tbuckley/cabot-search huggingface dataset:
Correlation of tissue plasminogen regulators expressed by esophageal adenocarcinoma with VEGF family members.
Authors: Evgeniy N. Kolesnikov, Oleg Ivanovich Kit, Elena Frantsiyants, Valeria A. Bandovkina, Larisa S. Kozlova, Mikhail Anatolievich Kozhushko, Tanzila Beksultanovna Kazieva, Sergey V. Sanamyants, Vladimir Trifanov
Journal: Journal of Clinical Oncology (2018)

37 Background: Esophageal cancer is known for its high potential of early lymphogenous metastases. The biological activity of plasminogen (PG) regulators, VEGFs and their receptors controls the growth and differentiation of cells, including malignant ones, the stability of the extracellular matrix, as well as processes of destruction of membranes and extracellular matrix, invasion of malignant cells, angio- and lymphangiogenesis. Our purpose was to study the role of PG regulators in the activation of VEGFs and their receptors in esophageal adenocarcinoma (EA) and its perifocal zone (PZ). Methods: Levels of uPA-Ag, uPA-act; tPA-Ag, tPA-act; PAI-1-Ag and PAI-1-act, VEGF-А, VEGF-R1, VEGF-С and VEGF-R3 were determined by ELISA in surgical specimens of EA (n = 28, st II, G2, T 2-3 N 0-1 M 0 ). Statistical analysis was performed using Microsoft Office Excel 2010. Results: Levels of all proteins, except tPA, were higher in tumor (T) tissues than in the resection line (RL, p &lt; 0.01). Protein levels, except uPA-Ag and tPA, in PZ were between levels in T and RL (p &lt; 0.01); uPA-Ag, tPA-Ag and tPA-act were decreased in T and PZ compared with RL (p &lt; 0.01); PAI-1-Ag in T and PZ was higher than in RL by 9.4 and 6.3 times, and PAI-1-act – by 10.7 and 1.9 times. Levels of VEGF-А, VEGF-R1, VEGF-С and VEGF-R3 were increased in T (p &lt; 0.001), and in PZ they were between levels in T and RL (p &lt; 0.001). Strong correlations were registered in EA T between uPA and VEGF-А (r = 86), uPA and VEGF-R1 (r = 81), uPA and VEGF-С (r = 79), uPA and VEGF-R3 (r = 76). A strong correlation between uPA and PAI-1 in T (r = 88) did not exclude PAI-1 biological effects in EA T and its PZ. PZ showed strong correlations between uPA and PAI-1 (r = 87), uPA and VEGF-А (r = 84), uPA and VEGF-С (r = 78). Conclusions: The strong correlations between the activation of uPA, PAI-1, VEGF-А, VEGF-С and their receptors in EA indicate interactions between them, realized both directly and through plasmin. The expression of the studied proteins in T and its PZ, compared to RL, demonstrates the effect of T on the content and activity of uPA, PAI-1, VEGF-A, VEGF-C and their receptors, with the following realization of biological properties that promote the progression of EA.
Association of single nucleotide polymorphisms (SNPs) in CYP17A1 and SLCO2B1 genes and clinical outcome in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: results of the ABIGENE prospective study.
Authors: Delphine Borchiellini, Hakim Mahammedi, Julien Viotti, Gwenaelle Gravis, Guilhem Roubaud, Philippe Beuzeboc, Remy Largillier, Claude Linassier, Ahmed Khalil, Regis Kaphan, Florence Joly, Jean-Christophe Eymard, Sabrina Falkowski, Emmanuelle Bompas, Sylvie Zanetta, Renaud Schiappa, Maeva Maurin, Marie-Christine Etienne-Grimaldi, Gerard A. Milano, Jean-Marc Ferrero
Journal: Journal of Clinical Oncology (2018)

