tbuckley/cabot-search huggingface dataset:
THU0149 Does Methotrexate Lower Serum Uric Acid Levels? Data from the Catch Cohort
Authors: J.J. Lee, V.P. Bykerk, G.K. Dresser, G. Boire, B. Haraoui, C. Hitchon, C. Thorne, D. Tin, S. Jamal, E.C. Keystone, J.E. Pope
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Methotrexate is the cornerstone DMARD in the treatment of rheumatoid arthritis. The exact mechanism of action is elusive, but it may be related to increase in adenosine levels. Methotrexate may be increasing the adenosine levels by blocking its natural conversion to uric acid. <h3>Objectives</h3> The purpose of this study was to determine if methotrexate therapy lowers serum uric acid levels in patients with early rheumatoid arthritis compared to controls who were not treated with methotrexate. <h3>Methods</h3> Data were obtained from CATCH (Canadian Early Arthritis Cohort), a prospective early RA cohort. This was a nested case control study. All patients with methotrexate use and a diagnosis of early rheumatoid arthritis (ERA) were included if they had a serum uric acid performed before starting methotrexate and again while taking methotrexate. Patients with ERA who did not receive any methotrexate were used as controls if they had serial uric acid measurements. <h3>Results</h3> Forty-nine ERA patients, out of 2524, in the CATCH database on methotrexate therapy with serial serum uric acid measurements were identified. In this group, the mean pre-methotrexate uric acid level was 300 μmol/L with a mean post-methotrexate uric acid level of 273 μmol/L (p 0.035). The control group of ERA patients not taking methotrexate during this time had a mean baseline uric acid level of 280 μmol/L and a follow-up level of 282 μmol/L (p 0.448). The mean change in uric acid levels in serum in patients treated with methotrexate was -26.8 μmol/L, while the control group had a mean change of 2.3 μmol/L (p=0.042). Patients who experienced a decrease in serum uric acid levels in relation to their methotrexate treatment had a DAS28 score of 2.37 at 18 months, while the control group had a DAS28 of 3.26 (p=0.042). Patients treated with methotrexate who experienced a decrease in uric acid levels had a SJC28 of 0.89 at 18 months, while patients on methotrexate who did not experience a decrease in uric acid levels had a SJC28 of 4.47 (p=0.035). <h3>Conclusions</h3> Methotrexate is fundamental in the treatment of ERA and it is thought to work through increase in adenosine levels. By this postulated mechanism of action, uric acid levels were shown to be decreased in a clinical setting for patients taking methotrexate for ERA. This could be an indirect mechanism whereby methotrexate improves cardiovascular risk <h3>Disclosure of Interest</h3> None declared
Linked claims and medical records for case management of breast cancer diagnosis
Authors: M. Eberl, G. Broffman, J. Pomerantz, N. Watroba, M. Reinhardt, M. C. Mahoney, C. Fox, S. B. Edge
Journal: Journal of Clinical Oncology (2006)

6000 Background: Real time linkage of medical records and administrative claims may assist physicians in managing cancer care. Failure to obtain requisite follow-up (f/u) of abnormal mammograms may delay cancer diagnosis and impact outcome with studies showing that up to 20% of women do not get recommened f/u. We tested the accuracy of claims data linked to medical records in identifying women who did not receive f/u for an abnormal mammogram (BI-RADS 0,3,4,5). Methods: Electronic medical records in a staff model practice affiliated with a single payer were scanned to identify the BI-RADS code for all mammograms performed by practice radiologists. For each woman covered by the payer with a BI-RADS 0,3,4 or 5 mammogram, claims were searched for f/u breast procedures (imaging, biopsy, surgery). For women with more than 1 abnormal mammogram in the study period, only f/u of the first abnormal mammogram was studied. Cases were censured if their insurance coverage with the payer terminated before the required period of follow-up. Medical records of cases defined by claims as not having recommended f/u were reviewed to determine the accuracy of claims analysis. Results: 17,329 women covered by the payer had at least one mammogram in the practice from 1/1/2001 to 12/31/2003. The BI-RADS was 0, 3, 4 or 5 in 1,319 (7.5%). Among 1,206 eligible for f/u, 189 (16%) did not receive the BI-RADS recommended f/u (see table ). Medical record review showed that the claims search accurately identified the follow-up care in 95% of these cases. Conclusions: Administrative claims accurately identify care for diagnostic management of abnormal mammograms. Real-time linkage of claims to mammogram BI-RADS data is being tested as a regional case management system to assist physicians in assuring approrpriate follow-up for abnormal mammograms. [Table: see text] No significant financial relationships to disclose.
The Comparative Value of Hematopoietic Stem Cell Transplantation and Chemotherapy in Cytogenetically Normal AML Subclassified By NPM1 Mutation Status and FLT3-ITD Allelic Ratio
Authors: Jurjen Versluis, Raynier Devillier, Florentien in 't Hout, Wim van Putten, Markus G Manz, Marie-Christianne Vekemans, Martyn Ronald Schaafsma, Jakob R Passweg, Johan Maertens, Jurgen H Kuball, Leo F. Verdonck, Bart J Biemond, Peter J.M. Valk, Marie-Joelle Mozziconacci, Norbert Vey, Harry C Schouten, Edo Vellenga, Thomas Pabst, Bob Lowenberg, Gert J Ossenkoppele, Didier Blaise, Gerwin A Huls, Jan J Cornelissen
Journal: Blood (2014)
Prescribing sodium oxybate for narcolepsy
Authors: Adam Zeman, Zenobia Zaiwalla
Journal: BMJ (2016)

