tbuckley/cabot-search huggingface dataset:
Antiproliferative Activity of Highly Purified Mouse Interferon: Brief Communication 2
Authors: Rita F. Buffett, Michio Ito, Alfred M. Cairo, William A. Carter
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Antiproliferative Activity of Highly Purified Mouse Interferon: Brief Communication Get access Rita F. Buffett, Rita F. Buffett 3Department of Medical Viral Oncology, Roswell Park Memorial Institute, 666 Elm St., Buffalo, N.Y. 14263. Search for other works by this author on: Oxford Academic PubMed Google Scholar Michio Ito, Michio Ito 3Department of Medical Viral Oncology, Roswell Park Memorial Institute, 666 Elm St., Buffalo, N.Y. 14263. Search for other works by this author on: Oxford Academic PubMed Google Scholar Alfred M. Cairo, Alfred M. Cairo 3Department of Medical Viral Oncology, Roswell Park Memorial Institute, 666 Elm St., Buffalo, N.Y. 14263. Search for other works by this author on: Oxford Academic PubMed Google Scholar William A. Carter William A. Carter 3Department of Medical Viral Oncology, Roswell Park Memorial Institute, 666 Elm St., Buffalo, N.Y. 14263. 4We thank Dr. Eugene Sulkowski for providing the mouse interferon and for valuable suggestions. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 1, January 1978, Pages 243–246, https://doi.org/10.1093/jnci/60.1.243 Published: 01 January 1978 Article history Received: 10 May 1977 Accepted: 05 August 1977 Published: 01 January 1978
P0782 : All-oral 12-week combination treatment with daclatasvir (DCV) and sofosbuvir (SOF) in treatment-experienced patients infected with HCV genotype (GT) 3: A subanalysis of the ALLY-3 phase 3 study
Authors: D. Nelson, D. Bernstein, B. Freilich, E. Lawitz, T. Hawkins, P. Pockros, P. Thuluvath, Z. Younes, M. Bennett, R. Ghalib, P.J. Ruane, M. Tong, R. Bhore, P.D. Yin, S. Noviello, K. Rana
Journal: Journal of Hepatology (2015)
Gemcitabine and docetaxel in patients with measurable unresectable or metastatic hepatocellular carcinoma (HCC), a North Central Cancer Treatment Group (NCCTG) phase II trial
Authors: G. P. Kim, S. R. Alberts, L. K. Tschetter, T. R. Fitch, S. R. Dakhil, B. W. Morlan, D. J. Sargent
Journal: Journal of Clinical Oncology (2004)

4270 Background: Few effective options are available for the treatment of unresectable HCC. Chemotherapy, in particular, has been of limited benefit. Several phase I trials suggest promising activity of a combination of gemcitabine and docetaxel. Methods: Patients with unresectable or metastatic HCC were treated with docetaxel 40 mg/m2 (later reduced to 30 mg/m2) and gemcitabine 800 mg/m2 on days 1, 8 every 3 weeks. A Simon study design called for accrual of 40 patients, with an interim analysis after 22, requiring at least 2 responses, with acceptable toxicity, to continue accrual. Results: 25 patients were enrolled in 26 months. Median age was 67 (range 27–78), 17 were male,15 had liver-only disease and10 had extrahepatic disease. 9 patients had cirrhosis, 6 viral hepatitis, and 1 hemachromatosis. Response –Of 21 patients evaluable for the primary endpoint (response), 2 (10%) have a confirmed response. TTP and Survival –The median TTP is 2.3 months (95% CI 1.3–5.6 months). Median survival is not yet reached with a median followup of 5.3 months (range 0–24 months). Toxicity –Two patients died on-study due to adverse events (1 hepatic and 1 renal failure), neither of which were attributed to the study medications. 17 patients (81%) have experienced grade 3+ adverse events, including 8 with grade 4+ adverse events. Hematologic toxicity and associated hemorrhage resulted in a reduction of the docetaxel dose. Conclusions: A response rate of 10% was observed in patients with HCC receiving gemcitabine and docetaxel. Patients experienced a high rate of grade 3+ toxicity including neutropenia and thrombocytopenia. Based on these results, accrual to the trial will not continue. The combination of gemcitabine and docetaxel at the dose and schedule used is not recommended for HCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Dementia risk after spontaneous intracerebral haemorrhage: a prospective cohort study
Authors: Solène Moulin, Julien Labreuche, Stéphanie Bombois, Costanza Rossi, Gregoire Boulouis, Hilde Hénon, Alain Duhamel, Didier Leys, Charlotte Cordonnier
Journal: The Lancet Neurology (2016)
Ovarian Hyperstimulation and Oocyte Harvesting Prior to Systemic Chemotherapy—A Possible Pitfall in 18F-FDG PET/CT Staging of Oncologic Patients
Authors: Sara Bacanovic, Ruth Stiller, Magdalena Pircher, Irene A. Burger, Martin W. Huellner
Journal: Clinical Nuclear Medicine (2016)

