tbuckley/cabot-search huggingface dataset:
FRI0196 Costs in Relation to Disability, Disease Activity and Health-Related Quality of Life in Rheumatoid Arthritis
Authors: J.A. Karlsson, J.K. Eriksson, J.-Å. Nilsson, T. Olofsson, L.-E. Kristensen, M. Neovius, P. Geborek
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> RA is associated with high societal costs. While disability predicts costs in RA, little is known about the relations between costs and disease activity or health-related quality of life. <h3>Objectives</h3> To study the associations between costs, disability, disease activity, and health-related quality of life. <h3>Methods</h3> RA patients receiving anti-TNF therapy in southern Sweden (n=2504; median disease duration 11y) were monitored between July 2005 and December 2010. At each visit (n=15732) HAQ, DAS28 and EQ-5D scores were collected, while costs of anti-rheumatic drugs, healthcare use and productivity losses were calculated from 30 days before to 30 days after the visit using nationwide registers. Associations between the clinical measures and healthcare (all patients, applying individual means) and work loss costs (patients &lt;65y; n=1806) were studied by linear regression, adjusting for demographics and disease characteristics, and by Spearman correlation. Confidence intervals were estimated by non-parametric bootstrapping. Due to the inclusion criteria, anti-TNF cost varied little between patients and was excluded from the analyses. <h3>Results</h3> Over 60 days, the mean (SD) healthcare cost of patients with ongoing anti-TNF therapy was €3189 (1290), encompassing an anti-TNF cost of €2470 (502; 77%). In patients &lt;65y, the mean work loss cost amounted to €4235 (3450). By linear regression, both healthcare (excl. anti-TNF) and work loss costs were most closely related to HAQ scores, while the association with work loss costs was also higher for EQ-5D than DAS28. Spearman results were similar, but did not detect a closer correlation of healthcare costs with HAQ than DAS28. Healthcare (excl. anti-TNF) costs: B = €440 (95%CI 324-557), 143 (85-201) and -652 (-948 to -355) for each 1.0 difference in HAQ, DAS28 and EQ-5D, respectively (p=0.030 for HAQ vs. DAS28 and p=0.027 for HAQ vs. EQ-5D by comparison of standardised B); r<sub>S</sub>=0.23, 0.18 and -0.16 for HAQ, DAS28 and EQ-5D, respectively (p=0.085 for HAQ vs. DAS28 and p=0.020 for HAQ vs EQ-5D). Work loss costs: B = €2574 (95%CI 2342-2807), 794 (668-919) and -4817 (-5392 to -4243) (p&lt;0.01 for HAQ vs. DAS28/EQ-5D, p=0.027 for EQ-5D vs. DAS28); r<sub>S</sub>=0.52, 0.32 and -0.40 (p&lt;0.001 for HAQ vs. DAS28/EQ-5D, p=0.008 for EQ-5D vs. DAS28). <h3>Conclusions</h3> In RA, work loss costs are more closely related to disability than to disease activity or health-related quality of life. HAQ disability is also a better marker of healthcare costs than health-related quality of life, while disease activity was not consistently inferior to HAQ in this regard. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1466
SP0207 Translating Genetic Findings into Applications for Individual Patients
Authors: S. Raychaudhuri
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> In the coming years the possibility of having access to a patient9s whole genome in the context of clinical care is becoming a real possibility. Recent discoveries in human genetics have begun to suggest that this data might have the potential to influence clinical management in the appropriate setting. Here we will discuss how personal genetic data might play an important role in the care of early rheumatic disease. We will also discuss how human genetic findings might influence the production of novel predictive biomarkers that might play an important role in the care of rheumatic diseases. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6305
Problems Evaluating Contamination of Dietary Supplements
Authors: Mary E. Palmer, Rama B. Rao
Journal: New England Journal of Medicine (1999)

Alternative Medicine -The Case of Herbal RemediesTo the Editor: With respect to the editorial on alternative medicine by you and Angell (Sept.17 issue), 1 if we look outside our own borders at the policies of other developed countries, we find a more rational approach to herbal medicine.In Germany, physicians are required to have some training in herbal medicine.Considerable research on herbal medicine -including double-blind, placebocontrolled trials -is ongoing. 2 Physicians recommend and patients use herbal medicines extensively.Manufacturers are required to meet standards of purity and pharmaceutical activity.Commission E, which has had oversight of herbal medicines and has determined their safety and efficacy, has published 387 monographs (recently translated into English by the American Botanical Council). 2Several other European countries 2 also have policies and procedures that allow rational oversight of herbal medicines.In the United States, herbs are used either as dietary supplements, with minimal standards of safety and efficacy, or as drugs, which require expensive and cumbersome testing procedures.I would argue for a more middle-of-the-road approach that acknowledges the long history of use of many herbal medicines, examines data from many sources including other countries, insists on strict production standards, and requires absolute safety and a classification of efficacy that may vary from "unproved" for some conditions to "demonstrated" for others.The use of the translated Commission E monographs would be very helpful for patients and physicians.