Demanding that a patient’s need is “exceptional” is irrational and should be abandoned

Narcolepsy affects around 4 in 10 000 people, making it about one quarter as common as multiple sclerosis in the United Kingdom.1 Its cardinal features are excessive daytime sleepiness causing frequent, irresistible naps; cataplexy, leading to collapse, embarrassment, and sometimes injury; and marked disturbance of nocturnal sleep. It is usually due to a specific deficiency of the hypothalamic neurotransmitter hypocretin and most often starts in the teens, probably as the result of an autoimmune process. Narcolepsy is far more than an occasional dose of sleepiness: it is a lifelong, pervasive, and potentially disabling disorder with a similar effect on quality of life to treatment resistant epilepsy.2

While potentially disabling, it is also highly treatable.3 A combination of stimulants (typically modafinil or dexamfetamine or both) and antidepressants (to reduce cataplexy) improves symptoms appreciably in most patients. But treatment response may be partial; contraindications or side effects can prevent their use; and none of these drugs deals with the third cardinal symptom of narcolepsy, which is sometimes the most distressing—the fragmentation of nocturnal …
Flexible Inkjet‐Printed Multielectrode Arrays for Neuromuscular Cartography
Authors: Timothée Roberts, Jozina B. De Graaf, Caroline Nicol, Thierry Hervé, Michel Fiocchi, Sébastien Sanaur
Journal: Advanced Healthcare Materials (2016)

Flexible Poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS) conductive‐polymer multielectrode arrays (MEAs) are fabricated without etching or aggressive lift‐off processes, only by additive solution processes. Inkjet printing technology has several advantages, such as a customized design and a rapid realization time, adaptability to different patients and to different applications. In particular, inkjet printing technology, as additive and “contactless” technology, can be easily inserted into various technological fabrication steps on different substrates at low cost. In vivo electrochemical impedance spectroscopy measurements show the time stability of such MEAs. An equivalent circuit model is established for such flexible cutaneous MEAs. It is shown that the charge transfer resistance remains the same, even two months after fabrication. Surface electromyography and electrocardiography measurements show that the PEDOT:PSS MEAs record electrophysiological activity signals that are comparable to those obtained with unitary Ag/AgCl commercial electrodes. Additionally, such MEAs offer parallel and simultaneous recordings on multiple locations at high surface density. It also proves its suitability to reconstruct an innervation zone map and opens new perspectives for a better control of amputee's myoelectric prostheses. The employment of additive technologies such as inkjet printing suggests that the integration of multifunctional sensors can improve the performances of ultraflexible brain‐computer interfaces.
A Selective Transforming Growth Factor-β Ligand Trap Attenuates Pulmonary Hypertension
Authors: Lai-Ming Yung, Ivana Nikolic, Samuel D. Paskin-Flerlage, R. Scott Pearsall, Ravindra Kumar, Paul B. Yu
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Transforming growth factor-β (TGF-β) ligands signal via type I and type II serine-threonine kinase receptors to regulate broad transcriptional programs. Excessive TGF-β–mediated signaling is implicated in the pathogenesis of pulmonary arterial hypertension, based in part on the ability of broad inhibition of activin-like kinase (ALK) receptors 4/5/7 recognizing TGF-β, activin, growth and differentiation factor, and nodal ligands to attenuate experimental pulmonary hypertension (PH). These broad inhibition strategies do not delineate the specific contribution of TGF-β versus a multitude of other ligands, and their translation is limited by cardiovascular and systemic toxicity.Objectives: We tested the impact of a soluble TGF-β type II receptor extracellular domain expressed as an immunoglobulin–Fc fusion protein (TGFBRII-Fc), serving as a selective TGF-β1/3 ligand trap, in several experimental PH models.Methods: Signaling studies used cultured human pulmonary artery smooth muscle cells. PH was studied in monocrotaline-treated Sprague-Dawley rats, SU5416/hypoxia–treated Sprague-Dawley rats, and SU5416/hypoxia–treated C57BL/6 mice. PH, cardiac function, vascular remodeling, and valve structure were assessed by ultrasound, invasive hemodynamic measurements, and histomorphometry.Measurements and Main Results: TGFBRII-Fc is an inhibitor of TGF-β1 and TGF-β3, but not TGF-β2, signaling. In vivo treatment with TGFBRII-Fc attenuated Smad2 phosphorylation, normalized expression of plasminogen activator inhibitor-1, and mitigated PH and pulmonary vascular remodeling in monocrotaline-treated rats, SU5416/hypoxia–treated rats, and SU5416/hypoxia–treated mice. Administration of TGFBRII-Fc to monocrotaline-treated or SU5416/hypoxia–treated rats with established PH improved right ventricular systolic pressures, right ventricular function, and survival. No cardiac structural or valvular abnormalities were observed after treatment with TGFBRII-Fc.Conclusions: Our findings are consistent with a pathogenetic role of TGF-β1/3, demonstrating the efficacy and tolerability of selective TGF-β ligand blockade for improving hemodynamics, remodeling, and survival in multiple experimental PH models.
. . . and below the level of the patient
Authors: R J Bray, C J Vallis
Journal: BMJ (1994)

