tbuckley/cabot-search huggingface dataset:
SP0137 Using Multiple International Healthcare Databases (The EU-ADR Project)
Authors: P. M. Coloma
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Knowledge of the safety profile of drugs prior to marketing is limited because of the small and selective groups of individuals included in clinical trials. A life-cycle approach to surveillance therefore needs to be adopted in order to learn the effects of drugs in 'real-world' practice. Safety surveillance of drugs post-marketing has traditionally been carried out by systematic manual review of reports of suspected adverse drug reactions from physicians, other healthcare professionals, consumers, and marketing authorisation holders and registered in national spontaneous reporting systems. Safety-related warnings and market withdrawals of widely used products in the first decade of the new millennium has fueled efforts to explore other data sources and develop new methodologies to offset the limitations of current surveillance systems. One of the important resources considered to have potential for active drug safety surveillance are electronic healthcare records (EHRs). Across the globe various public-private initiatives have been launched to investigate the secondary use of EHRs for this purpose. Databases containing electronic medical records as well as reimbursement claims for various healthcare services have been used for evaluation of drug safety issues in the past, but such studies were always conducted using one database at a time. This lecture will focus on the recently concluded EU-ADR Project (Exploring and Understanding Adverse Drug Reactions by Integrative Mining of Clinical Records and Biomedical Knowledge, http://www.euadr-project.org/). EU-ADR, launched in 2008, was funded by the European Commission under its Seventh Framework Programme. A computerised integrated framework using EHR and biomedical data was developed in EU-ADR for detection and evaluation of drug safety signals. The database network originally comprised eight population-based administrative claims databases and general practitioner databases in four European countries (Denmark, Italy, the Netherlands, and the United Kingdom). EU-ADR is now expanding its network and expertise through the EU-ADR Alliance, a more stable collaboration framework for conducting drug safety studies in a federated manner especially when engagement of several EHR databases is required. This lecture will further describe the opportunities and challenges that come with heterogeneity in database structure, with differences in language and coding of both drugs and diseases, and with the diversity in the organisation of European healthcare systems. <h3>Disclosure of Interest</h3> None Declared
Brush cytology vs. endoscopic biopsy for the surveillance of Barrett’s esophagus
Authors: A. Kumaravel, R. Lopez, J. Brainard, G. Falk
Journal: Endoscopy (2010)

See also: Commentaire de travail de A. Kumaravel et al., pp. 800Endoscopy 2010; 42(10): 883-883DOI: 10.1055/s-0031-1291881
Abstract 2328: 15N-backbone and side-chain dynamics of the mutant calcium-binding protein S100B D63N
Authors: Melissa Liriano, Kristen M. Varney, Rieko Ishima, David J. Weber
Journal: Cancer Research (2011)

Abstract Similar to calmodulin and other EF-hand-containing proteins, S100 proteins have no inherent enzymatic activity and perform their biological functions via calcium-dependent protein-protein interactions. Elevated protein levels of S100B have been linked to various types of cancers, including malignant melanomas, glioblastomas, and anaplastic astrocytomas. In the case of malignant melanomas, S100B contributes to cell proliferation by binding to p53 and inhibiting its tumor suppressing properties. However, one property of S100 proteins, including S100B, is that it only binds to calcium tightly when its target protein is bound, a feature that drug design studies for restoring p53 in melanoma must mimic. Therefore, the purpose of this study is to determine the mechanism for how target protein binding to S100B causes an increase in calcium-binding affinity. Previous studies suggest that the increase in calcium affinity in the presence of target is not the result of a structural modification. As an alternative explanation, the mechanism behind this event may involve a reduction in the ligand dynamics coordinating calcium in the canonical EF-hand when target peptide is present. To test this hypothesis with S100B, an asparagine mutant was made in order to have an 15N-probe in the tight-binding EF-hand of S100B for NMR side-chain dynamics with and without target peptide. 15N backbone dynamic experiments (T1, T2, and hetNOE) were collected for the S100B D63N mutant (+/- TRTK-12) at two magnetic fields to determine the effects of peptide binding at multiple time scales. Relaxation dispersion experiments were also collected for backbone and side-chain amides of S100B in the presence and absence of TRTK-12. For the backbone dynamic experiments, motion was detected in the hinge region and C-terminus of helix-4 at multiple timescales in the absence of TRTK-12 (ns-sec timescale). A similar profile was observed for those backbone residues undergoing motion in the chemical exchange time scale seen with the relaxation dispersion data. However, when a molecular target was introduced, the majority of these backbone amides that make up the hydrophobic pocket displayed a general decrease in dynamics. Side chain dynamics in the EF-hand was appreciated in the absence of TRTK-12 peptide, however when the target was present, no chemical exchange was seen with the 15N-D63N probe in the EF-hand. These findings imply that In the presence of target peptide, S100 proteins undergo a decrease in protein dynamics that translates from the site of target binding to the EF-hand. 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 2328. doi:10.1158/1538-7445.AM2011-2328
Commentary: Determining Exposure and Biochemical Effects in Human Population Studies
Authors: Renate D. Kimbrough
Journal: Environmental Health Perspectives (1983)

