tbuckley/cabot-search huggingface dataset:
Will second-line nonsteroidal antiandrogen drugs (NSAA) after the failure of bicalutamide affect the therapeutic efficacy of the sequential abiraterone treatment?
Authors: Jinge Zhao, Guangxi Sun, Xingming Zhang, Pengfei Shen, Junru Chen, Hao Zeng
Journal: Journal of Clinical Oncology (2018)

337 Background: Even in the era of novel targeted agents, second-line antiandrogens still have its effect on treating metastatic castration-resistant prostate cancer (mCRPC), especially for patients from undeveloped areas. Yet, it’s still uncertain if the prior use of second-line Non-steroidal antiandrogen Drugs (NSAA) would impact the efficacy of the sequential abiraterone (Abi) therapy. Methods: Eighty-seven patients from 2015 to 2017 were studied. All men were diagnosed with metastatic prostate cancer, and administrated with maximal androgen blockade (surgical or medical castration plus bicalutamide). After the median 32.0-Mo follow up, mCRPC was confirmed in the whole cohort. Abi was then administrated in these patients. Among them, 21 men previously received flutamide (FLU) as second-line NSAA hoping to postpone the initiation of the more expensive treatment. Therapeutic efficacy of Abi was analyzed and compared between those with and without prior second-line NSAA by Kaplan-Meier curves, Log-rank test and Cox regression models. Results: For patients with mCRPC, the prior exposure to FLU had no effect on the sequential treatment of Abi, in terms of either PSA progression-free survival (PSA-PFS, p = 0.967), radiographic progression-free survival (rPFS, P = 0.272), overall survival (OS, p = 0.606), or PSA response ( p = 0.370). However, when bringing ahead the observation point to the time of CRPC, those with second-line FLU showed better survival than those without, in either PSA-PFS (15.1 vs. 12.2-Mo, p = 0.120), rPFS (23.3 vs. 18.2-Mo, p = 0.029) or OS (not reach vs. 30.7-Mo, p = 0.306), though the difference of PSA-PFS and OS were not statistically significant. Conclusions: We firstly address the impact of the secondary NSAA on the efficacy of the sequential Abi treatment in mCRPC patients. Our study supported that, whether the patients received second-line NSAA prior to Abi should not be considered as an impact factor interfering physicians’ decision making of Abi treatment. Also, the switching treatment before Abi seemed to have a potential to extend the survival time of mCRPC patients by prolonging their PFS.
I am an Irish qualified and trained general practitioner, aged 63, who has worked in various countries abroad for some time. I am in good health, married, and have a young daughter. What would be the likelihood of my finding a position in a practice within 60 miles of London?
Authors: Judith Harvey
Journal: BMJ (2006)

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>
The role of proton beam therapy for patients with intermediate- and high-risk prostate cancer.
Authors: Takeshi Arimura, Naoaki Kondo, Kyoko Matsukawa, Kiyotaka Wada, Ikumi Kitano, Ikuko Chuman, Ichiro Nagata, Takashi Ogino
Journal: Journal of Clinical Oncology (2018)

97 Background: Although there are many patterns of treatment in localized prostate caner, proton beam therapy has no definite role in them. We aimed to assess the outcomes of proton beam therapy (PBT) alone for patients with intermediate- and high-risk prostate cancer, and to clarify the role of PBT in the treatments. Methods: Between Jan. 2011 and Sep. 2014, 204 patients with intermediate- and high-risk prostate cancer who declined to receive hormonal treatments until biochemical or clinical recurrence were enrolled in the study. All patients were irradiated a 70-78 GyE in 28-39 fractions, and pre-treatment risk groups were classified in accordance with the D’Amico criteria. The 5-year (biochemical or clinical) recurrence-free survival (RFS), late gastrointestinal (GI) and genitourinary (GU) toxicity (NCI-CTCAE ver.4.0) were evaluated. We conducted a survey on sexual quality of life (QOL) every six months to evaluate any long-term damage to the sexual function using the Expanded Prostate Cancer Index Composite (EPIC). Results: The mean age and the follow-up period were 66 (range: 39-86) and 52 months (range: 24-76 months), respectively. The 5-year RFS rates in intermediate- (n = 112) and high- (n = 92) risk groups were 96.9% and 83.4%, respectively. There was a significant difference between the two groups (p = 0.002). The incidence of grade 2+ GI and GU toxicity were 4% and 3%, respectively. We found a significant difference in the GI toxicity between the two radiation protocols of 78GyE/39fractions (n = 6, 11%) and 70GyE/28fractions (n = 0, 0%) (p &lt; 0.01). A 5.8% decrease in average after adjusting for aging was found in sexual summary score in six years after treatment, which was equivalent to aging of three years. Conclusions: Proton beam therapy alone demonstrated favorable results in patients with intermediate- and high-risk prostate cancer. Although more patients and longer follow-up are necessary to confirm the outcomes, these results suggested a hypothesis that proton beam therapy might not require androgen deprivation therapy in the treatment of localized prostate cancer, which could lead to a possibility of preserving of sexual function. Clinical trial information: MPTRC-N2 and N3.
All GPs should treat mental health problems so patients are not “ghettoised,” commissioner says
Authors: Matthew Limb
Journal: BMJ (2015)

