tbuckley/cabot-search huggingface dataset:
Cabozantinib versus sunitinib for previously untreated patients with advanced renal cell carcinoma (RCC) of intermediate or poor risk: Subgroup analysis of progression-free survival (PFS) and objective response rate (ORR) in the Alliance A031203 CABOSUN trial.
Authors: Daniel J. George, Colin Hessel, Susan Halabi, Ben L. Sanford, M. Dror Michaelson, Olwen Mary Hahn, Meghara K. Walsh, Thomas Olencki, Joel Picus, Eric Jay Small, Shaker R. Dakhil, Darren R. Feldman, Milan Mangeshkar, Christian Scheffold, Michael J. Morris, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2018)

582 Background: The randomized phase 2 CABOSUN trial (NCT01835158) compared cabozantinib (C) with sunitinib (S) as initial systemic therapy in patients (pts) with RCC of intermediate or poor risk. Compared with S, C improved both PFS and ORR as assessed by independent radiology review committee (IRC). Median PFS per IRC was 8.6 mo for C vs 5.3 mo for S (HR 0.48, 95% CI 0.31-0.74 two-sided p = 0.0008), and ORR per IRC was 20% vs 9%. Methods: 157 patients were randomized 1:1 to receive C (60 mg qd) or S (50 mg qd, 4 weeks on/2 weeks off) stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group and the presence of bone metastases. Subgroup analyses of PFS per IRC and ORR per IRC are presented based on stratification factors, age, sex, baseline ECOG status, and MET tumor expression by immunohistochemistry. The primary endpoint was investigator-assessed PFS. PFS and ORR were evaluated by IRC in a post-hoc analysis. Results: 45% of pts were ≥65 years, 78% were male, 54% were ECOG 1 or 2, 19% were poor risk, and 36% had bone metastases. MET status was determined in 131 pts; of these 47% were MET positive. The HR for PFS per IRC favored C over S across all subgroups analyzed (Table). Subgroups with poor prognostic characteristics (poor risk, ECOG 1 or 2, presence of bone metastases) had shorter median PFS for both C and S. Odds ratios for ORR also favored C over S, with the highest C ORR in the MET positive subgroup (34% C vs 10% S). Conclusions: C was associated with improved PFS and ORR compared with S in previously untreated pts with advanced RCC irrespective of baseline characteristics. Clinical trial information: NCT01835158. [Table: see text]
Pilots show feasibility of “credentialing” for secondary care medicine in the UK
Authors: Helen Jaques
Journal: BMJ (2012)

Three pilots overseen by the General Medical Council have shown the feasibility of using credentialing to certify the knowledge, skills, and competence of secondary care doctors with respect to providing particular services or performing specific procedures. 

The pilots looked at how to assess the competency of doctors in three areas of medical practice that have no formal recognition as specialties: breast disease management; forensic and legal medicine; and musculoskeletal medicine. 

In the breast disease management pilot doctors had to meet minimum requirements for experience …
ASSOCIATION OF WALKING PACE, WALKING FREQUENCY AND DURATION AND JOINT EFFECTS ON THE RISK OF HEART FAILURE IN POST-MENOPAUSAL WOMEN
Authors: Somwail Rasla, Xiaochen Lin, Amr El Meligy, Mary B. Roberts, Deepika Laddu, Matthew Allison, Aladdin H. Shadyab, Simin Liu, Lisa W. Martin, JoAnn Manson, Rowan Chlebowski, Gurusher Panjrath, Michael J. LaMonte, Charles B. Eaton
Journal: Journal of the American College of Cardiology (2018)
Evaluation of preoperative C-reactive protein: Albumin ratio in patients with clear cell renal cell carcinoma.
Authors: Dattatraya H Patil, Sierra Williams, Mersiha Torlak, Mehrdad Alemozaffar, Aaron Lay, John Pattaras, Omer Kucuk, Bradley Curtis Carthon, Mehmet Asim Bilen, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2018)

