Search

Objectives To investigate the impact of concomitant chronic kidney disease (CKD) on unfavourable clinical events and remission in Japanese patients with rheumatoid arthritis (RA). Methods We included 5103 patients with RA and CKD from the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort in 2012. CKD stages were classified into four groups: CKD with normal eGFR ≥60 ml/min/1.73 m2 and proteinuria; mild CKD, eGFR ≥45 to Results Of the 5103 patients with RA, 686 (86.6%) had CKD. Concomitant CKD was associated with hospitalised infections [adjusted hazard ratio (aHR) 1.52, 95% confidence interval (CI) 1.07–2.13, p = .02], especially in the moderate to severe CKD group (aHR 1.93, 95% CI 1.12–3.13, p = .02). Of all subjects, 2407 (47.2%) had active RA at baseline and 401 (16.7%) had CKD. Concomitant CKD was also associated with the failure of achieving remission (aHR 0.82, 95% CI 0.68–0.99, p = .04). Conclusions Concomitant CKD was a risk factor for hospitalised infections in Japanese patients with RA and failure of achieving remission in patients with active RA.

Objectives To evaluate the differences in patients’ population and efficacy/effectiveness of biological disease–modifying antirheumatic drugs (bDMARDs) between randomized controlled trials (RCTs) and clinical practice in patients with rheumatoid arthritis. Methods We reviewed inclusion criteria in Phase II or III RCTs of bDMARDs conducted in Japan. The Institute of Rheumatology, Rheumatoid Arthritis study participants during the period when each RCT was conducted (Cohort A) and new bDMARD users at our institute in 2016 (Cohort B) were assessed for the fulfilment of the inclusion criteria. The effectiveness of bDMARDs in our cohort and their efficacy in RCTs were compared using the inverse-variance method. Results Nineteen RCTs were selected. The mean proportions of patients fulfilling all inclusion criteria of each RCT in Cohorts A and B were 2.3% and 7.6%, respectively. The pooled proportion ratios (95% confidence interval) for achieving the American College of Rheumatology 20 (ACR20), ACR50, ACR70, and disease activity score 28 remission in non-eligible cases for eight RCTs versus all corresponding RCTs were 0.38 (0.30–0.51), 0.41 (0.30–0.57), 0.54 (0.35–0.82), and 1.28 (1.10–1.56), respectively. Conclusions Few rheumatoid arthritis patients fulfilled the inclusion criteria of the RCTs in clinical settings. There was a difference in the efficacy/effectiveness of bDMARDs between RCTs and clinical practice.

NERICA (New Rice for Africa) was produced by crossing Asian rice (Oryza sativa L.) and African rice (Oryza glaberrima Steud.) and recorded to be drought tolerance. This study aimed to examine the transpiration and water use efficiency affected plant aboveground dry matter in total 29 cultivars including 23 NERICA, 1 indica-type and 5 japonica-type cultivars. Seedlings were transplanted 2 plants per pot (1/5000 a Wagner pot) on June 14, 2021. When the flag leaf appeared, three water treatments with three replications were imposed for 14 days. The control plot (C) was watered daily to maintain the water content per pot at field capacity (SW). The water content of medium dry pots (MD) and hard dry pots (HD) were maintained at 40% and 10% of SW, respectively. Surface of the pots was covered to eliminate the evaporation. Samples for dry matter measurement were collected on the same day starting and ending water treatment. Water use efficiency (WUE) was significantly different among cultivars when soil moisture treatments were included, and the same observation on soil moisture treatments when included cultivars. NERICA 4 showed the lowest WUE while NERICA 9 and Hokuriku 193 had the highest WUE. Cultivars with higher transpiration rate (Tr) had higher dry matter production (ΔDW). Under high vapor pressure deficit, ΔDW was more correlated with transpiration corrected by vapor pressure deficit (Tr/VD) than with WUE.

Here we present a 45-year-old male patient who suffered from psoriatic arthritis (PsA), for which adalimumab (80 mg every other week) was effective. Dose escalation of a TNF-α antagonist should be considered for patients showing an inadequate response for disease stabilization in PsA.

Objectives To evaluate the efficacy and safety of biosimilars compared with reference biological disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) as a part of the process of developing the 2020 update of the Japan College of Rheumatology guidelines for the management of RA. Methods PubMed, Cochrane Library, and Japan Centra Revuo Medicina were searched for articles to conduct a systematic review (SR). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Results Twenty randomized controlled trials were included (biosimilars of infliximab, etanercept, and adalimumab). A meta-analysis revealed that the risk ratios (RRs) and 95% confidence intervals (CIs) of achieving the American College of Rheumatology 50% response (ACR50) at week 24 and serious adverse events (SAEs) for biosimilars compared with the reference bDMARDs were 1.04 (0.98–1.10) and 0.84 (0.61–1.18), respectively. The RRs of achieving ACR50 and SAEs at week 24 were respectively 0.93 (0.69–1.26) and 2.15 (0.55–8.35) in the patients who switched to biosimilars from the reference bDMARDs and 0.92 (0.76–1.12) and 1.41 (0.32–6.15) in those who continued the reference bDMARDs. Conclusion Biosimilars and reference bDMARDs were equally useful for the management of RA.

Objective.We elucidated the association of serum soluble CD163 (sCD163) with rapidly progressive interstitial lung disease (RP-ILD), autoantibody profiles, and serum ferritin in patients with polymyositis (PM), classic dermatomyositis (DM), and clinical amyopathic dermatomyositis (CADM).Methods.Serum sCD163 levels were retrospectively measured by ELISA in patients with PM, classic DM, and CADM, as well as in healthy controls (HC). Repeat sera samples were obtained posttreatment from available patients. The associations between serum sCD163 levels and clinical information were analyzed.Results.Serum sCD163 levels in patients with PM/classic DM/CADM were significantly higher than those in HC (n = 72, 56, 34, and 68, respectively; p < 0.001 for all comparisons). No significant difference was observed between serum sCD163 levels in patients with and without ILD (p = 0.16) or between those with RP-ILD and chronic ILD (p = 0.21). Serum sCD163 levels were significantly higher in patients with anti-MDA5 antibodies (n = 27) than in those without (p = 0.001). Serum sCD163 levels were weakly correlated with serum ferritin levels in the patients with PM, classic DM, and CADM (r = 0.21). Serum sCD163 levels decreased significantly following treatment in all patient groups (p = 0.003).Conclusion.The present results suggest an association of serum sCD163 with PM, classic DM, and CADM, especially in anti-MDA5 antibody–positive cases. However, serum sCD163 levels were not specifically associated with ILD or RP-ILD.

The patient was a 62-year-old man with anticitrullinated protein antibody-positive rheumatoid arthritis (RA) and a history of repeated respiratory tract infections and organizing pneumonia for eigh...

Toward the 1 MV power supply system for the ITER neutral beam injector consisting of various components with oil insulation, gas insulation and vacuum insulation, design and manufacturing of dc ultra-high-voltage component have been progressed. Thermal design of long transmission line up to 100 m was established. In order to design the high-temperature water channel for the plasma grid at 1 MV potential, the resistivity of high-purity water at 180 °C was measured for the first time. With the obtained resistivity, realistic high-temperature water circulating system was designed. A high-voltage bushing to transmit multiple voltages simultaneously has been also developed through a careful experimental study on vacuum insulation characteristics with multi-gaps coaxial electrodes. With the empirical scaling the electrostatic screen was designed taking into account effect of multi-gap and expected deformation such as thermal elongation during operation. After the assembly, stable voltage holding of 240 kV at each stage was confirmed in the manufactured HV bushing.