kPa (2 4 atmospheres absolute) 100% oxygen for 90 minutes three times daily for the first day and twice daily thereafter.5In cases of surgical delay for any reason and in cases in which the decision is taken not to operate, hyperbaric oxygen should be used immediately if it is available; this may also assist in distinguishing viable from non- viable tissue at subsequent surgery.The availability of hyperbaric oxygen facilities in Britain can be checked with the hyperbaric unit at
BMA annual representative meeting, Torquay: BMA chairman criticises erosion of clinical autonomy
Authors: Linda Beecham
Journal: BMJ (2003)

The morale sapping erosion of doctors' clinical autonomy will be one of Dr Ian Bogle's lasting memories of his five years as chairman of the BMA council.​council.




Figure 1





Dr Ian Bogle claims intrusive audit stifles innovation

Credit: BRUNO VINCENT




Giving his last address as chairman at the BMA's annual representative meeting in Torquay this week, Dr Bogle criticised the stifling of innovation by excessive, intrusive audit and the imposition of Department of Health diktats.

He said that the suffocation of professional responsibility by target setting and production line values had left little room for the professional judgment of individual doctors or the needs of individual patients. “Paranoid centralism... will turn professionals into bean counters answerable not to their patients but to politicians, auditors, commissioners, and managers.”

Dr Bogle said that when he became a doctor his motivation and satisfaction had come from knowing that he was able to apply his knowledge and exercise his judgment free from control or interference from outside the consulting room.

He accepted that national standards, quality markers, and assessment of performance were essential, but “remove the responsibility, remove the risk, remove the challenge of practising medicine and you remove a large part of what being a doctor is all about.” The healthcare system was now driven not by the needs of individual patients but by spreadsheets and tick boxes.

Dr Bogle criticised the lengths to which some hospitals went to meet targets, such as bussing in temporary staff, cancelling routine surgery, putting patients on reserve waiting lists, and making staff work double or extended shifts. There were, however, good targets, such as those drawn up by clinicians for clinicians to try to reduce death rates from heart disease and cancer.

But politically motivated national performance targets had driven a wedge between doctors and managers.