We all are surrounded by and exposed to many chemicals in our personal environment.These chem- icals are either naturally occurring or man-made.Such exposures may have profound impact on our health, such as cigarette smoking, excessive alcohol consumption, and abuse of illicit and legal drugs, or they may be necessary for our survival, such as nutrients, disinfectants, fertilizers and fuels.How- ever, this is not what will be discussed here.We are concerned about chemicals which have inadvertently contaminated the environment because of the way they were used and disposed of, such as pesticides and other industrial chemicals.Of all the chemicals produced in industry, only some metals, halogenated compounds, plastics, and organotin compounds are persistent in the envi- ronment and in people.Most chemicals, unless present in large quantities, biodegrade and photo- degrade rapidly in the environment.They are also rapidly metabolized and excreted by people.Therefore, unless exposure was relatively recent, it is not possible to measure such chemicals as mycotoxins, organophosphorus compounds, solvents, nitrosa- mines, and carbamates.It is not possible to esti- mate the past and present levels of exposure in people accurately.For a number of them, it has not been determined what the background levels might be in the general population.When 100 blood and/or urine samples of people from the southeastern part of the United States were analyzed, 23% of these samples contained trace amounts of aflatoxin related materials (1).Similarly, Fine et al. (2) were able to measure trace amounts of nitrosamines in human blood.It is, therefore, conceivable that we all have trace
THU0361 Paraneoplastic arthritis: A multi-centered experience
Authors: B. Kisacik, A.M. Onat, T. Kasifoglu, Y. Pehlivan, O.N. Pamuk, E. Dalkilic, S. Dönmez, S.Y. Bilge, S. Yilmaz, H. Erdem, R. Mercan, M.A. Ozturk, C. Bes, M. Soy, S. Erten, V. Cobankara, S. Senel, F.A. Oner, H. Direskeneli, S. Yilmaz, S. Kul, G.Y. Cetin, M. Sayarlioglu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Paraneoplastic syndromes may mimic many symptoms like rheumatologic disease manifestations, hematologic disease, and vascular disease. <h3>Objectives</h3> Paraneoplastic syndromes are defined by clinical, radiological or laboratory findings associated with malignant disease, but without a direct invasion of malign cells. Paraneoplastic syndromes precede cancer by no longer than two years. Musculoskeletal symptoms of paraneoplastic syndromes can be varied and difficult to differentiate. We attempt to report the laboratory and clinical findings of 55 patients admitted to different rheumatology clinics with rheumatic symptoms who were diagnosed with paraneoplastic arthritis. <h3>Methods</h3> Thirteen rheumatology centers participated in the study. The study population consist of 55 patients (male/female: 38/17) and 35 patients with rheumatoid arthritis (RA) patients as the control group (male/female: 21/14). Paraneoplastic group was divided into two sub-groups as hematologic malignancies and solid tumors. <h3>Results</h3> Mean age of patients with paraneoplastic arthritis and controls with RA control subjects were 48.7±16.2 and 51.9±12.1 respectively. The mean ages and gender distribution of the groups’ were similar. The mean age of the patients in solid tumor group were significantly higher than the hematological malignancy group (53.2±12.7 vs 43.2±15.5 <i>p=</i>0.001).When the clinical features and laboratory findings of RA group was compared with paraneoplastic arthritis, symmetric poly-arthritis, rheumatoid factor and anti cyclic cyctrullinated peptide (anti-CCP) presence were favorably higher among RA patients. <h3>Conclusions</h3> In our cohort, leukemia, lymphoma and lung cancers were the leading diseases emerged as the final diagnosis of paraneoplastic arthritis. Rheumatoid arthritis patients were differentiated from paraneoplastic arthritis with high symmetric joint involvement, higher rheumatoid factor and anti-CCP positivity. <h3>Disclosure of Interest</h3> None Declared
P145 CYTOTOXIC T LYMPHOCYTE ANTIGEN-4 (CTLA-4) SIGNALING EFFECTIVELY RETAINS REGULATORY T CELLS (TREG) TO ALLEVIATE LIVER INJURY OF PATIENTS WITH ACUTE-ON-CHRONIC HEPATITIS B (ACHB)
Authors: J. Li, W. Jiang, C.-Q. Yang
Journal: Journal of Hepatology (2014)
P31 Do Lung Cancer Patients Get a Better Deal If They Present By Two Week Wait Pathway?
Authors: E Nuttall, K Mitton, M Wilkoninson, G Jifon, A Ansari, S Bari
Journal: Thorax (2012)