Background:Patients with elderly-onset rheumatoid arthritis (EORA) are on the rise in the aging or super-aging society, especially in Japan. Patients with EORA have more comorbidities than those with younger-onset RA, a higher risk of adverse drug reactions due to reduced drug metabolism, and a higher risk of infections1). Therefore, patients with EORA tend to receive suboptimal treatment, resulting in insufficient control of disease activity2). Although several studies reported treatment responsiveness in patients with EORA, many of them have a limited observation period3-8), and long-term treatment responses and their associated factors need to be clarified.Objectives:We retrospectively evaluated treatment responses of patients with EORA for 3 years and their associated factors in a clinical setting.Methods:The Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort is a large, single institute-based, observational cohort of RA patients established at Institute of Rheumatology, Tokyo Women’s Medical University, in 2000. The subjects were RA patients who first enrolled in the IORRA cohort from 2010 to 2014, were over 60 years old with less than 1-year disease duration, and had a DAS28-ESR over 3.2 at entry. The primary endpoint was DAS28-ESR Results:Among a total of 250 patients in this study, 152 patients (60.8%) achieved DAS28-ESR Conclusion:The majority of the patients with EORA achieved DAS28-ESR References:[1]Nat Rev Rheumatol 2013;9:604-613[2]Ann Rheum Dis 2006;65:1226-1229[3]Ann Rheum Dis 2009;68:1470–1473[4]Joint Bone Spine 2015;82:25-30[5]J Rheumatol 2016;43:1974-1983[6]Rheumatology 2015;54:798-807[7]Rheumatology 2014;53:1075-1086[8]Japanese Journal of Geriatrics 2018;55:251-258Acknowledgments:We thank all patients who participated in the IORRA survey and all of the members of the Institute of Rheumatology, Tokyo Women’s Medical University, for the successful management of the IORRA cohort.Disclosure of Interests:Mai Abe: None declared, Eiichi Tanaka Consultant of: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue Speakers bureau: EI has received speaker fee from Bristol-Meyers, Pfizer, Merck serono., Eri Sugano: None declared, Naohiro Sugitani: None declared, Kumiko Saka: None declared, Moeko Ochiai: None declared, Yoko Shimizu: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Katsunori Ikari Speakers bureau: Asahi Kasei Pharma Corp., Astellas Pharma Inc., AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eis, ai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kaken Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp.Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd and UCB Japan Co. Ltd., Ayako Nakajima Grant/research support from: AN has received research grants from Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Consultant of: AN has consultant fee from Nippon Kayaku Co. Ltd., Speakers bureau: AN has received speaker’s fee from AbbVie Japan GK, Actelion Pharmaceuticals Japan LTD., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Teijin Pharma Ltd., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., Speakers bureau: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma.

Introduction/Background The major fact-finding survey on oncofertility care has not been conducted to date in the field of gynecologic oncology. Therefore, we examined AYA (adolescent and adult) cancer patients with ovarian germ-cell tumors (OGT) on fertility preserving therapy and from oncofertility liaisons to elucidate the situation in Japan by AMED survey. Methodology AYA (age 15–39 years) cancer patients with OGT who received fertility-preserving therapy at the JSOG (Japan Society of Obstetrics and Gynecology) specialist training facilities nationwide from January 2009 to December 2013 (430 cases) were surveyed with respect to surgery applications, surgical styles, outcomes of pregnancy. Results No postoperative recurrence was observed in approximately 90% of 415 cases. The ovarian residual function rate was low at 12.8%. Approximately 80% of the cases were stage I cancer. Of the 415 patients, 82.9% underwent adnexectomy during surgery and 13.5% underwent cyst extraction. Abdominal operation and laparoscopy were performed in approximately half of the patients who underwent cyst extraction. Of the 415 patients who underwent surgery, 97 (23.4%) became pregnant. In the pregnancy cases, the rate of referal to the REI (reproductive endocrinology and infertility) specialists in the overall and chemotherapy groups remained at approximately 15%. Meanwhile, the reference rate to the REI specialists was low in the non-pregnant cases (0.8%). Conclusion AYA patients with OGT in Japan undergo therapies described in JSGO (Japan Society of Gynecologic Oncology) clinical guidelines. However, their pregnancy rate is low, and referral to the reproductive is not sufficiently used. Even though the AYA patients with OGT has normal menstruation, the ovarian reserve should be followed by the specialists. Therefore, referring to the REI specialists early on may improve survivorship for this kind of patients. Disclosure Nothing to disclose.

Introduction/Background The purpose of the study is to determine if superb microvascular imaging (SMI) and shear wave elastography (SWE) can be used for the early diagnosis of uterine cervical intraepithelial neoplasia and cancer. Methodology A case-control study was carried out in St. Marianna University School of Medicine Hospital between April 2017 and January 2018 on patients with uterine cervical dysplasia and uterine cervical cancer. Seventeen controls with eight subjects were investigated. An evaluation using SMI and SWE was conducted in addition to the conventional ultrasonic tomography and color doppler tests before or after the treatment. The colored races plastic intensity in the SMI was evaluated for three phases, strong, mediate, weak, and the blood flow rate was measured. The SWE was measured at several locations and the mean value was used as signal intensity. Results The target breakdown was one patient with uterine cervical cancer and seven patients with high-grade squamous intraepithelial lesions. For the subject and control cases, the intensity of the conventional colored races plastic was 6% vs. 0% (n.s.), and 94% vs. 100% for strong and weak phase, respectively. While for the control the measure, it was 39% vs. 0% and 61% vs. 100% for strong and weak phase, respectively. In addition, one patient with uterine cervical cancer exhibited a strong phase. The SWE evaluation of the uterine cervical hardness resulted in SWE level of 4.4±1.2, 2.2±0.3 for case and control, respectively (p Conclusion An evaluation using SMI and SWE utility suggested the identification of histologic changes such as minute vascular hyperplasia or malignant transformation of the uterine cervical lesion. Disclosure Nothing to disclose.

ObjectiveWe aimed to study the usefulness of serum soluble CD163 (sCD163) as a biomarker for macrophage activation syndrome (MAS) associated with systemic lupus erythematosus (SLE).MethodsSerum sCD163 levels were retrospectively measured by enzyme-linked immunosorbent assay for SLE patients associated with MAS (SLE-MAS), lupus nephritis (LN), or autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) and healthy controls (HCs). Posttreatment samples were also evaluated in the available SLE-MAS patients. The associations between serum sCD163 levels and clinical information were statistically analyzed.ResultsThe serum sCD163 levels in SLE-MAS, LN and SLE-AIHA/ITP groups were significantly higher than those in HCs ( n = 17, 29, 13, and 68, respectively; p ConclusionsThe present study suggests the usefulness of serum sCD163 as a diagnostic and disease-activity biomarker for SLE-associated MAS. Serum sCD163 might also have a different role as a biomarker for SLE-associated MAS than serum ferritin does.

