tbuckley/cabot-search huggingface dataset:
AB0267 Baseline predictors of response to methotrexate in early rheumatoid arthritis
Authors: S. Rizvi, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The disease activity score (DAS28) is widely used to assess response to treatment in early rheumatoid arthritis. Few studies have looked at the individual components of the DAS at baseline to predict drop in DAS28 in early disease. Specifically at 3, 6 and 12 months. Predicting response early in disase would enable more targetted treatments to be given and patients selecteed early for more aggressive disease control. Although certain biomarkers have been advocated for use and have shown some promise.<sup>1,2</sup> there is still a place for exploring using more clinically derived indicators. <h3>Objectives</h3> To determine whether DAS28 response at 3, 6 and 12 months could be predicted by baseline components of the DAS28 <h3>Methods</h3> The study used patients from the multicentre UK based RAMS study. All patients with early rheumatoid arthritis starting methotrexate were enrolled. We used data from a single centre in the North west of England for the analysis. DAS28 and it's components were recorded at baseline and at 3 6 and 12 months. Baseline components of the DAS28 were used to predict the change in DAS from baseline to 3 6 and 12 months. Linear regression was used with subsequent adjustment for age and gender. <h3>Results</h3> 120 patients were enrolled in the study, median age was 62.4 years (IQR42.1, 72.5), 81 (67%) were female. Median das28 at baseline was 5.3 (IQR 4.2,6.2). Duration of symptoms was 9 months (IQR 2,11). There was a drop of DAS28 of 1.49 at 3 months (IQR 0.57,2.45) and at 6 and 12 months it was 1.84 (IQR 0.48,2.91) and 1.63 (IQR 0.72,2.85) respectively. At three months the only baseline predictor of change in DAS28 was the patient global assessment unadjusted and adjusted for age adjusted beta 0.012 95% CI 0.002, 0.023 (p=0.02). At six months the baseline tender joint count adjusted beta 0.08 95% CI 0.015, 0.154 (p=0.01) as well as swollen joint count adjusted beta 0.05 95% CI 0.004,0.095 (p=0.02) also predicted reposnse in addition to the patients global assessment adjusted beta 0.016 95% CI 0.002, 0.03 (p=0.01), but not the ESR or CRP at baseline (p=NS). At 12 months the only predictors of response was the baseline CRP adjusted beta 0.02 95% CI 0.005, 0.04(p=0.02). <h3>Conclusions</h3> In this cohort of patients with early disease, response to methotrexate could not be reliably predicted using baseline measures and the ability to predcit patients who would improve could not be found in this cohort. Further work on other clinical biomarkers to predict response is needed. <h3>References</h3> [1] Arthritis Res Ther. 2016Feb 1;18:37. [2] Rheumatology (Oxford). 2017Jun 1;56(6):973–980. <h3>Disclosure of Interest</h3> None declared
Association of Patient Perceptions of Cardiovascular Risk and Beliefs on Statin Drugs With Racial Differences in Statin Use
Authors: Michael G. Nanna, Ann Marie Navar, Pearl Zakroysky, Qun Xiang, Anne C. Goldberg, Jennifer Robinson, Veronique L. Roger, Salim S. Virani, Peter W. F. Wilson, Joseph Elassal, L. Veronica Lee, Tracy Y. Wang, Eric D. Peterson
Journal: JAMA Cardiology (2018)

African American individuals face higher atherosclerotic cardiovascular disease risk than white individuals; reasons for these differences, including potential differences in patient beliefs regarding preventive care, remain unknown.To evaluate differences in statin use between white and African American patients and identify the potential causes for any observed differences.Using the 2015 Patient and Provider Assessment of Lipid Management (PALM) Registry data, we compared statin use and dosing between African American and white outpatient adults who were potentially eligible for primary or secondary prevention statins. A total of 138 US community health care practices contributed to the data. Data analysis was conducted from March 2017 to May 2018.Primary outcomes were use and dosing of statin therapy according to the 2013 American College of Cardiology/American Heart Association guideline by African American or white race. Secondary