tbuckley/cabot-search huggingface dataset:
Neoadjuvant FOLFIRINOX and IMRT concurrent with FDR-gemcitabine in patients with borderline resectable pancreatic cancer (BRPC).
Authors: Nguyen H. Tran, Vaibhav Sahai, Kent A. Griffith, Hari Nathan, Ravi Kaza, Kyle Clifford Cuneo, Christopher J Sonnenday, Clifford Cho, Theodore Steven Lawrence, Mark Zalupski
Journal: Journal of Clinical Oncology (2018)

381 Background: Preoperative therapy in BRPC is intended to increase the likelihood of R0 resection although an optimal regimen is yet to be defined. Methods: Patients (pts) with BRPC (NCCNv.2.2010 guidelines) and ECOG PS 0-1 were enrolled in a single-institution, phase II trial (NCT01661088). Pts received FOLFIRINOX x 6, followed by IMRT (50 Gy in 25 fractions) concurrent with FDR-gemcitabine 1 g/m2 on days 1, 8, 22, 29. Two additional FDR-gemcitabine infusions completed pre-operative treatment. Pancreatic protocol CT scans (dual phase, 0.65 mm slices) were performed after 4 infusions of FOLFIRINOX, 3 weeks after IMRT, and at treatment completion. Pts without distant disease were offered surgical exploration. The primary objective was to determine R0 resection rate. Secondary objectives included progression free survival (PFS), overall survival (OS), response rate and safety. Results: A total of 25 pts (64% men) median age 60 years (range 47-77) were enrolled from 11/2011 through 01/2017. Twenty-one (84%) pts completed FOLFIRINOX and 19 (76%) all protocol therapy. Treatment-related grade 3-4 adverse events ( &gt; 10%) included neutropenia (40%), nausea/vomiting (28%), diarrhea (16%) and fatigue (12%). One early death and 1 discontinuation due to toxicity occurred during FOLFIRINOX. Response to pre-op therapy included 11 PR, 9 SD, 3 PD and 2 NE. Of 25 treated pts, 18 (72%) had laparotomy and 13 (52%) underwent resection (all R0). The median PFS and OS were 18.1 (95% CI, 10.6 to 25.1) and 24.2 (95% CI, 12.6 to 40.0) months, respectively. The median OS for R0 resected pts was 37.1 (95% CI, 15.4 – not reached) months. Conclusions: Neoadjuvant therapy with FOLFIRINOX, followed by IMRT with concurrent FDR-gemcitabine in BRPC is feasible and tolerated. While R0 resection rate was not obviously improved, OS of the entire cohort and especially in R0 resected pts was favorable. Clinical trial information: NCT01661088.
Atezolizumab (atezo) vs. chemotherapy (chemo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): Immune biomarkers, tumor mutational burden (TMB), and clinical outcomes from the phase III IMvigor211 study.
Authors: Thomas Powles, Yohann Loriot, Alain Ravaud, Nicholas J. Vogelzang, Ignacio Duran, Margitta Retz, Ugo De Giorgi, Stephane Oudard, Aristotelis Bamias, Hartmut Koeppen, Ning Leng, Edward E. Kadel, Priti S. Hegde, Na Cui, Xiaodong Shen, Christina Louise Derleth, Marjorie C. Green, Romain Banchereau, Sanjeev Mariathasan, Michiel Simon Van Der Heijden
Journal: Journal of Clinical Oncology (2018)

409 Background: IMvigor211 is a global study of atezo vs chemo in platinum-treated mUC. The study did not meet its primary endpoint of overall survival (OS) in programmed death-ligand 1 (PD-L1)–selected patients (pts), 1 but exploratory analyses showed improved OS for atezo in the intent-to-treat (ITT) population. Here we compare clinical outcomes in ITT and prespecified PD-L1 subgroups with those in subgroups defined by immune transcriptional gene expression (tGE) signatures and TMB. Methods: Pts with ≤ 2 prior lines of therapy for mUC who progressed during or following platinum treatment were randomized 1:1 to atezo or chemo (vinflunine, paclitaxel or docetaxel, per physician). The primary endpoint was OS, hierarchically compared between treatment arms in PD-L1–selected and ITT pts. Planned exploratory biomarker analyses included tGE (RNA-seq) and TMB (FoundationOne). Results: The ITT population included 931 pts (atezo arm, 467; chemo arm, 464), and biomarker-evaluable subgroups were representative of the ITT population. PD-L1 expression positively correlated with tGE (R = 0.61) but not TMB (R = 0.13). OS and hazard ratios (HRs) are listed in the Table. Conclusions: In this randomized Phase III study, we show that high PD-L1 and high tGE are associated with improved outcomes with both chemo and atezo. In contrast, higher TMB predicted OS in favor of atezo; however, clinical benefit with atezo was also seen in the ITT population. Clinical trial information: NCT02302807. [Table: see text]
Private school pupils still disproportionately represented in medical colleges
Authors: Caroline White
Journal: BMJ (2013)