690 Background: Multiple inflammatory markers have been evaluated in predicting preoperative risk in patient’s undergoing curative nephrectomy for Clear cell renal cell carcinoma. We propose that ratio of C-Reactive Protein to albumin (CA-ratio) would prove to be a good prognostic indicator for assessment of overall survival and comparable to established nomograms in clear call RCC. Methods: Patients that underwent nephrectomy for localized clear cell RCC between 2007 and 2016 were retrospectively identified. The optimal threshold for individual biomarkers among the panel was determined using grid search methodology, receiver operating characteristic (ROC) analysis, and sensitivity-specificity trade-off analysis. Prognostic value of CA-ratio was analyzed using the Kaplan-Meier method and Cox proportional regression models. ROC and chi-square analyses were performed to compare the predictive ability of CA-ratio to SSIGN, and UISS. Results: Among the 433 clear cell RCC patients treated with nephrectomy, mean age at surgery was 58.4±12, and mean BMI was 30.6±6.8. 158 (36.5%) had CA-ratio &lt; 0.1, while 164 (37.9%) were between 0.1-0.2, and 111 (25.6%) were 0.2+. Pathological T-stage was distributed as follows: T1: 294 (67.9%), T2: 29 (6.7%), T3: 106 (24.5%), and T4: 4 (0.9%). Overall, 60 (13.9%) patients died before end of the follow-up. Area under the curve (AUC) for CA-ratio was 0.72, comparable to SSIGN (AUC 0.73, p = 0.12). On multivariate COX proportional hazards analysis, patients with ratio 0.2 or more were more likely to die compared to patients with ratio &lt; 0.1 [HR:3.45 95%CI:1.68-7.10, p = &lt; 0.001], while adjusting for T-stage, grade, necrosis, and age. Conclusions: CA-ratio is an cost-effective , independent and significant predictor of overall survival in clear cell RCC with accuracy at least as good as other established prognostic tools including SSIGN and UISS. [Table: see text]
All foundation doctors will have to undertake community placements, HEE says
Authors: Abi Rimmer
Journal: BMJ (2014)

Foundation doctors will have to undertake at least one community based placement during their training, Health Education England (HEE) has said.

In a report HEE said that by undertaking a community or integrated placement trainees would gain a wider experience of community settings and community care.1 It recommended that by August 2015 80% of foundation doctors should undertake a community or integrated placement and that by 2017 this should apply to all foundation doctors.

The placements are likely to be carried out during the second year …
Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms
Authors: Valerio De Stefano, Alessandra Carobbio, Vincenzo Di Lazzaro, Paola Guglielmelli, Alessandra Iurlo, Maria Chiara Finazzi, Elisa Rumi, Francisco Cervantes, Elena Maria Elli, Maria Luigia Randi, Martin Griesshammer, Francesca Palandri, Massimiliano Bonifacio, Juan-Carlos Hernandez-Boluda, Rossella Cacciola, Palova Miroslava, Giuseppe Carli, Eloise Beggiato, Martin H. Ellis, Caterina Musolino, Gianluca Gaidano, Davide Rapezzi, Alessia Tieghi, Francesca Lunghi, Giuseppe Gaetano Loscocco, Daniele Cattaneo, Agostino Cortelezzi, Silvia Betti, Elena Rossi, Guido Finazzi, Bruno Censori, Mario Cazzola, Marta Bellini, Eduardo Arellano-Rodrigo, Irene Bertozzi, Parvis Sadjadian, Nicola Vianelli, Luigi Scaffidi, Montse Gomez, Emma Cacciola, Alessandro M. Vannucchi, Tiziano Barbui
Journal: Blood Cancer Journal (2018)

Abstract We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment.
Genomic biomarkers in relation to PD-1 checkpoint blockade response.
Authors: Tanguy Y. Seiwert, Razvan Cristescu, Robin Mogg, Mark Ayers, Andrew Albright, Xinwei Sher, Xiaoqiao Liu, Michael Nebozhyn, Chunsheng Zhang, Jared Lunceford, Andrew K. Joe, Jonathan D. Cheng, Andrea L Webber, Nageatte Ibrahim, Elizabeth R. Plimack, Patrick Alexander Ott, Antoni Ribas, Terrill McClanahan, Andrey Loboda, David Ross Kaufman
Journal: Journal of Clinical Oncology (2018)