<h3>Introduction</h3> Introduction of one stop lung cancer[LC] clinics have shortened the patient journey of 2 week wait [2WW] referral patients to reach diagnosis and treatment however because of multiple referral sources, non 2 week [N2WW] patients follow a different journey. Our aim was to find out whether there is significant difference in patient outcome in these two groups in a multisite NHS Trust. <h3>Method</h3> Between January 2008 &amp; December 2011 all patients who had a radiological &amp; or histological diagnosis (n=996) made in LCMDT were included in this study. Demography, time to diagnosis, time &amp; number of deaths, staging &amp; histology were compared. <h3>Results</h3> In 2WW group 439 [Age 71(35–95)years, 177 female and In N2WW group 557 [Age 72(22–95), 232 female were compared. No significant difference in age, however significant difference were noticed in time to diagnosis [referral to diagnosis] 24.9 (0–167) in 2WW &amp; 27.4(0–176) days in N2WW group [p=0.029]. 313 died in 2WW group and 451 in N2WW till June 2012. The time between date of referral to date of death was also significant between 2WW and N2WW group 258 [15–1328] days to 185[3–1271] days respectively (p=0.001)). In the 2WW group 62% [74%NSCLC, 15%SCLC, Others 10%] vs. 46% CLC 17% others 17%. 124(28%) of 2WW and 163(29%) of N2WW presented with metastatic disease [p=ns], 149(33.9%) of 2WW and 142(26%) of N2WW presented with T4 disease. Median PS was 1 and 2 respectively. <h3>Conclusion</h3> The data suggests there is a significant difference between patient journey and outcome between two groups despite no significant difference in staging. Poor documentation and use of upgrading to 2WW made it difficult to find out why so many were under N2WW. Physicians are encouraged to review and alter patient pathway for N2WW group to ensure equal access to health care and appropriate outcome for all patients with LC diagnosis.
OP0081 Concepts important to patients with rheumatoid arthritis in rehabilitation and their coverage by rehabilitation tools
Authors: J. Meesters, W. Pont, L. Beaart-van de Voorde, T. Stamm, T. Vliet Vlieland
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Despite important improvements in pharmacological care for patients with rheumatoid arthritis (RA), many patients with RA need additional care to achieve and maintain an optimal level of functioning (1). Delivery of comprehensive multidisciplinary care in a rehabilitation setting may be required if treatment by other health professionals has failed (2). <h3>Objectives</h3> This study aimed to explore whether RA patients' perspectives on rehabilitation are covered by current rehabilitation instruments. <h3>Methods</h3> A qualitative focus group study with RA patients about their experiences with rehabilitation was conducted. Meaningful units were derived from the recorded and transcribed texts, and concepts regarding essential aspects of rehabilitation contained in these meaningful units were extracted and were linked to the International Classification of Functioning, Disability and Health (ICF). Rehabilitation tools which have been validated among RA patients were identified using a structured literature search. Using the ICF as a common framework, we determined for each concept identified in the focus groups whether it was covered by each of the rehabilitation instruments. <h3>Results</h3> 19 patients participated in 4 focus groups. Fifty-one concepts were identified in the 368 meaningful units derived from the transcribed data. Four rehabilitation tools were selected from the literature: The ICF Core Sets for RA, the Canadian Occupational Performance Measure, the Rehabilitation Activities Profile and the WHO Disability Assessment Schedule II. The concepts from the focus groups were