Background:The risk of some types of malignancy is increased in patients (pts) with rheumatoid arthritis (RA), compared with the general population. We have previously reported the incidence of malignancy in Japanese pts with RA.1-4Objectives:This analysis further evaluated the incidence of malignancy in Japanese pts with RA using recent data from the large prospective observational study, IORRA.Methods:This analysis included all pts with RA aged ≥18 years who were enrolled in IORRA from April 2013 to October 2018, with follow-up through October 2019, and participated in ≥2 surveys. Index was defined as the date of the first entry in the IORRA database, with baseline defined as the 6-month period prior to the index date. Malignancies were identified in pt reports of biannual IORRA surveys and confirmed using medical records. Age- and sex-standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated.Results:In total, 8020 pts were included. At baseline, the majority (85.0%) of pts were female; mean disease duration was 12.8 years, 5.8% and 4.8% of pts had a past history of malignancy or comorbid malignancy at baseline, respectively, and the majority (75.9%) of pts were receiving methotrexate (Table). The SIR (95% CI) was 0.90 (0.80, 1.01). SIRs (95% CI) of site-specific malignancies were: breast cancer, 0.91 (0.69, 1.18); lung cancer, 0.67 (0.44, 0.97); colon cancer, 0.93 (0.62, 1.32); stomach cancer, 0.82 (0.56, 1.14); and lymphoma, 3.74 (2.73, 4.96).Table 1.Patient demographics and baseline disease characteristicsPatients with RA (N=8020)Age (years), mean (SD)59.3 (13.8)Female, n (%)6816 (85.0)Duration of RA (years), mean (SD)12.8 (10.3)Never smoked, n (%)5086 (66.2)DAS28, mean (SD)2.8 (1.1)J-HAQ, mean (SD)0.60 (0.72)Malignancy status, n (%)Past history of malignancy467 (5.8)Comorbid malignancy at baseline386 (4.8)Medication use, n (%)MTX6088 (75.9)Tacrolimus787 (9.8)Corticosteroids2641 (32.9)bDMARD use1508 (18.8)TNFi1163 (14.5)Tocilizumab311 (3.9)Abatacept106 (1.3)JAK inhibitors4 (0.05)bDMARD, biological disease-modifying antirheumatic drug; DAS28, Disease Activity Score in 28 joints; JAK, Janus kinase; J-HAQ, Japanese Health Assessment Questionnaire; MTX, methotrexate; N, the number of patients included in the analysis, the number of patients assessed for each characteristic may be fewer than N; n, the number of patients with each characteristic; SD, standard deviation; TNFi, tumour necrosis factor inhibitorConclusion:Overall risk of malignancy was similar to that in the general Japanese population, although a significantly higher risk of lymphoma was identified.References:[1]Sugimoto et al. Rheumatol Int 2017; 37: 1871-1878.[2]Shimizu et al. Clin Rheumatol 2017; 36: 1237-1245.[3]Askling et al. Ann Rheum Dis 2016; 75: 1789-1796.[4]Yamada et al. Rheumatol Int 2011; 31: 1487-1492.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Anthony G McCluskey, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:masayoshi harigai Speakers bureau: AbbVie Japan, Ayumi, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly Japan, GlaxoSmithKline, Kissei, Pfizer Japan Inc, Takeda, Teijin, Consultant of: AbbVie Japan, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Kissei, Teijin, Grant/research support from: AbbVie Japan, Asahi Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Kissei, Mitsubishi Tanabe, Nippon Kayaku, Sekiui Medical, Shionogi, Taisho, Takeda, Teijin, Naohiro Sugitani: None declared, Ryoko Sakai Speakers bureau: Bristol-Myers Squibb, Eisuke Inoue Speakers bureau: Pfizer Japan Inc, Bristol-Myers Squibb, Michika MOCHIZUKI Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Shigeyuki Toyoizumi Employee of: Pfizer R&D Japan, Noritoshi Yoshii Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Eiichi Tanaka Speakers bureau: AbbVie Japan, Asahi Kasei, Astellas, Ayumi, Chugai, Eisai, Eli Lilly Japan, GlaxoSmithKline, Kyowa, Janssen, Mochida, Pfizer Japan Inc, Takeda, Teijin, Hisashi Yamanaka Speakers bureau: Astellas, Bristol-Myers-Squibb, Pfizer Inc, Mitsubishi Tanabe, Teijin, YLBio, Consultant of: Corrona, LLC

To realize dc 1 MV power supply system for neutral beam injector in ITER, long-pulse dc ultrahigh-voltage (HV) insulation technologies have been developed. For a dc 1 MV insulating transformer, a composite bushing has been newly developed to overcome the manufacturing difficulty of a conventional condenser bushing (CB). The composite bushing has a small-sized CB and fiber reinforced plastic tube to sustain 1 MV stably inside and outside of the bushing. The mock-up of the insulating transformer has fulfilled the ITER requirement of dc 1.2 MV insulation for 3600 s. An HV bushing to transmit multiple voltages simultaneously has also been developed through a careful experimental study on vacuum insulation characteristics with multiple gaps between large electrodes. It has been found that the voltage holding is dominated not by number of the electrodes but by a total cathode surface area of electrodes. Based on this result, the vacuum insulation inside the HV bushing with five electrostatic screens has been designed to realize a stable vacuum insulation of 1 MV.

A Japanese woman in her thirties was diagnosed with systemic lupus erythematosus (SLE) for 15 years and was treated with 17.5 mg/day of prednisolone at the onset of this episode. She was ad...

Background:The mortality of patients with rheumatoid arthritis (RA) had been reported as being worse than that of the general population [1, 2], but is expected to have improved over time because the progress in treatment of RA during the past twenty years has been actively adopted to RA management [3, 4]. However, the change in the mortality still remains controversial in patients with early RA [5, 6].Objectives:To investigate whether the vital prognosis of patients with early RA has changed in the past twenty years.Methods:The IORRA cohort is a large observational cohort established in 2000 at the Institute of Rheumatology, Tokyo Women’s Medical University. Essentially, all Japanese patients diagnosed with RA at our institute were registered and clinical parameters were assessed biannually. As there is no National Death Registry in Japan, we obtained death report from residual families who responded to our mail query to patients who failed to conduct the subsequent IORRA survey, from physicians of affiliated hospitals and from police in case they found dead patient outside of a hospital. In this study, the patients with early RA (less than 2 years of disease duration) who participated in the survey for the first time from 2001 to 2012 were included and observed for five years from the date of the initial survey. We classified patients into group A (enrolled in 2001-2006) and B (enrolled in 2007-2012). Five-year survival rate and standardized mortality ratio (SMR) were calculated for each group. SMR was calculated using the life tables in Japanese general population reported by the Ministry of Health, Labour and Welfare, Japan. The effects of loss to follow-up cases were evaluated by multiple imputation method as a sensitivity analysis of SMR.Results:A total of 3,217 patients with early RA were analyzed. The number of patients was 1,609 (79.4% female) in the group A and 1,608 (81.8% female) in B. The median age at baseline was 55 in both groups. Among a total of 3,217 patients, 486 (15.1%) patients were lost during 5-year follow-up; 213 (13.2%) in the group A and 273 (17.0%) in B, respectively. During the observational period, deaths were confirmed in 47 cases (2.9%) in the group A and 45 (2.8%) in B. Major causes of death included malignancies (28% in the group A, 38% in B), respiratory involvement (23% in the group A, 40% in B), cerebrovascular disorders (11% in the group A, 2% in B), and cardiovascular disorders (11% in the group A, 0% in B). The five-year survival rate was 88.8% for the group A and 87.8% for B, and the SMR was 0.81 (95%CI: 0.59-1.08) for the group A and 0.78 (0.57-1.04) for B when assuming all the lost to follow-up patients were alive for 5 years. In the sensitivity analysis assuming that the mortality rate of patients who were lost to follow-up was twice as that of the general population, the SMR was 0.90 (0.68-1.19) for the group A and 0.92 (0.68-1.23) for B.Conclusion:The mortality of patients with early RA in the past twenty years has been comparable to that of the Japanese general population. In addition, the SMR and the five-year survival rate did not change overtime.References:[1]Cobb, S., et al. N Engl J Med 1953; 249(14): 553-556.[2]Nakajima, A., et al. Scand J Rheumatol 2010; 39(5): 360-367.[3]Smolen, J. S., et al. Ann Rheum Dis 2014; 73(3): 492-509.[4]Singh, J. A., et al. Arthritis Care Res 2016; 68(1): 1-25.[5]Lacaille, D., et al. Ann Rheum Dis 2017; 76(6): 1057-1063.[6]Humphreys, J. H., et al. Arthritis Care Res 2014; 66(9): 1296-1301.Disclosure of Interests:Naohiro Sugitani: None declared, Eiichi Tanaka Consultant of: Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue Speakers bureau: EI has received speaker fee from Bristol-Meyers, Pfizer, Merck serono., Mai Abe: None declared, Eri Sugano: None declared, Kumiko Saka: None declared, Moeko Ochiai: None declared, Yoko Shimizu: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Katsunori Ikari Speakers bureau: Asahi Kasei Pharma Corp., Astellas Pharma Inc., AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eis, ai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kaken Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp.Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd and UCB Japan Co. Ltd., Ayako Nakajima Grant/research support from: AN has received research grants from Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Consultant of: AN has consultant fee from Nippon Kayaku Co. Ltd., Speakers bureau: AN has received speaker’s fee from AbbVie Japan GK, Actelion Pharmaceuticals Japan LTD., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Teijin Pharma Ltd., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., Speakers bureau: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma.