25 Background: Somatic tumor mutational burden (TMB) and a T-cell inflamed gene expression profile (GEP) predict response to anti-PD-1/PD-L1 immunotherapies in multiple tumor types. We assessed the potential for GEP and TMB to jointly predict clinical response to pembrolizumab and to identify distinct, targetable patterns of biology that may modulate response/resistance. Methods: To assess the individual and joint clinical utility of TMB and GEP in a pan-tumor context, pembrolizumab-treated patients with advanced solid tumors and melanoma were stratified as 4 biomarker-defined clinical response groups (GEP low/TMB low, GEP low/TMB high, GEP high/TMB low, GEP high/TMB high; N &gt; 300) based on cutoffs for TMB (ROC Youden Index associated) and GEP (selected via analysis of pan cancer data). TMB and GEP were used to guide transcriptome and exome analysis of tumors in 2 large databases (Moffitt, n = 2944; TCGA, n = 6978). Results: TMB and GEP had a low, but significant, correlation in these clinical datasets. ORR was highest in GEP high/TMB high (37-57%), modest in GEP high/TMB low (12-35%) and GEP low/TMB high (11-42%), and lowest in GEP low/TMB low (0-9%) groups. Within the Moffitt and TCGA databases, GEP and TMB again had a low correlation, demonstrating their potential joint utility for stratifying additional transcriptomic and genomic features of these datasets. Specific gene modules showed strong positive or negative and highly statistically significant associations with TMB, GEP or both in each dataset, and patterns were consistent between datasets. In particular, gene set enrichment analysis identified proliferative, stromal and vascular biology corresponding to specific TMB-defined subgroups within GEP high tumors. In TMB-high tumors, indication-dependent somatic DNA alterations in key cancer driver genes showed a strong negative association ( P&lt; 1e-5) with GEP. Conclusions: This analysis shows that TMB and T-cell inflamed GEP score can stratify human cancers into groups with different response rates to pembrolizumab monotherapy, and identify patterns of underlying, targetable biology related to these groups. This approach may provide a precision medicine framework for evaluating anti-PD-1/L1-based combination therapy regimens. Clinical trial information: NCT01848834; NCT02054806; NCT01295827; NCT01866319.
HEMODYNAMIC PARAMETERS AND DIASTOLOGY OF PARADOXICAL LOW FLOW-LOW GRADIENT SEVERE AORTIC STENOSIS WITH NORMAL EJECTION FRACTION PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Allan Chen, Aarti Patel, Vishal Parikh, Gregory Coffman, Allen Brown, Christiano Caldeira, Tom Sullebarger, Robert Hooker, Fadi Matar, Arthur Labovitz
Journal: Journal of the American College of Cardiology (2018)
Postgraduate diploma in science of sports injuries
Authors: Kuntal J Patel
Journal: BMJ (2005)

It is mainly for doctors in the field of sports medicine, including general practitioners and surgeons. It can also be useful for allied specialists like physiotherapists or podiatrists who are actively involved in the field of sports medicine.

I did it from August 2004 to May 2005.

This is a comprehensive course giving a good insight into important aspects of sports injuries including sports biomechanics, sports psychology, nutrition, and rehabilitation. Since I am pursuing a higher surgical training in …
Delivering digital cognitive behavioral therapy for insomnia at scale: does using a wearable device to estimate sleep influence therapy?
Authors: Annemarie I. Luik, Pedro Farias Machado, Colin A. Espie
Journal: npj Digital Medicine (2018)

