tbuckley/cabot-search huggingface dataset:
THU0168 Monotherapy with Biological Disease-Modifying Anti-Rheumatic Drugs-Data from the Czech Registry Attra:
Authors: H. Mann, Š. Forejtová, K. Jarošová, L. Šenolt, J. Závada, M. Uher, K. Hejduk, K. Pavelka
Journal: Annals of the Rheumatic Diseases (2014)

Background The biological disease-modifying anti-rheumatic drugs (bDMARDs) should be used for the treatment of rheumatoid arthritis (RA) in combination with conventional synthetic DMARDs (csDMARDs). However a significant proportion of patients receive bDMARDs in monotherapy. Objectives To compare outcomes of RA patients receiving bDMARDs as monotherapy or in combination with csDMARDs. Methods Baseline demographic data and efficacy parameters of the first bDMARD treatment of RA patients initiating bDMARD monotherapy (MONO) or combination (COMBI)therapy between 2007 and 2012 were retrieved from the Czech national registry ATTRA. ATTRA is a centralized prospective computerized registry of patients receiving bDMARD therapy collecting data on efficacy, safety and quality of life. bDMARD therapy was indicated after failure of at least 1 csDMARD (DAS28 ≥5.1). Results 1378 patients initiated bDMARD treatment after 2007, data regarding disease activity were available for 924 of them and this subgroup was further analyzed. The 114 patients (12%) who were started on bDMARD monotherapy were older (58 versus 52 years; P<0.001) with longer disease duration (10.1 versus 6.8 years; P=0.001) and more failed csDMARDs in the past (4 versus 3; P=0.002). The baseline DAS28 scores were similar in both groups (5.9 versus 5.8; P=0.083). The most commonly used first line bDMARDs in both groups were antiTNFα drugs (93.9% vs 94.4%; p=0.8). 61.4% MONO patients remained on the same therapy after 12 months, further 21.1% had a csDMARD added to their initial bDMARD. 75.3% COMBI patients remained on the original therapy, 9.7% more were on monotherapy with the first bDMARD. Remission (DAS28<2.6) was reached by 37.8% MONO patients and 41.6% COMBI patients after 12 months. Longitudinal binary logistic regression model was used to calculate the likelihood of reaching remission for both groups at various time points ([Table 1][1]). View this table: The median survival on the first bDMARD was 42.3 months in the MONO and 56.5 months in the COMBI group (HR 1.29; P=0.073). Conclusions The results of this observational study suggest that bDMARD efficacy and retention is lower when used as monotherapy, however most observed differences did not reach statistical significance. Acknowledgements Supported by project 00023728 from Ministry of Health in the Czech Republic Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3140 [1]: #T1
P165 Ambulatory Management Of Suspected Pulmonary Embolism At A Districtgeneralhospital. A 2 Year Review
Authors: A. Griffiths
Journal: Thorax (2014)

<h3>Background</h3> Studies have suggested that outpatient (OP) management of suspected pulmonary embolism (PE) is feasable.<sup>1</sup> At our DGH (popn 289400) in 2012 we found that over a 2 month period most suspected PE patients (suitable for ambulatory care) were being identified resulting in significant (17 nights) bed savings.<sup>2</sup> The aims of repeating our study were 1) to ascertain the proportion of patients who had a CTPA that were managed as OP and subsequent nights saved 2) to identify any further patients that could have been managed as OP and potential nights saved 3) a comparison with 2012 <h3>Methods</h3> RADIS was used to collect all CTPA’s performed between 1st Jan 2014 and 28th February 2014. Inclusion criteria: Ambulatory, normal heart rate, respiratory rate, blood pressure and oxygen saturations, any patient who was managed as an OP. Simpflified PESI Score &lt;1. Exclusion criteria: Pre-existing in-patients that had a CTPA ordered where the primary admission (and in-patient stay) was not for suspected PE,patients who had their CTPA on the same day of discharge, OP CTPA where waiting time was &gt;2 weeks, sPESI Score &gt;1, clinical concern. <h3>Results</h3> For the above period 102 CTPA’s were performed (105 in 2012). Average time from request to CTPA was 4.7 h (0.5–24 h. 4.1 hrs in 2012) Figure 1 shows the excluded patients.9 patients were included;7 were female, average age 47 years (23–66 years). All had a sPESI score <h3>Conclusion</h3> The number of ambulatory patients investigated for PE has reduced from 2012 to 2014 which probably reflects an increased acute physician presence at our DGH but some bed savings (7 nights over our 2 month period) were still made. Over 2 years approximately 180 ambulatory patients have been investigated and managed for PE at our DGH with no adverse incidents to date. <h3>References</h3> Hogg K <i>et al</i>.<i> Emerg Med J</i> 2006;23:123–127 Benjamin JA <i>et al</i>. Thorax 2012;67:A123
OT2-01-02: First-Line Bevacizumab in Combination with Capecitabine or Paclitaxel for HER2−Negative Locally Recurrent or Metastatic Breast Cancer (LR/MBC): A Randomized Phase III Trial.
Authors: S Beslija, T Brodowicz, R Greil, MJ Inbar, Z Kahán, B Kaufman, I Lang, GG Steger, SM Stemmer, C Zielinski, Z Zvirbule
Journal: Cancer Research (2011)