358 Background: Abiraterone acetate (AA), a CYP17A1 inhibitor, has been approved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Germline polymorphisms in genes involved in androgen biosynthesis or transport may influence response and survival in this setting. Methods: ABIGENE is a multicentric prospective non-randomized pharmacogenetic study (NCT01858441). The primary objective was to investigate the association between 13 SNPs in genes related to AA pharmacology (CYP17A1, SLCO2B1 and SLCO2B3) and radiographic progression-free survival (rPFS), according to PCWG2 criteria, in pts with mCRPC treated with first-line AA + prednisone. The main secondary objectives were to evaluate the impact of these SNPs on radiographic and PSA response, overall survival (OS) and toxicity. SNPs were detected in blood samples before starting AA and analyzed by pyrosequencing or PCR-RFLP methods. Kaplan-Meyer’s curves with log-rank tests and cox regression models were used to identify relationships between SNPs and survival. Chi2 tests and student t-tests were used to identify association with response rate and toxicity. Results: 147 pts in 17 french centers were included between 2013 and 2017. Here are presented the results for the first 109 pts. The median follow-up was 28.7 months. Overall response rate (ORR) was 17%, and 74% pts had stable disease as the best response. Median rPFS was 10.9 months (95% CI 9.2-15.3). One SNP (rs10883782) in CYP17A1 was associated with rPFS on AA therapy (Table). Two other SNPs in CYP17A1 (rs4919683) and SLCO2B1 (rs1077858) were significantly associated with radiographic response. Data on PSA response, OS and toxicity will be presented at the meeting. Conclusions: This is the first prospective dedicated study to show an association between SNPs related to androgen metabolism and clinical outcome in mCRPC treated with AA. Clinical trial information: NCT01858441. [Table: see text]
Stressful life events and maltreatment in conversion (functional neurological) disorder: systematic review and meta-analysis of case-control studies
Authors: Lea Ludwig, Joëlle A Pasman, Timothy Nicholson, Selma Aybek, Anthony S David, Sharon Tuck, Richard A Kanaan, Karin Roelofs, Alan Carson, Jon Stone
Journal: The Lancet Psychiatry (2018)
I am an Egyptian doctor and I have passed the part 1 membership exam for the Royal College of Physicians. Can I work in England as an SHO?
Authors: Faisal Hanif
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 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. <b>www.bmjcareers.com/advicezone</b>
Abstract 12065: CPR Prompting Devices: Unintended Consequences Impacting High Performers
Authors: Christie L Mulvey, Sally J Rudy, David L Rodgers, Tammi J Bortner, Elizabeth H Sinz, Lawrence E Kass
Journal: Circulation (2015)

Introduction: Prompting devices for chest compressions have been advocated as a means of improving CPR quality in previous AHA guidelines. Studies have shown overall CPR quality improves with the use of these devices. Hypothesis: This study compared the impact of prompting devices on providers with varying levels of experience and proficiency. Methods: A convenience sample of 53 subjects with varying degrees of CPR experience, ranging from zero to frequent opportunities to perform CPR, were enrolled. Using a skills recording CPR manikin, data on each subject’s chest compression performance was obtained. All subjects performed an initial one-minute cycle of continuous chest compressions with no prompting device. After a brief rest, subjects were randomized to use one of two CPR prompting devices (Philips MRX with Q-CPR or Laerdal Medical CPRmeter). An additional one minute of CPR was conducted with the first device. Subjects were then crossed over to use the other prompting device after another brief rest. Results: Across the entire group, nearly all parameters significantly improved with the prompting devices, confirming previous studies on the efficacy of CPR prompting devices. However, when subjects’ results were examined by breaking the group into three performance levels (high, medium and low) based on the Overall CPR Score generated by the manikin software, there were differences in performance. Paired t -tests were conducted on the low and high performance groups. The low-level group significantly improved across 7 of 8 variables with both devices. The high-level group had only minor changes from baseline (both positive and negative) in most variables, but had significant or near significant decrease in proficiency in one variable - percent correctly released compressions ( p = 0.011 for Philips device; p = 0.052 for the Laerdal device). Conclusions: CPR prompting devices improve the overall quality of chest compressions. Individuals with existing high performance CPR skills could be distracted by the device, reducing the quality of compressions compared to using no device. When a CPR prompting device is introduced into a health care system, all providers, especially high performers, require practice with the device in order to acclimate to its use.
Is there a role for histology based treatment choice in advanced gastric cancer (GC)?
Authors: Rosalba Barile, Michela Squadroni, Federica Brena, Eleonora Cerchiaro, Valeria Zurlo, Giordano D. Beretta
Journal: Journal of Clinical Oncology (2018)