best covered by the ICF-CSRA 44 out of 51 (86%), followed by WHODAS-II (39%), RAP (35%) and COPM (16%). Concepts from the focus group within the ICF-component Activities and Participation showed the best coverage by the rehabilitation tools. Overall, the patient perspective regarding important concepts of rehabilitation was best covered by the ICF-CSRA (fig. 1). <h3>Conclusions</h3> Besides Activities and participation, current rehabilitation tools poorly cover the concepts that patients find essential during rehabilitation. The ICF-CSRA outstands and could serve as a checklist to guide multidisciplinary assessments and goal-setting in the rehabilitation of RA patients. <h3>References</h3> [1]Hallert E et al. Rheumatology 2006; 45(3):325-31. [2]Vliet Vlieland T. Rheumatology 2007; 46(9):1397-404 <h3>Disclosure of Interest</h3> None Declared
THU0026 Greater Diagnostic Delay in Early-Onset than in Late-Onset Systemic Lupus Erythematosus - Data from Reuma.Pt/Les: Table 1.
Authors: S. Sousa, M.J. Gonçalves, L. Inês, C. Duarte, S. Fernandes, G. Terroso, V.C. Romão, M. Cerqueira, A. Raposo, M. Couto, P. Nero, T. Novoa, P. Pinto, J.A. Melo Gomes, J. Canas da Silva, L. Costa, J. Pereira da Silva, L. Cunha-Miranda, J. Da Silva, H. Canhão, M.J. Santos
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic lupus erythematosus (SLE) affects predominantly women of reproductive age. However, in about 15% of patients SLE begins before the age of 18 years (early-onset) and in 10-20% of patients SLE is first diagnosed after the age of 50 years (late-onset). The age at disease onset significantly impacts on clinical presentation, disease course, response to treatment and prognosis. <h3>Objectives</h3> To compare demographic, clinical features and disease outcome between patients with early-onset and those with late-onset SLE and to determine whether patients9 age affects the time interval until diagnosis. <h3>Methods</h3> All SLE patients from the Portuguese registry Reuma.pt/LES with disease onset at age≤18 years-old or at age≥50 years-old were included. Patients9 data were cross-sectionally analyzed upon records from the last visit. The differences between groups with early and late onset were determined by Student t-tests, chi-square or Fisher9s exact tests. <h3>Results</h3> 313 SLE patients were included (157 early-onset; 156 late-onset). In the early-onset group, 88% were women, mean disease duration 16.8±10.5y and mean age of diagnosis 17±5.9y. Higher education level was noted in the younger group. 81.6% of patients with late-onset SLE were women, mean disease duration 9.37±5.2y and mean age of diagnosis 60.5±7.5y. Photosensitivity, arthritis and neurological disorder were statistically more prevalent in the late-onset group. Anti-Sm positivity was observed more frequently in early-onset SLE. Co-morbidities were also more common in this age group. Disease activity evaluated using the SLEDAI-2K was higher in the early-onset (3.0±3.3 vs 2.0±2.8; p=0.01) while accumulated damage was higher in the older age group (1.0±1.3 vs 0.69±1.4; p&lt;0.001). Diagnosis delay was significantly greater in patients with early-onset than in the late-onset group (3.1±5 vs 1.7±3 y; p=0.001). <h3>Conclusions</h3> Patients with late-onset SLE have more co-morbid conditions and greater accumulated damage despite shorter disease duration and lower disease activity. Age of onset has a significant impact not only on the clinical characteristics and disease outcome, but also on time until diagnosis. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5306
Abstract 1558: Imaging of metastatic B16F10 melanoma in mice using tumor-homing stem cells.
Authors: Tej B. Shrestha, Sivasai Balivada, Matthew Basel, Marla Pyle, Stefan H. Bossmann, Deryl L. Troyer
Journal: Cancer Research (2013)

