tbuckley/cabot-search huggingface dataset:
M264 Health And Economic Impact Of Prescribing Pirfenidone
Authors: N. Chaudhuri, C. Leonard
Journal: Thorax (2014)

<h3>Introduction</h3> Pirfenidone is the only licensed drug in Europe for Idiopathic Pulmonary Fibrosis (IPF). Clinical trials (1) have demonstrated efficacy in reducing decline in forced vital capacity (FVC), improving progression free survival and reducing mortality. The translation of clinical trial results to clinical practice is a focus of interest. <h3>Methods</h3> We describe our experiences in prescribing pirfenidone in a single centre observational study of 96 patients from September 2011 to April 2014. <h3>Results</h3> This is an extension of our published work (2). Prior to NICE approval we recruited 49 patients in twenty months. NICE approval resulted in a 140% increase in pirfenidone prescribing. Patient demographics at baseline are shown in Table 1. 54 (56%) patients continued treatment, 19 (20%) discontinued treatments due to adverse effects (AEs), there were 17 (17%) deaths and 4 (4%) patients were transplanted. Patients that died had lower diffusing capacity (DLCO) at baseline compared to those that continued treatment (32.9 vs 47.7 p &lt; 0.0001). Patients that discontinued treatment due to AEs did so within six months and had lower body mass index (25.1 vs 29 p = 0.002) and DLCO (38.8 vs 47.7 p = 0.007). There were a total of 206 AEs in 77 (79%) patients. The majority were gastrointestinal in nature. Of these adverse effects the majority were self-limiting and resolved with simple measures. 44 (21%) resulted in a dose reduction, 23 (11%) resulted in a temporary discontinuation, in 101 (45%) AEs treatment was unchanged and 38 (19%) AEs resulted in drug discontinuation. In selected patients we had one or more lung function results before (34%) and after (50%) pirfenidone treatment. Eighteen months prior to pirfenidone treatment there was an observed reduction in mean% predicted FVC over time. Accepting limitations of missing data, this decline appeared to stabilise over twelve months after commencement of pirfenidone. Based on an annual unit cost of £22, 245.96 for pirfenidone (without undisclosed discount). To date 96 patients have been treated for a total of 876 months at a total cost of £1,623,955 in two and a half years. <h3>Conclusion</h3> This study highlights both the health and economic impacts of pirfenidone over a two and a half year period of prescribing. <h3>References</h3> King TE Jr <i>et al</i>. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. ASCEND Study Group. <i>N Engl J Med.</i> 2014 May 29;370(22):2083-92 Chaudhuri N <i>et al</i>. Real world experiences: pirfenidone is well tolerated in patients with idiopathic pulmonary fibrosis. <i>Respir Med.</i> 2014 Jan;108(1):224-6
COMPARATIVE EVALUATION OF TWO-DIMENSIONAL VERSUS THREE-DIMENSIONAL ECHOCARDIOGRAPHIC VARIABLES TO PREDICT THE IMMEDIATE OUTCOME OF PERCUTANEOUS TRANSVENOUS MITRAL COMMISSUROTOMY
Authors: Jeet Ram Kashyap, Kewal Chand Goswami, Rakesh Yadav, Ganesan Karthikeyan, Neeraj Parakh, Vinay Kumar Bahl
Journal: Journal of the American College of Cardiology (2015)
Changes in mortality inequalities over two decades: register based study of European countries
Authors: Johan P Mackenbach, Ivana Kulhánová, Barbara Artnik, Matthias Bopp, Carme Borrell, Tom Clemens, Giuseppe Costa, Chris Dibben, Ramune Kalediene, Olle Lundberg, Pekka Martikainen, Gwenn Menvielle, Olof Östergren, Remigijus Prochorskas, Maica Rodríguez-Sanz, Bjørn Heine Strand, Caspar W N Looman, Rianne de Gelder
Journal: BMJ (2016)

