tbuckley/cabot-search huggingface dataset:
FRI0192 Too many patients in randomized controlled trials (RCTS) of ra? a critical reassesment of power and the actual numbers of patients enrolled
Authors: S. Celik, H. Yazici, Y. Yazici
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A proper power calculation and adequate sample size are critical for RCTs to avoid enrolling more than the needed number of patients leading to unnecessary exposure and adverse events (AE). On the other hand underpowered studies will fail to show any significant findings. Since in the real world ideal power calculations are not always possible, it would be expected that under and over enrolling would occur in roughly similar proportions in reports of RCTs. Nevertheless we had the impression that RCTs were very frequently over enrolling patients. <h3>Objectives</h3> To review power calculations of RCT in RA and determine if there is over-, under- enrollment of patients. <h3>Methods</h3> A Pubmed search was conducted for RCTs of infliximab, etanercept, adalimumab, abatacept, rituximab and tocilizumab in RA patients (n=291). Only original initial studies where the primary outcome was efficacy were analyzed (n=40). As a first analysis, based on a two equal arms study with an alpha error of 0.05 and a power of 80 %, recalculation of the sample size was done for each reported study by using the primary outcome results. Next the same was done only in those 2 arm studies, with equal number of patients in both arms, also in which all elements of the power calculation were adequately given in the manuscript. <h3>Results</h3> 40 studies were analyzed. In the first analysis, the recalculated mean sample size was 62 ± 27 (95% CI) for either arm while mean for the number of patients actually enrolled was 154 ± 46 (CI). There were more than the required number of patients in 32/40 studies (80 %) with a mean 131 ± 46 (CI) extra patients in the treatment groups of per study. Out of the 29 studies in which power was given 11 studies qualified for the second analysis. The mean power for sample size in these 11 studies was 0.88. The recalculated mean sample size was 76 ± 32 (CI) for the treatment arm while the mean for the actually enrolled patients, again in the treatment arm was 115 ± 49 (CI). There were still more patients with a mean 48 ± 19 extra patients enrolled in this group. <h3>Conclusions</h3> Most RCTs in RA enroll more patients than needed. While this practice is a misuse of the RCT, still a very important research tool, it also has the immediate consequence of exposing more than needed number of patients to potential AEs. <h3>Disclosure of Interest</h3> S. Celik: None Declared, H. Yazici: None Declared, Y. Yazici Consultant for: Abbott, BMS, celgene, genentech, Horizon, UCB, Pfizer
Detection of (11; 22)(q24;q12) Translocation-Bearing Cells in Peripheral Blood Progenitor Cells of Patients With Ewing's Sarcoma Family of Tumors
Authors: J. A. Toretsky, L. Neckers, L. H. Wexler
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Detection of (11; 22)(q24;q12) Translocation-Bearing Cells in Peripheral Blood Progenitor Cells of Patients With Ewing's Sarcoma Family of Tumors Get access Jeffrey A. Toretsky, Jeffrey A. Toretsky Pediatric Branch, Division of Cancer Treatment National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Leonard Neckers, Leonard Neckers Clinical Pharmacology Branch, Division of Cancer Treatment National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Leonard H. Wexler Leonard H. Wexler Pediatric Branch, Division of Cancer Treatment National Cancer InstituteBethesda, Md Leonard H. Wexler, M.D., Pediatric Branch, Bldg. 10 Rm. 13N240. 9000 Rockville Pike, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 5, 1 March 1995, Pages 385–386, https://doi.org/10.1093/jnci/87.5.385 Published: 01 March 1995 Article history Received: 26 July 1994 Revision received: 20 December 1994 Accepted: 27 December 1994 Published: 01 March 1995
P749 HIGH BURDEN OF FIBROSIS AND METABOLIC COFACTORS IN A COHORT OF PREDOMINANTLY GENOTYPE 3-INFECTED INJECTION DRUG USERS IN SOUTHERN INDIA
Authors: S.H. Mehta, S.S. Solomon, A.K. Srikrishnan, A. McFall, K. Bose, P. Nandagopal, S. Anand, M.S. Kumar, D.L. Thomas, S. Solomon, M.S. Sulkowski
Journal: Journal of Hepatology (2014)
PROGNOSTIC UTILITY OF NOVEL BIOMARKERS OF CARDIOVASCULAR STRESS IN PATIENTS WITH AORTIC STENOSIS UNDERGOING VALVE REPLACEMENT
Authors: Brian R. Lindman, Jared Breyley, Joel D. Schilling, Anna Wittenberg, Alan Zajarias, Hersh Maniar, Ralph Damiano, Marc Moon, Jennifer Lawton, Brian F. Gage, Marc Sintek, Alejandro Aquino, Christopher Holley, Neil M. Patel, Cassandra Lawler, John M. Lasala, Eric Novak
Journal: Journal of the American College of Cardiology (2015)
SP0137 Multidisciplinary working: Bridging the primary/secondary care gap
Authors: K. Stevenson
Journal: Annals of the Rheumatic Diseases (2013)