Private school pupils continue to be disproportionately represented among medical students, show figures from the Higher Education Statistics Authority.

A quarter of medical students in the first year of their first degree have had a private school education, despite these schools educating just 7% of pupils across the UK.1 From 2007-08 to 2011-12 the proportion of medical students who had been privately educated fell by just one percentage point, from 26.9% to 25.9%.

Over the same period the proportion of students of white ethnic background rose from 71.3% to 72.5% and that of students of Asian ethnic background fell from 20.6% to 18.9%. The proportion of medical students of black ethnic background rose from 2.5% in 2007-08 …
I have just started my AS subjects (in biology, chemistry, and maths) and would like to know if three subjects at AS and A2 next year are sufficient to apply for a medical degree at university? How can I increase my chances of getting into medical school?
Authors: Paul O'Neill
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>
CLINICAL OUTCOMES OF DIFFERENT CONTEMPORARY DRUG-ELUTING STENTS IN PATIENTS WITH AND WITHOUT DIABETES MELLITUS: MULTIGROUP PROPENSITY-SCORE ANALYSIS USING DATA FROM THE STENT-SPECIFIC, MULTI-CENTER, PROSPECTIVE REGISTRIES
Authors: Duk-Woo Park, Osung Kwon, Jung-Bok Lee, Cheol Hyun Lee, Do-Yoon Kang, Pil Hyung Lee, Jung-Min Ahn, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
High Rates of Violent Death Among Rohingya Refugees
Authors: M. J. Friedrich
Journal: JAMA (2018)

Violence was the direct cause of death for at least 6700 Rohingya civilians, including 730 children, living in the state of Rakhine, Myanmar, in the initial 31 days following the latest upsurge of unrest that began on August 25, 2017, according to surveys conducted by Médecins Sans Frontières (MSF).
German health service research group IQUO present daily routine results of adjuvant instillation therapy for the intermediate risk group NMIBC in out patient office management.
Authors: Gerson Luedecke, Goetz Geiges, Monica Lange, Matthias Schulze
Journal: Journal of Clinical Oncology (2018)

423 Background: The international guidelines for bladder cancer define adjuvant chemo-instillation therapy in intermediate risk NMIBC as standard of care. The health service research foundation IQUO has prospectively checked how strictly German urologists identify and follow the guidelines for intermediate risk BC with adjuvant Mitomycin C indication in daily routine. Methods: Via the Internet based data collection platform of the IQUO uro-oncology specialized office based urologists collected from 2012 to 2015 prospectively adjuvant NMIBC patients treated with Mitomycin C 20mg/20ml in a cohort analysis. Results: 854 patients were included in this study (19% female, 81% male). Median age 73 years, range (30-93). Recurrence risk was classified in 18.7% high-, 33.6% intermediate-, 37.2% low- and 10.5% minimal risk. Progression risk was classified in 3.4% high-, 16.7% intermediate-, 53.3% low- and 26.6% minimal risk. Early instillation was performed in 54% of the patients. The starting point of adjuvant instillation varied form day 1 after TUR to longer than 21 days. The induction phase varied from 4 weeks in minimum (12.9%) to 6 weeks (31.1%), 8 weeks (34%), 12 weeks (4.9%) and 17.1% individually. The maintenance was given in 68.9% of the patients varying from 3 month up to 3 years. Differences in treatment between the genders were not observed. The analysis of accordance to the guidelines in respect to adjuvant instillation in intermediate risk NMIBC showed a 70.7% accordance, an over treatment of 10.5%, and an under treatment of 18.7%. Conclusions: We have found a tremendous heterogeneity in the practiced adjuvant Chemo-Instillation therapy in NMIBC patients. This included early instillation post-operatively, adjuvant onset time point and duration of induction therapy and maintenance. The consequence of this health service research results is that standardization and education is one of our main duties for the near future to ensure consequent, complete and correct adjuvant treatment in intermediate NMIBC patients to ensure effectiveness.
MSc in surgical technology
Authors: Irfan Halim
Journal: BMJ (2005)