All GPs should be trained to treat mental health problems so that patients are not “ghettoised” or “siphoned off” to practitioners with a special interest, a mental health commissioner has said.

Lise Hertel, clinical lead for mental health at Newham Clinical Commissioning Group, in east London, said that mental health should be every practitioner’s concern. “I really strongly believe all GPs ought to be dealing with mental health problems, not ghettoising our patients,” she said. Training all GPs in mental health would also help them identify and pick up earlier on patients’ physical health needs and prevent some GPs regarding mental health as if it was “not their problem,” she argued.

Hertel spoke during a King’s Fund debate on 20 January highlighting key issues …
Campaigners win right to challenge NHS England over accountable care organisations
Authors: Clare Dyer
Journal: BMJ (2018)

JR4NHS, a group of campaigners including the renowned cosmologist Stephen Hawking, have won permission to launch a High Court challenge to NHS England’s plans to go ahead with accountable care organisations (ACOs).

Mr Justice Waller ruled that JR4NHS’s application arguing that the plans are unlawful can go to a full hearing as soon as possible after 14 March.

The health and social care secretary, Jeremy Hunt, has conceded one of the campaign’s points in agreeing not to go …
PROGNOSTIC VALUE OF LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN PATIENTS WITH BICUSPID AORTIC VALVE DISEASE AND PRESERVED LEFT VENTRICULAR EJECTION FRACTION
Authors: William K.F. Kong, Vasileios Kamperidis, Madelien Regeer, Arnold Ng, Miriam Shanks, Kian Keong Poh, Bogdan Popescu, Philippe Van Rosendael, Victoria Delgado, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2018)
LONG-TERM OUTCOME OF MEDICAL TREATMENT FOR CHRONIC ISCHEMIC MITRAL REGURGITATION
Authors: Duk-Hyun Kang, Ran Heo, Seung-Ah Lee, Sahmin Lee, Dae-Hee Kim, Jong-Min Song, Kee-Joon Choi, Jae-Kwan Song, Joo-Hee Zo
Journal: Journal of the American College of Cardiology (2018)
Prognostic model for high-tumor-burden follicular lymphoma integrating baseline and end-induction PET: a LYSA/FIL study
Authors: Anne Ségolène Cottereau, Annibale Versari, Stefano Luminari, Jehan Dupuis, Loïc Chartier, René-Olivier Casasnovas, Alina Berriolo-Riedinger, Massimo Menga, Corinne Haioun, Hervé Tilly, Vittoria Tarantino, Massimo Federico, Gilles Salles, Judith Trotman, Michel Meignan
Journal: Blood (2018)
PERCUTANEOUS VENTRICULAR ASSIST DEVICE VERSUS INTRA-AORTIC BALLOON PUMP FOR HEMODYNAMIC SUPPORT IN PATIENTS WITH CARDIOGENIC SHOCK: INSIGHTS FROM NATIONWIDE INPATIENT SAMPLE
Authors: Elena Dolmatova, Kasra Moazzami, Pallavi Solanki, James Maher, Marc Klapholz, Alfonso Waller
Journal: Journal of the American College of Cardiology (2018)
Abstract P1-07-33: Impact of family history of breast and/or ovarian cancer in triple negative breast cancer
Authors: Z Morante, G De la Cruz-Ku, J Pinto, D Enriquez, M Lujan, R Luque, E Eyzaguirre, A Saavedra, H Fuentes, S Neciosup, H Gomez
Journal: Cancer Research (2018)

