tbuckley/cabot-search huggingface dataset:
SAT0074 Persistence with metformin treatment and onset of rheumatoid arthritis
Authors: ME Naffaa, V Rosenberg, G Chodick, V Shalev, S Tiosano, H Amital
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Several studies have suggested that metformin, an oral hypoglycemic agent, possess an anti-inflammatory property and may have a role in the treatment of rheumatoid arthritis (RA)<sup>1,2</sup>, but little is known on its preventive effects. <h3>Objectives</h3> To examine the association between persistence with metformin and the onset of RA. <h3>Methods</h3> Using the computerized medical database of a large health organization in Israel (Maccabi Healthcare Services, MHS) we have identified incident RA cases among new users of metformin between 1998 and 2014. Included were patients aged 18 or above with one year of follow up before and after the therapy initiation. RA was defined according to physician diagnoses. Participants were followed until the earliest of the following dates: onset of RA, leaving MHS, death, end of follow up (1.1.2016). Persistence with metformin was assessed by calculating the mean proportion of follow-up days covered (PDC) with metformin during the study period. <h3>Results</h3> A total of 113,749 eligible patients were included. During the study follow up period (794,386 person-years) we identified 600 incident cases (incidence rate of 75 cases per 100,000 PY). The incidence of RA in women (111 per 100,000 PY) was higher compared to men (42 per 100,000 PY). In a multivariable model, persistence with metformin (PDC≥80%) was associated with lower risk of RA (hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.53–0.82) compared to non-persistent participants (PDC&lt;20%). Figure 1 shows the hazard function according to persistence with metformin treatment. Similar risk reduction was observed among men but did not reach statistical significance (HR=0.85; 95% CI 0.54–1.32). <h3>Conclusions</h3> In the present study, we observed an association between high persistence to metformin therapy and reduced risk of developing RA in women. <h3>Disclosure of Interest</h3> None declared
THU0645 Optimizing the efficiency of patient data capture using smartphone technology: evaluation of the correlation between promis instruments for pro data capture
Authors: WB Nowell, H Yun, J Beaumont, S Yang, J Willig, S Ginsberg, KV Clayton, S Hazel, C Wiedmeyer, JR Curtis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patient-reported outcomes (PROs) are key to enabling the comprehensive assessment of patient-centered benefits in comparative effectiveness research (CER). However, the relationships between different PROMIS instruments and condition-specific disease activity measures in diseases such as rheumatoid arthritis (RA) have not been well studied. <h3>Objectives</h3> The objectives of this analysis were to evaluate the longitudinal relationship between different PROMIS instruments and the RAPID3, a measure of self-reported patient disease activity. <h3>Methods</h3> Four NIH PROMIS instruments (Pain Interference, Physical Function, Sleep Disturbance and Fatigue) and the RAPID3 were administered to participants in the PCORI-funded ArthritisPower patient registry. After descriptive analytics, we estimated multiple correlations between PROMIS instruments and the RAPID3. For each PRO instrument and with each assessment used as the unit of measure, we calculated the R-squared using mixed models to evaluate how the PROs were related to each other. Using Pain Interference as an example, we evaluated R-squared for each model with additional PROs and demographic factors including enrollment age, sex, race, Twitter account, region, and visit times. <h3>Results</h3> A total of 1,590 unique participants who answered the survey one or more times were included in the analysis, with mean (SD) age of 49 (12) years. The mean score for Pain Interference was 63.7 (SD: 7.0), Physical Function 37.5 (8.7), Sleep Disturbance 58.4 (8.7), Fatigue 63.8 (8.8), and RAPID3 15.5 (5.7). Most PROMIS instruments were low to moderately correlated (around 0.2) with each other and the RAPID3. Using Pain Interference as an example, R-squared measures revealed a high total variance explained (R<sup>2</sup>=49%) between Pain Interference and Physical Function (Table); those involving Pain Interference, Physical Function, Fatigue, Sleep Disturbance and RAPID3 also revealed a higher variance contribution with these additional PROs (66%). Additional adjustment for demographic factors added little variance explanation (1.4%). <h3>Conclusions</h3> PROMIS Pain Interference, Physical Function, Sleep Disturbance, Fatigue instruments and RAPID3 are reasonably correlated to each other. Age, gender, race and other demographic factors play little role in explaining variance in PROs. These results suggest potential efficiencies in using some measures to predict or impute the values for other measures and to optimize the frequency of patient data collection using at-home technologies including Smartphone Apps like ArthritisPower. <h3>Disclosure of Interest</h3> None declared
Patient murders urologist 21 years after receiving diagnosis
Authors: Owen Dyer
Journal: BMJ (2017)