Abstract Background A number of phase III studies have shown significant progression-free survival (PFS) benefits with the combination of bevacizumab (Bev) and either first-line capecitabine (X) or taxane therapy in LR/MBC. The ongoing open-label, randomized, phase III CECOG-sponsored TURANDOT study (CECOG/BC.1.3.005) is investigating the efficacy and safety of first-line Bev plus paclitaxel (P) versus Bev plus X in this setting. Materials and methods: Eligible patients (pts) are aged ≥18 years with HER2−negative, chemonaïve LR/MBC, an ECOG performance status of 0–2 and a life expectancy &amp;gt;12 weeks. Prior chemotherapy and concomitant hormonal therapy for LR/MBC are not permitted, but prior (neo)adjuvant chemotherapy is allowed if completed ≥6 months before randomization or ≥12 months if taxane based. Pts are randomized to receive Bev 10mg/kg days 1, 15 plus P 90mg/m2 days 1, 8, 15, q28d (Arm A) or Bev 15mg/kg day 1 plus X 1,000mg/m2 bid days 1–14, q21d (Arm B) until disease progression, unacceptable toxicity or withdrawal of consent. The primary objective is to demonstrate non-inferiority in overall survival (OS) with Bev plus P versus Bev plus X (upper limit ≤1.33 for the two-sided confidence interval for hazard ratio [HR]). Secondary objectives are: comparison of overall response rate (RECIST criteria); PFS; time to response; duration of response; time to treatment failure; safety (CTCAE version 3); and quality of life (EORTC QLQ-30). The recruitment target is 560 pts. A sample size of 490 pts in the per-protocol population will be required to provide 80% power to reject the null hypothesis of inferiority at a one-sided significance level of 0.025, assuming a 24-month median OS with Bev plus P and an alternative hypothesis of HR=1. Data cut-off for adverse event reports was 12 Apr 2010. Interim and final efficacy analyses will be triggered after 175 and 389 events, respectively. Results: Recruitment to the study began in Sep 2008 and was completed in Aug 2010, with 561 pts randomized. Follow-up is ongoing. Conclusions: TURANDOT is the first study to examine the efficacy and safety of Bev plus P versus Bev plus X as first-line treatment for pts with LR/MBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-01-02.
OP0033 Radiographical follow-up data of a one-year open-label extension study of treatment with adalimumab in erosive osteoarthritis of the IP joints
Authors: R. Wittoek, D. Elewaut, G. Verbruggen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The first double-blind placebo controlled RCT (EudraCT nr 2006-000925-71) studied the efficacy and safety of adalimumab in 60 patients with erosive osteoarthritis of the interphalangeal finger joints (EOA) during 52 weeks. Inflamed IP joints (with palpable swelling) were found to be at risk to develop further destructive/erosive stages. 14.5% of the inflamed, and 3.7% of the non inflamed IP joints showed destructive/erosive evolution (p=0.009). Adalimumab treatment reduced the progresse to erosive stages of inflamed IP joints to 3.6% (1). <h3>Objectives</h3> To study the 1-year radiographic progression of an open-label extension (OLE) study with adalimumab (40mg, eow, sc). <h3>Methods</h3> Hand Xrays were taken after 6 and 12 months of treatment in the OLE. The progression was scored by the GUSS and anatomical phase scoring system. Comparison was made between the radiographs taken after 12 months and baseline of OLE. The number of new erosive joints was determined. Mean differences in total GUSS scores were calculated. <h3>Results</h3> Fifty of 60 patients enrolled in the OLE. One of 49 (2.0%) inflamed (i.e. effusion upon palpation) interphalangeal joints at baseline of this OLE and 6 of 228 (2.6%) non-inflamed joints became erosive under treatment with adalimumab (p = NS). The evolution in 148 of the initial 188 target joints (the RCT study phase) was analysed. Two joints became erosive (1.4%). Six joints showed extreme signs of remodellation (“F“ phase, ankylosis) (4.1%). The mean GUSS mean change after one year in OLE was +22.2 (SD 35) (p&lt;0.03), indicating overall remodellation. The mean GUSS change after 12 months in OLE between patients initially treated with adalimumab in RCT did not differ from patients initially treated with placebo (22.1 vs. 22.3, p=0.96). <h3>Conclusions</h3> Follow-up radiographic data confirm the potency of adalimumab to delay the radiographic progression in EOA. <h3>References</h3> G. Verbruggen, R. Wittoek, B. Vander Cruyssen and D. Elewaut. Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification. ARD 2011 Nov 29. [Epub ahead of print] <h3>Disclosure of Interest</h3> None Declared
Enrollment of Women in Cardiovascular Clinical Trials Funded by the National Heart, Lung, and Blood Institute
Authors: David J. Harris, Pamela S. Douglas
Journal: New England Journal of Medicine (2000)