Abstract Background: A family history of breast and/or ovarian cancer (FHBOC) is a risk factor for breast cancer. The influence of FHBOC in the prognosis of triple-negative breast cancer (TNBC) is controversial. The aim of this study was to analyze the impact of FHBOC on the prognosis in TNBC patients. Methods: We retrospectively reviewed a database of patients diagnosed of TNBC (period 2000-2014) and treated at “Instituto Nacional de Enfermedades Neoplasicas”. The patients were divided into two groups: with FHBOC and non-FHBOC. The clinical features and prognosis between groups were compared. Disease-free survival (DFS) and overall survival (OS) differences were calculated by the Kaplan-Meier Method and differences were evaluated by the Log- Rank test. Prognostic factors were identified by the Cox regression analysis. Results: Overall, 266 out of 2007 TNBC patients, had +FHBOC (13.3%). The median age for the general population was 49 years. Compared with the non-FHBOC group (51.1%), the 43.8% +FHBOC were premenopausal. Prevalence of +FHBOC in a first-, second- and a third-degree relative was 26.8%, 28.5%, and 44.7%, respectively. Regarding histological subtype, invasive ductal carcinoma was the most prevalent (93.5%). Clinical stages (CS) II/III was more frequent in both groups (86.3 vs. 86.1). A total of 59% of FHBOC patients underwent surgery and 52% for non-FHBOC (p=0.029- Conservative 41.1 vs. 30.7 - Mastectomy 58.9 vs. 69.3). The median of follow-up was 9 years. DFS rate was higher in FHBOC patients (53.6% vs. 42.9%, p=0.001). OS was significantly better In the FHBOC group (Table 1). In the multivariate analysis, poor prognosis variables to DFS were an advanced age at diagnosis (≥50 years) (p=0.006) and higher clinical stage (CS I vs. CS III, p&amp;lt;0.001) while chemotherapy (CT) and radiotherapy (RT) were associated with an improved DFS. In regard to the OS, FHBOC was associated with a better prognosis (HR:0.77, 95%CI:0.62- 0.95, p=0.016). Conclusion: Our results showed a better prognosis in TNBC patients with family history of breast and/or ovarian cancer in terms of DFS and OS. Table 1. +FHBOC group (DFS/OS rates) +FHBOCnon-FHBOCTotalPDFS (%) 5-years7162630.03210-years635052 OS (%) 5-years665455&amp;lt;0.00110-years584750 Citation Format: Morante Z, De la Cruz-Ku G, Pinto J, Enriquez D, Lujan M, Luque R, Eyzaguirre E, Saavedra A, Fuentes H, Neciosup S, Gomez H. Impact of family history of breast and/or ovarian cancer in triple negative breast cancer [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 P1-07-33.
Postgraduate diploma in medical education (DipMedEd)
Authors: Jason Ward
Journal: BMJ (2005)

Healthcare professionals interested in medical education: junior staff wishing to improve their skills and experienced teachers wanting to keep up to date.

During my third and fourth years of specialist registrar training.

I am interested in teaching and was keen to know more about educational theory and gain a formal qualification.

The units vary, but around 30 hours on each …
Association between response kinetics and outcomes in relapsed/refractory multiple myeloma: analysis from TOURMALINE-MM1
Authors: Laurent Garderet, Jacob P. Laubach, Anne-Marie Stoppa, Parameswaran Hari, Michele Cavo, Heinz Ludwig, María-Victoria Mateos, Katarina Luptakova, Jianchang Lin, Godwin Yung, Helgi van de Velde, Deborah Berg, Philippe Moreau, Paul G. Richardson
Journal: Leukemia (2018)

