tbuckley/cabot-search huggingface dataset:
Antiepileptic Drugs in Pregnancy—Quick Decisions With Long-term Consequences
Authors: Page B. Pennell
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
Treatment facility volume and survival in patients with metastatic renal cell carcinoma.
Authors: Daniel M. Geynisman, Elizabeth Handorf, Matthew R. Zibelman, Elizabeth R. Plimack, Robert Uzzo, Alexander Kutikov, Marc C. Smaldone
Journal: Journal of Clinical Oncology (2018)

594 Background: Higher treatment facility (TF) volume has been linked with improved surgical and hematologic malignancy outcomes. We evaluated the association between TF volume and overall survival (OS) in pts with metastatic renal cell carcinoma (mRCC). Methods: The National Cancer Data Base was queried for all pts with mRCC and survival data available (2004 to 2013, cohort A). We defined high volume TFs as those in the top 20 th percentile of mean number of mRCC pts treated per year ( &gt; 5 pts). The effect of volume on OS was determined using unadjusted Kaplan-Meier curves and Cox regression models (MVA) adjusting for pt (age, sex, race, ethnicity, insurance type, income, Charlson-Deyo Score), facility (location, practice setting) and clinical characteristics (histology, presence or absence of liver and lung metastasis). Increasingly more stringent inclusion criteria were used to confirm the overall cohort association (cohort B = mRCC pts with active treatment; cohort C = mRCC pts with systemic therapy; cohort D = mRCC pts with systemic therapy at the reporting institution; cohort E = mRCC pts with systemic therapy at the reporting institution with liver and lung metastatic status known). Results: There were 44,109 mRCC pts treated at 1,224 TFs. The median age was 65, 66% were men and 75% had clear cell mRCC. Median TF volume was 2.4 pts/year (range 0.1-46.8). High volume TFs treated 54% of all mRCC pts. The unadjusted median overall survival of mRCC patients (cohort A) treated at high vs low volume TFs was 9.2 vs 6.4 months (P &lt; 0.0001). This difference was maintained in all cohorts: cohort B = 13.7 vs 10.9, cohort C = 12.4 vs 10.0, cohort D = 12.5 vs 9.3, and cohort E = 13.4 vs 10.6 months (P &lt; 0.0001 for all cohorts). MVA confirmed that facility volume was associated with all-cause mortality after adjustment: HR = 0.85, [95% CI 0.82-0.88], P &lt; 0.001. These results were consistent regardless of inclusion criteria, e.g. for cohort E: HR = 0.839, [95% CI 0.785-0.897], P &lt; 0.0001. Considering the definition of high volume, all thresholds &gt; 5 pts/year showed a survival benefit, with the largest effects at ≥10 pts/year. Conclusions: Patients with mRCC treated at higher volume facilities had a longer survival compared with those treated at lower volume facilities.
Circulating tumor cells as a surrogate for treatment response in patients with metastatic pancreatic adenocarcinoma.
Authors: Hiral D. Parekh, Jason Scott Starr, Jose I. Varillas, Alison Marguerite Ivey, Isis Barnes, Margaret A. McEwan, Jose Gilberto Trevino, Jessica Cioffi, Steven J. Hughes, Joseph Grajo, Z. Hugh Fan, Carmen Joseph Allegra, Thomas J. George
Journal: Journal of Clinical Oncology (2018)