Background:It has been reported that female rheumatoid arthritis (RA) patients have a longer time to pregnancy than healthy women (1), and that high Disease Activity Score with 28 joint count (DAS28) -CRP in preconception increases the frequency of infertility (2). Before the era of biologics, RA treatment tended to be inadequate from pregnancy planning to the end of lactation. And it was not uncommon for female RA patients to be unable to get pregnant or develop physical dysfunction as a result of insufficient control of the disease. There are some reports of disease activity during pregnancy and postpartum in RA patients, and the effects of RA disease activity on pregnancy and childbirth outcomes (3-5), but there are few reports focusing on the physical function during pregnancy planning of RA patients.Objectives:To investigate disease activity and physical function in female patients with RA who planned and didn’t plan pregnancy.Methods:The IORRA cohort is a large, single institute-based, observational cohort of RA patients established at the Institute of Rheumatology, Tokyo Women’s Medical University, in 2000. We identified female RA patients aged 20-49 years who answered ‘pregnant’ or ‘delivered’ in the IORRA survey in 2010-2015 and whose pregnancy and the pregnancy planning time was confirmed in the medical records, and defined them as the pregnancy planning (PP) group. Matched control was extracted at 1:3 ratio from patients without pregnancy plan based on entry time, age, RA disease duration, DAS28-CRP, Japanese version of Health Assessment Questionnaire (J-HAQ) score, and comorbidities. The primary endpoint was J-HAQ at 3years from the baseline, which was defined as the most recent IORRA survey before planning pregnancy. The mixed-effect model for repeated measures was used to analyze group difference.Results:There were 40 patients in the PP group (average 32.2 years, disease duration 5.7 years, DAS28-CRP 1.7, J-HAQ 0.26), and 120 patients in the control group (average 32.4 years, disease duration 5.9 years, DAS28-CRP 1.7, J-HAQ 0.21). The proportion of user and dosage of MTX and glucocorticoid (GC) and bDMARDs user at baseline were comparable between the groups (MTX: PP 87.5% [9.8 mg/week], control 85.0% [8.8 mg/week]; GC: PP 32.5% [3.6 mg/day], control 27.5% [4.4 mg/day]; bDMARDs: PP 40.0%, control 27.5%). DAS28-CRP at year 3 of the PP group elevated and was higher than the control group (PP 2.3, control 1.7, pConclusion:Physical function in pregnancy planning patients with RA did not deteriorate as well as the control patients in clinical settings.References:[1]Arthritis Rheum. 2011;63:1517-1521.[2]Ann Rheum Dis. 2015;10:1836-1841.[3]J Rheumatol. 2015;42:1376-1382.[4]J Rheumatol. 2019;46:245-250.[5]Arthritis Care Res. 2017;69:1297-1303.Disclosure of Interests:Moeko Ochiai: None declared, Eiichi Tanaka Consultant of: ET has received lecture fees or consulting fees from Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Speakers bureau: ET has received lecture fees or consulting fees from Abbvie, Asahi Kasei pharma co., Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Co., Eisai Pharmaceutical, Janssen Pharmaceutical K.K., Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Taisho Toyama Pharmaceutical Co., and UCB Pharma., Eisuke Inoue Speakers bureau: EI has received speaker fee from Bristol-Meyers, Pfizer, Merck serono., Mai Abe: None declared, Eri Sugano: None declared, Naohiro Sugitani: None declared, Kumiko Saka: None declared, higuchi yoko: None declared, Rei Yamaguchi: None declared, Naoki Sugimoto: None declared, Ikari Katsunori Speakers bureau: KI has received speaker’s fee from Asahi Kasei Pharma Corp., Astellas Pharma Inc., AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eis, ai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Kaken Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp.Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd and UCB Japan Co. Ltd., Ayako Nakajima Grant/research support from: AN has received research grants from Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Consultant of: AN has consultant fee from Nippon Kayaku Co. Ltd., Speakers bureau: AN has received speaker’s fee from AbbVie Japan GK, Actelion Pharmaceuticals Japan LTD., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Teijin Pharma Ltd., Atsuo Taniguchi: None declared, Hisashi Yamanaka Grant/research support from: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., Speakers bureau: HY has received research grant or speaker fee from AbbVie, Astellas, Ayumi, Behringer, Bristol-Meyers, Chugai, Daiichi-Sankyo, Eisai, Kaken, Nippon-Shinyaku, Novartis, Ono, Pfizer, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Torii, UCB, YLbio., masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma.