This session will explore the benefits and strengths of multidisciplinary working within the context of a musculoskeletal interface service in the UK. Aspects of extending roles, redefining professional boundaries, clinical governance, team cohesion and academic and clinical partnerships will be explored. A project designed to integrateresearch evidence into local clinical practice will be shared in order to highlight key features of multidisciplinary working across health and academic settings. <h3>Disclosure of Interest</h3> None Declared
Abstract 2755: Effect of food on pharmacokinetics of zibotentan (ZD4054) in healthy subjects aged &amp;gt;65 years and ≤65 years
Authors: Helen Tomkinson, John Kemp, Thomas Wollseifen, Stuart Oliver, Thomas Morris
Journal: Cancer Research (2010)

Abstract The pharmacokinetic (PK) profile of zibotentan (ZD4054), a small-molecule, specific endothelin A (ETA) receptor antagonist, was evaluated under fed and fasting conditions in two Phase I studies in healthy male subjects. These two studies were open-label crossover studies in which half the subjects received a single zibotentan dose following a high fat meal and again after a 7-day washout in a fasted state. The other half received a single zibotentan dose in a fasted state initially and again 7 days later following a high fat meal. Study 1 (AstraZeneca study 4045IL/013) included nine subjects aged &amp;gt;65 years who received single-dose zibotentan 25 mg and study 2 (AstraZeneca study D4320C00028) included 30 male subjects aged ≤65 years who received single-dose zibotentan 10 mg. AUC and Cmax were log-transformed prior to analysis using an analysis of variance model fitting for the effects of sequence, subject, period and treatment. In subjects aged &amp;gt;65 years who received zibotentan 25 mg, there was no difference in AUC values between the fed (GLS mean 15041 ng.h/ml) and fasted groups (GLS mean 14740 ng.h/ml; treatment ratio of fed/fasted [90% CI], 1.02 [0.8-1.30]). However Cmax was lower for fed (GLS mean 1005 ng/ml) than fasted subjects (GLS mean 1262 ng/ml; treatment ratio of fed/fasted [90% CI], 0.8 [0.58-1.08]). In subjects aged ≤65 years who received zibotentan 10 mg, there was a statistically significant decrease in AUC for fed subjects (GLS mean 4031 ng.h/ml) compared with fasted subjects (GLS mean 4711 ng.h/ml; treatment ratio of fed/fasted [90% CI], 0.86 [0.80-0.91]), and Cmax for fed subjects (GLS mean 357 ng/ml) compared with fasted subjects (GLS mean 470 ng/ml; treatment ratio of fed/fasted [90% CI], 0.76 [0.71-0.81]). In both studies, median tmax was 4 hours in the fed group versus 2 hours in the fasted group. In study 2, a food effect on AUC was excluded because the corresponding 90% CIs were within the predefined limits of 0.8-1.25. However, a food effect could not be excluded for Cmax, because the lower limit of the 90% CI was below the predefined margin. The reduction in Cmax under fed conditions was consistent with a slower rate of absorption indicated by median tmax being delayed by 2 hours under fed conditions. The reduction in Cmax is not considered to be clinically relevant as efficacy is likely to be driven by AUC or time above a particular concentration, therefore future studies are being conducted without any food restrictions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2755.
Seizure Induced by Insufflation of Bupropion
Authors: Christopher J. Welsh, Suzanne Doyon
Journal: New England Journal of Medicine (2002)