OBJECTIVES--To measure effects on terminally ill cancer patients and their families of coordinating the services available within the NHS and from local authorities and the voluntary sector. DESIGN--Randomised controlled trial. SETTING--Inner London health district. PATIENTS--Cancer patients were routinely notified from 1987 to 1990. 554 patients expected to survive less than one year entered the trial and were randomly allocated to a coordination or a control group. INTERVENTION--All patients received routinely available services. Coordination group patients received the assistance of two nurse coordinators, whose role was to ensure that patients received appropriate and well coordinated services, tailored to their individual needs and circumstances. MAIN OUTCOME MEASURES--Patients and carers were interviewed at home on entry to the trial and at intervals until death. Interviews after bereavement were also conducted. Outcome measures included the presence and severity of physical symptoms, psychiatric morbidity, use of and satisfaction with services, and carers9 problems. Results from the baseline interview, the interview closest to death, and the interview after bereavement were analysed. RESULTS--Few differences between groups were significant. Coordination group patients were less likely to suffer from vomiting, were more likely to report effective treatment for it, and less likely to be concerned about having an itchy skin. Their carers were more likely to report that in the last week of life the patient had had a cough and had had effective treatment for constipation, and they were less likely to rate the patient9s difficulty swallowing as severe or to report effective treatment for anxiety. Coordination group patients were more likely to have seen a chiropodist and their carers were more likely to contact a specialist nurse in a night time emergency. These carers were less likely to feel angry about the death of the patient. CONCLUSIONS--This coordinating service made little difference to patient or family outcomes, perhaps because the service did not have a budget with which it could obtain services or because the professional skills of the nurse-coordinators may have conflicted with the requirements of the coordinating role.
Single-dose radiotherapy (SDRT) in the management of intermediate risk prostate cancer: Early results from a phase II randomized trial.
Authors: Carlo Greco, Nuno Pimentel, Oriol Pares, Vasco Louro, Zvi Y. Fuks
Journal: Journal of Clinical Oncology (2018)

128 Background: To report initial response, acute treatment-related toxicity and patient-reported quality of life (QoL) after 24Gy SDRT derived from a randomized Phase II study of patients with intermediate-risk adenocarcinoma of the prostate (NCCN definition). Methods: Between November 2015 and December 2016, 30 hormone-naïve patients were enrolled in an IRB-approved prospectively randomized phase II study to receive either 45Gy in 5 consecutive daily fractions (Hypo-SBRT) or 24Gy SDRT. Treatment was based on VMAT-IGRT with urethral sparing via a dose-painting technique and real-time motion management with beacon transponders. The PTV included the MR-delineated prostate gland and seminal vesicles with 2 mm margin. Precise PTV targeting and anatomical reproducibility was achieved via placement of an endorectal air-filled balloon (150 cc) and a Foley catheter. This setup also conferred organ motion mitigation, and online tracking ensured treatment delivery within the 2 mm PTV margin.. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were graded according to the NCI CTCAE v.4, and QoL was assessed by EPIC and IPSS questionnaires. Tumor response was assessed biochemically (PSA) and by follow-up MRI at 3 months after treatment and at 6 months intervals thereafter. Results: With a median follow-up of 16 months (range, 11-24), no grade ≥2 acute GI or GU toxicities were observed in either group. There were no significant differences in mean EPIC scores in all domains. An initial 6% and 8% drop in the EPIC urinary domain score occurred in the hypo and SDRT arm respectively, returning to baselines by 3 months. . PSA reduction kinetics were similar between the two regimens, reaching ≤1 ng/mL by 18 months. Of note, all cases, regardless of treatment regimen, converted to non-detectable disease on MRI at 6 months. Patients in this trial will receive a planned 24 months post-treatment biopsy to validate treatment outcome. Conclusions: These early trial outcomes indicate that 24Gy SDRT can be consistently and safely delivered, yielding the same low acute toxicity as demonstrated with the hypo 5x9Gy schedule, and is associated with excellent QoL measures. Clinical trial information: NCT02570919.
Decreased cellular and humoral immunity in patients with breast cancer.
Authors: Eva Zavadova, Jan Spacek, Michal Vocka, Bohuslav Konopasek, Lubos Petruzelka
Journal: Journal of Clinical Oncology (2018)