318 Background: The collection and enumeration of circulating tumor cells (CTCs) are feasible in metastatic breast, prostate and colorectal cancers. CTCs have diagnostic, prognostic and treatment monitoring implications, but have been challenging to detect in pancreatic cancer (PCa). We have proven feasibility of CTCs in PCa. This study is a pilot to assess use of CTCs as a surrogate for imaging response. Methods: Blood samples (7-10mL) from newly diagnosed metastatic PCa were collected within 1 month of treatment initiation (T 0 ) and at repeat scan after 2mo of treatment (T 1 ). Specimens were processed within 6 hours of collection. A UF developed microfluidic device was used to capture and identify EpCam+ CTCs. Isolated cells were verified as CTCs consistent with FDA-approved definitions (cytokeratin+, DAPI+, CD45-). CTC enumeration and changes were correlated with scan RECIST results at T 0 and T 1 . The study was approved by the UF IRB. Results: A total of 16 patients had matched pair CTCs collected and analyzed (Table 1). For the entire cohort, the median CTC count at T 0 was 7/mL of blood (range 2-11.5/mL) and decreased to 4.5/mL (range 2-8.5/mL) at T 1 (36% reduction). CTCs were reduced to some degree in all patients with therapy. Disease control at T 1 was confirmed in 13/16 (81%) with stable disease (n=11), partial (n=1) or complete (n=1) response. Progressive disease was noted in 3 patients. CTCs were reduced by 35% in radiographic stable or responders vs 24% in those with clear progressive disease. Conclusions: This study demonstrated the feasibility of microfluidic technology to reliably and consistently identify CTCs in advanced PCa. While all patients had reduced CTCs with therapy, a trend towards higher reductions were in those with radiographic stable or improved disease. Continued assessment of CTCs in PCa for treatment monitoring are warranted and are ongoing. [Table: see text]
Pharmacokinetic (PK) and pharmacodynamic (PD) study of the effect of imatinib (Ima) on tumor (T) vascularity (V) and on gemcitabine (Ge) uptake (U) using non-invasive dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and spectroscopy (MRS)—Study BUS228
Authors: W. Wolf, C. A. Presant, V. Waluch, E. J. Chen
Journal: Journal of Clinical Oncology (2006)

12006 Background: Ima has been reported to increase T U of other chemotherapy drugs and to reduce interstitial fluid pressure (IFP) in experimental animals. Poplin et al performed a phase 1 analysis of Ima plus Ge in solid tumors (AACR 95:405, 2004). We tested ImaGe to determine the T PK and PD effects of Ima, Ge, and the ImaGe combination using DCE-MRI and MRS. Methods: Patients (pt) with measurable and MRI-imagible refractory solid T possibly responsive to Ge were randomized to receive either: one course of Ima with PK/PD, followed by one course of Ge with PK/PD, followed by the combination ImaGe; or one course of Ge with PK/PD followed by one course of Ima with PK/PD, followed by ImaGe. Ge was given at 900 mg/m2 IV over 30 min. for PK/PD and at 10 mg/m 2 /min. for continued therapy. Ima was given at 400 mg daily for 5 d. with Ge given on day 3. Doses were adjusted for toxicity. T V was measured by the use of DCE-MRI, as described previously (AACR 95:490,2004), where the initial contrast accumulation rate (ICAR) was calculated as the slope of the influx curve, and the delayed contrast accumulation rate (DCAR), measured between 2–20 min post contrast administration, as an approximation of IFP. Ge U was measured by serial 19F-MRS for ∼ 1hr post Ge administration. Results: To date 7 pts have been evaluated for the trial. Two pts have entered the trial and completed one cycle of therapy for PK/PD evaluation. Ima produced moderate nausea in both pts. Other toxicity was negligible. In the first pt Ima produced an 18% increase in the ICAR and a 72% increase in the DCAR but there was no significant change observed in the Ge uptake. In the second pt, Ima produced a 60% increase in the ICAR and a 21% increase in the DCAR. Neither of the 2 pts responded to treatment. Further pts are under study and their PK/PD results will be presented. Conclusions: PK and PD can be measured using DCE MRI together with MRS to determine the clinical affects of Ima, Ge, and the Ima-Ge combination. Current results indicate that Ima has a measurable effect on T V, but its relation to drug U and pt response require further pt evaluations to be definitive. [Table: see text]
CESR and CEGPR candidates must work in UK for at least a year before application
Authors: Caroline White
Journal: BMJ (2012)

The General Medical Council is now formally recommending that prospective applicants for the certificates of eligibility for specialist (CESR) or general practice registration (CEGPR) must have clocked up at least 12 months of practice as a licensed doctor in the UK in the preceding three years before they apply.

These doctors will also have to undergo formal tests of their specialist knowledge and workplace assessments, although further discussions with the royal colleges, employers, and deaneries will be needed to flesh out the logistics.

