tbuckley/cabot-search huggingface dataset:
Risk-stratified surveillance and cost effectiveness of follow-up after radical cystectomy in patients with muscle-invasive bladder cancer.
Authors: Shingo Hatakeyama, Ayumu Kusaka, Shogo Hosogoe, Hayato Yamamoto, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2018)

430 Background: The cost effectiveness of oncological surveillance after radical cystectomy are not clear. We aimed to develop a risk stratification and a surveillance protocol with improved cost effectiveness after radical cystectomy. Methods: We retrospectively evaluated 581 patients with radical cystectomy for muscle-invasive bladder cancer at 4 hospitals. Patients with routine oncological follow-up were stratified into normal- and high-risk groups by a pathology-based protocol utilizing pT, pN, lymphovascular invasion, and histology. Cost effectiveness of the pathology-based protocol was evaluated and a risk-score-based protocol was developed to optimize cost effectiveness. Risk-scores were calculated by summing risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate-, and high-risk score. Estimated cost per one recurrence detection by the pathology and by risk-scores were compared. Results: Of 581 enrolled patients, 175 experienced disease recurrences. The pathology-based protocol presented significant differences in recurrence-free survival, but the medical expense was high, especially in normal-risk (≤pT2pN0) patients. Cox regression analysis identified six factors that associated with recurrence-free survival. Risk score-based 5-year follow-up was significantly more cost effective than the pathology-based protocol. Conclusions: Risk-score-stratified surveillance protocol has potential to reduce over-evaluation after radical cystectomy without adverse effects on medical cost.
Chronic E-Cigarette Exposure Alters the Human Bronchial Epithelial Proteome
Authors: Arunava Ghosh, Raymond C. Coakley, Teresa Mascenik, Temperance R. Rowell, Eric S. Davis, Keith Rogers, Megan J. Webster, Hong Dang, Laura E. Herring, M. Flori Sassano, Alessandra Livraghi-Butrico, Scott K. Van Buren, Lee M. Graves, Melissa A. Herman, Scott H. Randell, Neil E. Alexis, Robert Tarran
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

E-cigarettes vaporize propylene glycol/vegetable glycerin (PG/VG), nicotine, and flavorings. However, the long-term health effects of exposing lungs to vaped e-liquids are unknown.
Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes
Authors: Franco Cosmi, Li Shen, Michela Magnoli, William T. Abraham, Inder S. Anand, John G. Cleland, Jay N. Cohn, Deborah Cosmi, Giorgia De Berardis, Kenneth Dickstein, Maria Grazia Franzosi, Lars Gullestad, Pardeep S. Jhund, John Kjekshus, Lars Køber, Vito Lepore, Giuseppe Lucisano, Aldo P. Maggioni, Serge Masson, John J.V. McMurray, Antonio Nicolucci, Vito Petrarolo, Fabio Robusto, Lidia Staszewsky, Luigi Tavazzi, Roberto Teli, Gianni Tognoni, John Wikstrand, Roberto Latini
Journal: European Journal of Heart Failure (2018)
Robotic-Assisted vs Laparoscopic Radical Nephrectomy
Authors: Adam B. Weiner, Richard S. Matulewicz, Joshua J. Meeks
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract P1-12-01: Withdrawn
Authors: A Bardia, LT Vahdat, JR Diamond, K Kalinsky, J O'Shaughnessy, RL Moroose, SJ Isakoff, SM Tolaney, AD Santin, V Abramson, NC Shah, SV Govindan, P Maliakal, RM Sharkey, WA Wegener, DM Goldenberg, IA Mayer
Journal: Cancer Research (2018)

