tbuckley/cabot-search huggingface dataset:
PTH-173 Trends in the use of nsaids and aspirin and the use of proton pump inhibitors for gastro-duodenal protection in the uk: a cross-sectional study using the cprd database
Authors: N Lewis, Y Vinogradova, CJ Hawkey
Journal: Gut (2015)

<h3>Introduction</h3> NSAIDs consequences are amongst the commonest iatrogenic problems in medicine,resulting in &gt;40% of peptic ulcers<sup>1</sup>and thrombosis prompting guidance on their use.<sup>2</sup>Although aspirin has an established role in secondary prevention of vascular diseases,<sup>3</sup>guidelines recommend aspirin should not be used in primary prevention of vascular disease in those with hypertension or diabetes.<sup>4</sup>PPI play an important role in reducing the risk of peptic ulceration in NSAIDs with guidelines stating PPI should be used in all taking NSAIDs.<sup>5</sup>Guidelines recommend PPI use to prevent peptic ulceration with clopidogrel<sup>6</sup>though with PPI observed to reduce clopidogrel effects on platelet aggregation prompted guidance change, advising avoiding PPI use in those taking clopidogrel.<sup>7</sup>We performed a population-based study to observe how these changing recommendations have affected prescribing practice. <h3>Method</h3> Using the CPRD, prescribing rates were calculated in 6 month periods from 2003 to 2012 in a repeated cross-sectional study. For every observational period, we included patients between 45–100 years old, considering them exposed to a drug if they had at least 2 prescriptions for that drug. For prescribing rates the total number of patients was used as denominator, while for co-prescribing rates the number of patients exposed to NSAIDs or aspirin was used. Segmented regression was used to estimate changes in prescribing levels and in trends before and after guidelines were issued. <h3>Results</h3> The proportion of patients prescribed aspirin increased from 10.7% in 2003 (n = 127221) to 12.1% in 2012 (n = 169288). The trend change between observation periods before and after guidelines (4) was from a 37% (95% CI 32%, 42%) increase to a 35% (95% CI 23%, 48%) decrease. The trend change between observation periods before and after advice (2) was a 12% (95% CI 2%, 21%) increase to a 4% (95% CI 15%, 23%) decrease. PPI co-prescribing rates increased from 15% to 36% in aspirin users and from 12% to 46% in NSAID users, growing both before and after recommendations but without any statistically significant change in trend. A reduction (–11.7% [95% CI –12.6, –10.7]) was observed in co-prescription of PPI and clopidogrel in the year following recommendations of avoidance such practice. <h3>Conclusion</h3> Aspirin prescribing guidelines were associated with a significant impact on its prescription for primary prevention of vascular disease. PPI co-prescription with NSAIDs fall far short of the universal use that NICE recommends. Concerns raised about a harmful interaction between PPI and clopidogrel caused a substantial fall in PPI co-prescription. <h3>References</h3> Langman 2001 MHRA 2007 BMJ 2002 BHS 2004 NICE 2008 AHA 2008 FDA 2009 <h3>Disclosure of interest</h3> None Declared.
Response to “Comment on ‘Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes’”
Authors: Joseph G. Allen, Skye S. Flanigan, Mallory LeBlanc, Jose Vallarino, Piers MacNaughton, James H. Stewart, David C. Christiani
Journal: Environmental Health Perspectives (2016)
The Spectrum of Portal Hypertension in the Gastrointestinal Tract
Authors: A. Kassem
Journal: Endoscopy (2002)

Portal hypertension has a very complex pathophysiology and is associated with markedly deranged hemodynamics. In spite of this fact, it has long been considered that esophagogastric varices and their bleeding are the main consequences of portal hypertension and that otherwise it would be of little clinical significance [1]. This idea, however, seems to be changing with developments in various imaging modalities and more thorough studies on the manifestations of portal hypertension in the gastrointestinal tract. Though it is true that esophageal varices are the most commonly encountered sequel of portal hypertension, which may lead to life-threatening bleeding, a myriad of lesions with significant clinical implications can be attributed either directly or indirectly to portal hypertension.
