tbuckley/cabot-search huggingface dataset:
A pilot randomised clinical trial of mepolizumab in COPD with eosinophilic bronchitis
Authors: Angira Dasgupta, Melanie Kjarsgaard, Dante Capaldi, Katherine Radford, Fernando Aleman, Colm Boylan, Leonard C. Altman, Thomas N. Wight, Grace Parraga, Paul M. O'Byrne, Parameswaran Nair
Journal: European Respiratory Journal (2017)

Airflow limitation in chronic obstructive pulmonary disease (COPD) is associated with influx of various inflammatory cells ( e.g. eosinophils, neutrophils, lymphocytes, macrophages) into the airways. Approximately one-third of stable COPD patients and one in five COPD exacerbations are associated with eosinophilic bronchitis that usually responds to inhaled or ingested corticosteroids [1]. Specific anti-eosinophil agents like mepolizumab, a humanised monoclonal antibody against interleukin 5 (IL-5), reduce severe asthma exacerbations and improve lung function [2–4]. The improvement in forced expiratory volume in 1 s (FEV1) is also associated with a decrease in biomarkers of airway remodelling, such as sputum hyaluronan and versican, over a 6-month treatment period [5]. It is not known if the same benefits are observed in patients with COPD and eosinophilia in whom the airflow obstruction is due to cigarette smoke-related bronchitis and emphysema. Eosinophils may not directly contribute to luminal obstruction in COPD although they may predict steroid response <http://ow.ly/b3Au308wA0m>
Clinical utility and actionability of a combinatorial approach utilizing molecular diagnosis and biomarker profiling for cancers with unknown or differential diagnoses that were diagnosed as NSCLC.
Authors: Nitin Kapoor, Theresa N. Operana, Brock Schroeder, Catherine A. Schnabel
Journal: Journal of Clinical Oncology (2015)

e19101 Background: Optimal treatment of metastatic non-small cell lung cancer (NSCLC) requires testing a growing number of predictive biomarkers linked to targeted therapies. However, metastatic cancers with unknown or differential diagnoses may be at risk for nonoptimal treatment planning if a diagnosis of NSCLC is not established and appropriate predictive biomarkers are not assessed. The objective of this study was to assess the clinical actionability of a combinatorial approach utilizing molecular diagnosis by the 92-gene assay followed by multi-platform biomarker profiling in a large series of cases with unknown or differential diagnoses that were diagnosed as NSCLC by the 92-gene assay. Methods: Consecutive cases (N = 465) submitted for molecular diagnosis with the 92-gene assay (CancerTYPE ID, bioTheranostics) and subsequent multi-platform biomarker profiling (50 gene NGS hotspot panel; FISH amplifications, rearrangements, deletions; IHC) were included. 92-gene assay molecular predictions were evaluated. Biomarker detection rates and clinical actionability, defined as biomarkers with approved targeted therapies and/or associated phase II/III clinical trials, were analyzed in cases molecularly diagnosed as NSCLC. Results: Of 465 cases evaluated, 27 distinct tumor types were predicted. 70 cases (15%) were classified as NSCLC (70% subtyped as adenocarcinoma and 30% as squamous cell carcinoma). Actionable biomarker results were identified in 51% (36/70) of cases identified as NSCLC by the 92-gene assay. These included 8.6% of cases with EGFR, 2.9% with BRAF, 7.1% with PIK3CA, 25.7% with KRAS, and 21.4% with KIT mutations. A total of 27 distinct biomarkers were detected as positive. Conclusions: These results demonstrate the clinical utility of a combinatorial approach utilizing molecular diagnosis of tumor context and comprehensive multi-platform mutational profiling to enable a precision medicine approach with tumor-specific and molecularly-targeted options.
Rituximab Preferentially Eliminates BCR Signaling Proficient Chronic Lymphocytic Leukemia B Cells In Vivo
Authors: Gabriela Pavlasova, Marek Borsky, Katerina Musilova, Vaclav Seda, Katerina Cerna, Jitka Osickova, Eva Vojackova, Yvona Brychtova, Michael Doubek, Sarka Pospisilova, Jiri Mayer, Marek Mraz
Journal: Blood (2016)
Increasing Epic staging module adherence in an academic cancer center.
Authors: Julie Porter, Andrea Segura Smith, Marta Cook, Kristine Boncato, Mary Bruels, Erik Duda-Stavlund, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2017)

