tbuckley/cabot-search huggingface dataset:
OP0148 Reduced dose and frequency of anti-TNF therapy in rhemuatic diseases:
Authors: J. Gibson, H. Harris, J. McLaren, S. Cullinane
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The anti-TNFα drugs Adalimumab (ADA) and Etanercept (ETA) are given in standard doses and intervals. Many patients on these drugs achieve long-term remission or low disease activity yet continue on the standard doses. Departmental costs have escalated as increasing numbers of patients are treated. <h3>Objectives</h3> 1) Determine whether patients in long-term remission or low disease activity can reduce their dose or frequency of administration without disease flare. 2) Assess cost savings by alterations in dose or frequency of administration <h3>Methods</h3> Patients (&gt;17 years old) with Inflammatory Arthritis, who were receiving either ADA or ETA by self-administered subcutaneous injection, were asked to reduce the dose or frequency of administration of their drug. Patients were selected if they had persistent DAS28 ≤3.1. The following doses were commenced (numbers of patients): ETA: 50mg every 10 days (15), 50mg every 2 weeks (43), 25mg weekly (5). ADA: 40mg every 3 weeks (18), 40mg every 4 weeks (14). Patients reverted to their previous dosing schedule if they had a disease flare or perceived reduction in quality of life. Costs for subcutaneous anti-TNFα therapy at end of November 2010 were compared with end of November 2011. <h3>Results</h3> Overall, 86 patients changed their dosage, of which 72 have continued on reduced dose or frequency of administration for an average of 7 months (range 1 – 33 months, median 6 months). Twenty-two patients so far have changed dose for 9 months or more. Of the 14 patients who reverted to full dose, mean duration of reduced frequency of administration in this group was 3.6 months (range 0.5 – 9 months, median 3 months). Those who are successful in reducing their dose or frequency of administration are more likely to be lifelong non-smokers (46%) than those who have to restart their previous doses (21%). Those who fail usually do so within a few months. Botsios et al (1) have shown that patients succeeding on reduced dose are more likely to have shorter duration of disease but there is no data on the effect of smoking. Our data suggest that dose reduction could be targeted to patients who are lifelong non-smokers. <h3>Conclusions</h3> 1) Patients in remission or low disease activity are willing to try reducing their dose or frequency of administration of subcutaneous anti-TNFα injections 2) Patients are more likely to remain on reduced dose if they are lifelong non-smokers. 3) Considerable cost savings can be made by tailoring treatment in this way <h3>References</h3> [1]Botsios C, Furlan A., Ostuni P et al. Effects of low-dose etanercept in maintaining DAS-remission previously achieved with standard dose in patients with rheumatoid arthritis. Ann Rheum Dis. 2009;66:54 <h3>Disclosure of Interest</h3> None Declared
How can we keep patients with dementia safe in our acute hospitals? A review of challenges and solutions
Authors: Jim George, Susannah Long, Charles Vincent
Journal: Journal of the Royal Society of Medicine (2013)

Maintaining patient safety in acute hospitals is a global health challenge. Traditionally, patient safety measures have been concentrated on critical care and surgical patients. In this review the medical literature was reviewed over the last ten years on aspects of patient safety specifically related to patients with dementia. Patients with dementia do badly in hospital with frequent adverse events resulting in the geriatric syndromes of falls, delirium and loss of function with increased length of stay and increased mortality. Contributory factors include inadequate assessment and treatment, inappropriate intervention, discrimination, low staff levels and lack of staff training. Unfortunately there is no one simple solution to this problem, but what is needed is a multifactorial, multilevel approach at the seven levels of care – patient, task, staff, team, environment, organisation and institution. Improving safety and quality of care for patients with dementia in acute hospitals will benefit all patients and is an urgent priority for the NHS.