To the Editor: A 16-year-old boy with a history of depression was brought to the emergency department after he had a generalized, tonic–clonic seizure. His only medication was bupropion (Wellbutrin SR) at a dose of 150 mg twice daily. He reported using marijuana “occasionally” and drinking approximately two 40-oz servings of beer several times a month during the preceding year. He denied using any other illicit substances. The findings on medical evaluation were otherwise unremarkable, and he was discharged with a diagnosis of bupropion-induced seizure. The patient later reported that, approximately one hour before the seizure, he had crushed six . . .
Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX
Authors: F. Ciardiello, N. Normanno, E. Martinelli, T. Troiani, S. Pisconti, C. Cardone, A. Nappi, A.R. Bordonaro, M. Rachiglio, M. Lambiase, T.P. Latiano, G. Modoni, S. Cordio, F. Giuliani, M. Biglietto, V. Montesarchio, C. Barone, G. Tonini, S. Cinieri, A. Febbraro, D. Rizzi, F. De Vita, M. Orditura, G. Colucci, E. Maiello, Vincenzo Iaffaioli, Guglielmo Nasti, Gerardo Botti, F. Tatangelo, Nicoletta Chicchinelli, Mirko Montrone, Annamaria Sebastio, Tiziana Guarino, Gianni Simone, Paolo Graziano, Cinzia Chiarazzo, Gabriele Di Maggio, Laura Longhitano, Mario Manusia, Giacomo Cartenì, Oscar Nappi, Pietro Micheli, Luigi Leo, Sabrina Rossi, Alessandra Cassano, Eugenio Tommaselli, Guido Giordano, Francesco Sponziello, Antonella Marino, Antonio Rinaldi, Sante Romito, Andrea Onetti Muda, Vito Lorusso, Silvana Leo, Sandro Barni, Giuseppe Grimaldi, Michele Aieta
Journal: Annals of Oncology (2016)
Nuclear Oncology: Diagnosis and Therapy
Authors: Andrew M. Keenan
Journal: Clinical Nuclear Medicine (2001)

Prince George’s Hospital Center, Cheverly, Maryland CLINICAL NUCLEAR MEDICINE publishes in each issue a section of references to articles of interest to its readers taken from the world medical literature. Articles below were selected from listings received through June 1, 2001. Slavic and Oriental language articles have English summaries unless marked with an asterisk after language abbreviation.
Characterization of α<sub>1</sub>-Antitrypsin in the Inclusion Bodies from the Liver in α<sub>1</sub>-Antitrypsin Deficiency
Authors: Jan-Olof Jeppsson, Christer Larsson, Sten Eriksson
Journal: New England Journal of Medicine (1975)

alpha1-antitrypsin was isolated from periodic acid-Schiff-positive inclusion bodies from the hepatocytes of patients with alpha1-antitrypsin deficiency and further purified to enable more detailed chemical analysis. Amino acid and cyanogen bromide fragmentation studies showed a close similarity between hepatic and serum (PiMM) antitrypsin in contrast to the carbohydrate analysis, which revealed markedly deficient glycosylation of hepatic antitrypsin. A complete lack of sialic acid and a relative deficiency of all other carbohydrate components could fully explain the difference of approximately 6000 daltons in molecular size between the two proteins. The accumulation of hepatic globules is probably related to the physical properties of the defective antitrypsin, which include marked insolubility and tendency toward aggregation. The results strongly suggest an abnormal amino acid sequence in the peptide chain of the deficient antitrypsin. The interference with glycosylation may be related to steric hindrance.
A Trial of Minocycline Given after Exposure to Prevent Gonorrhea
Authors: William O. Harrison, Richard R. Hooper, Paul J. Wiesner, Axel F. Campbell, Walter W. Karney, Gladys H. Reynolds, Oscar G. Jones, King K. Holmes
Journal: New England Journal of Medicine (1979)