The association between depth of response in multiple myeloma (MM) and long-term outcomes is well recognized [1][2][3].Thus, clinicians and patients are often encouraged by a rapid decrease of M-protein when treatment is initiated, and achieving ≥very-good partial response (VGPR) by 4 months of initial diagnosis has been associated with decreased mortality [4].However, little is known about the association between response kinetics and outcomes.While some reports suggest that early responders may have compromised long-term outcomes compared with late responders [5,6], these studies were limited, confined to frontline setting only, and based in the era prior to novelagent availability.Here, we evaluated progression-free survival (PFS) and duration of response (DOR) by depth of response and time to best response using data from the double-blind phase 3 TOURMALINE-MM1 trial (NCT01564537) of ixazomiblenalidomide-dexamethasone (IRd) versus placebo-Rd in patients with relapsed/refractory MM (RRMM) [7].The study demonstrated superior PFS with IRd versus placebo-Rd (median 20.6 versus 14.7 months, hazard ratio [HR] 0.74; P = 0.01) with limited additional toxicity [7], leading to the approval of ixazomib, in combination with Rd, for MM patients who had received at least one prior therapy [8,9].The TOURMALINE-MM1 study (NCT01564537) has been described previously [7].Patients with RRMM were randomized 1:1 to receive IRd (n = 360) or placebo-Rd (n = 362) until disease progression (PD) or unacceptable toxicity.Response was assessed every cycle based on central laboratory results and by Independent Review Committee (IRC) evaluation [10].The primary endpoint PFS was met at the first prespecified analysis at a median follow-up of ~15 months (median PFS, IRd versus placebo-Rd: 20.6 versus 14.7 months; HR 0.74, 95% confidence interval 0.59, 0.94, P = 0.01); this was the final statistical analysis of PFS [7].A subsequent analysis for overall survival (OS) was performed after a median follow-up of ~23 months, which included a non-inferential sensitivity analysis for PFS (median PFS, IRd versus placebo-Rd: 20.0 versus 15.9 months; HR 0.82, 95% confidence interval: 0.67, 1.0) [7].The post-hoc analyses reported herein are from the 23-month follow-up.At this analysis, median OS was not reached in either arm, and the trial is continuing in a double-blind, placebo-controlled fashion to allow survival data to mature.
Abstract IS-2: The challenge of definition and adoption; perspective from the Middle East
Authors: S Al Sukhun
Journal: Cancer Research (2018)

Abstract Cancer has become one of the leading causes of morbidity and mortality worldwide. The World Health Organization has warned the number of cancer diagnoses in the Middle East (ME) in the next two decades will nearly double unless authorities take action. This means the ME will have the highest relative increase of all regions in the world. Breast cancer is the most common cancer in ME (15%) and the second most common in terms of cancer related mortality (9%). Across the world, the cost of healthcare is rising faster than economies are growing, creating the case for value based healthcare (VBHC), with value based medicine taking center stage. VBHC helps healthcare providers manage cost increases, make the best use of finite resources and deliver improved care to patients. The challenge for effective control of cancer is multifaceted. It mandates integration of effective cancer prevention, encouraging early detection, and utilization of resource adapted therapeutic and supportive interventions. Overly expensive drugs may consume resources; not just drugs for other conditions but paying for these may reduce the ability to invest in other cancer services like surgery, radiotherapy or early detection services. Access to cancer drugs is imperative but their price tag is creating a significant barrier to access. Countries in the ME are heterogeneous in terms of income. However, they all have different aspects of challenge when it comes to implementing value based models. Many have other priorities such as improving quality and increasing access to basic health services. Others struggle with the challenges of fragmented systems, and the limits of existing healthcare infrastructure and operations. A particular challenge among others is the deficiency in the core components focusing on objective measures of outcomes and costs; including policies and institutions for value in healthcare. These obstacles are, indeed, shared by many other countries. As technology advances and new value-based approaches take hold in wealthy economies, those countries that are still investing in developing their health systems have an opportunity to learn from their experience, saving precious resources and delivering better long-term care for their societies. Citation Format: Al Sukhun S. The challenge of definition and adoption; perspective from the Middle East [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 IS-2.
A Review of Signal Processing Techniques for Electrocardiogram Signal Quality Assessment
Authors: Udit Satija, Barathram Ramkumar, M. Sabarimalai Manikandan
Journal: IEEE Reviews in Biomedical Engineering (2018)