Dr Bogle said his successor must persuade the government that if it was prepared to engage the medical profession in a debate about the future of the NHS it could restore the profession's confidence in its handling of the service.
PTU-163 The role of serology testing and duodenal biopsy for the investigation of coeliac disease in patients with unexplained anaemia
Authors: VJ Wilson, A Parkins, D Mansouri, PJ O’Dwyer
Journal: Gut (2015)

<h3>Introduction</h3> Current guidelines recommend testing for Coeliac Disease in all patients undergoing investigation for anaemia with either serology testing, for tissue transglutimase antibody (TTG) or duodenal (D2) biopsies to confirm histological evidence of intestinal damage. The present study aimed to assess the approach for diagnosing Coeliac Disease by (i) examining current practice and (ii) assessing the efficacy of TTG testing. <h3>Method</h3> A retrospective audit of all adult patients undergoing upper GI endoscopy at a single centre, between August 2013 and July 2014 (inclusive), was performed. A database was created with demographics including age, sex, socioeconomic deprivation, haemoglobin level (Hb), TTG serology result, D2 biopsy result and findings at endoscopy. <h3>Results</h3> During the study period, 4,788 patients underwent upper GI endoscopy, of which unexplained anaemia was the indication in 814 (17%). Of these, complete results were available for 789 (97%), which were included for analysis. Mean age 66 years, 440 (56%) female, 296 (38%) socioeconomically deprived. Mean Hb levels were 102 g/L (males) and 97 g/L (females). Of these, 580 (74%) patients underwent investigation for Coeliac Disease (79 TTG serology only; 334 D2 biopsy only; 167 both) of which 14 (2%) patients had histological confirmation of the disease. Of the 209 patients who were not screened for Coeliac Disease, 144 (64%) had an alternative source of bleeding found at time of endoscopy. Patients with confirmed Coeliac Disease were likely to be younger (p = 0.017) than those without. There was no association between sex (p = 0.473), deprivation (p = 0.235) or Hb level (p = 0.856 (males), p = 0.543 (females)) and the risk of Coeliac Disease. Of those undergoing both TTG and D2 biopsy (n = 167), 2 patients had negative TTG serology and positive D2 biopsy and 1 patient had positive TTG and negative D2 biopsy, yielding an estimated sensitivity and specificity of TTG serology testing of 82% and 99% respectively. <h3>Conclusion</h3> The results of the present study indicate that the majority of patients undergoing endoscopy for investigation of anaemia, in our single centre, are appropriately investigated for Coeliac Disease. However, TTG has reduced sensitivity and within a cohort of patients who will be undergoing endoscopy its role is limited. <h3>Disclosure of interest</h3> None Declared.
TCTAP A-147 Five-Year Clinical Outcomes of Patients with Large Vessel and Single Coronary Artery Lesion: Comparison of Bare-Metal Stent, 1st Generation and 2nd Generation Drug-Eluting Stent
Authors: Jong Ho Nam, Byung-Jun Kim, Kangun Choi, Kyu-Hwan Park, Chan-Hee Lee, Jang-Won Son, Ung Kim, Jong-Seon Park, Dong-Gu Shin, Young-Jo Kim, Jeong-Hwan Cho, Sang Wook Kang
Journal: Journal of the American College of Cardiology (2016)
High Plasma Levels of TGF-α and IL-6 at Diagnosis Predict Early Molecular Response Failure and Transformation in CML
Authors: Eva Nievergall, John Reynolds, Chung H Kok, Dale Watkins, Mark Biondo, Samantha J Busfield, Gino Vairo, David T Yeung, Angel Lopez, Devendra K Hiwase, Deborah L White, Timothy P Hughes
Journal: Blood (2014)
<i>HLA-A*24</i>Carrier Status and Autoantibody Surges Posttransplantation Associate With Poor Functional Outcome in Recipients of an Islet Allograft
Authors: Simke Demeester, Else M. Balke, Bart J. Van der Auwera, Pieter Gillard, Robert Hilbrands, DaHae Lee, Ursule Van de Velde, Zhidong Ling, Bart O. Roep, Daniel G. Pipeleers, Frans K. Gorus, Bart Keymeulen
Journal: Diabetes Care (2016)

We investigated whether changes in islet autoantibody profile and presence of HLA risk markers, reported to predict rapid β-cell loss in pre-type 1 diabetes, associate with poor functional outcome in islet allograft recipients.Forty-one patients received ≥2.3 million β-cells/kg body wt in one to two intraportal implantations. Outcome after 6-18 months was assessed by C-peptide (random and stimulated), insulin dose, and HbA1c.Patients carrying HLA-A*24-positive or experiencing a significant autoantibody surge within 6 months after the first transplantation (n = 19) had lower C-peptide levels (P ≤ 0.003) and higher insulin needs (P < 0.001) despite higher HbA1c levels (P ≤ 0.018). They became less often insulin independent (16% vs. 68%, P = 0.002) and remained less often C-peptide positive (47% vs. 100%, P < 0.001) than recipients lacking both risk factors. HLA-A*24 positivity or an autoantibody surge predicted insulin dependence (P = 0.007).HLA-A*24 and early autoantibody surge after islet implantation associate with poor functional graft outcome.
Canine Malignant Lymphomas: Comparison of Morphologic and Immunologic Parameters 2 3
Authors: C. A. Holmberg, J. S. Manning, B. I. Osburn
Journal: JNCI Journal of the National Cancer Institute (1976)