64 Background: Documenting tumor staging (TS) is an important quality measure from ASCO’s QOPI program as a useful Core component of care. Real-time, actionable TS documentation in structured fields is important to identify patient cohorts for value-based measurement and to trigger patient care interventions. TS at our institution was usually documented in plain text progress notes in our electronic health record (Epic, Verona WI), making it difficult to use for automating support services, clinical trial evaluation, pre-authorization, business operations, value-based initiatives, and clinical research. Methods: Entry of TS into structured fields in the Epic Staging Module was agreed upon as an internal cancer quality measure in Fiscal Year (FY) 16 (9/15 – 8/16). Patients with &gt; 2 visits to an oncology outpatient department and who began surgical, radiation or chemotherapy treatment in the reporting month were included. The physician providing the first treatment was accountable. Monthly physician and patient-level reports were provided to physician leaders, in a phased roll-out. Targets were based off FY15 performance, which were doubled for a minimum of 40% and maximum of 70% adherence. Results: Nine cancer care programs (CCPs) participated. Average compliance increased from 24% in 9/15 to 79% in 8/16. 2089 of 2894 (72%) charts had clinical and/or pathologic TS entered in the Module. Adherence was driven by CCP leaders sharing data and allowing advanced practice providers staging privileges. We uncovered discordance among providers on what clinical information to input into the Module: original diagnosis or presenting diagnosis on which to base treatment. Conclusions: Our multidisciplinary care teams improved our ability to capture TS at first treatment. A rolled-out, rather than big-bang “hard stop,” approach was successful, as we uncovered unexpected flaws in the system including aligning clinical and staging privileges with Epic access privileges, inaccuracies in Module implementation, and unclear definition between stage and disease state. There are deficiencies in the current AJCC staging system, particularly in its use for relapsed or recurrent cancer, which make defining real-time actionable processes difficult.
Implementation of a systematic method for the identification, tracking, and treatment of malnutrition in pediatric patients with acute lymphoblastic leukemia.
Authors: Jennifer Mangino, Elizabeth Welin, Cheri Cole-Jenkins, Kathy Demmel, Brian D. Weiss
Journal: Journal of Clinical Oncology (2017)

184 Background: It is estimated that the prevalence of malnutrition in children with cancer may be as high as 50%. Optimization of nutritional status is known to be associated with improved tolerance of cancer therapy, decreased infection risk, increased quality of life and increased survival. There are established methods for improving nutrition, but we have observed barriers to the identification of at risk patients, adherence to recommended interventions and continued surveillance. Methods: We identified patients in the intensive phases of therapy for acute lymphoblastic leukemia/lymphoblastic lymphoma. Using improvement science methods, we developed a standardized approach to the identification, treatment and tracking of patients at risk for malnutrition. We utilized quality improvement techniques to identify the problems with the current system and implement change. These changes included standardization of an algorithm for nutritional treatment and follow up, creation of a daily electronic report for identification of at risk patients, and improved communication with providers in regard to patient nutrition. Results: At baseline, nearly 10% of our target patients were impacted by significant weight loss. Utilizing quality improvement techniques, we were able to establish the most common causes of failure in our system (awareness of the problem, identification of at-risk patients, tracking and monitoring at-risk patients and provider/patient adherence to recommended nutritional interventions). Interventions were employed using plan-do-study-act quality improvement methods, including the development of an electronic identification and tracking system designed for these patients. We were able to significantly decrease the number of patients with weight loss using these methods. Conclusions: Malnutrition is associated with poor outcomes in patients with cancer. Use of quality improvement methods allowed us to identify key drivers and test/implement specific interventions to combat this problem. In this proof of principle cohort, this has resulted in a significant improvement in the nutritional status of our patients.
Gene Therapy for Hemophilia
Authors: Arthur W. Nienhuis, Amit C. Nathwani, Andrew M. Davidoff
Journal: Molecular Therapy (2017)