In a prospective evaluation of antibiotic prophylaxis against gonorrhea, 1080 men were given 200 mg of oral minocycline or placebo after sexual intercourse with prostitutes in a Far Eastern port. Later, at sea, gonococcal infection was detected in 57 of 565 men given placebo and 24 of 515 men given minocycline (P less than 0.001). Minocycline prophylaxis completely prevented infection by gonococci susceptible to 0.75 microgram or less of tetracycline per milliliter, reduced the risk of infection or prolonged the incubation period in men exposed to gonococci susceptible to 1.0 to 2.0 micrograms per milliliter, but did not prevent infection or prolong incubation in men exposed to gonococci resistant to 2.0 micrograms. Minocycline did not increase the proportion of asymptomatic infections. Minocycline prophylaxis would probably have limited effectiveness as a public-health measure because of the tendency to select resistant gonococci.
IMPACT OF VALVULO-ARTERIAL IMPEDANCE ON LONG-TERM SURVIVAL IN PATIENTS WITH SEVERE AORTIC STENOSIS AND PRESERVED LEFT VENTRICULAR EJECTION FRACTION: A CARDIAC CATHETERIZATION STUDY
Authors: Dania Mohty, Julien Magne, Philippe Pibarot, Najmeddine Echahidi, Cyrille Boulogne, Marc Laskar, Patrice Virot, Victor Aboyans
Journal: Journal of the American College of Cardiology (2014)
Efficacy of Low-Dose Methotrexate in Rheumatoid Arthritis
Authors: Michael E. Weinblatt, Jonathan S. Coblyn, David A. Fox, Patricia A. Fraser, Donald E. Holdsworth, David N. Glass, David E. Trentham
Journal: New England Journal of Medicine (1985)

Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug.
Abstract 4437: HSA coated iron oxide nanoparticle as a drug delivery vehicle for cancer therapy
Authors: Xiaoyuan Chen, Qimeng Quan, Jin Xie
Journal: Cancer Research (2011)

Abstract An on-going effort in the field of nanomedicine is to develop nanoplatforms with both imaging and therapeutic functions, the so-called “nano-theranostics”. We have previously developed a human serum albumin (HSA) coated iron oxide nanoparticle (HINP) formula and used multiple imaging modalities to validate its tumor targeting attributes. In the current study, we sought to impart doxorubicin (Dox) onto the HINPs and to assess the potential of the conjugates as theranostic agents. In a typical preparation, we found that about 0.5 mg of Dox and 1 mg of iron oxide nanoparticles (IONPs, Fe content) could be loaded into 10 mg of HSA matrices. The resulting Dox-loaded HINPs (D-HINPs) retained a tumor targeting capability, as manifested by both in vivo MRI and ex vivo immunostaining studies. For therapeutic studies, 25 4T1 tumor mice were divided into 5 groups (5 mice/group), and were treated with 1) D-HINPs (3 mg Dox/kg); 2) free Dox (3 mg Dox/kg); 3) Doxil (3 mg Dox/kg); 4) HINPs and 5) PBS. For Group 4, HINPs were injected at the same Fe concentration as in Group 1. The drugs (including controls) were given every other day for a total of 4 doses. A dramatic increase in tumor volume was found in the PBS control group. The group injected with HINPs manifested a tumor growth pattern that was similar to the PBS group and showed no weight loss throughout the treatment, indicating that the HINPs alone had neither therapeutic nor toxic effects in the studied mice. Compared with the control group, the injection of Dox led to some tumor suppression in the first week of treatment but gradually lost efficacy. D-HINPs showed a striking tumor suppression effect that was comparable to Doxil and that greatly outperformed free Dox. Such a strategy can be readily extended to load other types of small molecules, making HINP a promising theranostic nanoplatform. 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 4437. doi:10.1158/1538-7445.AM2011-4437
Klippel-Trenaunay-Weber Syndrome With Adrenal Pseudocyst: Characterization by Blood Pool and Adrenocortical Iodocholesterol Scintigraphy
Authors: STEVEN A. YOUNG, BRAHM SHAPIRO
Journal: Clinical Nuclear Medicine (1998)