On Innovating and Inspiring the Clinical Trial Enterprise
Authors: Susan E. Bates
Journal: Clinical Cancer Research (2015)

Our modern clinical trial system in oncology was built in the years since World War II, after the discovery of the activity of nitrogen mustard and methotrexate in leukemia. Subsequently, much has been accomplished to ensure that clinical trials are safe for patients and accurate in their assessments of therapeutic effect. A clinical trial enterprise has been built in oncology—one that compartmentalizes development into phases I, II, and III with requisite endpoints and infrastructure to match. This structure has accounted for much of the progress that has been made in cancer therapy but over time has become a complex and at times difficult structure to navigate. Although there are transformative drugs that will succeed in any clinical trial structure, many cancer drugs are ultimately incremental in nature and require methodical study. With the number of potential targets steadily expanding due to cancer genome sequencing, the number of drugs in development for cancer exceeding 800, the need to develop some drugs in combination with others, the requirement for companion diagnostic development to aid in patient selection, and the accrual rates among patients with cancer fixed at less than 5%, often, it appears that success in drug development is too reliant on good luck. Guided by Guest Editors Eric Rubin and Patricia LoRusso, this CCR Focus examines various aspects of drug development—including both recent innovations and ongoing challenges. Lillian Siu and colleagues describe new approaches to clinical trials based on defining mutations in cancer genomes rather than on tissue of origin. Marc Theoret and colleagues outline considerations involved in the use of expansion cohorts in early drug development, with the recent approval of pembrolizumab based on data from such cohorts. Ian Tannock and colleagues take a data-driven approach to ask why phase III trials often do not validate results obtained in phase II. Finally, David Stewart and colleagues highlight regulatory hurdles that they believe encumber drug development. These articles are complemented by an overview that includes the viewpoints of Don Berry and Stuart Bailey on the next generation of clinical trials. This CCR Focus is meant to stimulate thought and conversation about how the next-generation clinical trial enterprise should look. And, as with every CCR Focus, it is meant to insnpire those working in the field, and to interest and inform those outside.Susan E. BatesDeputy Editor, CCR FocusNational Cancer InstituteSee all articles in this CCR Focus section, “Innovations to Speed Drug Development.”
KCa1.1, a calcium-activated potassium channel subunit alpha 1, is targeted by miR-17-5p and modulates cell migration in malignant pleural mesothelioma
Authors: Yuen Yee Cheng, Casey M. Wright, Michaela B. Kirschner, Marissa Williams, Kadir H. Sarun, Vladimir Sytnyk, Iryna Leshchynska, J. James Edelman, Michael P. Vallely, Brian C. McCaughan, Sonja Klebe, Nico van Zandwijk, Ruby C. Y. Lin, Glen Reid
Journal: Molecular Cancer (2016)

Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional roles in mesothelioma. We interrogated a significant collection of MPM tumors and normal pleural samples in our biobank in search for novel therapeutic targets. Utilizing mRNA-microRNA correlations based on differential gene expression using Gene Set Enrichment Analysis (GSEA), we systematically combined publicly available gene expression datasets with our own MPM data in order to identify candidate targets for MPM therapy. We identified enrichment of target binding sites for the miR-17 and miR-30 families in both MPM tumors and cell lines. RT-qPCR revealed that members of both families were significantly downregulated in MPM tumors and cell lines. Interestingly, lower expression of miR-17-5p (P = 0.022) and miR-20a-5p (P = 0.026) was clearly associated with epithelioid histology. We interrogated the predicted targets of these differentially expressed microRNA families in MPM cell lines, and identified KCa1.1, a calcium-activated potassium channel subunit alpha 1 encoded by the KCNMA1 gene, as a target of miR-17-5p. KCa1.1 was overexpressed in MPM cells compared to the (normal) mesothelial line MeT-5A, and was also upregulated in patient tumor samples compared to normal mesothelium. Transfection of MPM cells with a miR-17-5p mimic or KCNMA1-specific siRNAs reduced mRNA expression of KCa1.1 and inhibited MPM cell migration. Similarly, treatment with paxilline, a small molecule inhibitor of KCa1.1, resulted in suppression of MPM cell migration. These functional data implicating KCa1.1 in MPM cell migration support our integrative approach using MPM gene expression datasets to identify novel and potentially druggable targets.