Abstract 2668: Radiosensitization of solid tumor cell lines by an MDM2 inhibitor
Authors: David Cerna, Hongyun LI, Siobhan Flaherty, Donna Carter, C. Norman Coleman, Stephen Yoo
Journal: Cancer Research (2011)

Abstract The tumor suppressor p53 is a key molecule in the prevention of cancer. More than half of all human cancers have mutation or loss of the p53 gene. A significant percentage of the other half contain overexpression of Hdm2 which serves as a ubiquitin ligase (E3) to target p53 for degradation. While it has been established that an inhibitor of Hdm2 ubiquitin E3 ligase activity HLI373 (5-(3-dimethylaminopropylamino)-3,10-dimethyl-10H-pyrimido(4,5-b)quinoline-2,4-dione, NSC373989), selectively kills tumor cells harboring wild-type p53, we investigated the effect of the Hdm2 inhibitor HLI373, in the response to ionizing radiation in solid tumor lines expressing wild-type, mutant or null p53 in vitro and in vivo. We now report HLI373 enhances radiosensitivity in a panel of human tumor cell lines in p53 deficient and competent cell lines using clonogenic assay. HCT116 cells exposed to HLI373 (5-7.5 uM) for 16 hours before and maintained in the medium after irradiation had an increase in radiosensitivity. Cell cycle distribution of treated cells after 16 hours was measured using flow cytometry. In a comparison of wildtype and null cell lines, cell cycle arrest in G1 was only detected in cells with active p53 at 5uM of HLI373. In contrast, cells with a null or mutated p53 progressed to and arrested in G2. In addition, wild type p53 cells pretreated with 5 uM HLI373 and irradiated continued to be arrested in G1 and did not progress to a G2. However, cells without p53 treated with HLI373 and radiation increased in accumulation in G2. Treatment with higher dosages of HLI373 (&amp;gt;10uM) resulted in the accumulation of cells in G2 regardless of p53 status. These results indicate that HLI373 enhances tumor cell radiosensitivity in vitro and agents such as HLI373 may have potential for use in the clinics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2668. doi:10.1158/1538-7445.AM2011-2668
AB0293 Factors Influencing Physician Global Assessment of Rheumatoid Arthritis Disease Activity in Usual Clinical Practice
Authors: S.-H. Park, S.-K. Kim, H. Lee, J.-Y. Choe
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patient global assessment (PATGL) and physician global assessment (PhGL) of disease status are 2 of the 7 rheumatoid arthritis (RA) core data set measures. Several reports indicate considerable discordance between PATGL and PhGL [1]. Variation in PhGL appears to be explained by different factors in discordant patient group comparing with concordant group. <h3>Objectives</h3> To analyze variation in PhGL by examination of possible associations with all RA core data set measures, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), in patients monitored in usual care in a Korean rheumatology setting. <h3>Methods</h3> A cross-sectional study was conducted of patients with RA seen by 4 rheumatologists in a Korean usual care setting. All core data set measures, as well as RF and ACPA, are collected in each RA patient. A tender joint count (TJC28) and swollen joint count (SJC28) are performed on each patient, and laboratory tests – erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), RF and ACPA – are obtained. A PhGL is assigned by the rheumatologist after review of all data. All study population was divided in three groups: positive discordance; PATGL-PhGL&gt;1, no discordance; -1≤PATGL-PhGL≤1, negative discordance; PATGL-PhGL&lt;-1. In each group, correlations of all core data set measures, as well as RF and ACPA, with PhGL were analyzed using Spearman9s rho. Univariate and multivariate regressions were performed for each measure with PhGL as the dependent variable, and core data set measures and laboratory tests as independent variables. <h3>Results</h3> The study population was 89.2% female, with median age 55.0 years. PhGL was correlated significantly with all 7 core data set measures (Spearman9s rho 0.236-0.356, p&lt;0.001). PhGL was not correlated significantly with RF and ACPA. 270 patients (53.8%) were positively discordant and median disease activity score (DAS)28 was 3.9. TJC28, pain, PATGL, PhGL, DAS28 was significantly different between 3 groups. By multivariate regression, PhGL was associated independently with TJC28, PATGL and ESR in positive discordance group. TJC did not influence PhGL in concordant group. If a RF level was high, physicians seemed to rate disease activity higher than patients in negative discordant group. <h3>Conclusions</h3> PhGL is correlated significantly with all RA core data set measures. In multivariate regressions, PhGL was associated significantly with TJC28, PATGL, ESR and RF, but not with SJC28, physical function or pain score. These findings are consistent with other reports in the literature. Further research is needed to clarify the basis for variation in PhGL and concordance or discordance with PATGL. <h3>References</h3> Barton JL, Imboden J, Graf J, et al. Arthritis Care Res 2010;62:857-64 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3450
The Psychological Consequences of Predictive Testing for Huntington’s Disease
Authors: Sandi Wiggins, Patti Whyte, Marlene Huggins, Shelin Adam, Jane Theilmann, Maurice Bloch, Samuel B. Sheps, Martin T. Schechter, Michael R. Hayden
Journal: New England Journal of Medicine (1992)

Advances in molecular genetics have led to the development of tests that can predict the risk of inheriting the genes for several adult-onset diseases. However, the psychological consequences of such testing are not well understood.
Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV ‘real life’ trial on the variability of response to opioids
Authors: O. Corli, I. Floriani, A. Roberto, M. Montanari, F. Galli, M.T. Greco, A. Caraceni, S. Kaasa, T.A. Dragani, G. Azzarello, M. Luzzani, L. Cavanna, E. Bandieri, T. Gamucci, G. Lipari, R. Di Gregorio, D. Valenti, C. Reale, L. Pavesi, V. Iorno, C. Crispino, M. Pacchioni, G. Apolone, M. Monfredo, R. Mistretta, P.O. di Salemi, E. Zecca, C. Cartoni, G.A. Brunetti, D. Tassinari, F. Drudi, F. Rizzi, M. Pizzuto, F. Formaglio, M. Luzi, F. Narducci, G. Boscolo, M. Mangiapia, F. Artioli, M. Lazzari, M. Dauri, M. Diodati, A. Cupaiolo, S. Mameli, P. Preti, P. Ferrari, G. Vasini, M.T. Roy, L. Piva, L.F. Nardi, L. Montanari, V. Reina, F. Fusco, L. Orsi, E. Molinari
Journal: Annals of Oncology (2016)
TWELVE-YEAR FOLLOW-UP OF 213 PATIENTS WITH PERCUTANEOUS ATRIAL SEPTAL DEFECT CLOSURE GUIDED BY CMR IMAGING
Authors: Wassim Shatila, Robert Aertker, Jonathan Kochav, Asvin Ganapathi, Andrew Lodge, Anna Lisa Crowley, John Vavalle, Todd Kiefer, J. Kevin Harrison
Journal: Journal of the American College of Cardiology (2015)
Extended follow-up results from a prospective multi-center study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection, satisfaction, and anxiety.
Authors: SS Lo, PB Mumby, K Rychlik, J Smerage, J Kash, HK Chew, D Hayes, KS Albain
Journal: Cancer Research (2009)

Abstract Abstract #3113 Background: The 21-gene Recurrence Score (RS) assay has been validated to quantify the risk of distant recurrence in tamoxifen treated patients (pts) in node negative, estrogen receptor positive breast cancer (BC) and predict magnitude of chemotherapy benefit. We previously showed that the RS impacted medical oncologists (MOs) and pts adjuvant treatment decision making, decreased situational anxiety and decisional conflict, and improved pt satisfaction regarding adjuvant treatment decisions. Herein, we present the 12 month post-RS data for MOs and pts.&amp;#x2028; Material and Methods: MOs stated their treatment recommendation and confidence in it pre- and post-RS assay, and completed a 12 month questionnaire. Pts completed 4 questionnaires pre- and immediately post-RS, and 12 months later: 1) Patient Treatment Decision Making Questionnaire; 2) Decisional Conflict Scale (DCS); 3) State-Trait Anxiety Inventory; and 4) Functional Assessment of Cancer Therapy-Breast. Frequency distributions, means and standard deviations summarized data. Paired samples t-tests and repeated measures ANOVA assessed quality of life, decisional conflict and anxiety.&amp;#x2028; Results: Accrual goal was met with 89 evaluable pts. 16/17 (94%) MOs and 67 pts (75%) completed the 12 month assessment. There were no breast cancer recurrences recorded at 12 months. The majority of MOs reported increase confidence in their treatment recommendation (n=15, 93.8%), felt the RS provided additional information (n=15, 93.8%), and influenced treatment recommendation (n=14, 87.6%). Results from the DCS immediately post-RS indicate reduced conflict over treatment (p &amp;lt;.0001), greater pt satisfaction, and increased confidence with choice of adjuvant therapy (p &amp;lt;.0001). Pts reported they were glad they took the test 12 months later (n=62, 92.5%), found results easy to understand (n=60, 89.6%), and the test influenced treatment decision (n=54, 80.6%). Sixty four (95.5%) were satisfied with their adjuvant decision. State anxiety decreased over the year (mean 38.9 to 34.0, p. = 007), the most significant decline occurred pre- to immediately post-RS. Quality of life remained constant.&amp;#x2028; Conclusions: The RS assay has an immediate and enduring impact on MOs and pts adjuvant decision making. MOs and pts report continued confidence and satisfaction with the assay. Pts had a decrease in decisional conflict right after the test, situational anxiety declined over the next 12 months and quality of life remained stable.&amp;#x2028; Investigator initiated trial supported by an unrestricted clinical trials grant from Genomic Health Inc. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3113.