A California urologist who helped to diagnose urethral stricture in a patient was murdered two decades later by the same man, who was convinced that the resulting operation—in which the urologist took no part—had ruined his life.

Stanwood Elkus, 79, was sentenced to life in prison without parole for the murder of Ronald Gilbert, who was 53 in 2013 when Elkus booked an appointment under a false name, then shot him 10 times as he walked through the consulting room door. He told a nurse as he emerged: “I’m insane. Call the police.”

The retired barber’s grudge dated from 1992, …
NHS not ready to take on UK pensioners abroad if Brexit talks stall, peers are told
Authors: Adrian O’Dowd
Journal: BMJ (2017)

UK health services do not have the resources to care for British pensioners currently living in other EU countries if they have to return because of stalled Brexit negotiations, peers have been told.

Health experts have warned of the potential consequences if talks to ensure continuation of reciprocal healthcare arrangements stall.

At the end of August the government said that both sides in Brexit negotiations had reached agreement in principle to protect existing reciprocal healthcare rights for UK nationals in the EU and for EU citizens in the UK under the European Health Insurance Card (EHIC) arrangements.

Peers on the House of Lords EU home affairs subcommittee, holding the first evidence session on 13 September for …
Cognitive Behavioral Analysis System of Psychotherapy versus Escitalopram in Patients with Chronic Depression: Results from a Naturalistic Long-Term Follow-Up
Authors: Paul Bausch, Thomas Fangmeier, Elisabeth Schramm, Ingo Zobel, Sarah Drost, Knut Schnell, Henrik Walter, Mathias Berger, Dieter Schoepf, Claus Normann
Journal: Psychotherapy and Psychosomatics (2017)
Mitochondrial respiratory defects lead to significant alterations in cellular redox states and drug sensitivity
Authors: Weiqin Lu, Helene Pelicano, zhao chen, li feng, Peng Huang
Journal: Cancer Research (2007)

