tbuckley/cabot-search huggingface dataset:
Evaluation of the effect of baseline MRI sacroiliitis and C reactive protein status on etanercept treatment response in non-radiographic axial spondyloarthritis: a post hoc analysis of the EMBARK study
Authors: Matthew A Brown, Paul A Bird, Philip C Robinson, Philip J Mease, Filip van den Bosch, Christine Surian, Heather Jones, Annette Szumski, Lisa Marshall, Zirke Wiid, Maxime Dougados
Journal: Annals of the Rheumatic Diseases (2017)

The efficacy of tumour necrosis factor alpha (TNFα) inhibitors for patients with non-radiographic axial spondyloarthritis (nr-axSpA) has now been firmly established1–3; however, identification of objective markers, predictive of treatment response, will be of considerable benefit in optimising patient outcomes and ensuring the most appropriate treatment prioritisation and resource allocation. We have investigated this further using the findings of EMBARK (effect of etanercept on symptoms and objective inflammation in nr-axSpA, a 104 week study) (ClinicalTrials.gov identifier: NCT01258738), a phase IIIb, 104-week randomised controlled trial in >200 patients with nr-axSpA,4–6 which showed a possible association between higher baseline C reactive protein (CRP) levels or magnetic resonance imaging (MRI) sacroiliac joint (SIJ) scores and a placebo (PBO)-adjusted treatment effect. The objective of this post hoc analysis was to determine whether MRI sacroiliitis (positive/negative (+/−)) and/or high-sensitivity CRP (hs-CRP) (elevated/normal (+/−)) at baseline are predictive of changes in measures of disease activity on etanercept (ETN) treatment in patients with nr-axSpA.

Eligible patients were randomised to 12 weeks’ double-blind treatment with 50 mg ETN once weekly or PBO. Both groups continued stable non-steroidal anti-inflammatory drug (NSAID) therapy. MRI scanning of the SIJ and spine was performed at screening and …
Budget Impact Analysis of Treating Chemotherapy Patients with Patient-Administered Tbo-Filgrastim, Filgrastim-Sndz, and Filgrastim in the United States
Authors: Holly Trautman, Erika Szabo, Francesco Lo-Coco, Elizabeth James, Susan Gabriel, Jifang Zhou, Ashutosh Pathak, Boxiong Tang
Journal: Blood (2016)
Imaging response during therapy with radium-223 (Ra-223) for castration-resistant prostate cancer (CRPC) with bone metastases (BM): A multicenter analysis.
Authors: Aurelius Gabriel Omlin, Gedske Daugaard, Avivit Peer, Hermann Reichegger, Avivit Neumann, Eli Rosenbaum, Marie-Claire Desax, Victoria Neiman, Peter Meidahl Petersen, Joachim Mueller, Richard Cathomas, Maya Gottfried, David Sarid, Eli Gez, Wilmosh Mermershtain, Keren Rouvinov, Jann Mortensen, Silke Gillessen, Daniel Keizman
Journal: Journal of Clinical Oncology (2016)

5057 Background: Ra-223 is an alpha emitter that selectively targets BM. Ra-223 is an approved treatment option for CRPC patients (pts) based on a significant improvement in overall survival. The pivotal phase III ALSYMPCA trial did not mandate monitoring of antitumor activity by imaging. We aimed to describe the imaging response in pts treated with Ra-223. Methods: Retrospective evaluation of computed tomography (CT) and bone scintigraphy (BS) of consecutive CRPC pts treated with Ra-223. All patients had scans done at baseline. Patients were treated with Ra-223 in 8 centers across 3 countries. Therapy consisted of standard Ra-223 administration (50 kBq q4 weeks for up to 6 injections). Results: A total of 127 pts were included (median age 72), of which 68% (n = 86) were treated with Ra-223 post docetaxel chemotherapy. A total of 20% (n = 26) of patients received concomitant abiraterone or enzalutamide. 52% (n = 66) patients completed the planned 6 injections. Clinical benefit (improvement of skeletal pain and/or performance status) was noted in 48% (n = 40/83 pts with available data). Among 82 pts with available data, a transient increase in bone metastases related pain occurred in 33% (n = 27). Among 101 patients with BS data available at 3 months, stable disease (equal or less than 1 new lesion) was noted in 71% (n = 72), and 2 or more new lesions in 28% (n = 28). Among 72 patients with BS available at 6 months, stable disease was documented in 93% (n = 67), and progression with at least 2 new lesions versus the 3 months status in only 7% (n = 5) pts. Among 96 patients with available CT data, soft tissue progression during therapy was noted in 40% (n = 38), this progression was found in lymph nodes only in 61% (n = 23) and as progressive disease in lymph node and/or visceral (lung, liver, adrenal) metastases in 55% (n = 21). Conclusions: Progression as per PCWG2 criteria of BM during Ra-223 was uncommon. A bone flare (pain and radiological) may be noted during the first 3 months, and should not be confused with progression. A significant number of patients had soft tissue progression on therapy with Ra-223 supporting the rationale for combination trials.
The Final Rule: When the Rubber Meets the Road
Authors: P. Pearl O'Rourke
Journal: The American Journal of Bioethics (2017)