Oxacillin Treatment of Severe Staphylococcal Infections
Authors: Jerome O. Klein, Leon D. Sabath, Bruce W. Steinhauer, Maxwell Finland
Journal: New England Journal of Medicine (1963)

OXACILLIN (5-methyl-3-phenyl-4-isoxazolyl penicillin) is a new semisynthetic penicillin1 that has been demonstrated to be resistant to penicillinase2 3 4 and to possess the following readily recognized advantages over methicillin: acid stability, which permits absorption after oral administration, in contrast to the acid lability of methicillin, which is essentially unabsorbed when given orally1 , 2; greater activity in vitro against staphylococci,2 , 5 6 7 8 9 10 11 both those resistant to penicillin G that produce penicillinase and sensitive, nonpenicillinase producers; and greater activity against other susceptible gram-positive cocci.2 , 5 , 7 , 10 The present report is an analysis of the results of treatment with oxacillin of 124 patients with serious staphylococcal disease at the . . .
Prospective experimental study of transrectal viscerotomy closure using transanal endoscopic suture vs. circular stapler: a step toward NOTES
Authors: M. Diana, J. Leroy, J. Wall, V. De Ruijter, V. Lindner, P. Dhumane, D. Mutter, J. Marescaux
Journal: Endoscopy (2012)

Endoluminal full-thickness closure of the rectal wall is critical in emerging procedures including endoscopic submucosal dissection and transrectal natural orifice transluminal endoscopic surgery (NOTES). This study aimed to compare manual suture using the transanal endoscopic operation platform (TEO; Karl Storz, Tüttlingen, Germany) with the end-to-end anastomosis hemorrhoid circular stapler (EEA; Covidien, Dublin, Ireland) for closure of the rectal viscerotomy during transrectal NOTES segmental colectomy.A total of 12 swine underwent transrectal hybrid NOTES partial colectomies. Animals were divided into two groups according to the viscerotomy closure technique: 1) TEO manual suture; 2) EEA circular stapler closure.Mean (± SD) viscerotomy closure time was 67.5 ± 59.5 minutes and 31.5 ± 19.6 minutes for TEO and EEA, respectively. There was one conversion to laparoscopy in the TEO group and a misfiring in the EEA group that required a TEO salvage suture. There was one positive air-leak test in each group. Peritoneal fluid collected at the end of the procedure tested positive for bacterial contamination in all cases. A mild stenosis was present in 4 /6 viscerotomies (67 %) in the TEO group and in 1/6 (17 %) in the EEA group on endoscopic control. Inflammatory changes were mild in 3/5 (60 %) and 4/5 (80 %) viscerotomies in the TEO and EEA groups, respectively, whereas severe inflammation was found in 2/5 (TEO) and 1 /5 (EEA).Transrectal viscerotomy closure using the EEA circular stapler technique is feasible, easy to perform, and histologically comparable to suture closure through a TEO platform. It may offer an attractive alternative for NOTES segmental colectomies and endoscopic resections.