Background Recently, there were several reports that patients with systemic sclerosis (SSc) showed acute renal failure with anti-neutrophil cytoplasmic antibody (ANCA) positivity. On the other hand, it is also reported that 7%–13% of patients with SSc revealed myeloperoxidase-ANCA (MPO-ANCA) positivity without vasculitis manifestation in 1990s, but their clinical characteristics were unclear. It is also unknown whether ANCA positivity leads to AAV or not in patients with SSc. It is important for physicians to clarify the characteristics of SSc patients with ANCA positivity, and answer the question whether they will shift ANCA-associated vasculitis (AAV). Objectives To assess the prevalence of ANCA positive patients with SSc, and clarify the characteristics of these patients. Methods We enrolled the 333 consecutive patients with SSc who visited our clinic during October 2014 to September 2015, all of who were checked MPO-ANCA using fluorescent-enzyme immune-assay. Clinical manifestation and laboratorial data were obtained from medical chart. The data were assessed by chai-square analysis and Welch’s t test. Results Two patients were diagnosed AAV before October 2014. Eight patients (2.4%) revealed MPO-ANCA positivity without vasculitis manifestation. All of MPO-ANCA positive patients were female, and mean age and disease duration were 61.1 years old and 17.2 years, respectively, and there’s no statistically significant differences comparing MPO-ANCA negative patients. As a result of evaluating clinical manifestations, we found that patients with MPO-ANCA positivity more frequently had interstitial lung disease than patients without MPO-ANCA positivity (87.5% vs. 36.7%, p Conclusions The prevalence of MPO-ANCA positivity in SSc patients were lower than previous reports. MPO-ANCA positivity may be related to interstitial lung disease in SSc. MPO-ANCA positive patient may occasionally reveal AAV in the future, and careful observation are needed. Disclosure of Interest None declared

Background Airway disease (AD) has drawn attention both clinically and etiologically in rheumatoid arthritis (RA), but is still poorly understood. Objectives We aimed to elucidate the clinical and radiographic characteristics of AD in patients with RA. Methods We retrospectively reviewed high-resolution computed tomography (HRCT) images and clinical data of 131 consecutive RA patients in whom HRCT were scanned for clinical purposes and screening. Overlap patients with other collagen tissue diseases and patients complicated with active infection or lung cancer were excluded. Patients who had a history of drug-induced lung disease, thoracic radiation, or exposure to dust were also excluded. HRCT images were reviewed independently by a pulmonologist and a radiologist in blind fashions, and cases of disagreement were discussed to reach a final consensus. AD was radiographically sub-categorised into 3 sub-groups: central AD, small AD, and middle lobe and lingular bronchiectasis. The associations between AD and interstitial lung disease (ILD) and each pair of the subtypes of AD were analysed by Fisher’s exact test. The risk factors for AD and subtypes of AD were identified by multivariate logistic regression analyses. Results The mean age of the patients was 65 years old, the mean disease duration of the patients was 123 months, 69% of the patients were women, and 42% of the patients had past/current histories of smoking. The mean Disease Activity Score 28 (DAS28)-erythrocyte sedimentation rate (ESR) value was 2.87. AD and ILD were observed in 53 (40%) and 36 (27%) patients, respectively, and both in 19 (15%) patients. AD and ILD were not significantly associated (p=0.11). By multivariate logistic regression analyses, rheumatoid factor (RF) was identified as risk factors for whole AD (odds ratio [OR] 2.7; 95% confidence interval [CI], 1.0 to 6.9; p=0.04). Central AD, small AD, and middle lobe and lingular bronchiectasis were observed in 45 (34%), 31 (24%), and 17 (13%) patients, respectively. Each pair of these 3 subtypes were significantly associated with each other (p Conclusions Radiologically defined AD was frequent comorbidity in RA patients, and multiple subtypes of AD were observed and coexisted. Furthermore, AD may be related to the pathology of RA, and different AD subtypes may have distinct risk factors. Prospective studies with early RA patients were warranted to further clarify these findings and clinical impact of AD. Disclosure of Interest None declared

Background: Denosumab is a fully human monoclonal antibody (IgG 2 subclass) that inhibits bone resorption by inhibiting RANKL, a key mediator of osteoclast formation, function, and survival. The effect of denosumab on the progression of joint damage in patients with RA on csDMARDs background treatment from the first 12 months (double-blind, placebo-controlled) of the Phase 3 DESIRABLE study has previously been reported. 1 Objectives: To evaluate the safety and efficacy of long-term treatment with denosumab 60 mg every 6 months (Q6M) or every 3 months (Q3M) with RA patients in long term treatment phase of the DESIRABLE study. Methods: Upon completion of the 12-month, double-blind phase, all patients were to receive denosumab 60 mg/Q6M or 60 mg/Q3M and calcium and vitamin D daily during the 36-month, open-label extension phase. Patients were randomized in a 1:1:2:2 ratio to receive one of four treatments (figure 1). In this analysis, the continuous administration group received 36 months of denosumab treatment, and the cross-over group received 24 months of denosumab treatment (12 month of placebo in DB phase and 24 months of denosumab treatment phase). The radiographic evaluation was the change from baseline to 12, 24 and 36 months in the van der Heijde modified total Sharp score (mTSS). Radiographs of hands and feet at baseline, 12, 24 and 36 months were scored with blinded time order by 2 readers independently. Average score of the 2 readers is used for the analysis. Missing scores were imputed using linear extrapolation/interpolation. Results: 667 (placebo/Q6M (P/Q6M), n=113; placebo/Q3M (P/Q3M), n=110; Q6M, n=222; Q3M, n=222) received at least one dose of study drug, and 607 (P/Q6M, n=105; P/Q3M, n=103; Q6M, n=199; Q3M, n=200) completed the DB period and entered the long-term extension. In both continuous administration and cross-over group, sustained inhibition of mTSS and erosion score (ES) progression was observed during long-term treatment phase (table 1). No effect on joint space narrowing (JSN) was observed (table 1). Overall proportions of patients with no progression (ie, mTSS change ≤0.5) at 36 months were 56.8% in P/Q6M, 53.3% in P/Q3M, 66.3% in Q6M group, and 65.7% in Q3M group. Incidence of adverse events (AEs), serious AEs and AEs leading to discontinuation of study drug were similar across treatment groups. No events of atypical femoral fracture were observed. Conclusions: Denosumab treatment was associated with sustained inhibition of progression of joint destruction for up to 36 months and was generally well tolerated in Japanese patients with RA on csDMARDs. Denosumab has the potential to be a new therapeutic option to inhibit the progression of structural damage for patients with RA. Reference [1]Takeuchi T, et al. Ann Rheum Dis2017;76(suppl 2): Abstract SAT0186. Disclosure of Interest: T. Takeuchi Grant/research support from: Astellas, Bristol-Myers, Chugai, Daiichi Sankyo, Takeda, Teijin Pharma, AbbVie, Asahi Kasei Pharma, Mitsubishi Tanabe, Pfizer, Taisho Toyama, Eisai, AYUMI, Nipponkayaku, Consultant for: AstraZeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, AbbVie, Nipponkayaku, Janssen, Astellas, Taiho, Speakers bureau: AbbVie, Bristol-Myers, Chugai, Mitsubishi Tanabe, Pfizer, Astellas, Daiichi Sankyo, Y. Tanaka Grant/research support from: Mitsubishi Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, AbbVie, MSD, Daiichi Sankyo, Pfizer, Kyowa Hakko Kirin, Eisai, Ono, Speakers bureau: Daiichi Sankyo, Astellas, Pfizer, Mitsubishi Tanabe, Bristol-Myers, Chugai, YL Biologics, Eli Lilly, Sanofi, Janssen, UCB, S. Soen Grant/research support from: Chugai, Daiichi Sankyo, Speakers bureau: Asahi Kasei Pharma, Astellas, MSD, Daiichi Sankyo, Takeda, Chugai, Teijin Pharma, Pfizer, Eli Lilly Japan, Mitsubishi Tanabe, H. Yamanaka Grant/research support from: MSD, Astellas, AbbVie, BMS, Kaken, UCB, Ono, Ayumi, Eisai, Daiichi Sankyo, Takeda, Mitsubishi Tanabe, Chugai, Teijin Pharm, Torii, Nipponshinyaku, Pfizer, Consultant for: Pfizer, YL biologics, Takeda, Teijin Pharm, BMS, Nipponkayaku, Chugai, Mitsubishi Tanabe, Daiichi Sankyo, Astellas, T. Yoneda Grant/research support from: Grants-in-Aid for Scientific Research, MEXT #17H04377, Consultant for: Daiichi Sankyo, Employee of: Indiana University, S. Tanaka Consultant for: Amgen Astellas, MSD, AbbVie, Daiichi Sankyo, Eli Lilly, Ono, Asahi Kasei Pharma, Teijin Pharma, T. Nitta Employee of: Daiichi Sankyo, N. Okubo Shareholder of: Daiichi Sankyo, Employee of: Daiichi Sankyo, H. Genant Consultant for: Daiichi Sankyo, Pfizer, Amgen, Bioclinica, Eli-Lilly, Janssen, Servier, Novartis, Takeda, Merck, Biomarin, Clemencia, Agnovos, Regeneron, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB, Employee of: Imaging Rheumatology bv.

