tbuckley/cabot-search huggingface dataset:
Analysis of Pharmaceutical Industry Payments to UK Health Care Organizations in 2015
Authors: Piotr Ozieranski, Marcell Csanadi, Emily Rickard, Jordan Tchilingirian, Shai Mulinari
Journal: JAMA Network Open (2019)

Drug company payments to health care organizations can create conflicts of interest. However, little is known about such financial relationships, especially outside the United States.To examine the concentration and patterns of drug company payments to health care organizations in the United Kingdom.This cross-sectional study examined nonresearch payments reported in the industry-run Disclosure UK database. Companies participating in Disclosure UK in 2015 and health care organizations receiving their payments were included in the analysis. The data were analyzed descriptively at the health care organization, payment, and donor levels, considering health care organization categories, payment categories, and companies from February 5 through May 28, 2017, with follow-up checks from June 1 through August 31, 2018. Analysis was conducted from July 10 through December 20, 2018.Share of funding and the Gini index (GI) to measure payment concentration (0 indicates perfect deconcentration [eg, all drug companies provide the same value of payments]; 1, perfect concentration [eg, 1 company provides the entire value of payments]) and median and interquartile range (IQR) to measure payment patterns.A total of 4028 health care organizations received 19 933 payments, worth US $72 110 156.6, from 100 companies. This study identified 11 categories of health care organizations, with 3-public-sector secondary and tertiary care providers, education and research providers, and professional organizations-accumulating 67.2% of funding. The health care organization categories had varying GIs (range, 0.65-0.92), medians (range, $750.3-$45 862.4), and IQRs (range, $389.1-$1843.9 to $3104.4-$199 868.2). Of 4 payment categories, the top category-donations and grants-captured 50.6% of funding. Joint working (collaborative projects with nonindustry partners) had a lower GI (0.64) than other payment categories (range, 0.79-0.84). The median and IQR were the lowest for contributions to costs of events ($366.8; IQR, $229.3-611.3) and highest for joint working ($14 903.7; IQR, $3185.0-34,748.4). The top 10 firms (58.6% of funding) had payments with varying medians (from $366.8 [IQR, $244.5-611.3] to $9781.3 [IQR, $1834.0-48 906.7]).Although organizations from across the health care system received funding, the payments were concentrated on a few large donors, payments, and recipients. Different payment and recipient categories had different patterns of payment values, suggesting that the industry has diversified its funding strategies across different parts of the health care system. These results suggest that Disclosure UK requires improved transparency, particularly by including built-in recipient categories, and that organizational conflicts of interest need more policy attention, including disclosure of payments independent of the industry.
SAT0417 HOW EFFECTIVE IS GOUT EDUCATION PROGRAMME TO IMPROVE GOUT KNOWLEDGE AMONG PRIMARY CARE DOCTORS?
Authors: Hazlyna Baharuddin, Nur Aini Eddy Warman, Habibah Mohd Yusoof, Ing Soo Lau, Shereen Suyin Ch’ng, Mollyza Mohd Zain
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Gout is a potentially curable disease with simple pharmacological treatment, although its management remained suboptimal.<sup>1, 2</sup> A disconnection between primary care doctors who treat gout most frequently, and rheumatologists who lead the development of gout management guidelines, is one of the challenges in managing gout in primary care.<sup>3</sup> A concerted effort is needed to improve the quality of care of patients with gout and this includes physician education.<sup>4</sup> <h3>Objectives:</h3> To determine the effectiveness of gout educational programme in improving gout knowledge among primary care doctors. <h3>Methods:</h3> A gout education programme consisted of five 20-minute presentations on gout (challenges in gout, principles of gout management, treat to target, disease burden and gout diet) and a session on case discussion of two gout cases was conducted for primary care doctors. Participants were invited to complete the same set of questions distributed before (pre-test) and after (post-test) the programme. A set of 10 true/false multiple choice questions (MCQ) based on a clinical scenario of a patient with gout was constructed and vetted by two rheumatologists. Comparison between the pre-test and post-test scores were analysed using paired t-test. <h3>Results:</h3> Forty-four primary care doctors who attended gout educational programme, answered pre-test and post-tests and the scores are shown in Table 1. The scores for recall questions were higher than application questions.The mean scores for recall questions in post-test were significantly higher compared to pre-test (4.35±0.73 vs 3.51±0.47, p&lt;0.01) but not significant for application questions (2.91±0.71 vs 2.79±0.62, p=0.56). Less than half of participants obtained correct answers for 13 out of 50 options in the pre-test mainly in questions 2, 3, 4, 6 and 7. (Table 1) <h3>Conclusion:</h3> Gout educational programme for primary care doctors was effective in improving recall knowledge but not in application knowledge. Some specific areas of deficiency in gout knowledge identified were features of gout and management of acute and stable gout. <h3>References</h3> [1] Richette P, Doherty M, Pascual E, et al. 2016updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis2017; 76: 29–42. [2] Abhishek A, Doherty M, Education and non-pharmacological approaches for gout. Rheumatology, 57(suppl_1), 2018; i51-58. [3] Dalbeth N. Management of gout in primary care: challenges and potential solutions. Rheumatology. 2013; 52(1): 1549-1550 [4] JA Singh. Quality of Life and Quality of Care for patients with Gout. Curr Rheumatol Rep, 2009; 11(2): 154-160 <h3>Acknowledgement:</h3> We would like to thank the doctors who participated in gout education programme. <h3>Disclosure of Interests:</h3> None declared
Abstract 17874: Comparison of the Seattle Heart Failure Model (SHFM) and Cardiopulmonary Exercise Testing (CPET) for Predicting Mortality of Patients With Ischemic Heart Failure
Authors: Joerg Honold, Salvatore DeRosa, Ioakim Spyridopoulos, Ulrich Fischer-Rasokat, Birgit Assmus, Andreas M Zeiher
Journal: Circulation (2010)