OP0129 Effects of Blisibimod, an Inhibitor of B-Cell Activating Factor, on Markers of Renal Disease in Patients with SLE
Authors: R. Furie, M. Scheinberg, G. Leon, E. B. Ramiterre, M. Thomas, A. D. Chu, C. Hislop, R. S. Martin, M. A. Petri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Elevations of BAFF are observed in patients with SLE. Here we report renal findings from a Phase 2b clinical trial in patients with SLE treated with the subcutaneous BAFF inhibitor, blisibimod. <h3>Objectives</h3> To evaluate the effect of 24-week therapy with blisibimod on markers of renal disease in patients with proteinuria or active inflammation. <h3>Methods</h3> 547 patients with serologically-active SLE and SELENA SLEDAI ≥6 were randomized to receive placebo or blisibimod. 13.9% of patients had renal involvement at baseline per SELENA-SLEDAI. Proteinuria and inflammation biomarkers were evaluated throughout the study. <h3>Results</h3> In a subgroup of subjects with baseline urinary protein equivalent to 1–6g/24hr (n=49), significantly greater reductions in proteinuria were observed with blisibimod compared to placebo from Weeks 8 through 24 (respective mean reductions of 0.73g/24hr (-35.0%) and 0.24g/24hr (-5.1%) at Week 24, p=0.045). Similarly, significantly greater reductions in proteinuria were observed in a subgroup of subjects with active inflammation ie low C3 and high anti-dsDNA (n=195, figure 1 ). Treatment with blisibimod was also associated with significant improvements in markers of B-cell inflammation: anti–dsDNA antibodies, C3 and C4, and B-cell counts. <h3>Image/graph</h3> <h3>Conclusions</h3> These data confirm and extend the established role of BAFF in SLE by demonstrating that BAFF inhibition is associated with decreased renal inflammation. The findings support further evaluation of blisibimod in SLE, and other autoimmune kidney diseases such as lupus nephritis, IgA nephropathy and idiopathic membranous glomerulonephritis. <h3>Disclosure of Interest</h3> R. Furie Consultant for: Anthera Pharmaceuticals, M. Scheinberg: None Declared, G. Leon: None Declared, E. Ramiterre: None Declared, M. Thomas: None Declared, A. Chu: None Declared, C. Hislop Employee of: Anthera Pharmaceuticals, R. Martin Employee of: Anthera Pharmaceuticals, M. Petri Consultant for: Anthera Pharmaceuticals
Abstract P4-02-04: Tissue oxyhemoglobin dynamics measured with functional optical imaging immediately after starting chemotherapy correlates with markers of cellular proliferation and inflammation in a rat breast tumor model.
Authors: S Ueda, D Roblyer, A Cerussi, T Saeki, B Tromberg
Journal: Cancer Research (2012)

Abstract We have reported that a transient increase of oxyhemoglobin level measured 24 hours after the start of neoadjuvant chemotherapy using noninvasive Diffuse Optical Spectroscopic Imaging (DOSI) may be useful in discriminating nonresponding from reponding breast cancer patients (PNAS. 2011 Aug 30;108(35):14626–31). To elucidate the underlying biological mechanism, we compared optical measured hemoglobin levels to tissue biomarkers in a rat tumor model. Method: An orthotopic mammary tumor model using Fischer 344 rats and MAT3B cells was used for this experiment. 16 mg of cyclophosphamide was administered (i.p.) in 15 rats after tumors had grown to a significant size. A wide-field functional imaging device that utilizes structured near-infrared light was used to measure superficial absolute concentrations of oxyhemoglobin (ctO2Hb) and deoxyhemoglobin (ctHHb) of the tumors. Rats were imaged and sacrificed (two per timepoint) at each of the following timepoints: baseline, 2, 6, 12, 24, 48, 96 hours, and day 8 following the injection. Resected tumors were sectioned after paraffin-embedding and representative slides were used for immunohistochemistry. Cellular markers of proliferation (measured by Ki67), apoptosis (Caspase3), NK cells (ANK61), and macrophages (MAC387) were counted in each slide using Image J software. Result: Average tumors baseline values of ctO2Hb and ctHHb were 81.4 µM (±9.2 SD) and 22.4 µM (±4.1 SD) respectively. In most rats, both levels gradually increased from baseline to 24 hours after the injection and reached a maximum at 48 hours and then declined until Day 8. At 24 hours, ctO2Hb was significantly higher than baseline [96.8 µM (±8.8 SD) vs. 81.4µM (±9.2 SD), p = 0.003 using Student's t-test]. This trend was mimicked in the tissue markers of cellular proliferation and apoptosis, which peaked at 24 through 48 hours and then dropped. The average NK cell count was also found to rise consistently through the course of monitoring and reached the highest at day 8, while macrophage counts reached a peak at 48 hours and then declined. The differences between baseline and 24 hours for these were statistically significant: Ki67 [294 (±107 SD) vs. 115 (±68 SD), p = 0.0002], Caspase3 [2916 (±1383 SD) vs. 136 (±150 SD), p &amp;lt; 0.0001], NK cells [635 (±329 SD) vs. 159 (±110 SD), p = 0.0001], and macrophage markers [281 (±260 SD) vs. 39 (±31 SD), p = 0.01]. Conclusion: We observed an increase in oxyhemoglobin early after chemotherapy, closely linked to changes in cellular proliferation, apoptosis, NK cells and macrophage accumulation. Early optical changes may be linked to chemotherapy-induced tumor metabolic and acute inflammatory responses. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-04.