outcomes included lipid levels and patient-reported beliefs. Poisson regression was used to evaluate the association between race and statin undertreatment, a category combining people who were not taking a statin or those taking a dose intensity lower than recommended.A total of 5689 patients (806 [14.2%] African American) in the PALM registry were eligible for statin therapy. African American individuals were less likely than white individuals to be treated with a statin (570/807 [70.6%] vs 3654/4883 [74.8%]; P = .02). Among those treated, African American patients were less likely than white patients to receive a statin at guideline-recommended intensity (269 [33.3%] vs 2145 [43.9%], respectively; P < .001; relative risk, 1.07 [95% CI, 1.00-1.15]; P = .05, after adjustment for demographic and clinical factors). The median (interquartile range) low-density lipoprotein cholesterol levels of patients receiving treatment were higher among African American than white individuals (97.0 [76.0-121.0] mg/dL vs 85.0 [68.0-105.0] mg/dL; P < .001). African American individuals were less likely than white individuals to believe statins were safe (292 [36.2%] vs 2800 [57.3%]; P < .001) or effective (564 [70.0%] vs 3635 [74.4%]; P = .008) and were less likely to trust their clinician (663 [82.3%] vs 4579 [93.8%]; P < .001). Group differences in statin undertreatment were not significant after adjusting for demographic, clinical, and clinician factors, socioeconomic status, and patient beliefs (final adjusted relative risk, 1.03 [95% CI 0.96-1.11]; P = .35).African American individuals were less likely to receive guideline-recommended statin therapy. Demographic, clinical, socioeconomic, belief-related, and clinician differences contributed to observed differences and represent potential targets for intervention.
Abstract 12450: Trpv1 Responses to Heat and Induces Il-6 Production in Skeletal Muscle Cells
Authors: Syotaro Obi, Toshiaki Nakajima, Teruo Inoue
Journal: Circulation (2016)

Introduction: Interluekin-6 (IL-6) is released from skeletal muscle cells and induced by exercise, heat, catecholamine, glucose, lipopolysaccharide, reactive oxygen species, and inflammation. However, the mechanism, which induces release of IL-6 from skeletal muscle cells, remains unknown. Thermo-sensitive transient receptor potential subfamily V member 1 (TRPV1) plays vital roles in cellular functions. Hypothesis: We hypothesized thatTRPV1 senses heat, transmits a signal into the nucleus, and produces IL-6. We investigated the underlying mechanisms, where skeletal muscle cells sense heat and respond to it. Methods: Mouse C2C12 myoblast cells were cultured at 37°C under 5% CO 2 atmosphere. When cells were exposed to heat, culture dishes were placed in another incubator which was preset to an environment temperature of 39°C, 40°C, 41°C, and 42°C. The calcium influx concentration was measured by a fura-2 fluorescence dual-wavelength excitation method. The IL-6 mRNA expression level of IL-6 was analyzed by using real-time PCR. The protein density level of IL-6 released from myoblast cells was analyzed by using an ELISA. The phosphorylation level of TRPV1 was analyzed by using western blotting. Results: When myoblast cells were exposed to temperatures ranging from 37 degrees C to 42 degrees C for two hours, the mRNA expression of IL-6 increased in a temperature-dependent manner. Heat also increased IL-6 secretion. Heat increased the intracellular calcium flux temperature-dependently. TRPV1 agonists, capsaicin and NADA, increased the intracellular calcium flux and the IL-6 mRNA expression, while TRPV1 antagonists, AMG9810 and SB366791, and the siRNA mediated knockdown of TRPV1 decreased them. Western blotting with inhibitors demonstrated that heat increased the phosphorylation levels of TRPV1 followed by PKC and CREB. PKC inhibitors, Go6983 and staurosporine, CREB inhibitors, curcumin and naphthol AS-E, and the knockdown of CREB suppressed the heat induced increases of IL-6 mRNA. Conclusions: TRPV1 senses heat and increases IL-6 production in skeletal muscle cells through the PKC and CREB pathway. Moreover it suggests that hyperthermic conditioning is effective for the exercise therapy or rehabilitation.