135 Background: Medical management of advanced GC is mostly dependent on prognostic assessment based on tumor stage (TNM) and clinical patients (pts)’ characteristics, other than HER2 expression. Prognostic and predictive factors are clearly needed, and histotype could be proposed as a surrogate marker of disease biology. Methods: We retrospectively analyzed pts with advanced GC treated with first line chemotherapy (CT) at Oncology Unit of Humanitas Gavazzeni (Bergamo) and Policlinico Gemelli (Roma). Pts were divided in three subgroups according to histological diagnosis: diffuse type carcinoma, intestinal type carcinoma and signet ring cell carcinoma. HER2 positive tumors were excluded from the analysis. The aim of our analysis was to compare clinical outcomes of metastatic GC pts receiving first line CT according to histological classification (overall survival: OS and Progression Free Survival: PFS). Results: We analyzed 170 pts. Histological diagnosis was as follows: 24.1% (n=41) signet ring cell, 54.4% (n=92) diffuse type, 21.1%(n=37) intestinal type. Pts received a fluoropyrimidine-based doublet containing cisplatin, oxaliplatin or irinotecan; in three drugs regimen anthracycline was added. In diffuse type subgroup OS was: 11.3 months with oxaliplatin based CT, 7.3 months in cisplatin and 6.2 months in irinotecan (p=0.0054); PFS was 5.2, 3.5 and 4.4 months for oxaliplatin, cisplatin and irinotecan based CT respectively (p=0.0036). In signet ring cell carcinomas OS was 12.1 months with oxaliplatin 13.9 with irinotecan, and 5.6 months with cisplatin (p=0.04), and PFS was 6.5, 8.5 and 2.9 months in pts treated with oxaliplatin, cisplatin and irinotecan respectively (p=0.0008). Among pts with intestinal type we did not detect any significant difference in term of OS and PFS comparing first line schedules. Conclusions: Based on our results, histology may be used as a simple, costless and easy tool in advanced gastric cancer treatment management. Clinical use of biomarkers (with the exception for HER2) which are being evaluated as prognostic or predictive factors in GC, is still controversial. In this scenario, the prognostic / predictive value of histology could play a significant role in treatment decision making.
GMC and NCAS agree responsibilities for their advisers ahead of revalidation
Authors: Caroline White
Journal: BMJ (2012)

The General Medical Council (GMC) and the National Clinical Assessment Service (NCAS) have agreed a set of five joint principles in a bid to clarify their respective roles for dealing with doctors with performance concerns.

The principles, which are set out in a memorandum of understanding, are intended to govern the relationship between NCAS …
Scrapping GPs’ independent status could solve problems in general practice, academic argues
Authors: Matthew Limb
Journal: BMJ (2013)

Many problems in general practice could be solved if GPs gave up their independent contractor status or worked under a radically altered funding model, a leading GP academic has argued.

Azeem Majeed, head of the department of primary care and public health at Imperial College London, said that GPs were being blamed for wider NHS shortcomings when radical reforms were needed.

Majeed, who is also a part-time GP in south London, set out his case in an editorial1 published in the Journal of the Royal Society …
Review: In older adults, exercise alone and some combination interventions reduce injurious falls vs usual care
Authors: William J. Hall
Journal: Annals of Internal Medicine (2018)