OP0279 Inconsistent Treatment with Disease-Modifying Anti-Rheumatic Drugs: A Longitudinal Data Analysis: Table 1.
Authors: M.D. Mjaavatten, H. Radner, K. Yoshida, N.A. Shadick, M.L. Frits, C.K. Iannaccone, T.K. Kvien, M.E. Weinblatt, D.H. Solomon
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Current recommendations advocate treatment with disease-modifying anti-rheumatic drugs (DMARDs) in all patients with active rheumatoid arthritis (RA). However, results from contemporary RA cohorts show that even in specialized rheumatology clinics, a proportion of patients are not treated with DMARDs. <h3>Objectives</h3> We investigated the frequency of and reasons for inconsistent DMARD use among patients in a clinical rheumatology cohort. <h3>Methods</h3> Patients in the Brigham Rheumatoid Arthritis Sequential Study were studied for DMARD use (any or none) at each semi-annual study time point during the first two study years. Inconsistent use was defined as DMARD use at ≤40% of study time points. Characteristics were compared between inconsistent and consistent users (&gt;40%), and factors associated with inconsistent DMARD use were determined through multivariate logistic regression. A medical record review was performed to determine the reasons for inconsistent use. <h3>Results</h3> Of 848 patients with sufficient follow-up data, 55 (6.5%) were inconsistent DMARD users. Higher age, longer disease duration and rheumatoid factor negativity were statistically significant correlates of inconsistent use in the multivariate analyses (table). The primary reasons for inconsistent use identified through chart review, allowing for up to 2 co-primary reasons, were inactive disease (n=28, 50.9%), intolerance to DMARDs (n=18, 32.7%), patient preference (n=7, 12.7%), comorbidity (n=6, 10.9%), DMARDs not being effective (n=3, 5.5%), and pregnancy (n=3, 5.5%). During subsequent follow-up, 14/45 (31.1%) of inconsistent users with sufficient data became consistent users of DMARDs. <h3>Conclusions</h3> A small proportion of RA patients in a clinical rheumatology cohort were inconsistent DMARD users during the first two years of follow up. Several patient factors correlate with inconsistent use, and many patients re-start DMARDs and become consistent users over time. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2217
NI-54 * HYPERVASCULAR VOLUME ESTIMATED BY COMPARISON TO A LARGE-SCALE CEREBRAL BLOOD VOLUME (CBV) RADIOGRAPHIC ATLAS PREDICTS SURVIVAL IN RECURRENT GLIOBLASTOMA TREATED WITH BEVACIZUMAB
Authors: K. Leu, D. Enzmann, D. Woodworth, S. Teixeira, A. Lai, P. Nghiemphu, W. Pope, T. Cloughesy, B. Ellingson
Journal: Neuro-Oncology (2014)

BACKGROUND: Dynamic susceptibility contrast (DSC)-MRI is a well-established perfusion MR imaging technique for estimating relative cerebral blood volume (CBV) in primary brain tumors; however, tumors localized to regions with naturally elevated perfusion, including cortical tissue and common vascular territories, make evaluation of tumor vascularity difficult to assess. In the current study, we have constructed a large-scale radiographic atlas of CBV to assess treatment response to bevacizumab in individual patients with recurrent glioblastoma. METHODS: Z-score normalized CBV maps were registered to stereotactic atlas space in 450 patients with brain tumors. A CBV atlas was created by calculating the voxel-wise mean and variability in CBV. MRI and CBV maps from 32 recurrent glioblastoma patients were then obtained prior to and following treatment with bevacizumab, registered to and compared with the CBV atlas. The volume of tumor tissue with elevated CBV, percentage of enhancing tumor with elevated CBV, and the mean and maximum change in normalized CBV intensity relative to the atlas were computed. RESULTS: Voxel-wise comparison of individual patient CBV maps to the atlas allowed delineation of elevated tumor perfusion from artery and normal cortical tissue. An atlas-defined hypervascular tumor blood volume greater than 2.35 cc prior to treatment, 0.14 cc after treatment, and a decrease in atlas-defined hypervascular tumor volume less than 80% following treatment were characteristic of a shorter PFS and OS. Traditional measures of CBV were not predictive of PFS or OS. CONCLUSION: This study highlights the advantages of large-scale population maps to identify abnormal biological tissues.
