tbuckley/cabot-search huggingface dataset:
Clinical Implications of the Pharmacokinetics of Crizotinib in Populations of Patients with Non–Small Cell Lung Cancer
Authors: Erjian Wang, Dana J. Nickens, Akintunde Bello, Reza Khosravan, Michael Amantea, Keith D. Wilner, Kourosh Parivar, Weiwei Tan
Journal: Clinical Cancer Research (2016)

We assessed the effect of baseline patient demographic and disease characteristics on the crizotinib pharmacokinetic parameters oral clearance (CL/F), volume of distribution (V2/F), and area under the curve at steady state (AUCss) following multiple crizotinib 250-mg twice-daily dosing in patients with ALK-positive cancer.A pharmacokinetic model was fit to data from 1,214 patients. We identified statistically significant covariates (P ≤ 0.001) by evaluating their effects on CL/F and V2/F and estimated their magnitudes.Age, Eastern Cooperative Oncology Group performance status, aspartate aminotransferase (AST) levels, albumin levels, and smoking status had no effect on CL/F or V2/F. Statistically significant covariates were Asian race and female sex for CL/F and V2/F and body weight, creatinine clearance (CLcr), and total bilirubin for CL/F only. The model predicted that CL/F would be 9% lower or higher in a 40-kg or a 100-kg patient, respectively; 16% lower in patients with CLcr 30 mL/minute; 23% lower in Asians; and 11% lower in females than the reference patient (65-kg non-Asian male; baseline CLcr, 91.6 mL/minute; total bilirubin, 0.41 mg/dL). The effect of total bilirubin on CL/F was small. V2/F was 23% lower in Asians than non-Asians and females than males. Effects of all significant covariates on AUCss were not predicted to be clinically relevant.Crizotinib at a 250-mg twice-daily starting dose appears to be appropriate for all patients irrespective of age, sex, race, body weight, mild or moderate renal impairment, or hepatic function (in the range evaluated: bilirubin ≤ 2.1 mg/dL or AST ≤124 U/L). Clin Cancer Res; 22(23); 5722-8. ©2016 AACR.
THU0267 IL-17 Expression by Lymphocytes is Higher in Behcet's Disease Compared to Takayasu's Arteritis
Authors: A.U. Unal, R. Deniz, A. Tulunay-Virlan, F. Ture-Ozdemir, I. Aydin-Tatli, G. Ozen, F. Alibaz-Oner, G. Mumcu, T. Ergun, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Interleukin-17 (IL-17) has been associated with the pathogenesis of numerous autoimmune/inflammatory diseases. The aim of our study was to investigate the expression of Th17-related immunity in two phenotypically different disorders: Behcet9s disease (BD) with innate and Takayasu9s arteritis (TAK) with adaptive immune responses. <h3>Methods</h3> Peripheral blood mononuclear cells (PBMC) from 32 patients (age: 39.2±10.1 years) with BD, 13 patients (age: 50.9±15.5 years) with TAK and 18 HC (age: 40.9±6.9 years) were cultured in Th17 inducing condition (IL-6, PHA, IL-1beta and IL-23) for 6 days. Cultured cells were stained with CD4, CD8, CD3, TCRgamma/delta, CD19, IFN-g and IL-17 antibodies to determine the intracellular cytokine secretion by flow cytometry. <h3>Results</h3> In BD patients, IL-17 expression by CD4 T cells was observed to be higher than both TAK patients and HC (p=0.03 and p=0.02, respectively). IL-17 expression by gamma delta and CD8 T cells was also higher in BD compared to HC (p=0.03, p&lt;0.01 respectively). No differences were observed between the groups in the IL-17 production by B cells. Under Th17 inducing condition, production of IFN-g by CD4 and CD8 T cells were also higher in both BD and TAK patients compared to the HC (p&lt;0.05 in all). No differences were observed between the groups in IFNg production by B cells and gamma/delta T cells. <h3>Conclusions</h3> Our preliminary results suggest that under Th17 stimulating condition, T cells express higher IL-17 levels in BD. More prominent IL-17 and IFN-g production by all lymphocyte subsets in BD might be associated with the increased innate responses and early tissue neutrophil infiltrations in BD, which is not observed in TAK. <h3>Disclosure of Interest</h3> None declared
THU0230 Anti-TNF Alpha Drugs Retention Rate at Ankylosing Spondylitis and Axial Spondyloarthritis: HUR-BIO Real Life Results
Authors: U. Kalyoncu, H. Babaoglu, A. Erden, L. Kilic, M. Torgutalp, O. Karadag, S. Kilickap, A. Akdogan, S.A. Bilgen, I. Ertenli, S. Kiraz
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Anti-TNF alpha (TNFi) drug survival is one of the relevant outcome measure in rheumatological diseases. <h3>Objectives</h3> Objective of this study was to compare TNFi drug survival in ankylosing spondylitis (AS) and axial spondyloarthritis (AxSpA). <h3>Methods</h3> HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single center biological registry since 2005. HUR-BIO biological dataset included demographic data, education level, co-morbidities, smoking, BMI, HLA-B27, switch ratio, baseline and follow-up disease activity parameters (such as BASDAI, BASFI, CRP, ESR, global VAS). Patients with lost of follow-up searched regarding to last TNFi prescription date with either local computer system or national social security institution database. Inition and last date of TNFi were noted from those systems. First TNFi drug switch date (either advers event or inefficacy) was accepted as main variable for drug survival. Kaplan-Meier plots and log rank tests were used to assess drug survival. HUR-BIO is not sponsored by any pharmaceutical company. Missing data ratio of baseline disease activity measures were 38.5% at BASDAI, 22.1% at ESR, 23.9% at CRP and 60.6% at BASFI. <h3>Results</h3> There were 874 patients (747 AS and 127 AxSpA). Mean age was 40.7±11.4 years old. Overall, 533 (61%) of patients were male, mean disease duration was 8.3±7.1 years and mean symptom duration was 12.8±8.9 years. Initial biological drugs were etanercept 346 (39.6%), infliximab 270 (30.9%) and adalimumab 258 (29.5%). Overall, initial biological drugs were continued at 497 (56.9%) patients. Of 245 (29.7%) patients had at least one biological switch. First biological drug survival was more frequent at male sex (61.4% vs 49.8%, p=0.001) and patients with highest ESR level (31.6 (23.7) vs 27.8 (22.3) mm/hour, p=0.041). In logistic regression analysis, male sex had tendency of better TNFi drugs survival [OR 1.65 (95%CI 0.96-2.83), p=0.070]. Patients with use usage of etanercept had tendency of more frequent drugs survival than monoclonal antibodies (log-rank p=0.057) (Table and Figure 1). Retention rate was similar at both AS and AxSpA patients. <h3>Conclusions</h3> In this single center observational registry, etanercept had tendency of better drug retention rate than monoclonal antibodies. Overall, anti-TNF drugs retention rate was well both AS and AxSpA than rheumatoid arthritis. On the other hand, certain confounder factors such as baseline disease activity, functional status were not known in whole patients, thus our results should evaluate in this limitation <h3>Disclosure of Interest</h3> None declared
Value of influenza vaccine during an outbreak of influenza A in a nursing home, Pyrénées Atlantiques, France, November-December 1995
Authors: A Infuso, S Baron, H Fauveau, M Melon, H Fleury, J C Desenclos
Journal: Eurosurveillance (1996)