Abstract This abstract was withdrawn by the authors.
INTRAMYOCARDIAL CORONARY ARTERIES IN CHILDREN: NOT ALL ARE BENIGN BUT MOST ALLOW RETURN TO EXERCISE
Authors: Silvana Molossi, Hitesh Agrawal, Carlos Mery, Sara Kristen Sexson Tejtel, Rodrigo Zea-Vera, Athar Qureshi, Prakash Masand, Cory Noel, Charles Fraser
Journal: Journal of the American College of Cardiology (2018)
Xpert MTB/RIF as add-on test to microscopy in a low tuberculosis incidence setting
Authors: Giorgia Sulis, Angelica Agliati, Gabriele Pinsi, Giordano Bozzola, Pierfranco Foccoli, Maurizio Gulletta, Silvio Caligaris, Lina R. Tomasoni, Issa El-Hamad, Alberto Matteelli
Journal: European Respiratory Journal (2018)

Tuberculosis (TB) is a major public health concern worldwide. Early diagnosis, universal access to drug susceptibility testing and prompt initiation of treatment are key elements of the End TB strategy, and should therefore be implemented in all settings [1–5]. In order to reach TB elimination goals, the World Health Organization (WHO) currently recommends the use of a rapid molecular test, Xpert MTB/Rif (Xpert; Cepheid, Sunnyvale, CA, USA), as initial diagnostic tool when TB is suspected [6–8]. Although the excellent performance of this test in high TB burden areas is already supported by strong scientific evidence, few studies have been conducted so far to assess its impact on the diagnostic work-up of TB in low burden settings, sometimes with contrasting findings [7, 9, 10–12]. For example, according to Sohn et al. [10], Xpert testing might have limited impact in the ambulatory setting in Canada, owing to lower sensitivity and limited potential to expedite diagnosis beyond what is achieved with the existing, well-performing diagnostic algorithm. Xpert MTB/Rif should be used as an alternative test for microscopy for TB diagnosis in low incidence settings <http://ow.ly/JQCF30i8nO3>
Phase 1b trial of cabozantinib in combination with atezolizumab in patients with locally advanced or metastatic urothelial carcinoma (UC) or renal cell carcinoma (RCC).
Authors: Manuel C. Maia, Neeraj Agarwal, Bradley Alexander McGregor, Ulka N. Vaishampayan, Toni K. Choueiri, Marjorie C. Green, Colin Hessel, Christian Scheffold, Gisela Schwab, Thomas Powles, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