The Common Rule originally issued in 1991 and last amended in 2005 is scheduled to be replaced on January 19, 2018 by a revised Common Rule (the final rule). The goal of the revisions is to modernize and improve applicability of the rule to a research landscape that has dramatically changed since 1991. Translating these changes into action will require comprehensive understanding of the final rule and detailed implementation planning by Human Research Protection Programs. This paper presents select changes that require substantial attention; including for example: expansion of the exempt category, changes to continuing review requirements, changes to the informed consent form and the use of single IRBs for domestic multi-site research. In addition, myriad policies, procedures and workflows will have to be developed, drastically rewritten, or just mildly tweaked.
Clinico-epidemiological profile of gastric cancer in Algerian patients age 45 and under
Authors: Souad Bekouaci, El Hakim Boudjella Abdelkader, Yasmine Nefradji, Soumia Rekkache, Amina Menouer, Mohamed Mouaici, Farida Smaili
Journal: Annals of Oncology (2017)
A prospective multicenter phase II study of sorafenib combined with cisplatin plus gemcitabine for the treatment of patients with advanced renal collecting duct carcinoma (NCT01762150).
Authors: Xinan Sheng, Chuanliang Cui, Zhihong Chi, Lu Si, Si Ming Li, Li Li Mao, BIN LIAN, Bixia Tang, Xieqiao Yan, Xuan Wang, Yan Kong, Jianlin Yuan, Fangjian Zhou, Xiaodong Xie, Qiang Wei, Jun Guo
Journal: Journal of Clinical Oncology (2016)

4559 Background: Collecting duct carcinoma (CDC) of the kidney is a rare and aggressive neoplasm without any approved treatment. The anti-VEGF drugs can produce definite efficacy on renal clear cell carcinoma, but limited for advanced CDC. Gemcitabine plus cisplatin (GC) has showed some activity in patients with advanced CDC. This study was designed to evaluate the efficacy and safety of sorafenib combined with GC as first line treatment in patients with advanced CDC. Methods: This study is a prospective multicenter, single-arm phase II trial. Patients with metastatic, or unresectable CDC by central pathological confirmation and ≥ 1 measurable lesion per RECIST criteria, ECOG PS ≤ 2, and adequate organ function are enrolled. All patients received sorafenib (400mg Bid) combined with GC (cisplatin: 25mg/m2, d1-3; gemcitabine: 1000 mg/m2, d1,d8, for 4 cycles) until disease progression, unacceptable toxicity, or study discontinuation for any other reason. The primary endpoint is PFS. Overall survival, disease control rate, and safety will also be assessed. Results: Between Jun 2012 and Dec 2015, 26 patients with metastatic CDC were enrolled at 5 Chinese centers after central pathological confirmation. In these patients, 25 patients received prior nephrectomy. The sites of metastases included lung, mediastinal lymph node, local recurrence, retroperitoneal lymph node, skeleton and peritoneum. There were 0 complete and 8 partial responses for an objective response rate of 30.8% (95% CI: 13.1 to 48.5%). Fourteen patients (53.8%) were noted to have stable disease. The disease control rate was 83.8%. Median PFS and OS was 8.3 (95% CI: 2.9 to 13.7) and 11.5 months (95% CI 10.5 to 12.5), respectively. The treatment was well tolerated and toxicities were most grade 1/2. Grade 3/4 toxicities included neutropenia (5/26), thrombocytopenia (3/26), hand-foot syndrome (9/26). Conclusions: This is the largest study about advanced CDC and is the first prospective, multicenter, phase II study showing that sorafenib combined with GC regimen is active and safe as first line therapy in patients with advanced CDC. Clinical trial information: NCT01762150.
RNA Sequencing of Newly Diagnosed Multiple Myeloma to Identify a Predictive Signature for Proteasome Inhibitor-Based Therapy
Authors: Jonathan I Sive, John C Ambrose, Kwee L Yong, Claire Roddie, Nicholas Counsell, Paul Smith, Nivette Braganca, Toyin Adadayo, Rakesh Popat, James D Cavenagh, Roger G Owen, Matthew Streetly, Stephen A Schey, Mickey Koh, Josephine Crowe, Michael F Quinn, Shirley D'Sa, Andres Virchis, Gordon Cook, Charles Crawley, Guy E Pratt, Mark Cook, Michael A Chapman
Journal: Blood (2016)
Penicillin Allergy Is Not Necessarily Forever
Authors: Jason A. Trubiano, N. Franklin Adkinson, Elizabeth Jane Phillips
Journal: JAMA (2017)