To determine whether government efforts in reducing inequalities in health in European countries have actually made a difference to mortality inequalities by socioeconomic group.Register based study.Mortality data by level of education and occupational class in the period 1990-2010, usually collected in a census linked longitudinal study design. We compared changes in mortality between the lowest and highest socioeconomic groups, and calculated their effect on absolute and relative inequalities in mortality (measured as rate differences and rate ratios, respectively).All European countries for which data on socioeconomic inequalities in mortality were available for the approximate period between years 1990 and 2010. These included Finland, Norway, Sweden, Scotland, England and Wales (data applied to both together), France, Switzerland, Spain (Barcelona), Italy (Turin), Slovenia, and Lithuania.Substantial mortality declines occurred in lower socioeconomic groups in most European countries covered by this study. Relative inequalities in mortality widened almost universally, because percentage declines were usually smaller in lower socioeconomic groups. However, as absolute declines were often smaller in higher socioeconomic groups, absolute inequalities narrowed by up to 35%, particularly among men. Narrowing was partly driven by ischaemic heart disease, smoking related causes, and causes amenable to medical intervention. Progress in reducing absolute inequalities was greatest in Spain (Barcelona), Scotland, England and Wales, and Italy (Turin), and absent in Finland and Norway. More detailed studies preferably using individual level data are necessary to identify the causes of these variations.Over the past two decades, trends in inequalities in mortality have been more favourable in most European countries than is commonly assumed. Absolute inequalities have decreased in several countries, probably more as a side effect of population wide behavioural changes and improvements in prevention and treatment, than as an effect of policies explicitly aimed at reducing health inequalities.
Pulmonary Neuroendocrine Tumors: What (Little) Do We Know?
Authors: Lin-Chi Chen, William D. Travis, Lee M. Krug
Journal: Journal of the National Comprehensive Cancer Network (2006)

Pulmonary neuroendocrine tumors are a distinct subset of tumors composing approximately 20% of all lung cancers. The major categories of pulmonary neuroendocrine tumors include typical and atypical carcinoids, large cell neuroendocrine carcinoma, and the more common small cell lung cancer. They are classified into different categories in the 2004 World Health Organization system, but share structural and morphologic features. Despite these shared features, their clinical characteristics range from indolent to aggressive, and therefore the approach to treatment depends on the histologic subtype. This article discusses the current understanding of the epidemiology, pathologic characteristics, treatment, and prognosis of this spectrum of diseases.
A computer-assisted psychiatric assessment unit
Authors: T A Williams, J H Johnson, E L Bliss
Journal: American Journal of Psychiatry (1975)

The authors discuss the rationale and functional design for an innovative approach to psychiatric intake decision making, stressing the crucial role of an on-line computer support system. The description of the prototype computer-assisted psychiatric assessment process includes an outline of computer and staffing requirements. The authors discuss the initial impact of this psychiatric assessment unit on the hospital's mental health care delivery system.
White House Cases: psychiatric patients and the Secret Service
Authors: D Shore, C R Filson, T S Davis, G Olivos, L DeLisi, R J Wyatt
Journal: American Journal of Psychiatry (1985)

Delusional visitors to the White House or other government offices (often seeking a personal audience with the President) are interviewed by the Secret Service and then sent to Saint Elizabeths Hospital if they are considered mentally ill and potentially dangerous to themselves or others. A review of the demographic characteristics and diagnoses of 328 of these "White House Cases" treated at the hospital between 1970 and mid-1974 showed that these patients were most commonly unmarried, white, and male, and most had a diagnosis of paranoid schizophrenia. Although 22% of this group have threatened some prominent political figure, to date none of this study's patients has attempted to assassinate any such government official.