THE GANSER SYNDROME
Authors: HERBERT WEINER, ALEX BRAIMAN
Journal: American Journal of Psychiatry (1955)

1. Six cases of Ganser's syndrome are described, one occurring in a male prisoner, 5 occurring in civilian patients of whom 4 were women and one a man. 2. Three patients who are described in detail developed the syndrome intercurrently during other serious psychiatric illnesses. 3. It is pointed out that although the symptom of approximate answers has often been described as occurring in various entities, the syndrome as originally defined has rarely been so reported. 4. Certain clinical features are commented upon, in particular the coincidence with approximate answers of amnesia with loss of personal identity. 5. A possible explanation of some aspects of the Ganser syndrome is tendered.
Abstract 5682: Design and preclinical evaluation of single agents with combination chemotherapy potential.
Authors: Aleem Gangjee, Roheeth K. Pavana, Michael A. Ihnat, Jessica E. Thorpe, Bryan C. Disch, Anja Bastian, Lora C. Bailey-Downs, Ernest Hamel, Rouli Bai
Journal: Cancer Research (2013)

Abstract Antiangiogenic agents target tumor mechanisms involved in blood vessel formation vital for tumor growth and metastases. However, these agents are mainly cytostatic and usually not tumoricidal. Several combinations of antiangiogenic and cytotoxic agents have shown significant promise in the clinic, and several clinical trials are in progress. Single agents with both antiangiogenic activities and cytotoxicity would afford agents that would circumvent pharmacokinetic problems of multiple agents, avoid drug-drug interactions, could be used at lower doses to alleviate toxicity, be devoid of overlapping toxicities, and could delay or prevent tumor cell resistance. We designed, synthesized and evaluated a novel compound AG119 that inhibits both vascular endothelial growth factor receptor-2 (VEGFR-2) affording antiangiogenic effects and tubulin for cytotoxic effects in a single agent. Structural modifications of AG119 afforded AG321 that inhibited platelet derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) in addition to VEGFR-2 and tubulin. The novel compounds AG119 and AG321 were potent inhibitors (activity comparable to that of combretastatin A-4) of bovine brain tubulin assembly and of [3H]colchicine binding to tubulin, indicating that these compounds bind at the colchicine site on tubulin. Both compounds have potency comparable to those of sunitinib and semaxinib in tumor cell lines overexpressing VEGFR-2. AG321 has potency comparable to that of erlotinib in tumor cell lines overexpressing EGFR and potency comparable to those of erlotinib, DMBI and PD153035 in cell lines overexpressing PDGFR-β. Both AG119 and AG321 also inhibited angiogenesis in the chorioallantoic membrane (CAM) assay. AG321 is a unique compound with four separate mechanisms of action in a single agent including inhibition of tubulin. This is unprecedented and to our knowledge, is the first of its kind. In mice, AG119 reduced tumor size and vascularity in two flank xenograft models [the BLBC MDA-MB-435 model and U251 glioma model] and in a 4T1 triple negative breast orthotopic allograft model. In these in vivo models, the activity of AG119 was superior to those of temozolomide (U251), docetaxel and sunitinib (MDA-MB-435 and 4T1) without overt toxicity to the animals. Citation Format: Aleem Gangjee, Roheeth K. Pavana, Michael A. Ihnat, Jessica E. Thorpe, Bryan C. Disch, Anja Bastian, Lora C. Bailey-Downs, Ernest Hamel, Rouli Bai. Design and preclinical evaluation of single agents with combination chemotherapy potential. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5682. doi:10.1158/1538-7445.AM2013-5682
P779 PLATELET COUNT/SPLEEN DIAMETER RATIO (PSR) AS A PREDICTOR OF LIVER RELATED DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) AND LOW PLATELET COUNT
Authors: F. Fernandes, G. Pereira, Z. Veiga, D. Martins, A. Campos, J.C. Lino, J.L. Pereira
Journal: Journal of Hepatology (2014)
The Inheritance of Gilles de la Tourette's Syndrome and Associated Behaviors
Authors: David L. Pauls, James F. Leckman
Journal: New England Journal of Medicine (1986)