The GMC has, however, refuted the suggestion that it is set to create a two tier system by exempting doctors “of high international renown and proven expertise in their field” and assessing them purely …
Preoperative prognosis predictors for patients with gastric stump cancers.
Authors: Masanori Tokunaga, Shizuki Sugita, Masahiro Watanabe, Akio Kaito, Takahiro Kinoshita
Journal: Journal of Clinical Oncology (2018)

179 Background: The incidence of GSC is expected to increase as the survival outcome following gastrectomy for gastric cancer improves. Considering poor tolerability to postoperative adjuvant chemotherapy after completion of total gastrectomy, neoadjuvant chemotherapy (NAC) is a plausible treatment strategy for GSC, but it is unclear which clinical factors should make patients candidates for NAC, due to the lack of studies investigating the relationship between clinical factors and survival outcome. The aim of this study was to review preoperative prognostic factors and identify suitable candidates for NAC. Methods: A total of 71 patients with GSC who underwent curative completion total gastrectomy between 1998 and 2015 were included. Preoperative clinical factors and survival outcomes were investigated, and independent prognostic factors were analyzed by Cox proportional hazards model. Results: Median age (range) was 68 (42-82) years, and male-female ratio was 6.0:1. Initial surgery was for benign disease in 21 and for malignant disease in 49 patients. Preoperative diagnosis was cT2-4 in 30 (43%), and cN+, which was defined as lymph node ≥10mm in diameter, in 7 patients (10%). The 3-year recurrence free survival (RFS) rate was 79%. Multivariable analysis revealed cT2-4 as an independent prognostic factor (HR, 2.86; 95% C.I., 1.03-8.64), but clinical N+ was not (HR, 0.64; 95% C.I., 0.10-2.31). When survival curves were stratified by cT, 3-year RFS of cT2-4 (60%) was significantly worse than cT1 (92%, p=0.024) Conclusions: Survival outcomes of patients with cT2-4 seem worse enough for them to be selected as candidates for NAC. On the contrary, cN+ was not associated with worse survival outcome. NAC could be a treatment option for cT2-4 GSC patients irrespective of nodal status.
Near-infrared rechargeable “optical battery” implant for irradiation-free photodynamic therapy
Authors: Lidan Hu, Peiyuan Wang, Mengyao Zhao, Lu Liu, Lei Zhou, Benhao Li, Fahad H. Albaqami, Ahmed Mohamed El-Toni, Xiaomin Li, Yang Xie, Xiaofei Sun, Fan Zhang
Journal: Biomaterials (2018)
The Prognostic Value of Right Ventricular Deformation Imaging in Early Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Thomas P. Mast, Karim Taha, Maarten J. Cramer, Joost Lumens, Jeroen F. van der Heijden, Berto J. Bouma, Maarten P. van den Berg, Folkert W. Asselbergs, Pieter A. Doevendans, Arco J. Teske
Journal: JACC. Cardiovascular imaging (2018)
Factors Associated With Outcomes and Costs After Pediatric Laparoscopic Cholecystectomy
Authors: Gileh-Gol Akhtar-Danesh, Aristithes G. Doumouras, Cecily Bos, Helene Flageole, Dennis Hong
Journal: JAMA Surgery (2018)

The prevalence of pediatric cholelithiasis is increasing with the epidemic of childhood obesity. With this rise, the outcomes and costs of pediatric laparoscopic cholecystectomy become an important public health and economic concern.To assess patient and health system factors associated with the outcomes and costs after laparoscopic cholecystectomy among Canadian children.This was a retrospective, population-based study of children 17 years and younger undergoing laparoscopic cholecystectomy from April 1, 2008, until March 31, 2015. The data source was the Canadian Institute for Health Information. The Canadian Institute for Health Information Discharge Abstract Database includes data from all Canadian hospitals. The analysis was limited to inpatient cholecystectomies. All Canadian children undergoing laparoscopic cholecystectomy were included.The exposure in this study was laparoscopic cholecystectomy.The primary outcome was all-cause morbidity, a composite outcome of any complication that prolonged length of stay by 24 hours or required a second, unplanned procedure. The cost of the index admission was also calculated as a secondary outcome. These outcomes of interest were determined before data analysis. Odds ratios and 95% CIs were estimated using multilevel logistic regression models.During the study period, 3519 laparoscopic cholecystectomies were performed; of these, 79.1% (n = 2785) were in girls, and 98.0% (n = 3450) were for gallstone disease. The overall morbidity rate was 3.9% (n = 137). After adjustment, patients with comorbidities were more susceptible to morbidity (odds ratio, 2.68; 95% CI, 1.78-3.86; P < .001). Operations for gallstones were less morbid. High-volume general surgeons had lower morbidity rates compared with low-volume pediatric surgeons (odds ratio, 0.32; 95% CI, 0.12-0.69; P = .005) independent of pediatric volumes. The mean (SD) unadjusted cost of a laparoscopic cholecystectomy was $4115 ($7273). Operative indication, complications, comorbidities, emergency admission, and surgeon volume were associated with cost.The high-volume nature of adult general surgery translated to lower morbidity and cost after pediatric laparoscopic cholecystectomy, suggesting that adult volume is associated with pediatric outcomes. As the rate of pediatric gallstone disease increases, surgeon volume, rather than specialty training, should be considered when pursuing operative management.
Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings
Authors: Abraham R. Tzafriri, Fernando Garcia-Polite, Xiaojian Li, John Keating, Josep-Maria Balaguer, Brett Zani, Lynn Bailey, Peter Markham, Timothy C. Kiorpes, Wenda Carlyle, Elazer R. Edelman
Journal: Journal of Controlled Release (2018)
Cognitive ageing research methods for medical scientists
Authors: Gopalakrishnan Deivasikamani
Journal: BMJ (2011)