With the recognition that certain aspects of cardiovascular disease are specific to sex, the government has sought to ensure that federally funded clinical research yields adequate high-quality information about heart disease in women.We tabulated the numbers of men and women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute (NHLBI) between 1965 and 1998, recording both total numbers and the numbers for each type of cardiovascular disease. We analyzed the data according to the sex-specific prevalence of disease and assessed changes in enrollment over time. We performed a similar analysis after excluding all single-sex trials.A total of 398,801 subjects (215,796 women and 183,005 men) were enrolled in NHLBI-funded studies of cardiovascular disease. The overall enrollment rate for women (54 percent) exceeded the prevalence of cardiovascular disease in women in the general population (49 percent) and increased over time (P=0.002). With single-sex trials excluded, the enrollment rate for women was 38 percent, which did not change significantly over time. In studies of coronary artery disease and hypertension the rates of enrollment of women were similar to or exceeded the prevalence of these disorders in women. The enrollment rate increased significantly over time in studies of coronary artery disease (P<0.001) but not in studies of hypertension or arrhythmia. Women were under-enrolled in studies of heart failure, and the rate of enrollment did not change significantly over time. When single-sex trials were excluded from the analysis of enrollment rates according to the prevalence of disease, the results were similar. There was no change in enrollment rates overtime for any category of disease.Federal efforts to increase the representation of women in clinical trials have been moderately successful primarily because of the institution of a small number of large, single-sex trials involving coronary artery disease. There has been no change in the sex composition of cohorts in the majority of studies of cardiovascular disease.
Abstract 2382: A critical role of tumor-specific hedgehog signaling for pancreatic cancer metastasis
Authors: Tao Sheng, Jing He, Xiaoli Zhang, Piotr Rychahou, Ling Yang, Guorui Xie, Huamin Wang, Nark Evers, Jingwu Xie
Journal: Cancer Research (2011)

Abstract The hedgehog (Hh) pathway plays a vital role in embryonic development and tissue differentiation, and aberrant activation of this pathway is found in a variety of human cancer, including pancreatic cancer. Despite the significance of Hh signaling for cancer development, it is not clear whether Hh signaling in the tumor compartment is required for tumor metastasis of pancreatic cancer. Here we show that elevated expression of hedgehog target genes is highly associated with poor outcomes of pancreatic cancer patients, but not always with elevated expression of hedgehog molecules (SHH and IHH) or the known downstream signaling molecules. Target genes of Hh signaling were expressed in the tumor as well as in the stroma. We found that elevated Hh target gene expression is associated with increased expression of snail1 or loss of E-cadherin, implying that Hh signaling may be associated with the pancreatic cancer metastasis potential. To investigate how Hh signaling may affect cancer metastasis, we established an orthotopic mouse model of pancreatic cancer. We showed in this model that Hh signaling is elevated in lymph node and liver metastasis. The role of Hh signaling for pancreatic cancer metastasis was demonstrated in an orthotopic mouse model of pancreatic cancer, which involves activated hedgehog signaling. We found that knocking down Gli2 expression in the cancer cells, which was associated with reduced Hh target gene expression, prevents tumor metastasis to liver. Based on these data, we conclude that tumor specific Hh signaling activation is required for pancreatic cancer metastasis. 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 2382. doi:10.1158/1538-7445.AM2011-2382
PWE-158 Screening Immigrants Originating From High Prevalence Areas For Hepatitis B Using Primary Care Databases – Experience From A Single Gp Practice With A Large Migrant Population
Authors: VJ Appleby, A Khan, J Rehman, GR Foster, S Moreea
Journal: Gut (2014)