A 44-year-old woman with Klippel-Trenaunay-Weber syndrome (KTWS) was evaluated for an adrenal mass incidentally discovered on CT. An NP-59 scintigraph showed normal symmetric adrenal tracer uptake, and a Tc-99m labeled RBC scan showed no evidence for an adrenal hemangioma but did show characteristic dilated and tortuous vasculature at multiple other sites. The mass was removed and found to be an adrenal pseudocyst. The pseudocyst was believed to have arisen from a pre-existing, thrombosed and organized adrenal hemangioma. This case demonstrates the previously reported utility of RBC scintigraphy in the depiction of the vascular abnormalities in the diagnosis and treatment of patients with Klippel-Trenaunay-Weber syndrome, as well as the utility of NP-59 scintigraphy in evaluating patients with adrenal masses.
SAT0386 Monosodium Urate Crystal Enhanced Osteoclastogenesis Through Traf6 Signaling Pathway in RAW264.7 Macrophage Cells
Authors: S.-K. Kim, J.-Y. Choe, H. J. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Gouty is an arthritis disease characterized by metabolic disorder of monosodium urate (MSU) crystals, resulting in bone destruction in affected joints. MSU crystals induce secretion of interleukin-1b (IL-1b) that can enhance osteoclast differentiation and bone resorption. <h3>Objectives</h3> This study is to investigate action mechanisms by MSU crystals for the regulation of osteoclastogenic activity through tumor necrosis factor receptor-associated factor 6 (TRAF-6) signal pathways in RAW 264.7 macrophage cells. <h3>Methods</h3> Cell viability in RAW 264.7 macrophage cells was determined using a MTT assay after MSU crystal treatment. We examined the effects of MSU crystals on mitogen activated protein kinases (MAPK), their signaling cascade genes, and osteoclast differentiation markers were measured using real-time polymerase chain reaction and western blotting. Effects of TRAF6 knockdown using siRNA for TRAF6 on osteoclastic transcription factors and IL-1 b expression were measured by western blotting. We performed tartrate-resistant acid phosphatase (TRAP) staining to identify formation of osteoclasts. <h3>Results</h3> MSU crystals induced expressions of IL-1b and MAPK signaling molecules. MSU, in the presence of RNAKL, also resulted in significantly enhanced expressions of osteoclatogenesis related genes including cathepsin K, MMP9, and carbonic anhydrase II, and TRAP activity. Furthermore, inhibition of TRAF6 decreased expressions of IL-1b and its transcription factors such as c-Jun and NFATc1. <h3>Conclusions</h3> These results suggest that MSU crystal enhances osteoclast differentiation through TRAF6 signaling pathway. <h3>Disclosure of Interest</h3> None Declared
Artifacts Caused By Nonionic Contrast Media and a Portacath on a Dual-Energy X-Ray Absorptiometry Whole-Body Composition Study
Authors: MARY P. ANDRICH, MARJORIE CAWLEY, CLARA C. CHEN
Journal: Clinical Nuclear Medicine (1996)

A 13-year-old boy underwent a whole-body composition study using dual-energy x-ray absorptiometry soon after receiving intravenous contrast for a CT scan of the chest. Areas of increased density in the urinary collecting system and bladder were identified and presumed to be due to the presence of residual contrast. These abnormalities resolved on a follow-up study the next day. A third area of increased density was visualized on both examinations in the chest in the region of the patients' subcutaneous central lineport.