OP0091 Prediction of radiographic spinal progression using biomarkers in patients with ankylosing spondylitis who are at high risk for progression:
Authors: D. Poddubnyy, K. Conrad, G. Ruiz-Heiland, U. Syrbe, H. Haibel, H. Appel, M. Rudwaleit, G. Schett, J. Sieper
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Presence of radiographic spinal damage (syndesmophytes) is the strongest predictor of further radiographic progression in ankylosing spondylitis (AS). In the recent years several biomarkers have been found to be associated with radiographic spinal progression/syndesmophyte formation in AS, however, it is not clear, whether these biomarkers are also able to predict new bone formation in AS patients who are at high risk of radiographic progression due to a presence of syndesmophytes at baseline. <h3>Objectives</h3> To investigate the association of biomarkers with radiographic progression in the spine (new syndesmophytes formation or growth of the existing syndesmophytes) in patients with AS and risk factors for such progression. <h3>Methods</h3> Altogether 64 patients with AS from the German Spondyloarthritis Inception Cohort (GESPIC) were considered to be eligible for this analysis due to the presence of syndesmophytes at baseline. Radiographs of the lumbar and cervical spine performed at baseline and after 2 years of follow-up were scored independently by two trained readers. Two groups of patients were defined according to the scoring results: Group I (progressors, n=26) patients with syndesmophytes at baseline and new syndesmophyte or syndesmophytes growth after 2 years; Group II (non-progressors, n=38): patients with syndesmophytes at baseline but without progression after 2 years. Serum levels of the following biomarkers were examined: C-reactive protein (CRP), matrix metalloproteinase 3 (MMP3), sclerostin, Dickkopf 1 (DKK1), periostin, bone morphogenetic protein (BMP)2 and 7, osteoprotegerin (OPG), vascular endothelial growth factor (VEGF), procollagen type I and II N-propeptide (PINP and PIINP), CTX-II, BALP, sRANKL, COPM, and bone sialoprotein. <h3>Results</h3> There were statistically significant differences between Group I and Group II in the baseline serum levels of CRP (17.1±17.1 vs 8.7±9.9, p=0.031) and MMP3 (40.2±36.2 vs 19.5±23.2, p=0.016) that confirmed a predictive value of markers of active inflammation regarding radiographic spinal progression. However, in patients with both risk factors, syndesmophytes and elevated CRP at baseline, serum levels of MMP3, BMP2, PIINP, VEGF, and OPG demonstrated statistically significant inter-group differences (table). Protective trends were found also for sclerostin, DKK1 and periostin. No significant differences in serum levels were found for other tested biomarkers. <h3>Conclusions</h3> Here we were able to show for the first time that higher levels of MMP3, BMP-2, PIINP, and VEGF, and lower level of OPG might predict progression of structural damage in the spine in patients with AS who are already at high risk of such a progression due to the presence of syndesmophytes and elevated CRP. <h3>Disclosure of Interest</h3> None Declared
C-Cell Hyperplasia Preceding Medullary Thyroid Carcinoma
Authors: Hubert J. Wolfe, Kenneth E. W. Melvin, Sergio J. Cervi-Skinner, Abdul A. AL Saadi, Joseph F. Juliar, Charles E. Jackson, Armen H. Tashjian
Journal: New England Journal of Medicine (1973)

Two sisters at risk for hereditary medullary carcinoma and having small but progressive increases of serum calcitonin in response to calcium infusion underwent thyroidectomy. The thyroid glands were studied for C-cell distribution. Middle and upper portions of the lateral thyroid lobes showed marked increases and clustering of calcitonin-containing cells in comparison with normal thyroid glands. Elevated calcitonin content (670 to 4100 Medical Research Council mU per gram), as compared to similar regions in normal thyroid tissue (<0.6 to 50.0 Medical Research Council mU per gram), correlated precisely with the cytologic localization. Histologic characteristics of the cells had the appearance of a preinvasive hyperplastic process. A third case from another kindred was studied with similar findings. C-cells thus appear to be distributed inhomogeneously in normal human thyroid tissue; an early change in persons destined to development of hereditary tumors of these cells is a multicentric, but anatomically restricted, increase in numbers of cells. (N Engl J Med 289:437–441, 1973)