A public health officer of the Direction Départementale de l'Action Sanitaire et Sociale des Pyrénées Atlantiques in France was notified of an outbreak of acute respiratory illness among residents of a nursing home on 4 December, 1995. Over 50 of the 69 r
Progress in Europe towards the goal of poliomyelitis eradication
Authors: S Wassilak, G Oblapenko, S Dittmann
Journal: Eurosurveillance (1997)

In 1988, the World Health Assembly set a target of global eradication of poliomyelitis due to wild poliovirus by the year 2000. The strategies of the campaign are: reach and maintain high levels of routine vaccination coverage throughout the population; p
Response of Certain Mouse Tumors to Bis (β-Chloroethyl) Sulfide (Mustard Gas)&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Allan D. Bass, Marion L. H. Freeman
Journal: JNCI Journal of the National Cancer Institute (1946)

Journal Article Response of Certain Mouse Tumors to Bis (β-Chloroethyl) Sulfide (Mustard Gas) Get access Allan D. Bass, Allan D. Bass professor of pharmacology Department of Pharmacology, Syracuse University College of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar Marion L. H. Freeman Marion L. H. Freeman research assistant Department of Pharmacology, Syracuse University College of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 7, Issue 3, December 1946, Pages 171–176, https://doi.org/10.1093/jnci/7.3.171 Published: 01 December 1946 Article history Received: 13 November 1946 Published: 01 December 1946
SP0045 Lipids and NKT Cells in Fat
Authors: E. Kalkhoven
Journal: Annals of the Rheumatic Diseases (2015)