A 33-year-old woman with Hodgkin disease Ann Arbor stage IIA underwent baseline F-FDG PET/CT scanning. The scan showed gross multicystic enlargement of both ovaries and a nodule at the edge of the right ovary with intense FDG uptake (SUVmax = 14.8). Differential diagnosis would include ovarian lymphoma manifestation, endometrioma, and ovarian or pelvic neoplasia. However, chart analysis revealed previous superstimulation with gonadotropins and gonadotropin release hormone antagonist, and transvaginal oocyte retrieval the day before FDG PET/CT. This led to the diagnosis of ovarian hyperstimulation syndrome, with the FDG-avid focus representing a hemorrhagic follicle after transvaginal oocyte retrieval procedure.
Soundings: Just sign this . . .
Authors: Trisha Greenhalgh
Journal: BMJ (2001)

Every pile of paperwork contains one, but this particular request took the biscuit. A patient had sent in the usual scribbled note accompanied by a picture of her strapping youth and a blank passport application, asking me to “endorse the attached for identification reasons.” She would call by to pick it up that night.

I had never met the youth or his mother, who had been on the list for 18 months, nor had anyone else who currently worked at the practice. To the child's great credit, his last encounter with a health professional was for a preschool booster 11 years before. I wrote back, declining my services and gallantly refusing to accept the standard fee (which had not, incidentally, been offered).

The link between the medical profession and the mushrooming industry of countersigning passports and other official documents is surely a complete anachronism. Its origins lie in those halcyon days when the family doctor was not only the moral guardian of the community but someone who had, more often than not, personally delivered, circumcised, immunised, and managed the successive childhood exanthemata of the people concerned. Signing the passport application was the final rite of passage that certified them sufficiently healthy and moral to venture out into the world beyond.

Let's get real. Both general practitioners and patients move on from practice lists, the turnover being between 15% and 40% a year, with the variation explained largely by the deprivation index of the catchment area.

Furthermore, it is no accident that the patients applying for passports and visas are more mobile than most. The frequently quoted statistic that 97% of registered patients see their GP over a five year period is nonsense. “Routine” health care is provided by a combination of self management, nurses, and community pharmacists, and an increasing amount of it happens over the phone or by email.

The last time I applied for a passport I had my picture countersigned by my neighbour, who wrote “housewife” as her occupation; the application was not challenged. Surely it is time that doctors officially relinquished their claim to a role that any competent member of the community could perform as well as any of us?
Development of the ClinESSDAI: a clinical score without biological domain. A tool for biological studies
Authors: Raphaèle Seror, Petra Meiners, Gabriel Baron, Hendrika Bootsma, Simon J Bowman, Claudio Vitali, Jacques-Eric Gottenberg, Elke Theander, Athanasios Tzioufas, Salvatore De Vita, Manel Ramos-Casals, Thomas Dörner, Luca Quartuccio, Philippe Ravaud, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2016)