The X-linked bleeding disorder hemophilia causes frequent and exaggerated bleeding that can be life-threatening if untreated. Conventional therapy requires frequent intravenous infusions of the missing coagulation protein (factor VIII [FVIII] for hemophilia A and factor IX [FIX] for hemophilia B). However, a lasting cure through gene therapy has long been sought. After a series of successes in small and large animal models, this goal has finally been achieved in humans by in vivo gene transfer to the liver using adeno-associated viral (AAV) vectors. In fact, multiple recent clinical trials have shown therapeutic, and in some cases curative, expression. At the same time, cellular immune responses against the virus have emerged as an obstacle in humans, potentially resulting in loss of expression. Transient immune suppression protocols have been developed to blunt these responses. Here, we provide an overview of the clinical development of AAV gene transfer for hemophilia, as well as an outlook on future directions.
The Independent Effects of Frailty and Comorbidity On the Quality of Life in MDS Patients
Authors: Rena Buckstein, Shabbir M.H. Alibhai, Dina Khalaf, Adam Lam, Alex Mamedov, Lisa Chodirker, Liying Zhang, Martha Lenis, Matthew Cheung, Jeannie Callum, Janey Hsiao, Yulia Lin, Kenneth Rockwood, Richard A. Wells
Journal: Blood (2012)
Phase II feasibility study of paclitaxel (T) with trastuzumab (H) and lapatinib (L) for node-negative, HER2-positive breast cancer (BC).
Authors: Neil M. Iyengar, Monica Nancy Fornier, Steven Sugarman, Maria Theodoulou, Tiffany A. Troso-Sandoval, Gabriella D'Andrea, Pamela Drullinsky, Julie Fasano, Devika Gajria, Shari Beth Goldfarb, Elizabeth Anne Comen, Diana Lake, Shanu Modi, Tiffany A. Traina, Melanie Chen, Sujata Patil, Jose Baselga, Larry Norton, Clifford A. Hudis, Chau T. Dang
Journal: Journal of Clinical Oncology (2014)

633 Background: We previously demonstrated that weekly T + HL after anthracycline based therapy was not feasible due to high incidence of grade (G) 3 diarrhea, which led to modification of the ALTTO trial. Previous data showed that L could be given more safely with every (q) 3 week than weekly T. Given the low and similar diarrhea rates between T dosed q 2 versus 3 weeks (CALGB 9741), we studied dose dense (dd) T + H + full dose L (THL). Methods: This is a single center, phase II feasibility study of dd T + HL. Eligible patients (pts) had HER2+ BC (IHC 3+ or FISH amplified ≥ 2.0) with negative nodes (micrometastasis allowed) and tumor size ≤ 3 cm. Pts received T 175 mg/m2 x 4 q 2 weeks (w), H 4 mg/kg load → 2 mg/kg qw with T, and L 1000 mg daily. Pts received pegfilgrastim after each T, during the THL phase. Afterwards, H (6 mg/kg q 3 w) + L were continued x 1 year. Left ventricular ejection fraction (LVEF) monitoring was done at baseline, months 2, 6, 9, 12, and 18 by an echocardiogram. Primary endpoint was feasibility defined as ≥ 80% of pts who completed THL without dose delay or reduction. Allowable rate of G 3 diarrhea was set at 20% and cardiac event (symptomatic heart failure or cardiac death) at ≤ 4%. Results: From 05/13 – 11/13, 20 of 55 planned pts were enrolled; median age 49 (range 34 – 74 years). Overall, 17/20 (85%) had ER+ tumors. Tumors were T1a (20%), T1b (30%), T1c (40%), and T2 (10%). 1 pt had immediate T hypersensitivity and was deemed inevaluable. Only 12/19 (63%) evaluable pts completed the THL phase without dose delay/reduction or unacceptable toxicities. Diarrhea rates were: all G-16/19 (84%) and G 3-3/19 (16%). Rash rates were high: all G-18/19 (95%), G 2-7/19 (37%), G 3-1/19 (5%). Other G3-4 toxicities include: lymphopenia, 2/19 (11%); anemia, 1/19 (5%); cellulitis, 1/19 (5%); transaminases, 1/19 (5%); dehydration, 1/19 (5%). There were no cardiac events and LVEF was well preserved. The study was stopped early in November 2013 due to excess toxicity. Conclusions: The combination of full dose L with dd T and H was not feasible. There was an unexpected high incidence of rash. G 3 diarrhea incidence was acceptable. This important negative study provides additional feasibility data as we await the release of data from ALTTO. Clinical trial information: NCT01827163.
Inconclusive Supplement Benefit, but Undisputed Advantages of Healthy Foods
Authors: Linda Van Horn
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
The development of a prediction tool to identify cancer patients at high risk for chemotherapy-induced nausea and vomiting
Authors: G. Dranitsaris, A. Molassiotis, M. Clemons, E. Roeland, L. Schwartzberg, P. Dielenseger, K. Jordan, A. Young, M. Aapro
Journal: Annals of Oncology (2017)