Obesity-induced adipose tissue (AT) dysfunction results in a chronic low-grade inflammation that predisposes to the development of insulin resistance and type 2 diabetes. During the development of obesity, the AT-resident immune cell profile alters to create a pro-inflammatory state. Very recently, CD1d-restricted invariant (i)Natural Killer T (NKT) cells, a unique subset of lymphocytes that are reactive to so called lipid antigens, were implicated in AT homeostasis. Interestingly, recent data also suggest that human and mouse adipocytes can present such lipid antigens to iNKT cells in a CD1d-dependent fashion, but little is known about the lipid antigen presentation machinery in adipocytes. We have recently reported that adipocyte-induced Th1 and Th2 cytokine release by iNKT cells also occurred in the absence of exogenous ligands, suggesting the display of endogenous lipid antigen/CD1d complexes by 3T3-L1 adipocytes, and data will be presented on several cellular proteins implicated in this pathway. Overall, our findings indicate that adipocytes can function as non-professional lipid antigen presenting cells (APCs), which may present an important aspect of adipocyte-immune cell communication in the regulation of whole body energy metabolism and immune homeostasis. <h3>Disclosure of Interest</h3> None declared
Floating Pancreatic Duct Concrements in Chronic Pancreatitis
Authors: M.U. Schneider, G. Lux
Journal: Endoscopy (1985)

This report describes 3 patients with chronic relapsing pancreatitis, floating pancreatic duct concrements between 4 and 6 mm in diameter, moderate to advanced ductal changes, and repeated severe attacks of pain during acute relapses over a period of several months. Immediate relief of pain was achieved in all 3 patients by endoscopic papillotomy aimed at widening the main pancreatic duct and subsequent extraction or spontaneous passage of pancreatic duct concrements. On the basis of our experience with the patients presented here, endoscopic papillotomy widening the main pancreatic duct may be useful in some patients with chronic pancreatitis and floating pancreatic duct concrements.
Results of a survey of forensic psychiatrists on the validity of the sadistic personality disorder diagnosis
Authors: R L Spitzer, S Feister, M Gay, B Pfohl
Journal: American Journal of Psychiatry (1991)