AB0756 Patients with Psoriatic Arthritis Have Strong Beliefs about the Etiology of Their Disease: A Systematic Literature Review
Authors: P.E. Palominos, A. Gasparin, R.M.D.S. Chakr, R.M. Xavier, C. Hinckel, L. Gossec
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patient9s perceptions and beliefs are important to explain adherence to therapy, coping patterns, impact of disease and side effects. <h3>Objectives</h3> to gain knowledge on patient9s perceptions/beliefs about Psoriatic Arthritis (PsA). <h3>Methods</h3> This work is part of a systematic literature review accomplished on PubMed/Medline aiming to explore the fears and beliefs of patients with Rheumatoid Arthritis (RA), PsA, Ankylosing Spondylitis (AS) and other Spondyloarthritis (SpA). In this summary, we focus on results about PsA. Search terms used were: (("fears" OR "beliefs" OR "attitude to health/psychology" [MeSH Terms] OR "behavior and behavior mechanisms/psychology" [MeSH Terms]) OR "affective symptoms/psychology" [MeSH Terms]) AND ("arthritis/psychology" [MeSH Terms] OR "spondylarthropathies" [MeSH Terms] OR "spondylitis, ankylosing"[MeSH Terms]) OR "arthritis, rheumatoid" [MeSH Terms] OR "arthritis, psoriatic" [MeSH Terms]) AND ("interviews as topic" [MeSH Terms] OR "narration" [MeSH Terms]) OR "questionnaires"[MeSH Terms] OR "qualitative research" [MeSH Terms])). Original articles in English, French, Italian, Spanish or Portuguese reporting fear and/or beliefs of adult patients were included. Data analysis was descriptive <h3>Results</h3> 266 articles were found and 75 included: 25.3% (n=19) were qualitative studies, 65.3% (n=49) were quantitative studies (more frequently with cross sectional design, 66.1%, n=39) and 9.3% (n=7) had mixed designs. These 75 studies recruited 19,225 patients from 19 countries: 17178 RA, 1720 AS, 125 SpA and 202 PsA. Only 3 articles (4.1% of total) reported fear and/or beliefs of PsA patients, all were quantitative studies that reported patient9s opinion through questionnaires: the "Brief Ilness Perception Questionnaire", the "Willingness to pay-8 domains of HRQoL" and a modified version of the "Patient Knowledge Questionnaire". Among the 202 PsA patients, mean age was 48.2±6.9 years old, mean disease duration was 9.4±0.2 years and 53.9% (n=109) were men. These articles reported that physical comfort, emotional health, sleep and work are the most affected domains on patient9s opinion; they also described erroneous perceptions of PsA patients: 20.3% believe their disease is triggered by food, drugs, pollution; 13.5% found that psoriasis was caused by cold damp weather; 50.8% thought that psoriasis was the etiology of psoriatic arthritis. One author also showed that patient9 illness perception can affect measures of quality of life in PsA. <h3>Conclusions</h3> There is little work aiming to study patients9 beliefs and perceptions in PsA. It seems that the patients frequently have strong beliefs about the etiology of their disease and it should be discussed during medical visits. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1547
AB0099 Relation of mmps promoter polymorphisms to factors describing rheumatoid arthritis
Authors: M. Pavkova Goldbergova, J. Lipkova, N. Pavek, P. Nemec, J. Gatterova, J. Sevcikova, M. Soucek, A. Vasku