To develop and validate ClinESSDAI (Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index), ie, ESSDAI without the biological domain.The 702 fictive vignettes derived from 96 real cases of primary Sjögren's syndrome of the ESSDAI development study were used. As for ESSDAI development, the physician assessment of disease activity (0-10 scale) was used as the 'gold standard' in a multivariate model for weighting domains, after removing the biological domain. The reliability, assessed by intraclass correlation coefficient (ICC) between ClinESSDAI and ESSDAI, explored if ClinESSDAI was equivalent to ESSDAI. Its psychometric (ie, measurement) properties were compared with that of ESSDAI in an independent cohort. Also, its use was evaluated on data of two clinical trials.In multivariate modelling, all 11 domains remained significantly associated with disease activity, with slight modifications of some domain weights. Reliability between clinESSDAI and ESSDAI was excellent (ICC=0.98 and 0.99). Psychometric properties of clinESSDAI, disease activity levels and minimal clinically important improvement thresholds and its ability to detect change over time in clinical trials were very close to that of ESSDAI.ClinESSDAI appears valid and very close to the original ESSDAI. This score provides an accurate evaluation of disease activity independent of B-cell biomarkers. It could be used in various circumstances: (i) in biological/clinical studies to avoid data collinearity, (ii) in clinical trials, as secondary endpoint, to detect change independent of biological effect of the drug, (iii) in clinical practice to assess disease activity for visits where immunological tests have not been done.
Pharmacist-Led Chronic Disease Management: A Systematic Review of Effectiveness and Harms Compared With Usual Care
Authors: Nancy Greer, Jennifer Bolduc, Eric Geurkink, Thomas Rector, Kimberly Olson, Eva Koeller, Roderick MacDonald, Timothy J. Wilt
Journal: Annals of Internal Medicine (2016)

Background: Increased involvement of pharmacists in patient care may increase access to health care and improve patient outcomes. Purpose: To determine the effectiveness and harms of pharmacist-led chronic disease management for community-dwelling adults. Data Sources: MEDLINE, Cochrane Library, CINAHL, and International Pharmaceutical Abstracts from 1995 through February 2016, and reference lists of systematic reviews and included studies. Study Selection: 65 patient populations in 63 studies conducted in the United States of any design reported outcomes of pharmacist-led chronic disease management versus a comparator for community-dwelling adults in the United States. Studies set in retail pharmacies were excluded. Data Extraction: Data extraction done by a single investigator was confirmed by a second investigator; risk of bias was assessed by 2 investigators; and strength of evidence was determined by consensus. Data Synthesis: Pharmacist-led care was associated with similar numbers of office visits, urgent care or emergency department visits, and hospitalizations (moderate-strength evidence) and medication adherence (low-strength evidence) compared with usual care (typically continuing a prestudy visit schedule). Pharmacist-led care increased the number or dose of medications received and improved study-selected glycemic, blood pressure, and lipid goal attainment (moderate-strength evidence). Mortality and clinical events were similar (low-strength evidence). Evidence on patient satisfaction was mixed and insufficient. The reporting of harms was limited. Limitations: Interventions were heterogeneous. Studies were typically short-term and designed to assess physiologic intermediate outcomes rather than clinical events. Reporting of many clinical outcomes of interest was limited, and often they were not the study-defined primary end points. Conclusion: Pharmacist-led chronic disease management was associated with effects similar to those of usual care for resource utilization and may improve physiologic goal attainment. Further research is needed to determine whether increased medication utilization and goal attainment improve clinical outcomes. Primary Funding Source: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.
PTU-040 A retrospective survey on the long-term efficacy of the second biologic in the management of Crohn's disease: results from a combined English Irish cohort
Authors: E A Russo, S O'Donnell, J Dearden, S Campbell, J O Lindsay, C O'Morain, T R Orchard
Journal: Gut (2010)