<h3>Introduction</h3> Chronic Hepatitis B (HBV), a major cause of liver disease, is underdiagnosed in the UK with pockets of high prevalence in areas with large immigrant populations. Identifying individuals through a screening programme dedicated to high risk individuals would be beneficial if that target population could be defined. Our aims were to interrogate a Primary Care database (SystmOne) establishing the best way of identifying individuals suspected of having had a HBV test to exclude them from the target population. <h3>Methods</h3> We used four search terms: age (&gt;18), ethnic code, birth place, language spoken. Read codes (RC) were applied to identify individuals previously tested/diagnosed with HBV. RC were identified by using ‘HBV’ as a broad search term. <h3>Results</h3> We identified 4256 individuals aged ≥18. 718 (18%) were excluded because of lack of demographic data; 3210 (75%) qualified as the target population. 81 RC pertaining to HBV were found and generated 413 ‘hits’, only 224 ‘hits’ (54%) satisfied our criteria. 206 individuals (6.4%) had HBV serology recorded, 9/3210 (0.28%) were coded for chronic HBV, a further 2 HBsAg positive patients (0.9%) had no RC. After reviewing individual notes electronically we established the following 8 RC to be the ‘most useful’: XaIq7, XaFuS, X306n, X306i, 43B4, XaMBL, XaG1R, XaPEy which would have identified the latter. <h3>Conclusion</h3> We have identified the 8 most useful RC to help with a potential screening programme. Using all available HBV RC would be too time consuming. This study highlights that very few high risk immigrants are currently tested for HBV. <h3>Disclosure of Interest</h3> None Declared.
TR-12 * OKN-007: A NOVEL COMPOUND FOR TREATING PEDIATRIC GLIOBLASTOMA
Authors: S. Mallory, R. McNall-Knapp, P. C. DeSouza, N. Smith, D. Saunders, K.-M. Fung, R. Towner
Journal: Neuro-Oncology (2015)

Brain tumors are the most common solid tumor in children, and despite current treatment options including surgery, chemotherapy, and radiation for high-grade gliomas, survival in these patients remains very poor. This research represents promising pre-clinical data of a novel compound, OKN-007 (OKlahoma Nitrone 007, a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)), as a new clinical therapy for pediatric high-grade gliomas (pHGGs). The objective is to establish if pHGGs, which are often hard to surgically resect, can be treated with OKN-007, either as a single agent or in combination with currently used chemotherapeutic agents. OKN-007 may be an ideal candidate for treating pHGGs due to its multiple anti-cancer effects as seen in rat and adult gliomas, including inducing apoptosis, inhibiting cell proliferation and inhibiting angiogenesis. Morphological magnetic resonance imaging (MRI) of xenograft nude athymic mice injected with pHGG cells TCCC3752 is used in this study to assess brain tumor volumes for response to therapy. Preliminary data regarding the regression of pHGGs in mice following treatment with OKN-007 is presented. Mean survival was found to be significantly increased with OKN-007 treatment in responsive animals compared to an untreated group, p < 0.05. Immunohistochemistry and microarray will be used to assess levels of angiogenic markers (VEGF, HIF-1α, MVD), markers of cell differentiation (CAIX) and cell proliferation (Glut-1, MIB-1), apoptosis markers (cleaved caspase 3) and assess inhibition of TGFB and PDGFR complexes and downstream pathways, which are overexpressed in tumors and thought to play a role in oncogenesis and progression. OKN-007 is currently an investigational drug undergoing clinical trial evaluation for recurrent gliomas in adults but will still require FDA approval for use in pediatric patients. An outcome of the proposed research is to incorporate the pre-clinical data in an IND application in order to translate this research to the clinic and benefit children with pHGGs.
Folfirinox for Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (PDA); Clinical Outcomes and Prognostic Factors, the Royal Marsden (RM) Experience
Authors: Moorcraft Sing Yu, Khan Khurum, Peckitt Clare, Watkins David, Rao Sheela, Cunningham David, Chau Ian
Journal: Annals of Oncology (2014)
Why no mention of private sector in appraisal of GP led commissioning?
Authors: L. Moylett
Journal: BMJ (2012)