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Matrix metalloproteinases (MMPs) as a family of zinc-dependent endopeptidases have been involved in remodelling the extracellular matrix (ECM) not only in rheumatoid arthritis (RA). The promoter polymorphism variants in the MMPs genes can contribute to the onset, progression and severity of RA due to influence of promoter activity leading to altered expression. <h3>Objectives</h3> The aim of the study was to examine the relation among polymorphisms and serum levels of selected MMPs (MMP-2, MMP-3, MMP-7, MMP-12, MMP-13), production of auto-antibodies, and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp score. <h3>Methods</h3> A total of 156 RA patients according to the ACR criteria, and 100 control subjects were recruited into the study. The measurements of CRP, anti-CCP, presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp score (TSS), DAS28 and MMPs (MMP-3, MMP-13) levels in serum were obtained from all RA patients. <h3>Results</h3> Complete or almost complete linkage disequilibrium was observed for MMP-2 polymorphisms (-790T/G, -1575A/G, -1306C/T; p &lt; 0.001). All these MMP-2 promoter polymorphisms were related to RF IgG levels (p &lt; 0.05) and RF IgG positivity/negativity (p &lt; 0.01), IL-15 levels (p &lt; 0.05), and in a trend to TNF alpha levels. Higher prevalence of T allele (-790T/G), C allele (-1306C/T) and G allele (-1575A/G) in the RF IgG positive subgroup was observed. The -135G/C MMP-7 polymorphism was related to activity of the disease; the variation was associated to DAS28 score (p &lt; 0.01), TTS (p = 0.05) and HAQ (p = 0.03). A trend of relation between -77G/A MMP-13 polymorphism and TNF alpha levels was found (p = 0.06). No relation of promoter polymorphisms -11715A/6A MMP-3 and -77G/A MMP-13 to MMPs serum levels was proved. The MMP-3 serum level correlated to IL-6 (p = 0.02) and CRP (p = 0.05) levels. <h3>Conclusions</h3> In conclusion, we present an association of MMPs gene polymorphisms with the rheumatoid factor IgG, and disease activity. <h3>Disclosure of Interest</h3> None Declared
OP0053 Cremalpha destabilizes FOXP3 expression in regulatory T cells
Authors: K. Ohl, T. Rauen, K. Tenbrock
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The transcription factor cAMP response element modulator (CREM) is a widely expressed transcriptional repressor. CREMα is overexpressed in SLE (Systemic Lupus erythematosus) T cells and CREMα promoter activity correlates with disease activity. Occurrence of autoreactive B and T cells is a hallmark of this severe autoimmune disease. Autoreactive immune responses are normally controlled by regulatory T cells (Tregs). This T cell population is regulated by FoxP3 as the most important and lineage-specific transcription factor. Several studies observed that numbers and suppressive capacity of regulatory T cells are decreased in SLE patients and in murine lupus models. Until now the reason for these observations remains to be elucidated. We showed before that overexpression of CREMα accelerates onset of auto-immune mediated disease in a murine model of lupus. Interestingly these mice also show decreased levels of regulatory T cells. <h3>Objectives</h3> The aim of this study was to elucidate the role of CREMα in regulatory T cells. <h3>Methods</h3> We assessed the role of CREMα in regulatory T cells by analyzing numbers and suppressive capacity of this cell population in CREMα overexpressing and CREM deficient mice. We performed reporter gene assays to investigate transcriptional regulation of FoxP3 expression. <h3>Results</h3> We observed enhanced numbers of regulatory T cells in CREM deficient mice, as well as enhanced levels of FoxP3 mRNA expression and an increased differentiation towards FoxP3 positive cells <i>in vitro</i>. Vice versa FoxP3 mRNA expression and differentiation towards FoxP3 positive cells was reduced in mice which overexpress CREMα. Furthermore CREM deficient regulatory T cells showed an enhanced suppressive capacity <i>in vitro</i> and <i>in vivo</i>. We attribute these findings to an involvement of CREMα in transcriptional regulation of FoxP3 expression. We found that CREMα binds and trans-represses activity of the regulatory T cell-specific demethylated region in the FoxP3 locus, which is known to critically regulate FoxP3 expression. <h3>Conclusions</h3> We postulate that increased expression of CREMα in SLE T cells mediates an exaggerated down-regulation of FoxP3 expression and compromises stability and function of Tregs. This data provide further evidence for CREMα as a key player in the development of autoimmunity. <h3>Disclosure of Interest</h3> None Declared