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
Genetic deletion or small-molecule inhibition of the arginine methyltransferase PRMT5 exhibit anti-tumoral activity in mouse models of MLL-rearranged AML
Authors: S Kaushik, F Liu, K J Veazey, G Gao, P Das, L F Neves, K Lin, Y Zhong, Y Lu, V Giuliani, M T Bedford, S D Nimer, M A Santos
Journal: Leukemia (2017)
Use of a competitive probe in assay design for genotyping of the UGT1A1*28 microsatellite polymorphism by the SMart-amplification process
Authors: Jun Watanabe, Yasumasa Mitani, Yasushi Kogo, Paul Cizdziel, Alexander Lezhaval, Kenji Tatsumi, Yasushi Ichikawa, Shinji Togo, Yoshihide Hayashizaki, Hiroshi Shimada
Journal: Clinical Cancer Research (2007)

A46  The complexity of molecular diagnostic assays is a significant barrier to employment at point-of-care, despite the growing need for such technologies. We have developed a sensitive, accurate, rapid, and simple DNA amplification scheme that shows potential for translational medicine from pharmacogenomics-based drug discovery thru to point-of-care diagnostics. Called the SMart Amplification Process version 2 (SMAP-2), the method employs a unique primer design and background suppression technology to minimize background amplification uses Thermus aquaticus MutS (Taq MutS) that can amplify only target sequences from blood sample without thermocycling.  This time we report that use of SMAP-2 for polymorphism determination of the UGT1A1*28 allele required a further ancillary approach for complete background suppression. The UGT1A1*28 allele is a microsatellite copy number polymorphism. This is the first reported SMAP-2 assay designed for genotyping genetic variations of microsatellites. We found that by the addition of a primer to the amplification reaction, called a competitive probe (CP), assay specificity could be significantly enhanced. Including sample preparation time, we could rapidly detect the UGT1A1*28 polymorphism within 60 minutes using a CP-enhanced SMAP-2 assay. To test our method, we compared results from PCR-sequencing and the CP-enhanced SMAP-2 assay on 116 human blood samples for UGT1A1*28 polymorphism and demonstrated perfect concordance. These results illustrate the versatility of SMAP-2 for molecular diagnostics and provide a new approach for enhancing SMAP-2 assay specificity.
Meta-analysis of progression-free survival as a predictor of overall survival in locally advanced or metastatic non-small cell lung cancer trials.
Authors: Evadne Jane Turner, Philip McCloud, Peter Germanos, Francis Dehle, Sarah Norris, Jonathan Tan
Journal: Journal of Clinical Oncology (2012)