&lt;emph type="ital"&gt;Pièdouche Paperweight&lt;/emph&gt;
Authors: Robert M. Golub
Journal: JAMA (2008)

Glass paperweights have been classified as functional art, although their function is absurdly simple—to sit on and hold down papers of interest, something that every housecat can do. Their appeal as art, however, is personal, and for me the fascination began in childhood.
The Growth of Cells &lt;italic&gt;in Vivo&lt;/italic&gt; in Diffusion Chambers. II. The Role of Cells in the Destruction of Homografts in Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: J M WEAVER, G H ALGIRE, R T PREHN
Journal: JNCI Journal of the National Cancer Institute (1955)

The Growth of Cells in Vivo in Diffusion Chambers. II. The Role of Cells in the Destruction of Homografts in Mice Get access James M. Weaves, James M. Weaves Laboratory of Biology, National Cancer Institute,4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Glenn H. Algibe, Glenn H. Algibe Laboratory of Biology, National Cancer Institute,4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richmond T. Pbehn Richmond T. Pbehn Laboratory of Biology, National Cancer Institute,4Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 6, June 1955, Pages 1737–1767, https://doi.org/10.1093/jnci/15.6.1737 Published: 01 June 1955 Article history Received: 08 November 1954 Published: 01 June 1955
SAT0545 Panniculitis Associated with Rheumatic Diseases
Authors: O.N. Egorova, B.S. Belov, Z.S. Alekberova, Y.A. Karpova, O.V. Pushkova, S.G. Radenska-Lopovok, O.A. Antelava, E.G. Sazhina
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Panniculitis (Pn) is a group of heterogeneous rheumatic diseases characterized by inflammation of the subcutaneous fat (SF), disorders of the locomotor system and internals. Pn may be one of the rheumatic disease (RD) symptoms. <h3>Objectives</h3> To describe the symptoms of Pn associated with RD. <h3>Methods</h3> We studied 548 patients (76 men, 472 women), mean age 39±17 [16;75], with the referral diagnosis of erythema nodosum (EN) or panniculitis. Patient evaluation included physical examination, lab tests (levels of α1-antitrypsin, amylase, lipase, trypsin, ferritin, creatine phosphokinase (CPK) and liver fractions), radiological examination (chest CT scan), ultrasound examinations (dopplerography of the lower limb vessels and scanning of subcutaneous nodules), histopathology study and intradermal tuberculin skin test. <h3>Results</h3> In 40 (3 men, 37 women, mean age 42±15 [24;61]) out of 548 patients the following RDs were verified: <i>Behcet Disease</i> (12), <i>Systemic Lupus</i> Erythematosus (SLE) (10), Rheumatoid Arthritis (5), <i>Sjogren Syndrome</i> and <i>Dermatomyositis</i>(Dm) (4 cases each), <i>Reactive Arthritis</i>(3), Ankylosing Spondylitis and <i>Eosinophilic</i> Fasciitis (1 case each). Two types of Pn were identified: Lobular (LPn) and Septal (SPn). LPn was identified in 8 patients (4 with SLE and 4 with Dm). It was characterized with multiple "saucer-like" moderately painful nodules (VAS intensity of 46±19.3 mm), concentrated on the lower and upper extremities and occasionally on the chest and body, with further development of SF <i>atrophy</i>and high activity (ESR 32.7±12.2 mm/h, Hb 99±10.4 g/%, CK 1100±345 U/l, ds DNA 93.2±21U/ml). The LPn course was more severe and intractable, requiring prescription of glucocorticoids and cytostatic agents in high doses. SPn was more common in RD patients (n=32), and associated with EN with average duration of disease of 12±18 months [1;48] and moderate activity of the inflammatory process. Ultrasound scan and histological examination of the subcutaneous nodules confirmed SPn (with predominant inflammatory changes in septa) or LPn (with inflammatory changes in fat lobules) in RD patients. <h3>Conclusions</h3> Clinical and histopathological examination, as well as visual techniques may contribute to early diagnosis of Pn associated with RD. <h3>Disclosure of Interest</h3> None declared
AB0457 Patient Reported Adverse Events on Rituximab Treatment for Rheumatoid Arthritis: Table 1.