FRI0377 The relationship between remission and health related quality of life in a cohort of sle patients
Authors: M.W.P. Tsang-A-Sjoe, I.E.M. Bultink, M. Heslinga, L.H. van Tuyl, R.F. van Vollenhoven, A.E. Voskuyl
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> a treat-to-target approach for SLE was suggested by an international board of experts to further improve outcome in SLE. Remission was specifically identified as a suitable target. The Definition of Remission in SLE (DORIS) task force recently achieved international consensus on criteria for remission. <h3>Objectives</h3> to investigate the relationship between remission and health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) in a longitudinal observational cohort. <h3>Methods</h3> retrospective analysis of prospectively obtained data. HRQoL was assessed using the physical and mental component score (PCS and MCS, respectively) of the Short Form 36 (SF-36) questionnaire. DORIS remission categories (no remission/remission on therapy/remission off therapy) were applied. Determinants of PCS and MCS were identified with simple linear regression analyses. Association between remission and HRQoL was assessed using Generalised Estimating Equation (GEE) models. <h3>Results</h3> Data from 154 patients with 2 years of follow-up were analysed. At baseline 70/154 (45.5%) of patients were in either form of remission. Patients in remission had higher SF-36 scores in all subdomains compared to patients not in remission (figure 1). PCS was positively associated with remission and having employment and negatively associated with erythrocyte sedimentation rate, patient global assessment, SLICC damage index, prednisone use, immunosuppressant use, and body mass index. MCS was positively associated with Caucasian ethnicity and negatively associated with patient global assessment. In GEE analysis, a gradual and significant increase of PCS was observed from patients not in remission (mean PCS 36.0) to remission on therapy (41.8) to remission off therapy (44.8) (table 1). No significant difference in MCS was found between remission states. <h3>A. PCS</h3> <h3>B. MCS</h3> <h3>Conclusions</h3> we show a strong and persistent association between remission and PCS, but not MCS. These results support the relevance (construct validity) of the DORIS remission definitions and the further development of a treat-to-target approach in SLE. <h3>Disclosure of Interest</h3> None declared
Efficacy and Safety of Ozenoxacin Cream for Treatment of Adult and Pediatric Patients With Impetigo
Authors: Theodore Rosen, Nuria Albareda, Noah Rosenberg, Fernando García Alonso, Sandra Roth, Ilonka Zsolt, Adelaide A. Hebert
Journal: JAMA Dermatology (2018)

<h3>Importance</h3> Ozenoxacin, a novel topical antibacterial agent with potent bactericidal activity against gram-positive bacteria, has been developed as a cream with 1% active drug for the treatment of impetigo, a highly contagious bacterial skin infection. <h3>Objectives</h3> To evaluate the efficacy, safety, and tolerability of ozenoxacin cream, 1%, after 5-day twice-daily topical treatment in patients with impetigo. <h3>Design, Setting, and Participants</h3> This randomized, double-blind, vehicle-controlled clinical trial included patients 2 months or older with impetigo who were enrolled at centers in 6 countries from June 2, 2014, through May 30, 2015. Data were analyzed based on intention to treat from July 9 through July 22, 2015. <h3>Interventions</h3> Patients were randomized 1:1 to receive topical ozenoxacin or placebo control. <h3>Main Outcomes and Measures</h3> Efficacy was measured using the Skin Infection Rating Scale and microbiological culture. Safety and tolerability were also evaluated. <h3>Results</h3> Among the 411 patients who received treatment (210 males [51.1%]; mean [SD] age, 18.6 [18.3] years), ozenoxacin demonstrated superior clinical success compared with placebo, which was evident after 5 days of therapy (112 of 206 [54.4%] vs 78 of 206 [37.9%];<i>P</i> = .001). Ozenoxacin also demonstrated superior microbiological success compared with placebo after 2 days of therapy (109 of 125 [87.2%] vs 76 of 119 [63.9%];<i>P</i> = .002). Ozenoxacin was well tolerated, with 8 of 206 patients experiencing adverse effects, with only 1 of these potentially related to the study treatment; none were serious. <h3>Conclusions and Relevance</h3> Topical ozenoxacin is effective and well tolerated in the treatment of impetigo in patients 2 months and older. This effect is demonstrated by rapid onset of response and superior clinical and microbiological response compared with placebo. Topical ozenoxacin represents a novel option for the treatment of impetigo. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02090764