7604 Background: Access to new oncology treatments for non-small-cell lung cancer (NSCLC) could be expedited if progression free survival (PFS) was accepted by payers as a valid endpoint predictive for overall survival (OS). We investigated the relationship between PFS and OS in advanced NSCLC, which has previously been limited by available data. Methods: A systematic review of the published literature was conducted (1988 to August 2011; Medline/Embase/Cochrane). Identified studies were assessed against the following criteria for inclusion in the analysis: randomised design; NSCLC; advanced disease (Stage IIIb or IV); pharmacological treatment in 2 or more groups; reported outcomes included median OS and median PFS. For each pair of treatment groups compared, the median OS difference and the median PFS difference were calculated. The data were analysed with locally weighted least squares regression (LOWESS) to validate the linear relationship. Unweighted and weighted linear regression was used to test the significance of the relationship between OS difference and PFS difference. Results: A total of 124 clinical trials, with 40,568 patients, were included in the analysis. The studies ranged from middle aged cohorts to the elderly. Median performance status (ECOG/WHO) was 1. 70% of studies were first line and therapy type was predominantly chemotherapy (57%). 19 studies (15%) reported use of crossover or rescue therapy. Weighted linear regression demonstrated a highly significant linear relationship between OS difference and PFS difference (Table). The results suggest that a 1 month difference in PFS is associated with approximately 1.3 months difference in OS. Conclusions: Analysis of NSCLC trials showed the treatment effect on PFS was predictive of the treatment effect on OS. With increased use of multiple lines of treatment and crossover/rescue therapy in new NSCLC trials OS differences are frequently confounded, making PFS an important outcome for health care decision making. [Table: see text]
A SIGNIFICANT REDUCTION IN 'PRO-INFLAMMATORY' CD14LO/CD16HI MONOCYTES IN ACETAMINOPHEN-INDUCED ACUTE LIVER FAILURE: ASSOCIATION WITH OUTCOME AND CCR2 EXPRESSION
Authors: Daniel Abeles, Charalambos G. Antoniades, Maria Serena Longhi, Nicholas J. Taylor, Debbie L. Shawcross, William Bernal, Georg Auzinger, Nigel Heaton, Julia Wendon, Diego Vergani
Journal: Hepatology (2010)
A randomized, double-blind, single dose comparison of pharmacokinetics and safety of FKB238 with bevacizumab.
Authors: Hidekuni Kaito, Frans van den Berg, Andrew Niewiarowski, Malcolm Boyce
Journal: Journal of Clinical Oncology (2017)

e14007 Background: Bevacizumab is a recombinant humanized monoclonal antibody that binds selectively to vascular endothelial growth factor-A (VEGF-A). Bevacizumab was first approved for treatment of metastatic colon cancer under the brand name Avastin; it has since been approved for treating various other cancers. FKB238 is being developed as a biosimilar to Avastin. In this first-in-human study, safety, pharmacokinetics (PK) and immunogenicity of FKB238 were compared to those of branded Avastin from US and EU market. Methods: Ninety nine healthy male subjects were randomly assigned to receive a single 5 mg/kg intravenous infusion of either EU Avastin, US Avastin or FKB238 in a 1:1:1 ratio. Safety, PK and immunogenicity (anti-drug antibodies - ADA) were assessed up to 99 days after the infusion. Each PK parameter (AUC 0-inf and AUC 0–t as primary; C max and t 1/2 as secondary) was analysed to assess similarity between FKB238 and EU Avastin, FKB238 and US Avastin, and EU Avastin and US Avastin. PK similarity is established if for each of the 2 primary PK parameters, the 90% confidence interval (CI) of the ratio of geometric means for the said 3-way comparison falls within 0.80-1.25. Results: A total of 99 subjects were randomized and 96 completed the study. The 90% CI for the ratio of geometric LS means of all 3 comparisons (FKB238/EU Avastin, FKB238/US Avastin and US Avastin/EU Avastin) for all 4 PK parameters were entirely within the pre-defined equivalence margin (0.80-1.25). Overall, 81% of subjects experienced an adverse event (AE) after treatment (FKB238: 97.0%; EU Avastin: 76.5%; US Avastin: 71.9%). Most AEs were mild or moderate in intensity (Grade 1 or 2 by CTCAE ver. 4); the most common were headache (16.2%), epistaxis (8.1%) and fatigue (5.1%). There were no serious AEs. All subjects had a negative ADA against study drug at their last visit. Conclusions: The study demonstrated PK similarity of FKB238, EU Avastin and US Avastin in healthy male subjects. FKB238 was well tolerated, with no serious AEs. All three study compounds showed comparable safety profile with no significant AEs or evidence of a propensity to form ADAs. This results support further development of FKB238 as a proposed biosimilar to Avastin. Clinical trial information: 163882.
Pleckstrin-2 Plays an Essential Role in the Pathogenesis of JAK2V617F-Induced Myeloproliferative Neoplasms
Authors: Baobing Zhao, Yang Mei, Ronen Sumagin, Jing Yang, Chelsea Thorsheim, Liang Zhao, Timothy J. Stalker, Jeremy Q. Wen, John Crispino, Charles S. Abrams, Peng Ji
Journal: Blood (2016)
Efficacy and toxicity results of FOLFIRI-Aflibercept in advanced colorectal cancer (CRCm) in “real life”, retrospective study. Prognostic factors and specific populations.
Authors: Ana Fernandez Montes, López Carlos López, Alberto Carmona, David Paez, María Lopez Muñoz Ana, David Gutierrez Abad, López Carmen Castañón, del Carmen López Doldán Maria, de Castro Eva Martínez, Cánovas Manuel Sánchez, Maria Tobeña, Ayala Beatriz Llorente, Ignacio Juez Martel, Flores Mariana López, Beatriz García-Paredes, Diego Cacho Lanvin, Mercedes Salgado, Anna Virgili, Esparza Beatriz Arbeola
Journal: Annals of Oncology (2017)
Sex differences in cancer risk and survival.
Authors: Cecilia Radkiewicz, Anna Johansson, Paul Dickman, Mats Lambe, Gustaf Edgren
Journal: Journal of Clinical Oncology (2017)