Authors: I.M. Visman, R. Agca, A. Voskuijl, M. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> After the success of TNF blocking therapy, a number of new biological therapies have emerged for patients with rheumatoid arthritis (RA). Rituximab is a B cell blocking agent and a good alternative to TNF blocking therapy. One issue that arises with any therapy, but biological therapy in particular, is adverse events. Reporting on serious adverse events (SAE) is mandatory. However, most adverse events patients experience are mild or moderate, and do not come close to the seriousness of an SAE. Nevertheless, these patient reported adverse events (PRAE) directly affect patient satisfaction with treatment, and are an important reason to discontinue treatment. <h3>Objectives</h3> To ascertain the number and severity of PRAE of long- term rituximab treatment for RA <h3>Methods</h3> The first rituximab patient was included February 9th 2009 and up to February 20th 2014 a total of 97 patients have been included at the Jan van Breemen research centre in Amsterdam, the Netherlands. <h3>Results</h3> The median follow-up duration was 1.1 (IQR:0.6-1.9) years for patients currently still on rituximab treatment, and 0.6 (0.1-1.1) years for drop-outs. The maximum follow-up duration was 3.8 years. Of the 97 patients included a total of 66 (68%) are currently on drug, and 31 (32%) patients have dropped out. Lack of efficacy was the most common cause for drop-out, with 14 (45%) patients. In addition, 11 patients (35%) discontinued rituximab treatment due to adverse events. An additional 2 patients (6%) never started rituximab treatment after inclusion, and for 2 patients (6%) the reason for drop-out was not given and 2 patients (6%) died during treatment. A total of 203 PRAE were observed in a total of 68 (70%) of patients. Reaction at site of injection was the most common adverse event observed during the follow-up (table 1). In 1 case a patient was hospitalized due to leukopenic fever (viral in nature), and 4 times antibiotics were given. Two patients died during rituximab treatment, one of a brain tumor, for the other cause of death was unknown. <h3>Conclusions</h3> The vast majority of PRAE were mild (90%). Only one (25%) of the 4 severe AE fulfilled the criteria for an SAE report. In contrast, 11 patients (in consultation with their rheumatologist) found their subjective PRAE serious enough to permanently stop taking rituximab. Obviously, reporting SAEs only does not give an adequate representation of the adverse events patients suffer. The reporting of patient (dis)satisfaction measures such as PRAE is a valuable addition to the reporting of SAE9s in studies, and to the decision making processes of rheumatologists. <h3>Disclosure of Interest</h3> None declared
Treatment-related fatal sepsis from topotecan/cisplatin and topotecan/paclitaxel.
Authors: A A Miller, R C Lilenbaum, T J Lynch, G L Rosner, M J Ratain, M R Green, R L Schilsky
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.6.1964 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8656268 Treatment-related fatal sepsis from topotecan/cisplatin and topotecan/paclitaxel. A A MillerxA A MillerSearch for articles by this author , R C LilenbaumxR C LilenbaumSearch for articles by this author , T J LynchxT J LynchSearch for articles by this author , G L RosnerxG L RosnerSearch for articles by this author , M J RatainxM J RatainSearch for articles by this author , M R GreenxM R GreenSearch for articles by this author , R L SchilskyxR L SchilskySearch for articles by this author Show More https://doi.org/10.1200/JCO.1996.14.6.1964 PDF "Treatment-related fatal sepsis from topotecan/cisplatin and topotecan/paclitaxel.." Journal of Clinical Oncology, 14(6), pp. 1964–1965© 1996 by American Society of Clinical Oncology
Case 34-1967
Authors: Peter M. Yurchak, Benjamin Castleman
Journal: New England Journal of Medicine (1967)

PRESENTATION OF CASEA fifty-six-year-old man was admitted to the hospital because of dyspnea.Fifteen years previously phlebitis developed in one leg, and anticoagulants were administered for six months. There was no pleuritic pain or dyspnea. Ten years before entry he had two episodes of right pleuritic pain, which improved spontaneously. Twenty months before admission there was the gradual onset of dyspnea and retrosternal tightness after exertion. Four months later he experienced two episodes of pleuritic pain at the right-lung base; there was no hemoptysis. X-ray films of the chest taken at another hospital showed scattered areas of pneumonitis in . . .