SAT0550 Health-related quality of life in patients with giant cell arteritis treated with tocilizumab in a phase 3 randomised controlled trial
Authors: V. Strand, S. Dimonaco, K. Tuckwell, M. Klearman, N. Collinson, J.H. Stone
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Superior rates of sustained glucocorticoid (GC)–free remission were shown in patients with giant cell arteritis (GCA) treated with weekly or every-other-week (wk) subcutaneous tocilizumab (TCZ) 162 mg +26 wk GC taper for 52 wks compared with placebo +26 wk or 52-wk GC taper (PBO +26 or PBO +52) in the GiACTA trial. Statistically significant improvements in SF-36 Physical Component Summary (PCS) scores were reported for weekly TCZ vs PBO +52 and in patient-reported global assessment of disease activity for both TCZ groups vs both PBO groups.<sup>1</sup> <h3>Objectives</h3> To report further analysis of patient-reported outcomes (PROs) in GiACTA. <h3>Methods</h3> Analyses of SF-36 PCS and Mental Component Summary (MCS), SF-36 domains, and Functional Assessment of Chronic Illness Therapy (FACIT)–fatigue compared patients treated with weekly TCZ (n=100) vs PBO +26 (n=50; not shown) or PBO +52 (n=51) for 52 wks based on reported data, including all responders as well as patients with post-escape data following flare. <h3>Results</h3> Improvements in SF-36 PCS and MCS scores, 6 of 8 SF-36 domains, and FACIT–Fatigue at wk 52 were significantly greater with weekly TCZ vs PBO +52 (p&lt;0.01) (table 1, figure 1). At wk 52, mean scores met or exceeded age/gender (A/G)–matched normative scores in the weekly TCZ group; higher proportions of patients reported scores exceeding A/G norms in SF-36 PCS and MCS, all SF-36 domains, and FACIT-Fatigue (Table) compared with PBO groups. The median cumulative prednisone dose over 52 wks was lower with weekly .<sup>TCZ (1862</sup>0 mg) vs PBO +26 (3296.0 mg) or PBO +52 (3817.5 mg) (p&lt;0.01). <h3>Conclusions</h3> Patients with GCA treated with weekly TCZ 162 mg and a 26-wk GC taper reported statistically significantly greater improvements in health-related quality of life and fatigue that exceeded normative values compared with those receiving 52-wk GC taper alone, in part ascribed to lower steroid doses. <h3>Reference</h3> [1] Stone JH, et al. N Engl J Med2017;377:317–328. <h3>Disclosure of Interest</h3> V. Strand Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo, EMD Serono, Genentech/Roche, GSK, Janssen, Lily, Merck, Novartis, Pfizer, Protagen, Regeneron, Samsung, Sandoz, Sanofi, UCB, S. Dimonaco Employee of: Roche, K. Tuckwell Shareholder of: Roche, Employee of: Roche, M. Klearman Employee of: Genentech, N. Collinson Employee of: Roche, J. H. Stone Grant/research support from: Roche, Genentech, Xencor, Consultant for: Roche, Genentech, Xencor
Video-Based Assessments of Colonoscopy Inspection Quality Correlate With Quality Metrics and Highlight Areas for Improvement
Authors: Anna Duloy, Rena H. Yadlapati, Mark Benson, Andrew J. Gawron, Charles J. Kahi, Tonya R. Kaltenbach, Jessica McClure, Dyanna L. Gregory, Rajesh N. Keswani
Journal: Clinical Gastroenterology and Hepatology (2018)
Pembrolizumab Exposure–Response Assessments Challenged by Association of Cancer Cachexia and Catabolic Clearance
Authors: David C. Turner, Anna G. Kondic, Keaven M. Anderson, Andrew G. Robinson, Edward B. Garon, Jonathan Wesley Riess, Lokesh Jain, Kapil Mayawala, Jiannan Kang, Scot W. Ebbinghaus, Vikram Sinha, Dinesh P. de Alwis, Julie A. Stone