Background: Despite many therapeutic advances, prognosis of patients with heart failure remains poor. Assessment of prognosis and risk stratification remains a major diagnostic challenge. Cardiopul...
PB2266 HOW TO IMPROVE HEMATOLOGIC REFERRAL? ANALYSIS AND RECOMMENDATIONS
Authors: F. Saraiva, R. Postolachi, M. I. Vicente, A. Botelho de Sousa
Journal: HemaSphere (2019)

Background: Incidental laboratorial abnormalities detected in asymptomatic persons are increasingly becoming a frequent motive for referral to a haematological consultation, overloading outpatient units that are run by small teams. These referrals, along with the subsequent acceptance by the triage manager and further haematological investigation by a haematologist, originate from the fear of missing incipient severe haemopathies. Aims: To evaluate the adequacy and the result of these referrals to ascertain the hypothesis that a large proportion of the cases have no indication for specialized haematological care. Methods: Retrospective analysis of patients referred to the Haematology consult of a central hospital over a 2‐year period (Jan/16‐Dec/17), excluding the ones who already had a known diagnosis. We evaluated the reason for referral, the final diagnosis and at a second stage we tried to quantify the referrals which could be managed in primary care, and their origin. Results: Out of 1162 evaluable patients (236 still in study), the majority (65%) came from Primary Health Care. The motive, in 85% of the cases, consisted in blood count abnormalities (59% cytopenias). In 13% of the cases, the initial abnormality no longer existed upon arrival. Finding an underlying pathology was possible in only 48% of the cases. From these, 14% could have been managed in Primary Health Care (e.g. iron deficiency; vitamin deficits) and 86% were haematologically relevant. As for the referrals which could have been avoided (no underlying haematological pathology or unconfirmed motive) the most frequent causes were cytopenias (anaemia 33%, leukopenia 15%, thrombocytopenia 12%) and they originated from Primary Health Care (72%). Summary/Conclusion: In this sample, we confirmed that a high proportion of referrals are manageable in Primary Health Care, particularly cytopenias, part of which are no longer present at the first haematological evaluation. The probability of a haematological investigation resulting in a clinically relevant diagnosis is very low, seemingly not justifying the consult time, the costs for the system or the personal costs for the patient. The elaboration of specifically designed recommendations for Primary Health Care and the implementation of interaction/discussion networks of pre‐triage cases are indispensable measures to optimize the haematological referral process.
Improving genetic diagnosis in Mendelian disease with transcriptome sequencing
Authors: Beryl B. Cummings, Jamie L. Marshall, Taru Tukiainen, Monkol Lek, Sandra Donkervoort, A. Reghan Foley, Veronique Bolduc, Leigh B. Waddell, Sarah A. Sandaradura, Gina L. O’Grady, Elicia Estrella, Hemakumar M. Reddy, Fengmei Zhao, Ben Weisburd, Konrad J. Karczewski, Anne H. O’Donnell-Luria, Daniel Birnbaum, Anna Sarkozy, Ying Hu, Hernan Gonorazky, Kristl Claeys, Himanshu Joshi, Adam Bournazos, Emily C. Oates, Roula Ghaoui, Mark R. Davis, Nigel G. Laing, Ana Topf, Peter B. Kang, Alan H. Beggs, Kathryn N. North, Volker Straub, James J. Dowling, Francesco Muntoni, Nigel F. Clarke, Sandra T. Cooper, Carsten G. Bönnemann, Daniel G. MacArthur
Journal: Science Translational Medicine (2017)