<h3>Introduction</h3> A significant proportion of Crohn9s disease (CD) patients have been treated with two biologic therapies. Follow-up from current published retrospective or prospective open-label studies on patients who have already received 2 biologics does not extend beyond 1 year (1-4). <h3>Methods</h3> Our aim was to collect “real-life”, long-term data on the tolerability and efficacy of the second biologic agent in (re)-capturing response, and to assess whether the reason for stopping the first agent impacted on the successful use of the second agent. We carried out secure data collection from three teaching IBD centres on CD patients currently on, or already failed a second biologic. We collected data on disease duration, distribution and behaviour, and report on the aetiology in the failure of the first biologic and the subsequent outcome of the second biologic agent. Response to biologics was assessed by Harvey Bradshaw Index or Physicians Global Assessment. <h3>Results</h3> We collected data on 66 patients (F 46%, mean age at diagnosis: 25). The disease distribution was characterised as L1: 11%, L2:32% L3:56% L4:1% and the behaviour as B1:41% B2:35% B3:24%. 17% had perianal involvement. 36 patients have had a total of 41 resectional operations. First biologic: 64/66 patients had infliximab (IFX) first-line, followed by adalimumab (ADA), and 2/66 patients had ADA followed by IFX. Reasons for swapping were failure in 23%, secondary-loss of response in 38%, intolerance to the first agent in 29%, and fear of hypersensitivity reaction due to previous episodic exposure to IFX in 10% (irrespective of efficacy or tolerance). Second biologic: 70% of patients remained on the second biologic after a median follow-up of 22 months. Reasons for discontinuing therapy were 1o failure in 35%, secondary loss of response in 25%, intolerance (or patient concerns regarding potential side-effects) in 25%, and achieving remission in 5%; no reason provided for the remainder 5%. Neither the demographics, disease characteristics nor the reason for failing the first biologic had a statistically significant bearing in predicting the initial response to and subsequent outcome of the second biologic. <h3>Conclusions</h3> (1) We report an overall 70% retention on the second biologic at 22 months following all-cause failure of the first agent in CD patients from England and Ireland. (2) Patients responded equally well to the second biologic, irrespective of the reason for the failure of the first biologic.
Exome-Scale Discovery of Hotspot Mutation Regions in Human Cancer Using 3D Protein Structure
Authors: Collin Tokheim, Rohit Bhattacharya, Noushin Niknafs, Derek M. Gygax, Rick Kim, Michael Ryan, David L. Masica, Rachel Karchin
Journal: Cancer Research (2016)

Abstract The impact of somatic missense mutation on cancer etiology and progression is often difficult to interpret. One common approach for assessing the contribution of missense mutations in carcinogenesis is to identify genes mutated with statistically nonrandom frequencies. Even given the large number of sequenced cancer samples currently available, this approach remains underpowered to detect drivers, particularly in less studied cancer types. Alternative statistical and bioinformatic approaches are needed. One approach to increase power is to focus on localized regions of increased missense mutation density or hotspot regions, rather than a whole gene or protein domain. Detecting missense mutation hotspot regions in three-dimensional (3D) protein structure may also be beneficial because linear sequence alone does not fully describe the biologically relevant organization of codons. Here, we present a novel and statistically rigorous algorithm for detecting missense mutation hotspot regions in 3D protein structures. We analyzed approximately 3 × 105 mutations from The Cancer Genome Atlas (TCGA) and identified 216 tumor-type–specific hotspot regions. In addition to experimentally determined protein structures, we considered high-quality structural models, which increase genomic coverage from approximately 5,000 to more than 15,000 genes. We provide new evidence that 3D mutation analysis has unique advantages. It enables discovery of hotspot regions in many more genes than previously shown and increases sensitivity to hotspot regions in tumor suppressor genes (TSG). Although hotspot regions have long been known to exist in both TSGs and oncogenes, we provide the first report that they have different characteristic properties in the two types of driver genes. We show how cancer researchers can use our results to link 3D protein structure and the biologic functions of missense mutations in cancer, and to generate testable hypotheses about driver mechanisms. Our results are included in a new interactive website for visualizing protein structures with TCGA mutations and associated hotspot regions. Users can submit new sequence data, facilitating the visualization of mutations in a biologically relevant context. Cancer Res; 76(13); 3719–31. ©2016 AACR.
Mitochondrial Function, Biology, and Role in Disease
Authors: Elizabeth Murphy, Hossein Ardehali, Robert S. Balaban, Fabio DiLisa, Gerald W. Dorn, Richard N. Kitsis, Kinya Otsu, Peipei Ping, Rosario Rizzuto, Michael N. Sack, Douglas Wallace, Richard J. Youle
Journal: Circulation Research (2016)