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To investigate the relationship of pembrolizumab pharmacokinetics (PK) and overall survival (OS) in patients with advanced melanoma and non–small cell lung cancer (NSCLC). Patients and Methods: PK dependencies in OS were evaluated across three pembrolizumab studies of either 200 mg or 2 to 10 mg/kg every 3 weeks (Q3W). Kaplan–Meier plots of OS, stratified by dose, exposure, and baseline clearance (CL0), were assessed per indication and study. A Cox proportional hazards model was implemented to explore imbalances of typical prognostic factors in high/low NSCLC CL0 subgroups. Results: A total of 1,453 subjects were included: 340 with pembrolizumab-treated melanoma, 804 with pembrolizumab-treated NSCLC, and 309 with docetaxel-treated NSCLC. OS was dose independent from 2 to 10 mg/kg for pembrolizumab-treated melanoma [HR = 0.98; 95% confidence interval (CI), 0.94–1.02] and NSCLC (HR = 0.98; 95% CI, 0.95–1.01); however, a strong CL0–OS association was identified for both cancer types (unadjusted melanoma HR = 2.56; 95% CI, 1.72–3.80 and NSCLC HR = 2.64; 95% CI, 1.94–3.57). Decreased OS in subjects with higher pembrolizumab CL0 paralleled disease severity markers associated with end-stage cancer anorexia-cachexia syndrome. Correction for baseline prognostic factors did not fully attenuate the CL0–OS association (multivariate-adjusted CL0 HR = 1.64; 95% CI, 1.06–2.52 for melanoma and HR = 1.88; 95% CI, 1.22–2.89 for NSCLC). Conclusions: These data support the lack of dose or exposure dependency in pembrolizumab OS for melanoma and NSCLC between 2 and 10 mg/kg. An association of pembrolizumab CL0 with OS potentially reflects catabolic activity as a marker of disease severity versus a direct PK-related impact of pembrolizumab on efficacy. Similar data from other trials suggest such patterns of exposure–response confounding may be a broader phenomenon generalizable to antineoplastic mAbs. See related commentary by Coss et al., p. 5787
THU0245 Relative risk chart score for the assessment of the cardiovascular risk in young patients with ankylosing spondylitis
Authors: B. Atienza-Mateo, J.L. Martín-Varillas, L.C. Domínguez-Casas, N. Vegas-Revenga, J. Rueda-Gotor, F. Genre, A. Corrales, R. Blanco, P. Fuentevilla, V. Portilla, R. Expósito, C. Mata, T. Pina, C. González-Juanatey, L. Rodriguez-Rodriguez, M. Á. González-Gay
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ankylosing spondylitis (AS) is associated with increased rates of cardiovascular (CV) mortality. CV events can be prevented by identifying patients with high CV risk who can beneficiate from strict primary prevention measures. The systematic coronary risk evaluation (SCORE) is the predictive model recommended in Europe, but it underestimates the CV risk in individuals under 50 years old. <h3>Objectives</h3> To determine if the use of the relative risk (RR) chart score (figure 1) may help to identify young AS patients at high risk of CV disease. <h3>Methods</h3> A set of 73 AS patients younger than 50 years old without history of CV events, diabetes mellitus or chronic kidney disease was assessed. CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) and the RR chart score. A value of C-reactive protein (CRP) &gt;3 mg/L at diagnosis, cut-off point associated with an increased risk of CV events, and carotid ultrasound data performed at the time of the assessment were also analysed. <h3>Results</h3> Twenty (27.4%) of 73 patients exhibited carotid plaques and, consequently, they were classified into the category of very high CV risk. CRP&gt;3 mg/L at disease diagnosis was associated with the presence of carotid plaques after adjustment for confounding factors (odds ratio 5.66, 95% confidence interval 1.11–28.77; p=0.03). None of these young patients were included in the category of high/very high CV according to the TC-SCORE. Whereas only 5 (14.2%) of the 35 patients with RR=1 had carotid plaques, 15 (39.5%) of 38 with RR &gt;1 showed plaques. A model that included the performance of carotid US in patients with RR &gt;1 who had CRP&gt;3 mg/L at disease diagnosis allowed us to identify 60% of young AS with very high CV risk, with a specificity of 77.4% (area under the curve [AUC]: 0.69). The performance of carotid US in young AS patients with RR &gt;1 regardless of CRP data at diagnosis increased the sensitivity up to 75% at the expense of a significant decline in the specificity to 56.6% (AUC: 0.66) (table 1). The gold standard used to define high/very high cardiovascular risk was the presence of TC-SCORE ≥5% or carotid plaques. <h3>Conclusions</h3> RR chart score assessment may help to identify young AS at high risk who are underdiagnosed as having very high CV risk by the SCORE. <h3>Disclosure of Interest</h3> None declared