Transcriptome sequencing improves the diagnostic rate for Mendelian disease in patients for whom genetic analysis has not returned a diagnosis.
Outcomes of Patients with t(11;14) Multiple Myeloma: An International Myeloma Working Group Multicenter Study
Authors: Shaji K. Kumar, Jin Lu, Yang Terry Liu, Max Bittrich, Juan Du, Hartmut Goldschmidt, Charalampia Kyriakou, Donna E Reece, Kihyun Kim, Maria-Victoria Mateos, Veronica Gonzalez De La Calle, Wenming Chen, Heinz Ludwig, Giampaolo Merlini, Silvia Mangiacavalli, Meletios A. Dimopoulos, Eftathios Kastritis, Chang-Ki Min, Graca Esteves, Andrew J. Yee, Noopur S. Raje, Emily Rosta, Anja Haltner, Chris Cameron, Brian G.M. Durie
Journal: Blood (2019)
The Efficacy, Tolerability, and Joint Safety of Fasinumab in Osteoarthritis Pain: A Phase IIb/III Double‐Blind, Placebo‐Controlled, Randomized Clinical Trial
Authors: Paula Dakin, Stephen J. DiMartino, Haitao Gao, Jennifer Maloney, Alan J. Kivitz, Thomas J. Schnitzer, Neil Stahl, George D. Yancopoulos, Gregory P. Geba
Journal: Arthritis & Rheumatology (2019)

To prospectively assess the efficacy, general safety, and joint safety of fasinumab, an anti-nerve growth factor monoclonal antibody, in osteoarthritis (OA) hip and/or knee pain.Patients with moderate-to-severe OA pain (knee or hip) and history of inadequate response or intolerance to analgesics were randomized to receive fasinumab (at 1 mg, 3 mg, 6 mg, or 9 mg) or placebo every 4 weeks over 16 weeks and were followed up to week 36. Efficacy end points were the change from baseline to week 16 in the pain and physical function subscale scores of the Western Ontario and McMaster Universities OA Index (WOMAC), and patient global assessment (PGA) of OA. Joints were monitored at scheduled assessments (by plain film radiography and magnetic resonance imaging) during treatment and follow-up, and if prompted, at the time of active joint symptoms.Of the 421 patients randomized, 342 completed the 36-week study. All doses of fasinumab yielded statistically significant and clinically important reductions in pain compared to placebo (least squares mean difference in WOMAC pain subscale scores at week 16 ranging -0.78 to -1.40), without any clear dose dependence. Physical function and PGA scores improved in parallel. Treatment-emergent adverse event rates were 17% with fasinumab and 10% with placebo, and 4% and 1% of patients, respectively, discontinued treatment. Arthropathies (25 in total, 7% of fasinumab-treated patients and 1% of placebo-treated patients) occurred in a dose-dependent manner, with 2 occurring in patients receiving the lowest dose of fasinumab and 10 in patients receiving the highest dose. Most of the arthropathies (16 of 25) were discovered with scheduled radiographs and not based on symptoms. Destructive arthropathy (in 1 of 337 treated patients) occurred in 1 patient who was receiving 6 mg fasimumab.Fasinumab provided improvements in OA pain and function, even in those benefitting little from previous analgesics. The observed benefit-to-risk relationship favors further clinical development to explore the lowest doses of fasinumab in patients with knee or hip OA.
The Partial AdeNosine A1 receptor agonist in patients with Chronic Heart failure and preserved Ejection fraction (PANACHE) trial
Authors: Edoardo Bertero, Christoph Maack
Journal: Cardiovascular Research (2019)