Background: Foot and ankle joint disorders are serious issues for patients with rheumatoid arthritis (RA). Rheumatoid foot is reported as the first symptom of the disease in 20–53% of RA patients1–3. However, there are few studies investigating the features of patients with RA whose debut joint is a foot or ankle joint. Objectives: The aim of this study is to compare the differences between RA patients whose first symptom was a foot or ankle joint (FOOT group) and was other joints (OTHER group) by using the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort in our institute. Methods: In the IORRA survey conducted in April 2016, patients were asked about first symptom at RA onset. Disease activities, clinical laboratory variables, functional disability, quality of life, and the use and ratio of anti-inflammation and anti-rheumatic drugs were compared between the FOOT group and OTHER group. Results: Among 5,637 Japanese patients with RA who participated in the IORRA survey on April 2016, 5,479 patients (97.2%) responded to the questionnaire regarding debut joint. Of these 5,479 patients, 2,402 (43.8%) reported their first symptom of RA were a foot or ankle. Comparing the two groups, the FOOT group had higher disease activity, higher disabilities, lower quality of life, low activities of daily living, and poorer mental health and used higher dose and rate of anti-inflammatory drugs significantly than the OTHER group (all P Conclusions: Patients whose debut joint was a foot or ankle had higher disease activity, higher dysfunction, lower quality of life, and used higher dose and rate of anti-inflammatory drugs than patients whose debut joint was the other joints on RA onset. Clinicians should have more attentions to foot and ankle joints in daily practice so as not to underestimate the disease activity of RA. References [1] Grondal L, Tengstrand B, Nordmark B, Wretenberg P, Stark A. The foot: still the most important reason for walking incapacity in rheumatoid arthritis: distribution of symptomatic joints in 1,000 RA patients. Acta Orthop2008;79:257–61. [2]Otter SJ, Lucas K, Springett K, Moore A, Davies K, Cheek L, et al. Foot pain in rheumatoid arthritis prevalence, risk factors and management: an epidemiological study. Clin Rheumatol2010;29:255–71. [3]Vainio K. The rheumatoid foot; a clinical study with pathological and roentgenological comments. Ann Chir Gynaecol Fenn Suppl1956;45:1–107. Disclosure of Interest: K. Yano Speakers bureau: Bristol-Meyers, Pfizer, Eisai, Tanabe-Mitsubishi, Chugai, AbbVie, Janssen Pharmaceutical, Asahi-Kasei and Takeda., K. Ikari Grant/research support from: Astellas, UCB, Bristol-Meyers, Pfizer, Eisai, Tanabe-Mitsubishi, Chugai, AbbVie, Janssen Pharmaceutical, Otsuka, Kaken, Asahi-Kasei, Hisamitsu and Takeda., Speakers bureau: Astellas, UCB, Bristol-Meyers, Pfizer, Eisai, Tanabe-Mitsubishi, Chugai, AbbVie, Janssen Pharmaceutical, Otsuka, Kaken, Asahi-Kasei, Hisamitsu and Takeda., K. Okazaki: None declared, A. Taniguchi Grant/research support from: AbbVie, Eisai, Takeda, Speakers bureau: AbbVie, Eisai, Takeda, Tanabe-Mitsubishi, Teijin Pharma and Pfizer., H. Yamanaka Grant/research support from: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers., Consultant for: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers., Speakers bureau: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers.

Toward ITER, the long-pulse acceleration of MeV-class negative ion beams has been successfully demonstrated and R&Ds and the procurement of high-voltage components of 1 MV power supply system have been progressed. In the accelerator development after the production of 1 MeV beams, an extraction grid, where a water cooling is reinforced and the beam is steered by aperture offset to suppress grid heat loads, has been newly developed to extend the pulse duration of the MeV-class beams. As the result, a total grid heat load has been reduced from 20% to 10% of the total beam power. The beam pulse was successfully increased from 0.4 s to 60 s at 0.68 MeV, 100 A/m 2 and 12 s at 0.89 MeV, 156 A/m 2 beams. As for the procurement of the 1 MV power supply system, 1 MV insulating transformer as the critical component has been developed. In the mock-up, a dc 1.2 MV for 1 h with the margin of 20% was stably sustained. Through the R&Ds of the critical components, design of five power supplies procured by JAEA has been finalized, and out of which a testing power supply has been completed in June 2014.

The association between interstitial lung disease (ILD) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA), has been described in a number of case reports and case series reports in the last 2 decades. In addition, patients with pulmonary fibrosis and ANCA positivity but without other manifestations of systemic vasculitis have also been reported. Pulmonary fibrosis was clinically manifested at the time of diagnosis in the majority of AAV patients that developed this condition. Moreover, ANCA-positive conversion occurs in patients initially diagnosed with idiopathic pulmonary fibrosis, and as a result, other manifestations of systemic vasculitis develop in some of these patients. There is significant predominance of myeloperoxidase (MPO)-ANCA and MPA in patients with AAV and ILD. Radiological and pathological findings generally demonstrate usual interstitial pneumonia (pattern) in the lungs of these patients. In most studies, AAV patients with ILD have a worse prognosis than those without it.

We aimed to validate the reliability of the Medical Outcomes Study Short Form-36 (SF-36) among Japanese patients with systemic lupus erythematosus (SLE). Japanese patients with SLE ( n = 233) completed the SF-36 and other related demographic questionnaires, and physicians simultaneously completed the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Patients were prospectively followed for a repeat assessment the following year. The SF-36 subscales demonstrated acceptable internal consistency (Cronbach’s α of 0.85–0.89), and an overall good test–retest reliability (intraclass correlation coefficient >0.70). The average baseline SF-36 subscale/summary scores except for “bodily pain” were significantly lower than those of the Japanese general population ( p