AB0269 Destruction Patterns of the Hip Joint in Rheumatoid Arthritis
Authors: H. Tanaka
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis (RA) in hip can cause severe joint destruction and may require total hip replacement surgery to retain normal joint function. With continuing synovial inflammation within the hip joint, the joint destruction progresses. It results in joint space narrowing, marginal and central erosions, and acetabular protrusion. In most of studies on joint damage in RA patients, the evaluation of joint destruction focuses only on small joints, because radiographic damage was scored according to the Sharp method as modified by van der Heijde, which includes the hands and feet. However, there is limited data on joint destruction of large load-bearing joints such as the hip. <h3>Objectives</h3> To study the destruction patterns of the hip joint in RA patients and to examine the relationships between destruction patterns and variables. <h3>Methods</h3> Serial hip radiographs of 50 RA patients (62 hips) undergoing total joint replacement were evaluated. The male/female ratio of the subjects was 38/2. The mean age was 59.8 years, and the mean duration of illness was 18.2 years. The mean duration of the period between hip pain onset and the time of surgery was 2.0 years. Biologics were used in six patients. 70% were concomitantly receiving prednisolone (mean dose: 3.0 mg/day). The relationships between destruction patterns of hip joint and variables was analyzed. <h3>Results</h3> Joint space narrowing (JSN) was seen in 28% of patients and acetabular protrusion (AP) in 45%. Additional destruction patterns included axial migration of the femoral head with hip dysplasia, avascular necrosis of the femoral head and rapidly destructive arthropathy (RDS). In patients with long-standing disease, JSN developed to acetabular protrusion in serial hip radiographs. In AP, mean protrusion distance was 5.1mm (1-15mm). Patients with biologics showed secondary osteoarthritis-like findings such as osteophytosis and subchondral sclerosis. AP and RDS were more frequently seen in patients with multiple joint destruction, compared with JSN. In AP, CRP and rheumatoid factor were significantly higher compared with JSN (p&gt;0.05). The duration of illness and the duration of the period between hip pain onset and the time of surgery were long and prednisolone dose were high in AP compared with JSN, although no significant difference was observed. <h3>Conclusions</h3> Joint space narrowing of the hip joint developed to acetabular protrusion in RA patients with high activity and long-standing disease. <h3>Disclosure of Interest</h3> None declared
FRI0032 Patient Reported Outcomes Correlated with the Concentrations of Glycoprotein Acetyls in Patients with Early Untreated Rheumatoid Arthritis: Table 1
Authors: A. Kononoff, L. Arstila, H. Kautiainen, P. Elfving, E. Savolainen, H. Niinisalo, O. Kaipiainen-Seppänen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Insulin resistance is increased in inflammatory conditions like RA. The glycosylation of the acute phase glycoprotein a-acid glycoprotein (AGP) in human sera is subject to marked changes during acute inflammation. <h3>Objectives</h3> To investigate relationship between glycoprotein acetyls (GP, mainly a1-acid glycoprotein) and patient reported outcomes: general health (GH, VAS), pain (VAS) and HAQ, among patients with newly diagnosed rheumatoid arthritis (RA) in a population based cohort. <h3>Methods</h3> For quantification of GP serum nuclear magnetic resonance platform operating at 500 MHz was used in native serum samples from patients with RA participating in Northern Savo 2010 Study. Crude and age-and BMI-adjusted correlation between GH, pain, HAQ and GP were counted. The 95% confidence intervals for the correlations were obtained by bias-corrected bootstrapping (5,000 replications). <h3>Results</h3> Serum samples from 63 patients, 34 females and 29 males, with RA satisfying the ACR/Eular 2010 classification criteria were studied. The mean age (SD) of patients was 59.1 (12.0) years and the BMI 27.3 (5.4) kg/m<sup>2</sup>. 69.8% had anti-CCP antibodies. The mean DAS28 was 4.4 (1.3), GH 52.7 (25.7), pain 56.4 (29.1), HAQ 0.70 (0.65), and GP 1.62 (0.29) mmol/L. GP correlated with CRP, r=0.79, p&lt;0.001, and with DAS28(CRP), r=0.38, p=0.004. Crude and age- and BMI-adjusted correlations for GH/GP, pain/GP and HAQ/GP are shown in table. <h3>Conclusions</h3> In untreated RA glycation of proteins has adverse influence on patients9 welfare. <h3>References</h3> Svenson KLG, et al. Metabolism 1987;36:940–3. Soininen P, et al. Analyst 2009;134:1781-5. <h3>Disclosure of Interest</h3> None declared