TPS42 Background: Cabozantinib (CABO) is an oral receptor tyrosine kinase inhibitor of MET, VEGFR, and TAM family receptors (TYRO3, AXL, and MER). It is approved for patients (pts) with RCC after prior therapy with antiangiogenic therapy, and has demonstrated clinical activity in UC. In clinical studies, CABO exposure increased circulating CD8+ T cells and reduced immune-suppressive monocytes and Tregs. In preclinical tumor models, CABO increased MHC class 1 expression on tumor cells and reduced myeloid-derived suppressor cells. CABO may facilitate an immune-permissive tumor environment and may enhance response to immune checkpoint inhibitors. Atezolizumab (ATEZO), an anti-PD-L1 mAb, is approved for: locally advanced/metastatic UC in pts who are cisplatin-ineligible or have disease progression during/following platinum-containing chemo; pts with metastatic NSCLC and disease progression during/following platinum-containing chemo. We present the study design of an ongoing phase 1b study combining CABO with ATEZO in pts with locally advanced/metastatic UC or RCC. Methods: This multicenter, phase 1b, open-label study aims to assess safety, tolerability, preliminary efficacy, and pharmacokinetics of CABO in combination with ATEZO (NCT03170960). The study will enroll pts with advanced UC (bladder, renal pelvis, ureter, urethra) or RCC. It consists of two stages: dose escalation and expansion. In the dose-escalation stage (3+3 design), a recommended CABO dose for the combination will be established. In the expansion stage, four tumor-specific cohorts will be enrolled: 1) pts with UC who have progressed on/after platinum-containing chemo; 2) chemo-naïve pts with UC who are cisplatin ineligible; 3) chemo-naïve pts with UC who are cisplatin eligible; and 4) untreated pts with RCC with clear cell histology; the primary objective is to determine the objective response rate in each cohort. Exploratory objectives include correlation of tumor and plasma biomarkers, and changes in immune cell profiles with clinical outcome. The study has been initiated and enrollment target is 120 pts across the 4 expansion cohorts. Clinical trial information: NCT03170960.
Enhanced Intratumoral Delivery of SN38 as a Tocopherol Oxyacetate Prodrug Using Nanoparticles in a Neuroblastoma Xenograft Model
Authors: Ferro Nguyen, Ivan Alferiev, Peng Guan, David T. Guerrero, Venkatadri Kolla, Ganesh S. Moorthy, Michael Chorny, Garrett M. Brodeur
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Currently, &amp;lt;50% of high-risk pediatric solid tumors like neuroblastoma can be cured, and many survivors experience serious or life-threatening toxicities, so more effective, less toxic therapy is needed. One approach is to target drugs to tumors using nanoparticles, which take advantage of the enhanced permeability of tumor vasculature. Experimental Design: SN38, the active metabolite of irinotecan (CPT-11), is a potent therapeutic agent that is readily encapsulated in polymeric nanoparticles. Tocopherol oxyacetate (TOA) is a hydrophobic mitocan that was linked to SN38 to significantly increase hydrophobicity and enhance nanoparticle retention. We treated neuroblastomas with SN38-TOA nanoparticles and compared the efficacy with the parent prodrug CPT-11 using a mouse xenograft model. Results: Nanoparticle treatment induced prolonged event-free survival (EFS) in most mice, compared with CPT-11. This was shown for both SH-SY5Y and IMR-32 neuroblastoma xenografts. Enhanced efficacy was likely due to increased and sustained drug levels of SN38 in the tumor compared with conventional CPT-11 delivery. Interestingly, when recurrent CPT-11–treated tumors were re-treated with SN38-TOA nanoparticles, the tumors transformed from undifferentiated neuroblastomas to maturing ganglioneuroblastomas. Furthermore, these tumors were infiltrated with Schwann cells of mouse origin, which may have contributed to the differentiated histology. Conclusions: Nanoparticle delivery of SN38-TOA produced increased drug delivery and prolonged EFS compared to conventional delivery of CPT-11. Also, lower total dose and drug entrapment in nanoparticles during circulation should decrease toxicity. We propose that nanoparticle-based delivery of a rationally designed prodrug is an attractive approach to enhance chemotherapeutic efficacy in pediatric and adult tumors. Clin Cancer Res; 24(11); 2585–93. ©2018 AACR.
Systematic Training in Acute Illness Recognition and Treatment for surgery
Authors: Robbie Ray
Journal: BMJ (2007)

Systematic Training in Acute Illness Recognition and Treatment for surgery (START surgery) is a new one day pilot course in surgical skills for the critically ill patient offered by the Royal College of Surgeons of England.

START surgery is aimed at foundation year doctors wishing to pursue a career in surgery. The course is designed to enhance the theoretical and practical skills necessary for dealing with critically ill surgical patients at a ward level by anticipating and recognising early signs of deterioration and dealing with them systematically, thereby improving the quality of care and outcome.

Having completed my house officer job in surgery, I remembered the daunting experience of trying to manage acutely unwell patients and wondering whether I was dealing with them appropriately. I thought learning a tried and tested system for assessing acutely …
In patients with rheumatoid arthritis, bDMARD therapy was not associated with malignant neoplasms
Authors: Anne Holbrook
Journal: Annals of Internal Medicine (2018)

Source Citation Wadström H, Frisell T, Askling J; Anti-Rheumatic Therapy in Sweden Study Group. Malignant neoplasms in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors, tocilizumab, abatacept, or rituximab in clinical practice: a nationwide cohort study from Sweden. JAMA Intern Med. 2017;177:1605-12. 28975211
Do junior registrar training posts in Australia count towards training in the United Kingdom?
Authors: Evelyn Ong
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>
Editor’s Choice: Keeping pace with a changing world
Authors: Tom Moberly
Journal: BMJ (2015)

Thirty years ago, patients’ trust in their doctors was wrapped up in a neat bundle of behaviours and expectations. Doctors took a paternalistic attitude towards their patients, and patients in turn deferred to their doctors on questions of health. Questions of compliance, adherence, and concordance with treatment plans did not concern most patients or their doctors. Patients simply trusted …
Acne and hidradenitis suppurativa
Authors: A. Pink, F. Anzengruber, A.A. Navarini
Journal: British Journal of Dermatology (2018)

