling prophecy—such that we end up with huge swathes of the country where training places are not filled—is something …