A phase IB/IIA, multicentre, randomised, double-blind placebo controlled study to evaluate the safety and pharmacokinetics of Z-360 in subjects with unresectable advanced pancreatic cancer in combination with gemcitabine
Authors: T. Meyer, M. Caplin, D. Palmer, J. W. Valle, M. Larvin, J. Waters, F. Coxon, I. Borbath, M. Peeters, E. Nagano, H. Kato
Journal: Journal of Clinical Oncology (2008)

4636 Background: Pre-clinical evidence demonstrates that the human Cholecystokinin-2 receptor antagonist Z-360, can inhibit pancreatic tumour growth and prolong survival when combined with gemcitabine. Methods: Thirty three previously untreated patients with histologically/cytologically proven advanced pancreatic adenocarcinoma, KPS ≥ 70% with a life expectancy of ≥ 3 months and no major organ dysfunction were randomly allocated to oral Z-360 120mg, 240mg or placebo. A single dose of Z-360 or placebo was given on day - 3 and gemcitabine 1,000mg/m2 commenced on day 1 followed by Z-360 on day 2. Thereafter Z-360/placebo was given BID and gemcitabine weekly for 3 weeks out of 4 for a total of 12 weeks. PK for both drugs was measured as a single agent and in combination. We also measured serial serum gastrin, toxicity and response according to RECIST. The use of proton pump inhibitors was not allowed during the study period. Results: Thirty three subjects were randomised, of which 6 had locally advanced and 26 had metastatic disease. The median age was 62 years (range 41–77). Nine patients were allocated to the 120mg dose, 12 to 240mg and 12 to placebo. Analysis of AUC, Cmax(obs) and Tmax(obs) for Z-360, gemcitabine and dFdU, failed to exclude a difference when co-administration of Z-360 and gemcitabine was compared with single agent administration. In patients receiving Z-360 there was an increase in the median level of gastrin, while in those on placebo there was a decrease. The most commonly reported AEs were nausea, abdominal pain, vomiting and fatigue but no dose related trends were noted. No patients achieved an objective response but 62.5%, 25% and 60%, had stable disease at the end of the study in the 120mg, 240mg and placebo group respectively. Conclusions: Z-360 is safe and well tolerated at doses of 120mg and 240mg BID when combined with gemcitabine 1,000mg/m2. A Phase III trial is planned to determine whether the combination of Z-360 and gemcitabine is superior to gemcitabine alone in advanced pancreatic cancer. This work was sponsored and funded by Zeria Pharmaceutical Co. Ltd. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Zeria
Beyond Whole-Body Imaging
Authors: James Barnwell, Constantine A. Raptis, Jonathan E. McConathy, Richard Laforest, Barry A. Siegel, Pamela K. Woodard, Kathryn Fowler
Journal: Clinical Nuclear Medicine (2014)

PET/MRI is a hybrid imaging modality that is gaining clinical interest with the first Food and Drug Administration-approved simultaneous imaging system recently added to the clinical armamentarium. Several advanced PET/MRI applications, such as high-resolution anatomic imaging, diffusion-weighted imaging, motion correction, and cardiac imaging, show great potential for clinical use. The purpose of this article is to highlight several advanced PET/MRI applications through case examples and review of the current literature.
EFFECT OF ADDITIONAL INTRACORONARY NICORANDIL ADMINISTRATION DURING FRACTIONAL FLOW RESERVE MEASUREMENT WITH INTRAVENOUS ATP INFUSION
Authors: Hironori Takami, Shinjo Sonoda, Yoshitaka Muraoka, Yoshinori Sanuki, Yuki Tsuda, Masaru Araki, Yutaka Otsuji
Journal: Journal of the American College of Cardiology (2016)