e13074 Background: The ongoing global cancer increase poses immense challenges for cancer care. Few comprehensive analyses of sex differences in cancer risk and survival based on robust data have been conducted. Methods: We performed a large cohort study using nationwide Swedish Cancer Register data for years 1970-2014, including all adult incident, non-breast, non-genital cancer cases (504,379 male, 368,018 female). To assess the strength of association between sex and cancer we estimated male-to-female incidence rate ratios†. Relative survival models were used to quantify differences in survival and were expressed as excess mortality ratios*. We applied Poisson regression and adjusted for age and calendar year in both. Results: Men were at significantly increased risk for 34 of 39 sites, and had significantly poorer prognosis for 27 of 39, compared to increased risk for 5 of 39 sites and poorer survival for 2 of 39, in women. Incidence rate ratios in male predominant sites ranged from 1.05; 95% CI, 1.03-1.08 (lung adenocarcinoma) to 8.00; 95% CI, 7.50-8.53 (larynx), corresponding to 0.38; 95% CI, 0.36-0.39 (thyroid well-differentiated) to 0.69; 95% CI, 0.63-0.75 (thyroid anaplastic) in female predominant sites. In sites with poorer survival in men, excess mortality ratios ranged from 1.07; 95% CI, 1.03-1.10 (colon) to 2.08; 95% CI, 1.53-2.84 (well-differentiated thyroid). Conclusions: Male sex is an independent risk factor and associated with poorer survival for a large majority of cancer sites. The excess risk in men remains elevated over time for most sites. Identifying and eliminating factors driving sex differences may reduce global cancer burden considerably. [Table: see text]
Randomised controlled trial of transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND Study)
Authors: Renée M Barendse, Gijsbert D Musters, Eelco J R de Graaf, Frank J C van den Broek, Esther C J Consten, Pascal G Doornebosch, James C Hardwick, Ignace H J T de Hingh, Chrisiaan Hoff, Jeroen M Jansen, A W Marc van Milligen de Wit, George P van der Schelling, Erik J Schoon, Matthijs P Schwartz, Bas L A M Weusten, Marcel G Dijkgraaf, Paul Fockens, Willem A Bemelman, Evelien Dekker
Journal: Gut (2017)

Objective Non-randomised studies suggest that endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM), but EMR might be more cost-effective and safer. This trial compares the clinical outcome and cost-effectiveness of TEM and EMR for large rectal adenomas. Design Patients with rectal adenomas ≥3 cm, without malignant features, were randomised (1:1) to EMR or TEM, allowing endoscopic removal of residual adenoma at 3 months. Unexpected malignancies were excluded postrandomisation. Primary outcomes were recurrence within 24 months (aiming to demonstrate non-inferiority of EMR, upper limit 10%) and the number of recurrence-free days alive and out of hospital. Results Two hundred and four patients were treated in 18 university and community hospitals. Twenty-seven (13%) had unexpected cancer and were excluded from further analysis. Overall recurrence rates were 15% after EMR and 11% after TEM; statistical non-inferiority was not reached. The numbers of recurrence-free days alive and out of hospital were similar (EMR 609±209, TEM 652±188, p=0.16). Complications occurred in 18% (EMR) versus 26% (TEM) (p=0.23), with major complications occurring in 1% (EMR) versus 8% (TEM) (p=0.064). Quality-adjusted life years were equal in both groups. EMR was approximately €3000 cheaper and therefore more cost-effective. Conclusion Under the statistical assumptions of this study, non-inferiority of EMR could not be demonstrated. However, EMR may have potential as the primary method of choice due to a tendency of lower complication rates and a better cost-effectiveness ratio. The high rate of unexpected cancers should be dealt with in further studies.