Acne and hidradenitis suppurativa (HS) both centre on hair follicles. They often occur together as part of the acne tetrad, but are found in distinct localizations. Acne is primarily defined by the presence of comedones and inflammatory lesions. However, in HS the intertriginous localization and chronicity play equally important roles for the diagnosis to the inflammatory lesions. Genetics, bacteria, environmental factors and innate inflammation have all been found to play a role in acne and/or HS. Surprisingly, there is little overlap between the findings so far. The genetics of acne and HS are distinct, bacteria have not been shown convincingly to play a role in HS, and the important risk factors obesity and smoking in HS cannot be easily translated to acne. The one driving factor central to both diseases is innate inflammation, most strikingly involving interleukin‐1. Hence the interleukin‐1 family, as already shown in autoinflammatory conditions associated with acne, could represent attractive treatment targets.
Consultants are concerned about input of secondary care to CCGs
Authors: Helen Jaques
Journal: BMJ (2013)

Most consultants are dissatisfied with the level of involvement of secondary care in their local clinical commissioning group (CCG), a survey by the BMA has indicated.

More than three quarters (77%) of the 284 consultants surveyed by the association said that they were not happy with the degree of secondary care input to their local CCG. Almost a 10th (8%) said that they knew of a local CCG that had no input at all from a secondary care clinician. 

Nearly all respondents (90%) believed that involving secondary care …
Unacceptable to publish article on forensic gynaecology
Authors: George Fernie
Journal: BMJ (2005)

EDITOR—I would like to register the concern felt by the BMA's Forensic Medicine Committee about the recent article on forensic gynaecology outlining the views of four authors from the Haven Sexual Assault Referral Centres.1 Before I give my comments in detail, I will emphasise that I appreciate the value of the work conducted by the Haven Centres and do not want to be perceived as over-reacting to the article. However, a number of comments appear to undermine the important work carried out by forensic physicians in the United Kingdom and seem to edge close to breaching General Medical Council (GMC) guidance on good medical practice. The essence of my representation to BMJ Careers regarding this article is as follows:
Low-level lead exposure and mortality in US adults: a population-based cohort study
Authors: Bruce P Lanphear, Stephen Rauch, Peggy Auinger, Ryan W Allen, Richard W Hornung
Journal: The Lancet Public Health (2018)

BackgroundLead exposure is a risk factor for cardiovascular disease mortality, but the number of deaths in the USA attributable to lead exposure is poorly defined. We aimed to quantify the relative contribution of environmental lead exposure to all-cause mortality, cardiovascular disease mortality, and ischaemic heart disease mortality.MethodsOur study population comprised a nationally representative sample of adults aged 20 years or older who were enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III) between 1988 and 1994 and followed up to Dec 31, 2011. Participants had completed a medical examination and home interview and had results for concentrations of lead in blood, cadmium in urine, and other relevant covariates. Individuals were linked with the National Death Index. This study presents extended follow-up of an earlier analysis.FindingsWe included 14 289 adults in our study. The geometric mean concentration of lead in blood was 2·71 μg/dL (geometric SE 1·31). 3632 (20%) participants had a concentration of lead in blood of at least 5 μg/dL (≥0·24 μmol/L). During median follow-up of 19·3 years (IQR 17·6–21·0), 4422 people died, 1801 (38%) from cardiovascular disease and 988 (22%) from ischaemic heart disease. An increase in the concentration of lead in blood from 1·0 μg/dL to 6·7 μg/dL (0·048 μmol/L to 0·324 μmol/L), which represents the tenth to 90th percentiles, was associated with all-cause mortality (hazard ratio 1·37, 95% CI 1·17–1·60), cardiovascular disease mortality (1·70, 1·30–2·22), and ischaemic heart disease mortality (2·08, 1·52–2·85). The population attributable fraction of the concentration of lead in blood for all-cause mortality was 18·0% (95% CI 10·9–26·1), which is equivalent to 412 000 deaths annually. Respective fractions were 28·7% (15·5–39·5) for cardiovascular disease mortality and 37·4% (23·4–48·6) for ischaemic heart disease mortality, which correspond to 256 000 deaths a year from cardiovascular disease and 185 000 deaths a year from ischaemic heart disease.InterpretationLow-level environmental lead exposure is an important, but largely overlooked, risk factor for cardiovascular disease mortality in the USA. A comprehensive strategy to prevent deaths from cardiovascular disease should include efforts to reduce lead exposure.FundingThe Artemis Fund and Simon Fraser University.
Certificate in counselling
Authors: Sharon McConville
Journal: BMJ (2007)