The study by Safy-Khan, <i>et al</i> in the current issue of <i>The Journal of Rheumatology</i><sup>1</sup> reports that in a methotrexate (MTX)-based treatment regimen for patients with early arthritis, current smoking was significantly associated with a smaller reduction of Disease Activity Score in 28 joints (DAS28) over time compared to noncurrent smoking. This negative effect of current smoking on DAS28 was dose-dependent: patients who smoked 10–19 cigarettes per day did worse than patients who smoked 1–9 cigarettes per day.
Relative Frequency of Upper Gastrointestinal and Colonic Lesions in Patients with Positive Fecal Occult-Blood Tests
Authors: Don C. Rockey, Johannes Koch, John P. Cello, Linda L. Sanders, Kenneth McQuaid
Journal: New England Journal of Medicine (1998)

Although bleeding lesions anywhere in the gastrointestinal tract can cause a positive reaction on guaiac-based fecal occult-blood tests, the relative frequency of upper gastrointestinal and colonic lesions is unknown.During a period of 30 months, we prospectively studied all patients with at least one stool specimen containing fecal occult blood who were referred for further evaluation. Fecal occult blood was detected by standard guaiac-based tests of stool specimens obtained as part of routine screening or of stool obtained by digital rectal examination. Patients with documented iron-deficiency anemia or active gastrointestinal bleeding were excluded from the study. All participants had a detailed history taken and underwent colonoscopy, followed by esophagogastroduodenoscopy.Of the 409 patients with fecal occult blood who were referred, 310 were potentially eligible to participate, and 248 (mean age, 61 years; range, 40 to 89) were studied; 40 percent were women. We identified lesions consistent with occult bleeding in 119 patients (48 percent); in 71 bleeding lesions were found in the upper gastrointestinal tract, and in 54 they were identified in the colon. Six patients had abnormalities in both areas. The most common upper gastrointestinal lesions were esophagitis (23 patients), gastric ulcer (14), gastritis (12), and duodenal ulcer (10). Thirty patients with lesions in the upper gastrointestinal tract were long-term users of aspirin, ethanol, nonsteroidal antiinflammatory drugs, or a combination of these substances. The most common colonic lesions were adenomas more than 1.0 cm in diameter (29 patients), carcinoma (13), colitis (5), and vascular ectasia (5). Although the overall sensitivity of symptoms for the detection of gastrointestinal lesions was low, logistic-regression analysis demonstrated that the presence of symptoms in the upper gastrointestinal tract was associated with the detection of lesions in the upper gastrointestinal tract (odds ratio, 2.6; 95 percent confidence interval, 1.4 to 4.7). In both patients with symptoms and those without symptoms, the prevalence of lesions in the upper gastrointestinal tract was greater than or equal to that of colonic lesions.In a group of patients with positive fecal occult-blood tests who were referred for further evaluation, from which those with iron-deficiency anemia and active bleeding had been excluded, upper gastrointestinal lesions were identified more frequently than colonic lesions.
REMOTE ISCHEMIC PRECONDITIONING FOR PREVENTION OF POST-OPERATIVE ATRIAL FIBRILLATION IN PATIENTS UNDERGOING CARDIAC SURGERY: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Amartya Kundu, Partha Sardar, Sreeparna Ghosh, Saurav Chatterjee, David McManus
Journal: Journal of the American College of Cardiology (2016)
Familial Primary Cryofibrinogenemia
Authors: Philippe Begin, Georgette Leclerc
Journal: New England Journal of Medicine (2013)

A 50-year-old woman presented with a history of painful lesions involving cold-exposed areas of skin, a condition that had worsened every fall and disappeared every spring since childhood. The physical examination revealed ulcers, livedo, and bluish-purple discolorations with crusts and scar tissue on the ears (Panel A), hips, knees, fingers, and toes (Panel B). Many other members of the patient's family reported having similar symptoms. Laboratory evaluation showed a plasma cryofibrinogen level of 850 mg per liter. Cryofibrinogenemia is diagnosed when plasma that is clear at 37°C (Panel C) develops a precipitate when it is cooled to 4°C (Panel D). . . .