Electrocardiogram (ECG) signal quality assessment (SQA) plays a vital role in significantly improving the diagnostic accuracy and reliability of unsupervised ECG analysis systems. In practice, the ECG signal is often corrupted with different kinds of noises and artifacts. Therefore, numerous SQA methods were presented based on the ECG signal and/or noise features and the machine learning classifiers and/or heuristic decision rules. This paper presents an overview of current state-of-the-art SQA methods and highlights the practical limitations of the existing SQA methods. Based upon past and our studies, it is noticed that a lightweight ECG noise analysis framework is highly demanded for real-time detection, localization, and classification of single and combined ECG noises within the context of wearable ECG monitoring devices which are often resource constrained.
Abstract PD7-04: Contribution of radiation therapy to the overall cost of cancer care for clinical stage IA breast cancer patients
Authors: T Dvorak, D Coltey, J Waters, P Kelly, D Buchholz
Journal: Cancer Research (2018)

Abstract Background: Cost of cancer care continues to rise and there is an increasing interest in episode-of-care and bundled payments. Radiation therapy is a well-established component of clinical Stage IA breast cancer care. However, the contribution of radiation to the cost of breast cancer care is not well understood. We were interested in evaluating the contribution of radiation cost to our overall Cancer Center breast cancer care cost, by using revenue received as a proxy. Methods: Patients with clinical Stage IA breast cancer managed completely at our Cancer Center between 1/1/2014 and 12/31/2014 were identified from cancer registry. An IRB-approved retrospective review of clinical charts and financial data of patients was performed. Individual chart review identified whether and which kind of surgery, chemotherapy, and radiation therapy was delivered. Financial review identified actual technical revenue received for 365 days after the date of first contact, and apportioned it accordingly to the various cost centers, including radiation oncology. All patients were included regardless whether they were Commercial, Medicare, Medicaid, self-pay, or free-care. Results: There were 110 patients treated with clinical Stage IA breast cancer. All patients (100%) underwent surgery (lumpectomy 69%; mastectomy 5%, mastectomy with reconstruction 26%). Chemotherapy was delivered in 20% of patients (neoadjuvant 13%; adjuvant 7%). Seventy seven percent saw a radiation oncologist, and 57% received radiation therapy. Radiation technique was 3D in 92% and IMRT in 8%. Fractionation was conventional in 55%, accelerated in 43%, and APBI in 2%. Most common treatment pathways were lumpectomy with radiation (46%), mastectomy with reconstruction alone (18%), and lumpectomy alone (14%). Concordance with national guidelines was ≥90%. Overall cost of care for these patients was $6.3 million. Medicare accounted for 35% of patients. Radiation cost was $1.1 million (17%), compared with $2.1 million (33%) for surgery, $2.4 million (38%) for chemotherapy, and $0.7 million for other costs (imaging, lab, ED visits, etc). Conclusions: Radiation therapy was used in ˜60% of clinical Stage IA patients, but accounted for only ˜20% of the overall cost to the health care system. Given the demonstrated survival benefit of radiation therapy in the care of breast cancer patients, and our high concordance with national guidelines, radiation therapy in our Cancer Center provides high value to our patients, as we move toward value-based episodes of care. Citation Format: Dvorak T, Coltey D, Waters J, Kelly P, Buchholz D. Contribution of radiation therapy to the overall cost of cancer care for clinical stage IA breast cancer patients [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 PD7-04.
RF-assisted gadofullerene nanoparticles induces rapid tumor vascular disruption by down-expression of tumor vascular endothelial cadherin
Authors: Xue Li, Mingming Zhen, Ruijun Deng, Tong Yu, Jie Li, Ying Zhang, Toujun Zou, Yue Zhou, Zhigao Lu, Mirong Guan, Hui Xu, Chunying Shu, Chunru Wang
Journal: Biomaterials (2018)

The tumor vasculature with unique characteristics offers an attractive target for anti-cancer therapy. Herein, we put forward a novel antitumor therapeutic mechanism based on the gadofullerene nanocrystals (GFNCs), the agent we have previously shown to efficiently disrupt tumor vasculature by size-expansion with assistance of radiofrequency (RF). However, the tumor vascular disrupting mechanism of RF-assisted GFNCs treatment was not further studied. In the present work, a rapid tumor blood flow shutdown has been observed by the vascular perfusion imaging in vivo and vascular damages were evident 6 h after the RF-assisted GFNCs treatment. Importantly, a significant down-expression of tumor vascular endothelial cadherin (VE-cadherin) treated by RF-assisted GFNCs was further investigated, which caused vascular collapse, blood flow shut-down and subsequent tumor hemorrhagic necrosis. These findings set forth a systematic mechanism on the superior anti-tumor efficiency by RF-assisted GFNCs treatment.