Contemporary developments, such as digital Cognitive Behavioral Therapy (CBT) and wearable devices estimating sleep, could support the implementation of CBT for insomnia at a large scale. We assessed what characterizes those users who connected a wearable device to the program to estimate sleep diary variables, and whether connecting a wearable device affected insomnia symptom improvement, related well-being, and program interaction. In total, 3551 users (63% female, mean age 44.50 ± 14.78 years) of a dCBT program who completed a post-therapy survey, including 378 users (10.6%) who used a device, were selected. Within-subject, pre-therapy to post-therapy, the Sleep Condition Indicator (SCI, 7 Items) was used to assess insomnia. Two-item measures (depression, anxiety) and single item measures (perceived stress, life satisfaction, work productivity) of well-being were analyzed, in addition to program interaction. For all participants, insomnia symptoms significantly improved following dCBT (t(3504) = 83.33,
Appointment day—the tip of an iceberg
Authors: Anya de Iongh
Journal: BMJ (2018)

Appointment day-the tip of an icebergAnya de Iongh gives a snapshot of what a rare appointment with a consultant feels like for the patient, and suggests how to make things better Anya de Iongh BMJ patient editorTo you, my appointment might just be another slot in a hectic day.My perspective is different.As a person with long term conditions, my one hospital appointment a year with a consultant is an important event, with a build-up, an aftermath, and a barrage of emotions.
GMC highlights work to reduce stress and support vulnerable doctors
Authors: Abi Rimmer
Journal: BMJ (2015)

The General Medical Council has highlighted the work it is doing to reduce stress among doctors it investigates and to support vulnerable doctors, ahead of a BMA debate on the issue.

Niall Dickson, chief executive of the GMC, spoke about the issue ahead of the BMA’s annual representative meeting in Liverpool on 21-25 June, where delegates will debate a motion saying that the GMC was “creating a climate where doctors practise in fear for their registration.”1

He said that the regulator had a duty of care to the doctors that it investigated and that it was aware that investigations were a very stressful experience …
I am a first year senior house officer considering a career in genitourinary medicine. Should I be following an obstetrics and gynaecology career path or a medical path with MRCP?
Authors: Alison Bigrigg
Journal: BMJ (2004)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
Seven day working will require investment in staff, says BMA
Authors: Abi Rimmer
Journal: BMJ (2014)

Seven day working among doctors will require investment in staff and resources, the BMA has said.

Delegates at the association’s Annual Representative Meeting voted unanimously in favour of a motion that recognised that many doctors “already provide seven day emergency services.” The motion said that delivering seven day routine and elective services “is not feasible within the current NHS budget constraints leading to reduced clinical services Monday to Friday and/or closure of hospitals.”

The conference also voted in favour of a motion that said that “provision of seven day healthcare requires investment in medical staff and supporting resources and not merely the reorganisation of services.” …
CARDIOMYOCYTE- AND NOT ENDOTHELIAL-SPECIFIC (β3-ADRENERGIC RECEPTOR STIMULATION PROTECTS THE HEART AGAINST ISCHEMIA/REPERFUSION INJURY
Authors: Andrés Pun, Monica Gomez, David Sanz-Rosa, Belen Prados, Jose Luis de la Pompa, Borja Ibanez
Journal: Journal of the American College of Cardiology (2018)
Genetic variants associated with Alzheimer’s disease confer different cerebral cortex cell-type population structure
Authors: Zeran Li, Jorge L. Del-Aguila, Umber Dube, John Budde, Rita Martinez, Kathleen Black, Qingli Xiao, Nigel J. Cairns, Joseph D. Dougherty, Jin-Moo Lee, John C. Morris, Randall J. Bateman, Celeste M. Karch, Carlos Cruchaga, Oscar Harari
Journal: Genome Medicine (2018)