2][3] It is estimated that in 50% of cases, the clinical syndrome of HF results from impaired ventricular relaxation in spite of normal systolic function, a condition denoted as HF with preserved ejection fraction (HFpEF).Whereas agents blocking neurohormonal activation have an established impact on the outcome of HF patients with compromised contractile function (i.e.HF with reduced ejection fraction, HFrEF), no therapeutic approaches were demonstrated to reduce morbidity and mortality in HFpEF patients. 1Therefore, the quest for a disease-modifying treatment option in HFpEF remains a major long-standing challenge in the cardiovascular field.
A Targeted Agent for Sickle Cell Disease — Changing the Protein but Not the Gene
Authors: Alexis Thompson
Journal: New England Journal of Medicine (2019)

Affecting an estimated 100,000 Americans and millions worldwide, sickle cell disease is among the most common inherited blood disorders in humans and is associated with profound complications and premature death.1,2 The pathophysiology of sickle cell disease begins with a single amino acid substitution in the β-globin chain that creates mutant hemoglobin S (HbS) that can polymerize in red cells under certain conditions. HbS polymerization results in a very complex cascade of processes that include erythrocyte sickling, intravascular hemolysis with release of cell-free hemoglobin, increased adhesion of red cells to the endothelium of blood vessels, activation of platelets, production of inflammatory . . .
Abstract 15528: Percutaneous Mitral Valve Intervention with Mitraclip Reduces Backward Failure Quantified as the Pulmonary Blood Volume Measured by Cardiovascular Magnetic Resonance Imaging
Authors: John Maret-Ouda, Magnus Settergren, Martin Ugander
Journal: Circulation (2012)

INTRODUCTION: Mitral regurgitation is associated with backward failure and pulmonary congestion, and can be challenging to assess quantitatively by echocardiography. The pulmonary blood volume (PBV...
Abstract 277: Microrna-33 Promotes Cardiac Fibrosis by Maintaining Cellular Lipid Homeostasis
Authors: Masataka Nishiga, Takahiro Horie, Yasuhide Kuwabara, Osamu Baba, Tetsushi Nakao, Tomohiro Nishino, Daihiko Hakuno, Yasuhiro Nakashima, Noriko Nakazeki, Yuya Ide, Satoshi Koyama, Koji Hasegawa, Toru Kita, Takeshi Kimura, Koh Ono
Journal: Circulation Research (2016)