We examined specific genetic hypotheses about the mode of transmission of Gilles de la Tourette's syndrome, by performing segregation analyses in 30 nuclear families identified through 27 index cases. Because data from earlier family studies had suggested that chronic tics and obsessive-compulsive disorder may be alternative phenotypic expressions of the diathesis of Tourette's syndrome, we used three diagnostic schemes to specify affected family members (Tourette's syndrome only; Tourette's syndrome or chronic tics; and Tourette's syndrome, chronic tics, or obsessive-compulsive disorder). The estimates of penetrance for the genotypes AA, Aa, and aa (A denotes the abnormal allele) in the analyses of subjects with Tourette's syndrome, chronic tics, or obsessive-compulsive disorder were 1.000, 1.000, and 0.002, respectively, for male subjects and 0.709, 0.709, and 0.000 for female subjects. These results predict that approximately 10 percent of all patients are phenocopies. We conclude that our analyses provide strong support for the hypothesis that obsessive-compulsive disorder is etiologically related to Tourette's syndrome and chronic tics in these families, and that Tourette's syndrome is inherited as a highly penetrant, sex-influenced, autosomal dominant trait.
Handful of Cancer Centers Exempt From Prospective Payment System
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Handful of Cancer Centers Exempt From Prospective Payment System Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 13, 3 July 1991, Pages 907–908, https://doi.org/10.1093/jnci/83.13.907 Published: 03 July 1991
Abstract 4455: Mild and moderate early-life stressors differentially affect stress reactivity and mammary tumorigenesis in BALB/c mice: A new look at the stress and breast cancer relationship
Authors: Leslie R. Kerr, Allison Boyd, Ryan Heighton, Meagan Munro, Ayesha Salleh
Journal: Cancer Research (2012)

Abstract Many studies have produced inconsistent support for the hypothesized role of stressful life events in breast cancer risk. One major factor contributing to the inconsistent data could be that differences in premorbid physiological (e.g., endocrine levels) and psychological (e.g., emotional reactivity to challenges) characteristics were not taken into account and therefore, nor was the enduring impact of these differences on many aspects of endocrine activity and mammary gland development. It is difficult to gain information on human childhood variables that affect breast development and even more still on the influence of those variables into adulthood. Thus, evidence for factors influencing breast development and increased cancer risk during this time is limited. To this end, we use an established rodent model in which mild and moderate chronic neonatal stressors of brief and long maternal separation (BMS and LMS, respectively) over the first 3 weeks of life cause enduring functional changes to limbic-pituitary-adrenal axis activity. With this model, we show that BMS and LMS experiences differentially alter emotion- and stress-related behaviors of adult female BALB/c offspring. Circulating, corticosterone (CORT) and estrogen (E2) levels were also differentially altered by the BMS and LMS experiences as were transcript or protein levels of estrogen receptor (ER)α and ERα in ‘normal’ mammary glands. Interestingly, increased mammary tumorigenesis in LMS mice following adulthood carcinogen (7,12-dimethylbenz[α]anthracene; DMBA) administration was related to lower circulating plasma CORT and E2 levels, higher ERα protein (but not transcript), and lower ERα transcript (but not protein) levels in mammary glands. We suggest that early-life physical and psychosocial environments influence breast cancer risk by shaping the behavioral phenotype and altering circulating hormone levels which in turn alter the cellular and molecular architecture of the breast predisposing some to increased risk of carcinogenesis. A better understanding of the biobehavioral pathways that govern the complex interplay among environment, phenotype, and normal and malignant breast development will facilitate the creation of effective behavioral and cellular strategies for cancer prevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4455. doi:1538-7445.AM2012-4455