This postgraduate course aims to equip students with a critical understanding of cognitive ageing and cognitive epidemiology. It also helps participants develop critical appraisal skills, an understanding of the research governance framework covering cognitive research, and the intellectual and practical skills needed to design and carry out cognitive research.

The course is for anybody with an interest in cognitive ageing, dementia, and delirium and postgraduate students who need training in setting up a research proposal.

During my third year of higher specialist training as a specialty trainee 5 in geriatric medicine. …
Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study
Authors: Rachael F. Grace, Paola Bianchi, Eduard J. van Beers, Stefan W. Eber, Bertil Glader, Hassan M. Yaish, Jenny M. Despotovic, Jennifer A. Rothman, Mukta Sharma, Melissa M. McNaull, Elisa Fermo, Kimberly Lezon-Geyda, D. Holmes Morton, Ellis J. Neufeld, Satheesh Chonat, Nina Kollmar, Christine M. Knoll, Kevin Kuo, Janet L. Kwiatkowski, Dagmar Pospíšilová, Yves D. Pastore, Alexis A. Thompson, Peter E. Newburger, Yaddanapudi Ravindranath, Winfred C. Wang, Marcin W. Wlodarski, Heng Wang, Susanne Holzhauer, Vicky R. Breakey, Joachim Kunz, Sujit Sheth, Melissa J. Rose, Heather A. Bradeen, Nolan Neu, Dongjing Guo, Hasan Al-Sayegh, Wendy B. London, Patrick G. Gallagher, Alberto Zanella, Wilma Barcellini
Journal: Blood (2018)
BEDSIDE TESTING OF CYP2C19 GENOTYPE TO GUIDE ANTIPLATELET THERAPY: IMPLEMENTATION IN THE CATHETERIZATION LABORATORY
Authors: Paul A. Gurbel, Rachel Bell, Kevin Bliden, Shahram Yazdani, Hamid Taheri, Marjaneh Akbari, Behnam Tehrani, Heather Russell, Ramaswamy Iyer, Udaya Tantry
Journal: Journal of the American College of Cardiology (2018)
BMA urges government to define “seven day services”
Authors: Abi Rimmer
Journal: BMJ (2015)

The BMA has called for the government to clearly define “seven day services,” after the government refused to release correspondence relating to the scope of such services.

Mark Porter, the BMA’s chair of council, said, “The government should clearly define what it means when it uses the term ‘seven day service’ so that we know how much the additional services would …
RNAScope as a platform to detect IDO1 expression in tumor tissue sections.
Authors: Michael Pratta
Journal: Journal of Clinical Oncology (2018)