ACP Journal Club20 March 2018Review: In older adults, exercise alone and some combination interventions reduce injurious falls vs usual careWilliam J. Hall, MD, MACPWilliam J. Hall, MD, MACPUniversity of Rochester School of Medicine and Dentistry, Rochester, New York, USA (W.J.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-168-6-027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationTricco AC, Thomas SM, Veroniki AA, et al. Comparisons of interventions for preventing falls in older adults: a systematic review and meta-analysis. JAMA. 2017;318:1687-99. https://pubmed.ncbi.nlm.nih.gov/29114830Clinical Impact RatingsGIM/FP/GP: Geriatrics: References1 Bergen G, Stevens MR, Burns ER. Falls and fall injuries among adults aged ≥ 65 years–United States, 2014. MMWR Morb Mortal Wkly Rep. 2016;65;993-8. [PMID: 27656914] Google Scholar2 Larson EB. Evidence supports action to prevent injurious falls in older adults [Editorial]. JAMA. 2017;318:1659-60. [PMID: 29114812] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Rochester School of Medicine and Dentistry, Rochester, New York, USA (W.J.H.)This article was published at Annals.org on 6 March 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 March 2018Volume 168, Issue 6Page: JC27KeywordsElderlyExerciseFallsGeriatricsHospitalizationsNetwork analysisOdds ratioQuality improvementResearch designSystematic reviews ePublished: 20 March 2018 Issue Published: 20 March 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
My first year as a doctor
Authors: Ali S Hassan, Tabassum A Khandker, Clinton Vaughn, Omar Barbouti, Nida Gul Ahmed, Yasmin Akram
Journal: BMJ (2010)

Last August, six medical graduates wrote an account for <i>BMJ Careers</i> about their first day as doctors. One year on they reflect on what they wrote and how their perceptions have changed over the first year
Medical acupuncture foundation course
Authors: Zishan Ali
Journal: BMJ (2010)

I have always been interested in Western medical acupuncture and its potential role in primary care. Patients often ask for alternative treatment options that don’t involve drugs. The British Medical Acupuncture Society course was recommended to me by a couple of colleagues, one who had already been on it and another who was planning to attend it. The aspect of acupuncture that most interested me was its use in the management of musculoskeletal pain, because I felt that there is scope for its use in primary care.

The course is run by the British Medical Acupuncture Society. It takes place over …
HCC incidence in patients treated with DAA for chronic hepatitis C compared to PEG-interferon/ribavirin treated patients: HORRID study.
Authors: Alexander Rheinhard Siebenhuener
Journal: Journal of Clinical Oncology (2018)

219 Background: Direct antiviral agents (DAA) have revolutionized the treatment of chronic hepatitis C (CHC) and have quickly become the standard of care. Despite this effective treatment CHC patients are known to have an increased risk to develop hepatocellular carcinoma (HCC). The incidence of HCC is about 3-5% in this population and regular surveillance is highly recommended. To date the correlation between eradication of viral hepatitis and the risk of HCC development in CHC patients is not well understood. Surprisingly several studies show a frequent incidence of HCC after DAA treatment. The aim of this study is to demonstrate treatment of CHC with DAA or PEG-INF/RBV and patients' outcome into context of HCC development and success of CHC treatment. Methods: We performed a retrospective analysis of 300 patients that received treatment with PEG-IFN and RBV and 346 patients that received DAA treatment for CHC in our institution. HCC viral load, genotype, treatment type, duration and outcome, fibrosis grade, age, gender, BMI as well as AFP and serum albumin were recorded. A Cox-proportional hazard model was fit to compare survival in patients treated with PEG-IFN and patients that received DAA regarding HCC, need for liver transplantation and death. Results: While death and need for liver transplantation was not different in both groups, there was a significant difference in the incidence of HCC. Patients that received DAA developed HCC post-treatment significantly earlier than PEG-IFN/RBV treated patients. In a Cox-proportional hazard model, DAA treatment remained a significant predictor for occurrence of HCC after adjusting for confounders. Conclusions: Our data demonstrates a significantly increased incidence of HCC in patients that were cured from CHC with DAA compared to patients after PEG-IFN/RBV treatment. In contrast to earlier studies using historic data, our study limited confounders by directly comparing HCC differential incidence of HCC after PEG-INF/RBV and DAA treatment within the same institution. Further prospective studies are warranted to precisely determine the HCC risk in patients that receive DAA for CHC.
"Why my parent is ill?" A specific, multidisciplinary intervention to enhance comunication to cancer patients' children.
Authors: Marina Elena Cazzaniga, Francesca Gallina, Marco Bani, Francesca Riva, Lorenzo Tagliabue, Paolo Bidoli, Moncilo Jankovic, Claudio Verusio, Umberto Mazza
Journal: Journal of Clinical Oncology (2015)