The purpose of this study was to determine how often forensic psychiatrists evaluated individuals with sadistic personality disorder; their views about the usefulness of the diagnosis; the frequency of certain childhood factors; and the sensitivity and specificity of the individual diagnostic criteria.A questionnaire to be answered anonymously was sent to all of the 1,390 members of the American Academy of Psychiatry and the Law. Two hundred seventy-nine usable questionnaires were returned for data analysis.Approximately 50% of the respondents had, at some time, evaluated in a forensic setting a subject who exhibited behavior that met the criteria for the disorder. Four percent of the cases seen in the preceding year by those respondents who had ever seen a case would have met the criteria for the disorder. Most of the forensic psychiatrists who had experience with the disorder believed that the diagnosis is useful for a variety of clinical and forensic purposes, but most also believed that the category has significant potential for being misused in legal settings. Almost all cases described by the respondents involved male patients, and there was frequently a history of childhood abuse and parental loss. The diagnostic criteria in these cases had high sensitivity and specificity.In forensic settings the diagnosis of sadistic personality disorder is probably not rare. The results of this study suggest that the diagnosis has both descriptive and construct validity and that further study of the disorder with the DSM-III-R diagnostic criteria is needed.
P2-129: Galectin-9 in stroma is a better prognostic indicator in lung cancer -Tissue Microarray Analysis
Authors: Haruhisa Kitano, Naoko Kumagai, Yuta Sakai, Tomonori Tanaka, Yoshitomo Ozaki, Shozo Fujino, Junya Fukuoka
Journal: Journal of Thoracic Oncology (2007)
FRI0442 Prognostic Role of Exhaled Breath Condensate in Patients with Pulmonary Involvement Associated to Systemic Sclerosis
Authors: A. Guillen-Del Castillo, S. Sánchez-Vidaurre, C.P. Simeόn-Aznar, M.J. Cruz, V. Fonollosa-Pla, F. Morell, X. Muñoz
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Lung involvement due to interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH) is the most important cause of death in systemic sclerosis (SSc). <h3>Objectives</h3> To assess the clinical usefulness of exhaled breath and exhaled breath condensate (EBC) biomarkers in the study of scleroderma pulmonary involvement (PI), and their correlation with disease progression. <h3>Methods</h3> Fraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in exhaled breath and pH, nitrite, nitrate and interleukin-6 in EBC were prospectively collected from 35 patients with SSc. Fourteen had established PI as presence of ILD or PAH, and 21 patients with no lung involvement. Pulmonary function tests (PFT) and clinical approaches were performed annually during 4 years of follow-up. A progression-free survival (PFS) analysis was performed defining end point as a decrease from baseline FVC of at least 10%, or a 15% diminution in DLCO, or death during follow-up. <h3>Results</h3> There were no statistical differences in demographic data and the baseline characteristics between both groups. Median (interquartile range, IQR) age was 59.0 (42.0 to 68.0) years. Limited SSc was the most common cutaneous subset (28, 80%). The median of pulmonary duration disease was 1.7 years in PI group. Regarding lung function data at baseline, lower median FVC % and DLCO % values were identified in the PI group (76.5 vs. 94.2, p&lt;0.01) and (45.6 vs. 71.7, p&lt;0.001), respectively. Lower baseline pH levels were found in PI group (7.5 vs 8.0, p=0.04), with no other biomarker differences. Respecting the correlations between EBC biomarkers and PFTs during monitoring, lower pH levels were associated with lower DLCO % at 4 years of follow-up (r=0.45, p=0.01). Reduced FeNO levels were correlated with low FVC % at baseline (r=0.41, p=0.03), 4 years of follow-up (r=0.46, p=0.02) and with a decrease of FVC % (r=0.65, p&lt;0.001) and DCLO % during monitoring (r=0.50, p=0.01). Among the PI patients, high eCO measurements were related to low baseline FVC % (r=0.69, p&lt;0.01), and high IL-6 levels were correlated with low DLCO % at 4 years of follow-up (r= -0.64, p=0.03). The progression-free survival analysis identified that a pH equal or lower than 7.85 showed a decrease in lung function parameters or death during follow-up (log Rank p=0.03). FeNO levels equal or lower than 11.0 ppb were related to worse PFS (log Rank p&lt;0.01) (figure). <h3>Conclusions</h3> The pH and FeNO levels are implicated in the pathophysiology of the scleroderma lung. Exhaled breath and EBC may reflect the pulmonary inflammation with a non-invasive test, in which the biomarkers are correlated with a different outcome. <h3>Disclosure of Interest</h3> None declared
Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study
Authors: E Solary, B Witz, D Caillot, P Moreau, B Desablens, JY Cahn, A Sadoun, B Pignon, C Berthou, F Maloisel, D Guyotat, P Casassus, N Ifrah, Y Lamy, B Audhuy, P Colombat, JL Harousseau
Journal: Blood (1996)
Epidemiology of Cancers of Uterine Cervix and Corpus, Breast and Ovary in Israel and New York City
Authors: Harold L. Stewart, Lucia J. Dunham, Julian Casper, Harold F. Dorn, Louis B. Thomas, John H. Edgcomb, Alexander Symeonidis
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Epidemiology of Cancers of Uterine Cervix and Corpus, Breast and Ovary in Israel and New York City Get access Harold L. Stewart, Harold L. Stewart Laboratory of Pathology and Pathologic Anatomy Branch, National Cancer Institute,5Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Lucia J. Dunham, Lucia J. Dunham Laboratory of Pathology and Pathologic Anatomy Branch, National Cancer Institute,5Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Julian Casper, Julian Casper Laboratory of Pathology and Pathologic Anatomy Branch, National Cancer Institute,5Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Harold F. Dorn, Harold F. Dorn Laboratory of Pathology and Pathologic Anatomy Branch, National Cancer Institute,5Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Louis B. Thomas, Louis B. Thomas Laboratory of Pathology and Pathologic Anatomy Branch, National Cancer Institute,5Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar John H. Edgcomb, John H. Edgcomb Laboratory of Pathology and Pathologic Anatomy Branch, National Cancer Institute,5Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Alexander Symeonidis Alexander Symeonidis Laboratory of Pathology and Pathologic Anatomy Branch, National Cancer Institute,5Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 37, Issue 1, July 1966, Pages 1–95, https://doi.org/10.1093/jnci/37.1.1 Published: 01 July 1966 Article history Received: 02 May 1966 Published: 01 July 1966
A multi-tiered screening system for the least restrictive setting
Authors: R H Allen, M Weinman, R Lorimor, J L Claghorn
Journal: American Journal of Psychiatry (1980)