Background While dramatic progress has been made in this decade with treatments for rheumatoid arthritis (RA), such as methotrexate (MTX) and biological agents, concern about the safety, including the occurrence of malignancy, of these highly effective drugs still exists in daily clinical practice. There has not been an evident association between the use of biological agents and the occurrence of malignancy in most reports from clinical trials1 and observational studies2, although MTX use might be associated with the development of malignant lymphoma, called MTX-associated lymphoproliferative disorder3, in patients with RA. In an analysis of risk factors for overall and site-specific malignancies in Japanese patients with RA, higher disease activity was identified to be a risk factor for overall malignancies (hazard ratio [HR] 1.10, 95% CI 1.02–1.19), suggesting that tight control of RA disease activity would reduce the occurrence of malignancies in patients with RA4. However, the risk of malignancies with RA treatments including MTX and biological agents was not assessed in that analysis. Objectives We investigated the association between the occurrence of malignancies (overall and malignant lymphoma) and drug use (MTX and biological agents) in a large observational cohort of Japanese patients with RA over a long-term period. Methods Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort from April 2000 to September 2013, data for all malignancies were extracted from patients9 self-reports and confirmed by medical records. Data for malignancies occurring in patients who dropped out of the IORRA study during the subsequent three months were also collected from medical information from affiliated hospitals. We analysed whether MTX and biological agents were risk factors for overall malignancy and malignant lymphoma using a marginal structural Cox proportional hazards model5 adjusted for age, gender, smoking history, body mass index, RA disease duration, rheumatoid factor positivity and disease activity (28-joint disease activity score). Results Among 11,106 Japanese patients with RA representing 68,483 person-years, 507 overall malignancies, including 68 malignant lymphomas, were confirmed. Neither MTX nor biological agent use was a significant risk factor for overall malignancy, with an HR (95% CI) of 1.18 (0.77–1.81) and 1.01 (0.65–1.57), respectively, or for malignant lymphoma, with an HR (95% CI) of 1.17 (0.55–2.48) and 1.26 (0.43–3.64), respectively. Conclusions The use of MTX and biological agents was not significantly associated with the occurrence of overall malignancy or malignant lymphoma during long-term longitudinal observation of Japanese patients with RA. References Moulis G, et al. PLoS One. 2012;7:e48991. Mariette X, et al. Ann Rheum Dis. 2011;70:1895–904. Kameda T, et al. Arthritis Care Res (Hoboken). 2014;66:1302–9. Sugimoto N, et al. EULAR Congress 2016;FRI0143. Choi HK, et al. Lancet. 2002;359:1173–7. Disclosure of Interest N. Sugimoto Speakers bureau: Takeda Pharmaceutical and Bristol Myers Squibb., E. Tanaka Consultant for: Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Pfizer, Takeda Pharmaceutical, and Ayumi Pharmaceutical., Speakers bureau: Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Pfizer, Takeda Pharmaceutical, and Ayumi Pharmaceutical., E. Inoue: None declared, M. Kawano: None declared, M. Ochiai: None declared, Y. Shimizu: None declared, R. Yamaguchi: None declared, K. Ikari Grant/research support from: Astellas, UCB, Bristol-Meyers, Pfizer, Eisai, Tanabe-Mitsubishi, Chugai, AbbVie, Janssen Pharmaceutical, Otsuka, Kaken, Asahi-Kasei, Hisamitsu and Takeda., Speakers bureau: Astellas, UCB, Bristol-Meyers, Pfizer, Eisai, Tanabe-Mitsubishi, Chugai, AbbVie, Janssen Pharmaceutical, Otsuka, Kaken, Asahi-Kasei, Hisamitsu and Takeda., A. Nakajima Consultant for: Bristol-Meyers, Mitsubishi Tanabe Pharma, Nippon Kayaku Co. Ltd., Novartis Pharma, Pfizer, Siemens Healthcare Diagnostics K.K. and Takeda Pharmaceutical Company., Speakers bureau: Bristol-Meyers, Mitsubishi Tanabe Pharma, Nippon Kayaku Co. Ltd., Novartis Pharma, Pfizer, Siemens Healthcare Diagnostics K.K. and Takeda Pharmaceutical Company., A. Taniguchi Grant/research support from: AbbVie, Eisai, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Pfizer., Speakers bureau: AbbVie, Eisai, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Pfizer., H. Yamanaka Grant/research support from: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers., Consultant for: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers., Speakers bureau: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers.

Background Recently, presepsin (soluble CD14-subtype) and procalcitonin are reported as a good diagnostic markers of bacterial infection, especially sepsis. However, their utility in patients with connective tissue diseases (CTDs) has been unknown. Objectives To assess the diagnostic value of presepsin and procalcitonin in patients with CTDs. Methods We enrolled the consecutive patients with CTDs, who checked the level of procalcitonin and/or presepsin during January to September, 2016, retrospectively. We divided two groups; the infection group and non-infectious group. Infection was diagnosed by symptoms, micro-bacterial methods and the good response to antibiotics. The data analysis were assessed using IBM SPSS statistics 22. Results Eighty-four patients with CTDs were enrolled, including 42 patients with rheumatoid arthritis (RA). The level of procalcitonin was evaluated in all patients, and the level of presepsin was in 48 patients. Thirty-six patients were classified in infection group; 38 patients in the CRP-positive non-infection group; and 10 patients in CRP-negative non-infection group. The level of presepsin was significant higher in infection group than CRP-positive non-infection group (693 +/- 577 pg/mL vs. 250 +/- 101 pg/mL, p Conclusions Procalcitonin and presepsin may be of diagnostic value for bacterial infection in patients with CTDs, especially may distinguish bactrial infection from active phase in patients with CTDs. Disclosure of Interest None declared

Background TNF inhibitors are first-line biologic therapy used in combination with MTX for treatment of RA. However, in Japan, limited real-world data exist on this combination with relatively higher doses of MTX (>8 to ≤16 mg/week). Objectives The HAWK study was designed to assess real-world, long-term safety and effectiveness of the TNF inhibitor ADA with MTX (≥12 mg/week) in Japan. Week 52 results are presented. Methods This multicenter, prospective, observational study, enrolled biologic-naive, early (≤2 years) RA patients with DAS28-CRP>3.2 despite MTX therapy for ≥3 months. Eligible patients received ADA + MTX (≥12 mg/week at beginning of ADA) for 104 weeks. Primary endpoint was DAS28-CRP Results As of April 15, 2016, 346 patients were enrolled (safety set 301; effectiveness set 293). Effectiveness set comprised 73% women; mean (±SD) age, 54.3 (13.9) years; duration of RA, 12.1 (6.2) months; MTX dosage, 13.4 (1.8) mg/week; DAS28-CRP, 4.5 (0.9); and mTSS, 7.7 (10.0) at baseline. At week 52, DAS28-CRP Conclusions Results show that ADA with MTX (≥12 mg/week at the beginning) displayed a consistent safety profile and was effective with a DAS28-CRP remission rate of 77% in routine clinical practice. The ADR rate of 26% was similar to a previous, short-term (28 weeks) postmarketing surveillance report (1). References Koike et al. Mod Rheumatol 2014; 24:390–8. Acknowledgements This study (NCT01736189) was funded by AbbVie GK and Eisai Co., Ltd. AbbVie participated in the collection, analysis, and interpretation of the data, and in the drafting, review, and approval of the abstract. AbbVie GK and Eisai Co., Ltd. provided funding to EPS Corporation for data analysis and to Cactus Communications for editorial assistance. Disclosure of Interest Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, Eisai, Consultant for: Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, GlaxoSmithKline, T. Mimori Grant/research support from: Acterion, Ayumi, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi Tanabe, Speakers bureau: Chugai, Mitsubishi Tanabe, H. Yamanaka Grant/research support from: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer, UCB. Nippon Kayaku, YL biologics, Bayer, Bristol-Meyers, Consultant for: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer, UCB, Nippon Kayaku, YL biologics, Bayer, Bristol-Meyers, R. Nakajima Employee of: AbbVie GK, K. Morita Employee of: AbbVie GK, J. Kimura Employee of: AbbVie GK, T. Takeuchi Grant/research support from: AbbVie, Astellas, Bristol-Myers, Chugai, Daiichi Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer, Sanofi, Santen, Takeda, Teijin, Consultant for: AstraZeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, Asahi Kasei Medical, Speakers bureau: AbbVie, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, Takeda