Background: A highly conserved microRNA, miR-33 is considered as a potential therapeutic target for atherosclerosis, because recent reports, including ours, indicated miR-33 has atherogenic effects by reducing HDL-C. However, the functions of miR-33 in heart failure remain to be elucidated. Methods and results: To clarify the functions of miR-33 involved in cardiac hypertrophy and fibrosis in vivo, we investigated the responses to pressure overload by transverse aortic constriction (TAC) in miR-33 deficient (KO) mice. When subjected to TAC, miR-33 expression level was significantly up-regulated in wild-type (WT) left ventricles, whereas miR-33 KO hearts displayed no less hypertrophic responses than WT hearts. However, interestingly, histological and gene expression analyses showed ameliorated cardiac fibrosis in miR-33 KO hearts compared to WT hearts. Furthermore, we generated cardiac fibroblast specific miR-33 deficient mice, which also showed ameliorated cardiac fibrosis when they were subjected to TAC. We also found that cardiac fibroblasts were mainly responsible for miR-33 expression in the heart, because its expression was about 4-folds higher in isolated primary cardiac fibroblasts than cardiomyocytes. Deficiency of miR-33 impaired cell proliferation in primary fibroblasts, which was considered due to altered lipid raft cholesterol content by up-regulated ATP-binding cassette transporter A1/G1. Conclusion: Deficiency of miR-33 impaired fibroblast proliferation in vitro, and ameliorated cardiac fibrosis induced by pressure overload in vivo.
Treatments for primary squamous cell carcinoma and squamous cell carcinoma in situ of the skin: A systematic review and network meta-analysis
Authors: Aaron M. Drucker, Gaelen P. Adam, Valerie Rofeberg, Abhilash Gazula, Bryant Smith, Farah Moustafa, Martin A. Weinstock, Thomas A. Trikalinos
Journal: Journal of the American Academy of Dermatology (2019)
HDAC Inhibition Enhances the <i>In Vivo</i> Efficacy of MEK Inhibitor Therapy in Uveal Melanoma
Authors: Fernanda Faião-Flores, Michael F. Emmons, Michael A. Durante, Fumi Kinose, Biswarup Saha, Bin Fang, John M. Koomen, Srikumar P. Chellappan, Silvya Stuchi Maria-Engler, Uwe Rix, Jonathan D. Licht, J. William Harbour, Keiran S.M. Smalley
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The clinical use of MEK inhibitors in uveal melanoma is limited by the rapid acquisition of resistance. This study has used multiomics approaches and drug screens to identify the pan-HDAC inhibitor panobinostat as an effective strategy to limit MEK inhibitor resistance. Experimental Design: Mass spectrometry–based proteomics and RNA-Seq were used to identify the signaling pathways involved in the escape of uveal melanoma cells from MEK inhibitor therapy. Mechanistic studies were performed to evaluate the escape pathways identified, and the efficacy of the MEK-HDAC inhibitor combination was demonstrated in multiple in vivo models of uveal melanoma. Results: We identified a number of putative escape pathways that were upregulated following MEK inhibition, including the PI3K/AKT pathway, ROR1/2, and IGF-1R signaling. MEK inhibition was also associated with increased GPCR expression, particularly the endothelin B receptor, and this contributed to therapeutic escape through ET-3–mediated YAP signaling. A screen of 289 clinical grade compounds identified HDAC inhibitors as potential candidates that suppressed the adaptive YAP and AKT signaling that followed MEK inhibition. In vivo, the MEK-HDAC inhibitor combination outperformed either agent alone, leading to a long-term decrease of tumor growth in both subcutaneous and liver metastasis models and the suppression of adaptive PI3K/AKT and YAP signaling. Conclusions: Together, our studies have identified GPCR-mediated YAP activation and RTK-driven AKT signaling as key pathways involved in the escape of uveal melanoma cells from MEK inhibition. We further demonstrate that HDAC inhibition is a promising combination partner for MEK inhibitors in advanced uveal melanoma.
OP0008 SUSTAINED LOW DISEASE ACTIVITY AFTER WEIGHT LOSS TREATMENT IN PATIENTS WITH PSORIATIC ARTHRITIS AND OBESITY; A 12-MONTHS FOLLOW-UP
Authors: Eva Klingberg, Sofia Björkman, Björn Eliasson, Ingrid Larsson, Annelie Bilberg
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Obesity is over-represented in patients with psoriatic arthritis (PsA) and associated with increased disease activity. We have previously shown in 41 patients with PsA (Caspar criteria) and obesity (body mass index BMI ≥33 kg/m<sup>2</sup>) that weight loss treatment with Very Low Energy Liquid Diet (VLED), 640 kcal/day during 12-16 weeks, followed by a structured reintroduction of an energy restricted diet resulted in a median weight loss of 18.6% and concomitantly a significant improvement of the disease activity in joints, entheses and skin. At 6-months follow-up Psoriatic Arthritis Response Criteria (PsARC) was reached by 46.3% and American College of Rheumatology (ACR) 20, 50, 70 criteria for treatment response by 51.2%, 34.1% and 7.3% of the patients. <h3>Objectives</h3> To study the effects of the weight loss treatment on disease activity in longer term (12 months) in patients with PsA and obesity, when the patients are on a weight loss maintenance diet. <h3>Methods</h3> The patients were assessed with 66/68 joints count, Leeds enthesitis index, body surface area (BSA), questionnaires, CRP and BMI at the 12-months follow-up. <h3>Results</h3> Totally 39 PsA patients, median age 56 (IQR 49-63) years, 64% women were examined at the 12-month follow-up. The median weight reduction since baseline was 16.1 kg (IQR 10.5–22.8) or 16.0% (10.5–22.4). A majority of the disease activity parameters remained significantly improved (Table). At the 12-months follow-up PsARC was still fulfilled by 35.9% (n=14) and ACR 20, 50, 70 response criteria by 53.8% (n=21), 35.9% (n=14) and 15.5% (n=6) respectively. <h3>Conclusion</h3> Weight loss treatment with VLED in patients with PsA and obesity was associated with sustained weight reduction and lowered disease activity at 12-months follow-up. <h3>Disclosure of Interests</h3> Eva Klingberg Grant/research support from: Unrestricted grant from Roche, Consultant for: Novartis, Speakers bureau: Speakers fee from Lilly, Sofia Björkman: None declared, Björn Eliasson: None declared, Ingrid Larsson: None declared, Annelie Bilberg: None declared