LB-115   Mitochondrial malfunction, which can lead to decreased ATP generation through oxidative phosphorylation and altered drug sensitivity, has long been observed in many cancer cells, but the underlying mechanisms remain to be investigated. Here we report the establishment of an inducible cell model in which the mitochondrial respiratory function can be controlled by tetracycline and the use of this system as a tool to investigate on the relationship between mitochondrial respiratory malfunction, redox alterations, and drug sensitivity. A dominant negative form of the DNA polymerase gamma (POLGdn) was expressed in the T-ReX293 tetracycline inducible system. Mitochondrial malfunction was induced by doxocycline, which led to a almost complete suppression of oxygen consumption, caused by a depletion of the mitochondrial DNA-encoded respiratory chain complex I, III, IV, and V components, despite an increase of nuclear encoded complex II subunit proteins. Accompany with this mitochondrial respiratory defect, superoxide generation from the respiratory chain decreased, whereas cellular hydrogen peroxide level increased, as shown by fluorometric detection using hydroethedine and DCF-DA, respectively. The increase in hydrogen peroxide level was further confirmed by using the catalase to eliminate its specific fluorescent signal. Surprisingly, cellular nitric oxide level also increased when mitochondrial respiration was suppressed. The increase in nitric oxide could be inhibited by the NOS inhibitor L-NMMA. Biochemical analyses showed total cellular glutathione content and the expression of glutathione peroxidase (GPX-1) protein were elevated in the mitochondrial defective cells, whereas the levels of SOD1 and SOD2 proteins remained unchanged. These alterations in cellular redox states were associated with significant changes (increase or decrease) in cellular sensitivity to anticancer agents, depending on the mechanisms of action of the specific drugs. Compounds with pro-oxidant property are more effective in killing the cells with increased hydrogen peroxide and nitric oxide. These observations may have clinical implications in selecting proper drug to kill cancer cells with mitochondrial dysfunction.
SP0075 Ultrasound and magnetic resonance imaging fusion of images evaluation of tenosynovitis – a pilot study on a new imaging technique in rheumatoid arthritis patients
Authors: MA Danielsen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background/Purpose</h3> Image fusion is an advanced imaging technology, which enables fusion of ultrasound (US) and magnetic resonance imaging (MRI). This fusion gives for each US probe position an exact projection of the corresponding anatomical area on a previously obtained MR image, during a live US assessment. This study is the first to address image fusion of US and MRI tenosynovitis. The aim of this study was to assess and compare US and MRI visualisation of tenosynovitis using image fusion technique. <h3>Methods</h3> Fifteen rheumatoid arthritis patients with US verified tenosynovitis in the wrist or hand had an MRI performed of the affected wrist or hand. A subsequent image fusion was performed, i.e. the MR images and a live US assessment of one tendon sheath were fused. In order to compare the two imaging modalities quantitatively, the area of the tendon and tendon sheath in the transverse axis was measured on US and MRI for each image fusion. Due to partial volume artefacts (voxel containing two different tissues and therefore possessing a signal average of tendon and tendon sheath) on MRI two measures were performed; area 1) the circumference of the black tendon, i.e. excluding voxels containing two types of tissue 2) the circumference of the grey line that surrounds the black tendon, i.e. including voxels containing two types of tissue. Tenosynovitis was assessed using the proposed OMERACT semi-quantitative scoring system for US and MRI. US scoring was therefore based on both grey scale and Doppler, whereas MRI scoring was based only on post-contrast tenosynovial enhancement, measured as distance from the tendon to end of the enhanced tendon sheath. <h3>Results</h3> The median circumference area of the tendons and tendon sheaths on US and MRI 1 and 2 were respectively 0.16 (25;75 pctl: 0.10;0.25), 0.9 (0.06–0.18) and 0.13 of (0.10;0.25) for the tendons and 0.18 (0.13–0.26), 0.27 (0.20–0.45) and 0.23 (0.16–0.40) for the tendon sheaths. Statistically significant differences were found for all measured areas between US and MRI, except for the US tendon area and the MRI tendon area 2 (Wilcoxon9s test; p=0.47). Overall agreement between US and MRI tenosynovitis scoring systems was good (see table 1). <h3>Conclusion</h3> In conclusion, we found that US and MRI have good agreement for quantitative assessment of tendons and scoring of tenosynovitis, when comparing the two modalities using image fusion, if the partial volume artefacts on MRI are included in the measure. <h3>Disclosure of Interest</h3> None declared
Prevalence study of germline BRCA1/2 mutation in Korean patients with high-grade serous and/or endometrioid epithelial ovarian, Fallopian tube, or primary peritoneal cancer.
Authors: Eun Jin Heo, Byoung Kim, Chel Hun Choi, Jeong-Won Lee, Yoo-Young Lee, Yong-Man Kim, Jong-Won Kim, Sang-Yong Song, Jae Weon Kim, Jae Hoon Kim, Sokbom Kang
Journal: Journal of Clinical Oncology (2016)