Twenty-three canine malignant lymphomas were studied to correlate morphologic and immunologic properties of the neoplastic cells. Morphotologic characterization included histologic classification of cell type and growth pattern, anatomic distribution of lesions, and transmission electron microscopic examination. Parameters examined to indicate B- or T-cell nature of lymphoma cells included demonstration of mitogen responsiveness, cell-surface Ig, spontaneous rosette formation with human red blood cells, and scanning electron microscope (SEM) examination of cell-surface features. Results indicated that the cells from histiocytic lymphomas were lymphocytes rather than histiocytes or macrophages. Most cells from lymphomas examined possessed cell-surface ig, indicating B-cell nature. The cell types represented by the different Ig-positive lymphomas were compatible with maturation arrest at different stages in normal lymphocyte differentiation. For the two most common histiologic cell types, nitogen responsiveness and the presence of cell-surface Ig indicated that diffuse, poorly differentiated lymphocytic cases were biologically heterogenous, whereas nodular histiocytic lymphomas were biologically homogenous. Most canine lymphomas had a multicentric anatomic distribution; however, one thymic and two alimentary forms were observed. Lymphomas with a nodular pattern in lymph nodes had multifocal splenic involvement centered on small arteries, whereas lymphomas with a diffuse pattern in lymph nodes had diffuse involvement of splenic white pulp. The cells of Ig-positive and Ig-negative neoplasms examined by SEM were predominantly of the smooth-cell type.
Disentangling the Association between Statins, Cholesterol, and Colorectal Cancer: A Nested Case-Control Study
Authors: Ronac Mamtani, James D. Lewis, Frank I. Scott, Tariq Ahmad, David S. Goldberg, Jashodeep Datta, Yu-Xiao Yang, Ben Boursi
Journal: PLoS Medicine (2016)

Background Several prior studies have found an association between statin use and reduced risk of colorectal cancer. We hypothesized that these findings may be due to systematic bias and examined the independent association of colorectal cancer risk with statin use, serum cholesterol, and change in cholesterol concentration. Methods and Findings 22,163 colorectal cancer cases and 86,538 matched controls between 1995 and 2013 were identified within The Health Improvement Network (THIN) a population-representative database. Conditional logistic regression models estimated colorectal cancer risk with statin use, serum total cholesterol (mmol/L), and change in total cholesterol level. We confirmed a decreased risk of colorectal cancer with statin use (long-term: odds ratio [OR], 0.95; 95% confidence interval [CI], 0.91–0.99; short-term: OR, 0.92; 95% CI, 0.85–0.99). However, to assess whether the observed association may result from indication bias, a subgroup analysis was conducted among patients prescribed a statin. In this subgroup (n = 5,102 cases, n = 19,032 controls), 3.1% of case subjects and 3.1% of controls discontinued therapy. The risk of colorectal cancer was not significantly different among those who continued statin therapy and those who discontinued (OR, 0.98; 95% CI, 0.79–1.22). Increased serum cholesterol was independently associated with decreased risk of colorectal cancer (OR, 0.89 per mmol/L increase; 95% CI, 0.87–0.91); the association was only present if serum cholesterol was measured near the cancer diagnosis (<6 mo: OR, 0.76; 95% CI, 0.47–0.61; >24 mo: OR, 0.98; 95% CI, 0.93–1.03). Decreases in serum total cholesterol >1 mmol/L ≥1 year prior to cancer diagnosis were associated with subsequent colorectal cancer (statin users: OR, 1.25; 95 CI%, 1.03–1.53; nonusers: OR, 2.36; 95 CI%, 1.78–3.12). As an observational study, limitations included incomplete data and residual confounding. Conclusions Although the risk of colorectal cancer was lower in statin users versus nonusers, no difference was observed among those who continued versus discontinued statin therapy, suggesting the potential for indication bias. The association between decreased serum cholesterol and colorectal cancer risk suggests a cholesterol-lowering effect of undiagnosed malignancy. Clinical judgment should be used when considering causes of cholesterol reduction in patients, including those on statin therapy.