4 Background: A growing body of evidence over the past few years suggests that the presence of immune elements within the tumor or in the tumor stroma has prognostic and predictive value in breast cancer. Immunotherapy is successfully used in many types of cancer, and modulation of immune system became standard part of the cancer patients treatment Responses in breast cancer have been more recently reported. However it has yet to be determined whether predictable biomarkers of response can be identified. Therefore in recent years, research focused on a precise description of the status and function of the immune system.The purpose of the study was to monitor immune responses in patients with breast cancer, particularly the examination of cellular (CD4, CD8, B cells) as well as humoral immunity (IgG, IgG1, IgG2, IgG3, IgG4. It appears that a factor contributing to the immunosupression may be a transforming factor-beta (TGF-beta).It is highly immunosuppressive factor that inhibits the natural and specific immunity against tumors. Methods: 50 patients included in the research project were implemented routine cancer treatment. Basic parameters (histological type and grade, the degree of expression of ER and PR, HER2, and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. Anti-tumor cellular immunity (CD4, CD8, CD19) was measured by flow citometry, humoral immunity (IgG, IgG1, IgG2, IgG3, IgG4) was measured and TGF beta and VEGF production was monitored by ELISA. Results: In breast cancer patients mainly depression in cellular immunity was found. Immunglobuline plasma level was decreased as well (mainly IgG4 subtype). TGF beta as well as VEGF plasma level were increased. Most patients have shown clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections).Those patient could benefit from immunomodulation. Conclusions: The state of anticancer immunity could contribute to the selection of targeted immune therapy in breast cancer patients and to help to find optimal combination of immunotherapy. This project was supported by governmental grant AZV CR 15-28188A.
Mental health workforce will suffer under Brexit, providers warn
Authors: Abi Rimmer
Journal: BMJ (2018)

Mental health service providers have warned that Brexit could prevent them from recruiting the staff they need.

The Mental Health Network, which represents mental health and learning disability service providers in England, said that one in 10 posts in specialist mental health services was currently vacant.

Sean Duggan, chief executive of the network, warned that the situation will get worse …
Exercise and the older brain: Trump should walk rather than take the buggy on the golf course
Authors: Damian M Bailey, Thomas A Calverley, Martin Steggall
Journal: BMJ (2018)

Although President Donald Trump does not seem to have any cognitive deficits,1 he should be made aware of the brain’s susceptibility to neurodegeneration and decline in cognitive function with age. But there is good news for Trump: regular physical activity can decrease the risk of cognitive impairment and dementia in elderly people.2 Although the underlying mechanisms are not entirely …
Normal Tissue Complication Probability (NTCP) model for erectile dysfunction (ED) following external beam radiotherapy (RT) for prostate cancer.
Authors: Julia Murray, Clare Griffin, Emma Hall, Jamie Dean, Isabel Syndikus, John Staffurth, Helen Mayles, Sarah Gulliford, David P. Dearnaley
Journal: Journal of Clinical Oncology (2018)

135 Background: ED remains a common toxicity of prostate RT despite technological advances. Penile bulb (PB) dose has been proposed as a predictor of ED post RT. The main objective of this study was to develop NTCP models for ED. Methods: 162 men treated within the CHHiP IGRT substudy (CRUK/06/16) had baseline clinical data, PB dosimetric data &amp; evaluation of ED using EPIC-26 at least 3 years post RT. Planning CT and reference dose distributions were imported into analysis software (VODCA, MSS GmbH) and PB retrospectively contoured by one clinician. The defined endpoint (severe ED) was a standardised average value of 0-33 for EPIC-26 sexual domain. Predictive models of ED were generated using PB dose in EQD2 (α/β ratio = 3Gy) &amp; clinical data (age, diabetes, hypertension, NCCN risk group, baseline PSA, hormone therapy, IGRT, margin size, PB volume). Multivariate logistic regression method using resampling methods was applied to select model order and parameters. Models were fitted using logistic regression of the form Probability = e A(x) /1+e A(x) , where A(x) = constant + sum of (variables * associated regression coefficients). Model performance was evaluated through area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow (HL) goodness-of-fit test. Results: 101/162 (62%) men had severe ED with statistically significant difference in PB max and mean dose between those patients with or without severe ED (max: 61.8Gy vs 43Gy &amp; mean: 27.4Gy vs 14Gy respectively; p = 0.001). In the univariate analyses, age, diabetes, risk group, PB mean and max doses were significantly associated with EPIC calculated severe ED. The optimal NTCP model (AUC 0.78; CI 0.71-0.86: p for HL = 0.75) for EPIC calculated severe ED included age, PB mean dose and diabetes where A(x) = -10.13+(0.14*age)+(0.03*PB mean dose)+(2.88 if diabetic). A comparable model using clinician completed outcomes will be reported. Conclusions: This study provides the first known clinical prediction model for ED including PB dose, with good model performance. The determined predictors for the NTCP model of severe ED in this cohort were PB mean dose, age &amp; diabetes. External validation of this model is desirable. Clinical trial information: 97182923.
LOW HEART RATE IN COMBINATION WITH LOW BLOOD PRESSURE IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE ASSOCIATES WITH INCREASED RISK OF CARDIOVASCULAR MORTALITY
Authors: Masaru Hiki, Hiroshi Iwata, Kiyoshi Takasu, Go Ishikawa, Yuichi Chikata, Takatoshi Kasai, Tetsuro Miyazaki, Kenji Inoue, Yasumasa Fujiwara, Masataka Sumiyoshi, Hiroyuki Daida
Journal: Journal of the American College of Cardiology (2018)
GP workforce gap should be filled by UK medical graduates rather than overseas doctors, says Migration Advisory Committee
Authors: Abi Rimmer
Journal: BMJ (2015)