e17043 Background: To investigate the prevalence and clinically characterize the germline BRCA 1/2 mutation in Korean patients with high grade (HG) serous and/or endometrioid epithelial ovarian cancer (EOC). Methods: In a nationwide case-control study on EOC conducted in Korea between 2010 and 2015, 298 Korean women with HG serous and/or endometrioid EOC were tested for gBRCA 1/2 mutation, regardless of the family history. Mutation screening was performed using the Ion AmpliSeq BRCA1/2 Panel (Life Technologies, Carlsbad, CA, USA) and Ion PGM platform according to the manufacturer’s instructions. Clinical characteristics including survival outcome was assessed in gBRCAm carriers. Results: A total of 43 different mutations were identified in 70 patients (23.5%, 70/298), where 8 novel mutaions and 12 recurrent mutations were identified. Haplotype analysis demonstrated founder effects in three recurrent mutations (p.Y130X, p.E1210fs, and c.5467+1G > Ain BRCA1). The ratio of gBRCA 1/2 mutation was 4:1 (56 vs 14 patients). In gBRCAm carriers, incidence of prior diagnosed breast cancer and family history of ovarian cancer was higher than non-carriers (12.9% vs 3.1%, p= 0.004, 17.1% vs 3.9%, p= 0.002, respectively). 64.3% of gBRCAm carriers had no family history of breast or ovarian cancer (45 of 70 patients). In both univariate and multivariate analysis, gBRCAm carriers had significantly better overall survival (p= 0.009 in log-rank test, p= 0.046 in Cox regression model). Interestingly, the median treatment free interval after 1st line chemotherapy was significant longer in gBRCAm carriers (19.10 vs 11.97 months; p= 0.032), although progression free survival did not showed significant difference (p= 0.152). There was a trend of consistantly higher response rate to platinum based chemotherapy in gBRCAm carriers from 1st to 3rdline chemotherapy. Conclusions: The prevalence of gBRCA 1/2 mutation was 23.5% in Korean HG serous and/or endometrioid EOC. In this study, we observed gBRCAm carriers had better survival and distinctive clinical characteristics compared with other ethnic groups.
Empagliflozin and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease
Authors: Christoph Wanner, John M. Lachin, Silvio E. Inzucchi, David Fitchett, Michaela Mattheus, Jyothis George, Hans J. Woerle, Uli C. Broedl, Maximilian von Eynatten, Bernard Zinman
Journal: Circulation (2017)

Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus and established cardiovascular disease in the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Urinary glucose excretion with empagliflozin decreases with declining renal function, resulting in less potency for glucose lowering in patients with kidney disease. We investigated the effects of empagliflozin on clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease.Patients with type 2 diabetes mellitus, established cardiovascular disease, and estimated glomerular filtration rate (eGFR) ≥30 mL·min-1·1.73 m-2 at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. We analyzed cardiovascular death, hospitalization for heart failure, all-cause hospitalization, and all-cause mortality in patients with prevalent kidney disease (defined as eGFR <60 mL·min-1·1.73 m-2 and/or urine albumin-creatinine ratio >300 mg/g) at baseline. Additional analyses were performed in subgroups by baseline eGFR (<45, 45-<60, 60-<90, ≥90 mL·min-1·1.73 m-2) and baseline urine albumin-creatinine ratio (>300, 30-≤300, <30 mg/g).Of 7020 patients treated, 2250 patients had prevalent kidney disease at baseline, of whom 67% had a diagnosis of type 2 diabetes mellitus for >10 years, 58% were receiving insulin, and 84% were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. In patients with prevalent kidney disease at baseline, empagliflozin reduced the risk of cardiovascular death by 29% compared with placebo (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.98), the risk of all-cause mortality by 24% (HR, 0.76; 95% CI, 0.59-0.99), the risk of hospitalization for heart failure by 39% (HR, 0.61; 95% CI, 0.42-0.87), and the risk of all-cause hospitalization by 19% (HR, 0.81; 95% CI, 0.72-0.92). Effects of empagliflozin on these outcomes were consistent across categories of eGFR and urine albumin-creatinine ratio at baseline and across the 2 doses studied. The adverse event profile of empagliflozin in patients with eGFR <60 mL·min-1·1.73 m-2 was consistent with the overall trial population.Empagliflozin improved clinical outcomes and reduced mortality in vulnerable patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01131676.
Current status and strategies for viral hepatitis control in Korea
Authors: Dong Hyun Sinn, Eun Ju Cho, Ji Hoon Kim, Do Young Kim, Yoon Jun Kim, Moon Seok Choi
Journal: Clinical and Molecular Hepatology (2017)