BackgroundDespite the availability of effective antiemetics and evidence-based guidelines, up to 40% of cancer patients receiving chemotherapy fail to achieve complete nausea and vomiting control. In addition to type of chemotherapy, several patient-related risk factors for chemotherapy-induced nausea and vomiting (CINV) have been identified. To incorporate these factors into the optimal selection of prophylactic antiemetics, a repeated measures cycle-based model to predict the risk of ≥grade 2 CINV (≥2 vomiting episodes or a decrease in oral intake due to nausea) from days 0 to 5 post-chemotherapy was developed.Patients and methodsData from 1198 patients enrolled in one of the five non-interventional CINV prospective studies were pooled. Generalized estimating equations were used in a backwards elimination process with theP-value set at <0.05 to identify the relevant predictive factors. A risk scoring algorithm (range 0–32) was then derived from the final model coefficients. Finally, a receiver-operating characteristic curve (ROCC) analysis was done to measure the predictive accuracy of the scoring algorithm.ResultsOver 4197 chemotherapy cycles, 42.2% of patients experienced ≥grade 2 CINV. Eight risk factors were identified: patient age <60 years, the first two cycles of chemotherapy, anticipatory nausea and vomiting, history of morning sickness, hours of sleep the night before chemotherapy, CINV in the prior cycle, patient self-medication with non-prescribed treatments, and the use of platinum or anthracycline-based regimens. The ROC analysis indicated good predictive accuracy with an area-under-the-curve of 0.69 (95% CI: 0.67–0.70). Before to each cycle of therapy, patients with risk scores ≥16 units would be considered at high risk for developing ≥grade 2 CINV.ConclusionsThe clinical application of this prediction tool will be an important source of individual patient risk information for the oncology clinician and may enhance patient care by optimizing the use of the antiemetics in a proactive manner.
Clinic level variation in emergency department and inpatient utilization in a community setting.
Authors: Laura Panattoni, Catherine R. Fedorenko, Karma L. Kreizenbeck, Stuart Greenlee, Julia Rose Walker, Mikael Anne Greenwood-Hickman, Sarah Barger, John Whitelaw Rieke, Ted Conklin, Sharon Chance, Keith D. Eaton, Rose Guerrero, Mary Gunkel, Renato G. Martins, Marilyn Moorhouse, Bruce Smith, Gary H. Lyman, Scott David Ramsey
Journal: Journal of Clinical Oncology (2017)