e20581 Background: Different studies underline the efficacy of an open communication with children about the parent’s illness to reduce the family distress and the difficulties of parents to explain their illness to children. This multidisciplinary intervention is addressed to cancer patients and their underage children. Aims of the project are: - to inform improving the children’s knowledge of their parent’s cancer, - to facilitate children coping with the illness, - to enhance parents’ competence and communication about cancer in the family. Methods: At the beginning of the parent’s cancer treatment, the pediatric hemato-oncologist and the psychologist, without parents’ presence, explain to children, with the support of metaphors and images, the parent’s disease and understand their needs. Then counseling sessions to parents are organized to increase the parental competence. To evaluate the intervention it has been realized a specific questionnaire, administered to parents 9 months after the communication to children, that describes the family atmosphere, the parents’ satisfaction, the level of communication and the children’s psychological conditions after the intervention. Results: since 2012 33 families participated in the program. Preliminary and partial analyses of 27 questionnaires underline the presence of more collaboration (18.5% totally, 40.7% very, 29.6% quite and 11.2% no more) in the family and the parents’ satisfaction (33.3% very satisfied and 66.7% extremely). 63% of parents showed that in their family, after the intervention, it was totally possible to have an open communication about the cancer. Regards children’s conditions the majority of parents noted that their sons weren’t more irritable (55.6% never, 25.9% rarely, 7.4% sometimes and 11.1% often), anguished (70.4% never, 18.5% rarely, 7.4% sometimes, 3.7% often), depressed (92.6% never, 7.4% rarely) and that children didn’t have more aggressive behaviors (81.5% never, 11.1% rarely, 3.7% sometimes, 3.7% often). Conclusions: The project shows the advantages of the direct engagement of children in the communication of parent’s cancer to facilitate the relationship and to reduce the family distress.
Rise in hospital workload outstrips growth in medical workforce
Authors: Abi Rimmer
Journal: BMJ (2017)

The rise in outpatient appointment numbers is outstripping the growth in the number of hospital doctors, data from NHS Digital show.

Between 2005 and 2015, the number of full time equivalent consultants increased by 45%, from 29 613 to 42 903. Over the same period, outpatient appointment attendances increased by 79%, from 50 038 667 in …
Length of surgical training must be reviewed, BMA annual meeting hears
Authors: Abi Rimmer
Journal: BMJ (2014)

Surgical training must be reviewed by the General Medical Council, the BMA, and the royal colleges to decide whether it is long enough to train an NHS consultant surgeon, delegates at the BMA’s annual representative meeting have said.

Delegates voted in favour of a motion that called on the BMA, the GMC, the surgical royal colleges, the Joint Committee on Surgical Training, and the surgical specialty associations to determine whether the current length of training was “fit for purpose.”

The motion included concerns that “the implementation of Working Time Regulations (EWTR) …
ASSOCIATIONS BETWEEN CIRCULATING LEVELS OF PLASMA OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 AND VASCULAR OUTCOMES IN AFRICAN AMERICAN DIABETIC PATIENTS
Authors: Ayobami Eluwole, Ajibola M. Adedayo, Fasika Tedla, Arye Kremer, Nicole Mastrogiovanni, Mohammed Afzal, Carl Rosenberg, Paul Dreizen, John La Rosa, Mohamed Boutjdir, Mary Ann Banerji, Clinton Brown, Moro Salifu, Jason Lazar, Ahmed Bakillah
Journal: Journal of the American College of Cardiology (2018)
Pay body condemns application of efficiency savings to GP contract uplift
Authors: Helen Jaques
Journal: BMJ (2012)

The Review Body on Doctors’ and Dentists’ Remuneration (DDRB) has branded the Department of Health’s decision to apply efficiency savings to the formula used to calculate contract uplifts for general practitioners as “both unnecessary and inappropriate.”

The independent pay review body argues that GPs operate as small businesses in a competitive market and therefore already have an incentive to achieve efficiency savings where possible.

The impact of any efficiency savings that GPs make will subsequently become apparent in the data used in the formula, so it is inappropriate to apply efficiency savings to the funding formula itself, the organisation says.

The …