Viral hepatitis is one of major global health challenges with increasing disease burden worldwide. Hepatitis B virus and hepatitis C virus infections are major causes of chronic liver diseases. They can lead to cirrhosis, hepatocellular carcinoma, and death in significant portion of affected people. Transmission of hepatitis B virus can be blocked by vaccination. Progression of hepatitis B virus-related liver diseases can be prevented by long-term viral suppression with effective drugs. Although vaccine for hepatitis C virus is currently unavailable, hepatitis C virus infection can be eradicated by oral direct antiviral agents. To eliminate viral hepatitis, World Health Organization (WHO) has urged countries to develop national goals and targets through reducing 90% of new infections and providing universal access to key treatment services up to 80%. This can lead to 65% reduction of viral hepatitis-related mortality. Here, we discuss some key features of viral hepatitis, strategies to control viral hepatitis suggested by WHO, and current status and strategies for viral hepatitis control in South Korea. To achieve the goal of viral hepatitis elimination by 2030 in South Korea, an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention (CDC) needs to be established to organize and execute comprehensive strategy for the management of viral hepatitis in South Korea.
THU0206 The jak1-selective inhibitor filgotinib reduces multiple markers of inflammation linked to various pathologic cell types and processes in rheumatoid arthritis patients
Authors: P Taylor, R Westhovens, A Van der Aa, C Jamoul, W Li, L Goyal, Y Pan, P Harrison, C Tasset, J Tarrant, R Galien
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> JAK1, 2, 3 and TYK2 are cytoplasmic tyrosine kinases that mediate intracellular signaling of many cytokines and growth factors. Filgotinib (GLPG0634, GS-6034) is a JAK inhibitor with high selectivity for JAK1 over other JAK family members. Filgotinib has a favorable safety and efficacy profile in two Phase 2B studies in active rheumatoid arthritis (RA) patients who were methotrexate (MTX) inadequate responders. <h3>Objectives</h3> To assess the effect of filgotinib on a background of MTX treatment on markers of inflammation in RA patients. <h3>Methods</h3> Serum samples from RA patients who were on a stable dose of MTX and received either placebo (PBO), filgotinib 100mg or 200mg once daily (QD), were collected at baseline, week 4 and week 12 and analyzed for 35 soluble serum biomarkers by validated single-plex or multiplex immunoassays. Median % changes from baseline for biomarkers are reported. Wilcoxon rank-sum test assessed the significance of difference between filgotinib treated groups and PBO. <h3>Results</h3> Filgotinib treatment induced a dose-dependent and significant decrease in a variety of biomarkers implicated in RA pathogenesis including inflammation (IL-1β, IL-6, TNFα and SAA), matrix degradation and cartilage destruction (MMP1 and MMP3), immune cell trafficking (CXCL10, ICAM-1 and VCAM-1) and angiogenesis (VEGF). Cytokines involved in T<sub>H</sub>1 (IFN-γ, IL-2, IL-12) and T<sub>H</sub>17 (IL-1β, IL-6, IL-21, IL-23) cell subset differentiation and activity were significantly decreased. Additionally, decrease in the B-cell chemoattractant CXCL13 and the myeloid growth factor GM-CSF supports the anti-inflammatory effects of filgotinib treatment. <h3>Conclusions</h3> Treatment with filgotinib decreased several factors that have key roles in RA for matrix degradation, cartilage destruction, angiogenesis, leukocyte adhesion and recruitment. The changes were accompanied by decreases in cytokines that promote and activate T<sub>H</sub>1, T<sub>H</sub>17, B-cells and myeloid cells that are important in RA. These findings provide insights into filgotinib mechanism of action and are consistent with its efficacy observed in RA patients. <h3>Disclosure of Interest</h3> P. Taylor Consultant for: Galapagos NV, Pfizer, Eli Lilly, UCB, GSK, R. Westhovens: None declared, A. Van der Aa Employee of: Galapagos NV, C. Jamoul Employee of: Galapagos NV, W. Li Employee of: Gilead Sciences, L. Goyal Employee of: Gilead Sciences, Y. Pan Employee of: Gilead Sciences, P. Harrison Employee of: Galapagos NV, C. Tasset Employee of: Galapagos NV, J. Tarrant Employee of: Gilead Sciences, R. Galien Employee of: Galapagos SASU