226 Background: Early studies of the oncology medical home suggest that intensive outpatient care (e.g. 24-hour phone triage, same-day infusion) reduces emergency department (ED) and inpatient (IP) use during cancer treatment. Little is known about which services are most cost-effective. One strategy is to measure observed variation in ED and IP rates to pinpoint care features associated with low-use clinics. This study examined clinic-level variation in ED and IP use in a community setting. Methods: Cancer registry records for Western Washington from 2011 to 2015 were linked with claims from two regional commercial insurers. Included patients were diagnosed with breast, lung, colorectal, or prostate cancer and treated with chemotherapy or radiation. All ED and IP use was tracked 1 year after treatment start using claims data. Observed clinic rates were measured as the percentage of patients with 1 or more visits. Expected clinic rates were determined from regional average rates weighted by clinic’s cancer-specific stage mix. Observed-to-expected clinic ratios were calculated and the Wilson Score test (95% CI) was used to determine statistically different rates. Results: The 18 clinics included 4,558 eligible patients (median 196 pts/clinic; range: 35-859). Unstaged lung patients had the highest ED rates (38.5%); unstaged breast had the lowest (13.3%). The highest IP rate was among unstaged colorectal (66.7%); the lowest in local breast (11.1%). One clinic had an observed rate that was significantly above its expected rate in both ED only and ED to IP. One clinic was significantly below its expected rate in both ED to IP and IP only. Conclusions: Even after adjusting for cancer-specific stage, there was sizable clinic-level variation in the percentage of patients visiting the ED or IP. Investigation into care delivery features and practice characteristics, along with further risk adjustment, may yield insights into best practices and identify clinics for intervention. [Table: see text]
Annals Story Slam - Poor Decision Making at 3 a.m.
Authors: Brian W. Roberts
Journal: Annals of Internal Medicine (2017)

Web Exclusives4 April 2017Annals Story Slam - Poor Decision Making at 3 a.m.FREEBrian W. Roberts, MDBrian W. Roberts, MDFrom Cooper Medical School of Rowan University, Camden, New Jersey.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0035 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Poor Decision Making at 3 a.m. "Poor Decision Making at 3 a.m.," by Dr. Brian W. Roberts (Duration 4:29)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Cooper Medical School of Rowan University, Camden, New Jersey.Current Author Address: Brian W. Roberts, MD, Cooper Medical School of Rowan University; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 April 2017Volume 166, Issue 7Page: SS1KeywordsDecision making ePublished: 4 April 2017 Issue Published: 4 April 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
An open-label phase I dose escalation study of KRN951, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 1 in a 4 week on, 2 week off schedule in patients with advanced solid tumors
Authors: F. A. Eskens, A. Planting, L. Van Doorn, T. Isoe, K. Hayashi, S. Hussain, L. Ekman, H. Burger, J. Verweij
Journal: Journal of Clinical Oncology (2006)

2034 Background: KRN951 inhibits VEGF induced phosphorylation of VEGF receptors (VEGFR)2 and 1 (IC 50 of 0.16 and 0.21 nM) and phosphorylation of c-Kit and Platelet Derived Growth Factor Receptor (PDGFR), (IC 50 of 1.63 and 1.72 nM). Methods: The principal objectives of this study were (1) to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of KRN951 administered once daily (OD) for 28 days followed by 14 days off treatment, (2) to characterize safety and tolerability, (3) to characterize single and multiple dose pharmacokinetics, (4) to explore inhibitory effects on tumor blood flow, and (5) to look for evidence of antitumor activity. Results: 10 male and 5 female patients, median age 57 yrs (28–72) have been enrolled at dose levels of 1 mg (n=6), 2 mg (n=8), and 1.5 mg (n=1). The total number of courses given is 63 (1–15 per patient) At 2 mg DLT consisting of grade 3 asymptomatic proteinuria, grade 3 ataxia and grade 4 intracranial hemorrhage was seen in three patients. In the next-lower dose level of 1 mg one DLT (grade 3 fatigue) was seen. An intermediate dose of 1.5 mg is currently studied. Hypertension occurred in 14/15 patients but could be medically controlled. Pharmacokinetic analysis revealed dose dependent drug exposure and peak plasma concentrations. Plasma levels of sVEGFR2 decreased following exposure to KRN951. Exploratory analysis by means of Dynamic Contrast Enhanced MRI analysis indicated a decrease in tumorperfusion in selected patients. One confirmed partial response lasting more than 80 weeks in a patient with renal cell carcinoma was seen, and stable disease lasting more than 2 courses of treatment was seen in 6 patients. Conclusion: Once daily KRN951 can be administered safely when given for 28 days followed by 14 days off treatment. The recommended phase II dosing is currently being defined. No significant financial relationships to disclose.