The authors evaluated the placement process in a large psychiatric facility with both inpatient and outpatient services. They examined 71 inpatient and 90 outpatient new admissions using standardized tests of psychopathology and sociodemographic status. After correcting for response bias, the authors found, in contrast to other studies, that the level of morbidity in the inpatient service was significantly different from that in the outpatient unit. The measures of sociodemographic data indicate that inpatients were more dependent on social support systems and that this finding was not influenced by response bias.
Website of the week: Evaluating complex interventions
Authors: Douglas Carnall
Journal: BMJ (2000)

Doctors work in the real world so although in principle all medical decisions should be made on the basis of empirical evidence, some interventions—such as deciding whether to admit a patient to a stroke unit—are complex. This week a paper in the BMJ presents a model (p 694) with which researchers can clarify the stage of evaluation that a particular complex intervention is at and discusses which methodologies are most appropriate at each stage. The examples given mainly come from interventions in which a social or educational component is important.

On the web, readers have a choice of two papers: the BMJ version or the original version published by the Medical Research Council in PDF format (www.mrc.ac.uk/complex_packages.html), which runs to 19 pages and uses most of the space to explain its message on complex evaluations in more detail and with more examples. Aspiring grant holders will certainly want it.

At www.hta.nhsweb.nhs.uk/index.htm the publications page of the NHS Health Technology Assessment programme has a long list of methodological reports as well as several examples of evaluations of complex interventions. The problem with both sites is that only PDF files are available for downloading. Although PDF is an open standard and free readers for the files are readily available, using PDF format for everything can be burdensome and wastes bandwidth, as it requires you to download the whole document before you can read any of it. That said, making a PDF from a single word processed document and putting it on the web is a trivial task, whereas modifying information so that it can easily be read on the web is difficult and time consuming.
THU0266 Patient Age as a Risk Factor of Coronary Artery Lesions in Kawasaki Disease
Authors: A. Torbyak, G. Lyskina
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> KD is a leading cause of acquired heart disease in children in developed countries mostly because of its coronary artery complications. Patient age has been mentioned among other risk factors for coronary artery lesions (CALs) such as male gender, recurrent cases, late IVIG treatment, and refractoriness to initial IVIG treatment. Still there is no consensus about influence of the patient age on the complications of KD. <h3>Objectives</h3> The medical records of 168 KD patients in the age of 1 month 13 days-13 years 6 months treated in the University Children9s Clinical Hospital from 2003 to 2014 were reviewed. 24 (14,29%) of them were &lt;6 months, 31 (18,45%) - 6-&lt;12 months, 94 (55,95%) - 12 months-&lt;5 years, 19 (11,31%) - ≥5 years. To evaluate the contribution of patient age to the development of CALs clinical, laboratory data and IVIG treatment were analyzed. <h3>Methods</h3> The presence of CALs was measured using 2-DE performed at 8 weeks after disease onset. The patients9 data were compared between two groups: patients with or without CALs at 8 weeks after disease onset. Differences were tested using the Mann-Whitney test, Fisher9s exact test, chi-square, Student9s t-test. The odds ratios (ORs) with 95% confidence intervals (CIs) for the presence of CALs were determined by multiple logistic regression models. <h3>Results</h3> The age group, natural logarithm of patient age, the total duration of fever, pre-IVIG fever duration, anemia in a acute phase, leukocytosis more than 17x10<sup>9</sup>/l in acute phase, thrombocytosis, elevated ESR, more than 5 times elevated CRP, diagnostics terms, the day of IVIG introduction were significant separately and in joint models. The effect of interaction was noted in the analysis of influence of fever duration in different age groups. For example, chances to have CALs with each day of high temperature increased in different degree for patients of different age groups: for children &lt;6 months – by 1,32 times, for children of 5 years and older – by 1,02 times (1,3 times less). <h3>Conclusions</h3> Patient age is an important independent risk factor for CALs. It can also modify the action of the other factors. <h3>Disclosure of Interest</h3> None declared