Alzheimer's disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, the specific effects that pathological mutations and coding variants associated with AD have on the cellular composition of the brain are often ignored. We developed and optimized a cell-type-specific expression reference panel and employed digital deconvolution methods to determine brain cellular distribution in three independent transcriptomic studies. We found that neuronal and astrocyte relative proportions differ between healthy and diseased brains and also among AD cases that carry specific genetic risk variants. Brain carriers of pathogenic mutations in APP, PSEN1, or PSEN2 presented lower neuron and higher astrocyte relative proportions compared to sporadic AD. Similarly, the APOE ε4 allele also showed decreased neuronal and increased astrocyte relative proportions compared to AD non-carriers. In contrast, carriers of variants in TREM2 risk showed a lower degree of neuronal loss compared to matched AD cases in multiple independent studies. These findings suggest that genetic risk factors associated with AD etiology have a specific imprinting in the cellular composition of AD brains. Our digital deconvolution reference panel provides an enhanced understanding of the fundamental molecular mechanisms underlying neurodegeneration, enabling the analysis of large bulk RNA-sequencing studies for cell composition and suggests that correcting for the cellular structure when performing transcriptomic analysis will lead to novel insights of AD.
I am a vocationally trained general practitioner with MRCGP and I have been working in Africa since 1997. How can I return to general practice in the United Kingdom?
Authors: Roger Charlton
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
The Search for Primary Tumor in a Patient With Oncogenic Osteomalacia
Authors: Gaurav Malhotra, Archi Agrawal, Nirmala A. Jambhekar, Vijaya Sarathi, Varsha Jagtap, Manish G. Agarwal, Mukta Kulkarni, Ramesh V. Asopa, Nalini S. Shah
Journal: Clinical Nuclear Medicine (2010)

We report a case of oncogenic osteomalacia in which F-18 FDG PET imaging played a crucial role in detecting the occult neoplasm. A 39-year-old female patient presented with low backache and bilateral lower limb pain of 3-year duration. On evaluation, she was found to have hypophosphatemic osteomalacia and was referred for F-18 FDG PET scan because her initial clinical and radiologic evaluation failed to detect a tumor. F-18 FDG PET scan revealed a hypermetabolic focus in right popliteal fossa, which was correlated as a tumor in soft tissues of right popliteal fossa on magnetic resonance imaging. Following surgical excision of tumor, final histopathology revealed a benign phosphaturic mesenchymal tumor of mixed connective tissue origin. Postoperatively, her symptoms alleviated and serum phosphates normalized within 2 weeks. We suggest that F-18 FDG PET should be performed in such cases to localize occult neoplasm that may be otherwise missed on conventional radiologic imaging.
Assessing best practices on short-term medical service trips: an eDelphi-based theoretical model
Authors: Christopher Dainton, Charlene Hsuan-Li Chu, Christina Gorman, William Cherniak
Journal: The Lancet Global Health (2018)

BackgroundShort-term, primary-care medical service trips (MSTs) are a controversial modality for addressing the health of marginalised populations and responding to the burden of communicable and non-communicable diseases. As a health-care delivery model, MSTs are challenged by concerns over sustainability, fragmentation of care in host communities, and degree of preparedness among volunteers. Despite the increasing prevalence of such trips, no single framework is routinely used to evaluate their quality. We aimed to develop a literature-based tool for assessing the practices of volunteer MSTs and to validate this tool among stakeholders.MethodsWe reviewed recent literature to construct a preliminary list of commonly discussed MST best practices. A multidisciplinary panel of academic experts, medical professionals, MST programme coordinators, and non-medical MST volunteers participated in a three-round e-Delphi consensus-building exercise to revise the preliminary list. A 7-point Likert scale was used, with mean scores of 4–7 resulting in rejection of the element, scores less than 2 resulting in acceptance, and scores in between being redistributed for further discussion in rounds two and three.FindingsThe preliminary framework consisted of 30 elements sorted into six domains: preparedness, impact and safety, efficiency, cost-effectiveness, sustainability, and education. The 26 stakeholders on the eDelphi panel reached consensus on 18 desirable elements to include in the final framework for an effective MST. The elements of the final framework were directly adapted to create a rating scale for medical professionals and trainees to evaluate the practices of volunteer-sending organisations listed in a large online database (http://www.medicalservicetrip.com).InterpretationEvaluation of such practices will allow volunteers to select quality opportunities with effective, sustainable health-care delivery models. Future research should extend this study by initiating a dialogue on best practices between host communities, local clinicians, and MST-sending organisations.FundingNone.