CORONARY ARTERY CALCIUM BURDEN DIFFERENCE IN TWO ASYMPTOMATIC HISPANIC POPULATIONS
Authors: Erasmo De La Pena-Almaguer, Cesar Ivan Avila, Alejandro Trevino, Luis Pérez, Neel Ravela, Indra De La Cruz-Isidro, Yoezer Flores-Sayaveedra, Murali Pendela, Edward Ramos-Santiago, Mohammad Badii, Su Min Chang
Journal: Journal of the American College of Cardiology (2016)
IMPACT OF MYOCARDIAL DEFORMATION IMAGING ON THE DIAGNOSIS OF MYOCARDIAL BRIDGE: PHYSIOLOGIC AND STRAIN ECHOCARDIOGRAPHIC STUDY
Authors: Yukari Kobayashi, Jennifer Tremmel, Yuhei Kobayashi, Shigemitsu Tanaka, Ian Rogers, Armaghan Gomari, Francois Haddad, Ingela Schnittger
Journal: Journal of the American College of Cardiology (2015)
REG3β Plays a Key Role in IL17RA Protumoral Effect—Letter
Authors: Qing Li, Jun-Li Liu, Zu-Hua Gao
Journal: Cancer Research (2016)

We have read with great interest the recent report by Loncle and colleagues ([1][1]) investigating the role of REG3β in mediating protumoral effects of IL17. We agree in principal with their conclusion that Reg3β is involved in the initiation of pancreatic ductal adenocarcinoma (PDAC) and its
CS-02 * SHP2 PROMOTES TUMOR PROGRESSION IN GBM VIA RAS ACTIVATION
Authors: S. Bunda, P. Heir, K. Burrell, M. Ohh, G. Zadeh
Journal: Neuro-Oncology (2014)

Mutations in Ras GTPase and various other components of the Ras signaling pathways are among the most common genetic alterations in human cancers and have also been identified in several familial/developmental syndromes. Ras is also an important factor in many cancers where it is not mutated but functionally activated through inappropriate function of other signal transduction elements. One such example is the overexpression of growth factor receptors in glioblastoma (GBM). Elucidating the mechanistic details of the GTPase reaction has been an important scientific goal and the subject of intensive research for many years. However to this day, targeting Ras directly remains elusive. Our laboratory recently demonstrated that Src binds to and phosphorylates Ras on a conserved tyrosine residue markedly reducing the binding of effector Raf to Ras and concomitantly increasing the rate of GTP hydrolysis leading to Ras inactivation. Furthermore we demonstrate that tyrosine phosphorylated Ras can be dephosphorylated by the phosphatase SHP2 resulting in Ras activation. We also demonstrate that increased Ras activity in human primary GBM cell lines and astrocytes derived from GBM-prone mice, as well as in human GBM patient samples results from elevated SHP2 activity. Finally we show that the highly specific SHP2 inhibitor II-B08 promotes tyrosine phosphorylation of Ras leading to attenuation of downstream proliferative MAPK/ERK signaling and reduction in tumor burden in mouse models of GBM.
Coronary Bypass — Survival Benefit in Heart Failure
Authors: Robert A. Guyton, Andrew L. Smith
Journal: New England Journal of Medicine (2016)

Velazquez and colleagues report the outcomes from the 10-year extended follow-up of the surgical revascularization component of the Surgical Treatment for Ischemic Heart Failure (STICH) study.1 This STICH Extension Study (STICHES) was a tenacious 15-year effort, achieving a 98% rate of follow-up from 99 institutions of 1212 patients with heart failure and severe left ventricular dysfunction who were randomly assigned to receive either medical therapy alone or medical therapy plus coronary-artery bypass grafting (CABG). CABG was found to confer a significant and substantial survival benefit at 10 years, with a rate of death from any cause that was 16% lower . . .