116 RNAScope is a sensitive, specific platform to detect IDO1 expression in tumor tissue sections. M Pratta, M Rupar, P Waeltz, T Burn, G Hollis, M Covington, M Smith, and R Newton. Incyte Corp. Wilm. DE. Background: Indoleamine 2,3-Dioxygenase 1 (IDO1) catalyzes the primary and rate-limiting step in tryptophan catabolism to generate N-formyl-kynurenine (Kyn). Through a combination of local depletion of tryptophan and an increase in Kyn concentrations, IDO-1 activity can result in the suppression of antitumor immune responses. Because IDO-1 inhibitors are now in the clinic for treatment of multiple tumor types, immunohistological approaches are employed to demonstrate IDO1 expression in tumor biopsies. However, using a commercially available antibody to detect IDO1 by immunohistochemistry (IHC), the level of sensitivity was inadequate. Methods: In order to improve the sensitivity of IDO1 detection, we evaluated in situ hybridization (ISH) using RNAScope technology and digital quantitation by HALO analysis in collaboration with Advanced Cell Diagnostics (ACD). The technology was cross-validated using IDO1 qRT-PCR, Western blot, and activity analysis and compared with standard IHC. We initially evaluated IDO1 expression in HeLa cells stimulated with various concentrations of IFNγ, and then extended the observations using tissue sections from multiple tumor types. Results: In the HeLa cell model, IFNγ induced a time- and concentration-dependent increase of IDO1 at the mRNA, protein, and activity level. Although IDO1 was successfully detected in the HeLa cell samples by IHC, comparison of the platforms indicated IFNγ EC 50 values were in strong agreement between RNAScope (193.8 pg/ml) and Western blot analysis (170.8 pg/ml), but was much higher by IHC analysis (2206 pg/ml). A strong positive correlation (*p &lt; 0.0001) between RNAScope and Western blot analysis was observed, suggesting a highly coordinated induction of IDO1 by IFNγ at both the mRNA and protein levels. FFPE tumor tissue from melanoma, HNSCC, bladder, renal, ovarian, and lung cancers visualized by RNAScope all show varying levels of IDO1 expression. Conclusions: These data support the use of RNAScope for the analysis of IDO1 expression in clinical trials.
Downregulation of USP28 confers poorer overall survival to melanoma patients and causes resistance to RAF inhibitors
Authors: A. Saei, M. Palafox, T. Benoukraf, N. Kumari, P. Iyengar, Z.F. Bin Adam Isa, H. Yang, W.L. Tam, V. Serra, P. Eichhorn
Journal: Annals of Oncology (2018)
Phase II Study of the Dual EGFR/HER3 Inhibitor Duligotuzumab (MEHD7945A) versus Cetuximab in Combination with FOLFIRI in Second-Line <i>RAS</i> Wild-Type Metastatic Colorectal Cancer
Authors: Andrew G. Hill, Michael P. Findlay, Matthew E. Burge, Christopher Jackson, Pilar Garcia Alfonso, Leslie Samuel, Vinod Ganju, Meinolf Karthaus, Alessio Amatu, Mark Jeffery, Maria Di Bartolomeo, John Bridgewater, Andrew L. Coveler, Manuel Hidalgo, Amy V. Kapp, Roxana I. Sufan, Bruce B. McCall, William D. Hanley, Elicia M. Penuel, Andrea Pirzkall, Josep Tabernero
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. Experimental Design: Metastatic colorectal cancer (mCRC) patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. Results: Of 134 randomly assigned patients, 98 had RAS ex2/3 wild-type. Duligotuzumab provided no progression-free survival (PFS) or overall survival (OS) benefit compared with cetuximab, although there was a trend for a lower objective response rate (ORR) in the duligotuzumab arm. No relationship was seen between PFS or ORR and ERBB3, NRG1, or AREG expression. There were fewer skin rash events for duligotuzumab but more diarrhea. Although the incidence of grade ≥3 AEs was similar, the frequency of serious AEs was higher for duligotuzumab. Conclusions: Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared with cetuximab + FOLFIRI. Clin Cancer Res; 24(10); 2276–84. ©2018 AACR.
ASSOCIATION BETWEEN DIABETES MELLITUS AND POOR PATIENT OUTCOMES AFTER OUT-OF-HOSPITAL CARDIAC ARREST: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Dinesh Voruganti, Michael C. Giudici, Adithya Chennamadhavuni, Rohan Garje, Ghanshyam P.S. Shantha, Marin Schweizer, Saket Girotra
Journal: Journal of the American College of Cardiology (2018)
Chronic urticaria can be caused by cancer and resolves with its cure
Authors: D. Larenas‐Linnemann, S. S. Saini, A. A. Azamar‐Jácome, M. Maurer
Journal: Allergy (2018)

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Doctors trained outside the UK are more likely to be assessed by the GMC, say researchers
Authors: Abi Rimmer
Journal: BMJ (2017)

Doctors trained outside of the UK are more likely to undergo performance assessments with the General Medical Council than doctors trained in the UK, researchers have found.1

Researchers from University College London found that doctors who trained in Bangladesh were 13 times more likely to have a performance assessment than UK graduates, while doctors trained in Nigeria or Egypt were eight times more likely to be assessed.

The GMC can …