FURTHER INFORMATION 

Many institutions offer courses in counselling. Contact the British Association for Counselling and Psychotherapy (www.bacp.co.uk; 0870 443 5252) to find a course near you.

The certificate is for anyone working with people who face difficult circumstances—my classmates included nurses, mental healthcare assistants, social workers, and a medical receptionist—as well as for those interested in becoming professional counsellors.

I did it at Queen's University during a gap year between my fourth and fifth years at medical school.

I was volunteering as a support worker for …
GPs in Scotland avoid most of the negative QOF changes highlighted by BMA
Authors: Helen Jaques
Journal: BMJ (2013)

GPs in Scotland will not be subject to most of the changes to the Quality and Outcomes Framework (QOF) that the BMA thinks will have a negative effect on general practice.1

Most of the changes to QOF recommended by the National Institute for Health and Clinical Excellence (NICE) for the 2013-14 general medical services (GMS) contract will go ahead in Scotland. However, the Scottish General Practitioners Committee and the Scottish government have negotiated “substantial amelioration” of the recommendations.

The committee’s chairman, Alan McDevitt, said, “I believe these arrangements will improve patient care and go some way to mitigating workload pressures. The success of the …
Mutant IDH1 Cooperates with ATRX Loss to Drive the Alternative Lengthening of Telomere Phenotype in Glioma
Authors: Joydeep Mukherjee, Tor-Christian Johannessen, Shigeo Ohba, Tracy T. Chow, Lindsey Jones, Ajay Pandita, Russell O. Pieper
Journal: Cancer Research (2018)

A subset of tumors use a recombination-based alternative lengthening of telomere (ALT) pathway to resolve telomeric dysfunction in the absence of TERT. Loss-of-function mutations in the chromatin remodeling factor ATRX are associated with ALT but are insufficient to drive the process. Because many ALT tumors express the mutant isocitrate dehydrogenase IDH1 R132H, including all lower grade astrocytomas and secondary glioblastoma, we examined a hypothesized role for IDH1 R132H in driving the ALT phenotype during gliomagenesis. In p53/pRb-deficient human astrocytes, combined deletion of ATRX and expression of mutant IDH1 were sufficient to create tumorigenic cells with ALT characteristics. The telomere capping complex component RAP1 and the nonhomologous DNA end joining repair factor XRCC1 were each downregulated consistently in these tumorigenic cells, where their coordinate reexpression was sufficient to suppress the ALT phenotype. RAP1 or XRCC1 downregulation cooperated with ATRX loss in driving the ALT phenotype. RAP1 silencing caused telomere dysfunction in ATRX-deficient cells, whereas XRCC1 silencing suppressed lethal fusion of dysfunctional telomeres by allowing IDH1-mutant ATRX-deficient cells to use homologous recombination and ALT to resolve telomeric dysfunction and escape cell death. Overall, our studies show how expression of mutant IDH1 initiates telomeric dysfunction and alters DNA repair pathway preferences at telomeres, cooperating with ATRX loss to defeat a key barrier to gliomagenesis.Significance: Studies show how expression of mutant IDH1 initiates telomeric dysfunction and alters DNA repair pathway preferences at telomeres, cooperating with ATRX loss to defeat a key barrier to gliomagenesis and suggesting new therapeutic options to treat low-grade gliomas. Cancer Res; 78(11); 2966-77. ©2018 AACR.