Cardiovascular disease is a major leading cause of morbidity and mortality in the United States and elsewhere. Alterations in mitochondrial function are increasingly being recognized as a contributing factor in myocardial infarction and in patients presenting with cardiomyopathy. Recent understanding of the complex interaction of the mitochondria in regulating metabolism and cell death can provide novel insight and therapeutic targets. The purpose of this statement is to better define the potential role of mitochondria in the genesis of cardiovascular disease such as ischemia and heart failure. To accomplish this, we will define the key mitochondrial processes that play a role in cardiovascular disease that are potential targets for novel therapeutic interventions. This is an exciting time in mitochondrial research. The past decade has provided novel insight into the role of mitochondria function and their importance in complex diseases. This statement will define the key roles that mitochondria play in cardiovascular physiology and disease and provide insight into how mitochondrial defects can contribute to cardiovascular disease; it will also discuss potential biomarkers of mitochondrial disease and suggest potential novel therapeutic approaches.
Medical resource utilization (MRU) and costs associated with paclitaxel poliglumex (PPX) compared to gemcitabine (Gem) or vinorelbine (Vin) in non-small cell lung cancer (NSCLC) patients
Authors: F. B. Oldham, K. P. Anastassopoulos, K. O'Byrne, M. S. Maxon, C. P. Schaefer
Journal: Journal of Clinical Oncology (2007)

18172 Background: NSCLC accounts for 80% of lung cancer cases and is commonly treated with taxanes. PPX is a phase III, biologically-enhanced, investigational, chemotherapeutic for treatment of NSCLC that links paclitaxel to a biodegradable polyglutamate polymer that potentially spares normal tissue exposure to chemotherapy toxicities. Methods: MRU data were collected as part of a multinational, randomized trial that compared PPX (n=191) to Gem or Vin (n=190) in chemotherapy-naïve advanced NSCLC patients with a performance status of 2. MRU and costs associated with chemotherapy administration and non-protocol-driven care were compared over the study period. Costs (2005 U.S. dollars) were assigned from a U.S. payer perspective. Results: Patient demographics were similar (p&gt;0.05) between groups (mean age: 62 yrs, 72% male, 89% Caucasian). PPX had slightly longer median survival (220 vs. 198; p=0.686) with significantly fewer adverse events (all grades; 2.0 vs. 3.0; p=0.011) and significantly more chemotherapy cycles (3.4 vs. 3.9; p=0.007), per subject. Additionally, PPX had fewer outpatient visits (0.6 vs. 1.7; p&lt;0.001), diagnostic tests (0.6 vs. 1.9; p&lt;0.001), and days on non-chemotherapy medications (64.4 vs. 91.2; p&lt;0.001), per subject. There was no significant difference in number of hospitalizations (0.04 in both groups; p=0.786), length of stay among those hospitalized (8.4 days PPX vs. 6.1 days Gem or Vin; p=0.301), or procedures (0.02 PPX vs. 0.04 Gem or Vin; p=0.238), per subject. Average costs per subject were significantly lower in PPX for outpatient visits ($34 vs. $78; p=0.014), non-chemotherapy medications ($717 vs. $911; p&lt;0.001), and chemotherapy administration ($1,557 vs. $3,601; p&lt;0.001) and similar for inpatient stays ($210 PPX vs. $244 Gen or Vin; p=0.794). Conclusions: This analysis suggests that, in addition to providing a clinical benefit of fewer adverse events, PPX results in reduced MRU and associated costs compared to Gem or Vin in treating NSCLC. These cost savings can be weighed against the cost of PPX and may provide a pharmacoeconomic advantage. Further research is warranted to confirm these results in routine clinical practice. [Table: see text]
Blood eosinophil count to predict bronchial eosinophilic inflammation in COPD
Authors: Florence Schleich, Jean-Louis Corhay, Renaud Louis
Journal: European Respiratory Journal (2016)

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the airways. There is evidence that maintenance treatment with inhaled corticosteroids (ICS) in COPD results in a reduction in the mean rate of exacerbations, and improvement in quality of life and lung function [1]. However, ICS therapy has been associated with increased risk of oropharyngeal candidiasis, hoarseness and pneumonia [1]. In COPD, ICS are now recommended in cases of frequent exacerbations and severe obstruction [2]. Blood eosinophil counts, but not F eNO , may predict airway eosinophilic inflammation <http://ow.ly/WXgkA>
Consolidation treatment of adult acute lymphoblastic leukemia: a prospective, randomized trial comparing allogeneic versus autologous bone marrow transplantation and testing the impact of recombinant interleukin-2 after autologous bone marrow transplantation. BGMT Group
Authors: M Attal, D Blaise, G Marit, C Payen, M Michallet, JP Vernant, C Sauvage, X Troussard, G Nedellec, J Pico
Journal: Blood (1995)