Abstract Tumors, like wounds, recruit cells from surrounding tissues and bone marrow. Some of these cells provide support and nutrition, while others participate in an inflammatory response. Bone marrow mesenchymal stem cells (MSCs) exhibit this tropism toward wounds and other areas of pathology. Consequently, stem cell technology for diagnostic and therapeutic purposes is an emerging field in cancer biology. Like bone marrow MSCs, mouse neural progenitor cells (NPCs) tend to migrate toward cancer sites. We found that these cells migrate toward B16F10 lung melanomas, making them very good candidates for delivery of chemotherapeutic drugs, genes of interest, and imaging contrast agents. Among imaging techniques, bioluminescent imaging is non-invasive. Gaussia luciferase (Gluc) is particularly useful, as it is non-toxic and has stronger luminescence than other known luciferases. In the presence of its substrate coelenterazine (coel), Gluc luminescence peaks near 470 nm. In this study, we engineered NPCs to secrete Gluc. These Gluc-engineered cells were injected systemically to C57BL/6 mice bearing metastatic B16F10 lung melanoma and mice were given coel intravenously. Imaging of the mice on the Caliper IVIS Lumina II showed bioluminescence in disseminated areas. The distribution of bioluminescence suggested that the engineered NPCs migrated to the tumor sites and secreted Gluc. In confirmation, necropsy revealed black metastatic tumors in the locations emitting bioluminescence. Although IV injection of metastatic B16F10 lung melanoma cells usually generates lung tumors, we found dissemination of melanoma in other parts of the body. The Gluc-expressing NPCs could find the tumors as early as 2 days post tumor-cell injection, long before tumors were palpable. Thus, this system offers promise for improving cancer diagnosis. For improved imaging, this bioluminescence system can be coupled with other fluorescent dyes for red shifted output. Finally, the same sensitivity and tumor tropism suggests that the NPCs could be useful delivery cells for tumor-targeted therapeutics. Citation Format: Tej B. Shrestha, Sivasai Balivada, Matthew Basel, Marla Pyle, Stefan H. Bossmann, Deryl L. Troyer. Imaging of metastatic B16F10 melanoma in mice using tumor-homing stem cells. [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 1558. doi:10.1158/1538-7445.AM2013-1558
Case 29-1998
Authors: Michael J. Barza, Jonathan H. Blum, Fiona M. Graeme-Cook
Journal: New England Journal of Medicine (1998)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 29-1998 — A 57-Year-Old Man with Fever and Jaundice after Intravesical Instillation of Bacille Calmette-Guerin for Bladder Cancer
Hormone replacement therapy increases risk of breast cancer
Authors: J. Wise
Journal: BMJ (1997)

The risk of breast cancer increases slightly in women using hormone replacement therapy (HRT), and this risk increases the longer the treatment is used, according to a thorough reanalysis of data on more than 160000 women.

Many individual studies of the effects of HRT on the risk of breast cancer have been published, but because results differ it has not been clear until now how great the increased risk might be and even if a risk existed at all.

Professor Valerie Beral, director of the Imperial Cancer Research Fund's Cancer Epidemiology Unit in Oxford, and her collaborators collated and analysed data on 52 705 women with breast cancer and 108411 women without breast cancer from 51 studies in 21 countries ( Lancet 1997;350:1047-59). More than 900 of the women in the analysis had been taking HRT for 15 years or more.



Cancers in women who use HRT tend to be more localised KING'S COLLEGE SCHOOL OF MEDICINE/SPL



The relative risk of having breast cancer diagnosed in-creased by a factor of 1.023 for each year of use among current users of HRT or those who had stopped using it in the previous four …