General practice does not need to be added to a list of shortage occupations, as gaps can be filled by UK graduates rather than by doctors from overseas, the Migration Advisory Committee has said.

The shortage occupation list is an official list of jobs for which not enough UK workers are available to fill the vacancies. Employers who want to recruit someone from outside the European Economic Area for a job that is on the list can do so without carrying out a resident labour market test.

The committee said that general practice was currently 400 trainees short of the …
Locum numbers fall in secondary care as permanent doctor numbers continue to grow
Authors: Helen Jaques
Journal: BMJ (2012)

In January 2012 a total of 2279 locum doctors were employed by NHS hospitals and community health services, down 255 (10%) from 2534 in January 2011.

However, the number of non-locum doctors rose by 1898 (2.1%), from 90 382 to 92 280, in the same period.

In particular, the number of non-locum registrars rose …
The coupling of MDSCs with a computational analytic method to detect solid tumors.
Authors: George Dominguez, Cyrus Sholevar, Alexander Polo, John Roop, Anthony Campisi, Dmitry Gabrilovich, Frank J. Rauscher, Amit Kumar
Journal: Journal of Clinical Oncology (2018)

24 Background: Myeloid-derived suppressor cells (MDSCs) are key contributors in supporting tumor progression and tumor escape through their ability to suppress anti-tumor responses mediated through T cell and natural killer (NK) cell activity. Several studies have demonstrated their utility as indicators of tumor progression and possible predictors of clinical outcomes, but there is significant overlap with healthy individuals preventing discrete and accurate calls. The objective of our study was to create a non-invasive cancer detection assay that analyzes flow cytometry data in an objective method using an artificial neural network (NN) to distinguish between cancer patients (CPs) and healthy donors (HDs) based upon the flow cytometry profiles of MDSCs and other leukocytes. Methods: We used standard multiparametric flow cytometry techniques to immunophenotype MDSCs and other leukocytes found in the peripheral blood of 52 biopsy-confirmed CPs with solid tumors and 70 HDs. A series of NNs utilizing pattern recognition computational algorithms are then created using three data sets: 1) the training set - this ‘teaches’ the two output categories of cancer and not cancer, 2) the validation set – this uses backpropagation to improve the accuracy of the trained networks, and 3) the testing set – this is used to rank the trained networks against each other. Finally, a naïve testing set is then used to determine the overall sensitivity and specificity for the top-ranking networks. Results: Using traditional flow cytometry gating methods to analyze MDSCs as a biomarker for cancer detection, it is difficult to achieve both high sensitivity and specificity due to the substantial overlap with healthy individuals. Here, we incorporated a standard 12 marker flow cytometry assay with NN technology to achieve a sensitivity of 92.3% and a specificity of 90.0% with an area under the ROC curve (AUC) of 0.9477. Conclusions: Pairing the advanced analytical capabilities of our NN with surface biomarker based analysis of MDSCs and certain leukocytes measured in peripheral blood has enabled us the ability to objectively identify patterns indicative for the existence of a solid tumor.