Background With the introduction of biologic disease-modifying antirheumatic drugs (DMARDs) and the increase in the approved maximum dose of methotrexate in our country, the treatment of rheumatoid arthritis (RA) has advanced dramatically in the past 2 decades. Consequently, many patients were able to achieve clinical remission and low radiographic progression rates1–3. In view of these dramatic changes in RA treatment, we investigated whether the Japanese version of the Health Assessment Questionnaire (J-HAQ) improved chronologically due to improved treatment over time. Objectives To investigate chronological changes in achieving J-HAQ remission and the factors related to J-HAQ remission in Japanese patients with an early stage of RA. Methods RA patients who enrolled in the IORRA cohort for the first time between 2000–2002 (Term 1), 2005–2007 (Term 2), and 2010–2012 (Term 3) and were within 2 years of disease onset were examined. For each patient in Term 3, one patient was extracted from Term 1 and Term 2 by matching the sex, age, and J-HAQ score. Among them, patients with J-HAQ >0.5 at study entry (baseline) were selected; the time to achieve J-HAQ remission (J-HAQ ≦0.5) and the J-HAQ remission rate at 3 years were analyzed. Multivariate analysis was performed to assess factors related to achieving J-HAQ remission. Results In each term, 348 RA patients were extracted. At baseline, the average J-HAQ of all 1,044 patients was 0.52. Baseline characteristics of 408 patients with baseline J-HAQ >0.5 were as follows: female, 89.0%; mean age, 56.3 years; anti-cyclic citrullinated peptide (anti-CCP) antibody positivity, 78.0%; mean Disease Activity Score with 28-joint count (DAS28), 4.37; and mean J-HAQ, 1.11. The mean time from baseline to achieving J-HAQ remission became significantly shorter chronologically (Term 1: 2.2 years; Term 2: 1.8 years; Term 3: 1.7 years; p Conclusions Along with the improvement in RA treatment, patients were able to achieve J-HAQ remission more frequently and more quickly. References Mod Rheumatol. 2007;17:283–9.2) J Rheumatol. 2015; 42:2279–87.3) Rheumatology. 2016;55:1053–1065. Disclosure of Interest M. Ochiai: None declared, E. Tanaka Consultant for: Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Pfizer, Takeda Pharmaceutical, and Ayumi Pharmaceutical., Speakers bureau: Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Pfizer, Takeda Pharmaceutical, and Ayumi Pharmaceutical., E. Inoue: None declared, R. Yamaguchi: None declared, Y. Shimizu: None declared, N. Sugimoto Speakers bureau: Takeda Pharmaceutical and Bristol Myers Squibb., K. Ikari Grant/research support from: Astellas, UCB, Bristol-Meyers, Pfizer, Eisai, Tanabe-Mitsubishi, Chugai, AbbVie, Janssen Pharmaceutical, Otsuka, Kaken, Asahi-Kasei, Hisamitsu and Takeda., Speakers bureau: Astellas, UCB, Bristol-Meyers, Pfizer, Eisai, Tanabe-Mitsubishi, Chugai, AbbVie, Janssen Pharmaceutical, Otsuka, Kaken, Asahi-Kasei, Hisamitsu and Takeda., A. Nakajima Consultant for: Bristol-Meyers, Mitsubishi Tanabe Pharma, Nippon Kayaku Co. Ltd., Novartis Pharma, Pfizer, Siemens Healthcare Diagnostics K.K. and Takeda Pharmaceutical Company, Speakers bureau: Bristol-Meyers, Mitsubishi Tanabe Pharma, Nippon Kayaku Co. Ltd., Novartis Pharma, Pfizer, Siemens Healthcare Diagnostics K.K. and Takeda Pharmaceutical Company, A. Taniguchi Grant/research support from: AbbVie, Eisai, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Pfizer., Speakers bureau: AbbVie, Eisai, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Pfizer., H. Yamanaka Grant/research support from: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers., Consultant for: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers., Speakers bureau: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers.

Background Cyclic phosphatidic acid (cPA) is one of bioactive lipid, has been implicated as a mediator of various biological effects including inhibitory effects of proliferation, invasion and metastasis of cancer cells. cPA is naturally occurring mediator even exists in human serum. 2-carba-cPA (2ccPA) is structurally modified formula of cPA and has shown improved bioactivity. We have previously confirmed that 2ccPA stimulated HAS-2 production on human osteoarthritic chondrocytes and synovial fibroblasts (SFs) in vitro. Furthermore, intra-articular administration of 2ccPA has shown its suppressing effect of pain, swelling, and articular cartilage destruction in rabbit experimental osteoarthritis (OA). We have shown that 2ccPA might had direct inhibitory effect of cartilage degrading enzymes on rheumatoid synovial fibroblasts (SFs) in vitro. Inflammatory arthritis such as rheumatoid arthritis (RA) and early stage of OA involves synovial inflammation and subsequent production of cartilage degrading enzymes also from chondrocytes. 2ccPA may be possible another therapeutic option for degenerative arthritis. Objectives The aim of this study was to evaluate the direct effects of 2ccPA on cartilage matrix degrading enzymes using SFs and articular chondrocytes under influence of inflammatory cytokines. Methods In vitro studies were performed using SFs and chondrocytes obtained from arthritis patients (RA and OA) at joint replacement surgery. First, 2ccPA 0–25 μM was added to cell cultures and effects of 2ccPA on ADAMTS-4, -5, MMP-3, 9, -13 expression was assessed by real time PCR using specific primers to corresponding genes. Beta-actin was used as endogenous expression control for PCR. As we confirmed that 2ccPA had dose-dependent inhibitory effects on expression of above enzymes, the second experiment was performed. SFs or chondrocytes were pre-cultured with IL-1β (1 ng/ml) and/or TNF-α (10 ng/ml) for 24 hours, then added 10 μM 2ccPA to study attenuated effect of 2ccPA on synthesis of above cartilage matrix degrading enzymes. Newly synthesized MMP-3, -13 from SFs or chondrocytes in cultured media after 24 hours of 2ccPA addition were measured by sandwich ELISA. Results 2ccPA itself repressed cartilage degrading enzymes, ADAMTS-4, ADAMTS-5, MMP-3, MMP-9 and MMP-13 expression in both SFs and chondrocytes was all repressed by low dose of 2ccPA. Even after cells had been stimulated by cytokines, 10 μM 2ccPA repressed expression of cartilage degenerating enzymes in SFs or chondrocytes. Expression of MMP-13 were repressed more in chondrocytes by 2ccPA. ELISA results also confirmed the inhibitory effect of 2ccPA on MMP-13 production in RA SFs (n=5) by 52% or in RA chondrocytes (n=3) by 43%. In OA, MMP-13 production was reduced by 31% in OA SFs (n=6) and 34% in OA chondrocytes (n=4). However, not significant reduction of MMP-3 in both SFs or chondrocytes. MMP-9 expression by ELISA was under the detectable limit. Conclusions The in vitro results confirmed that 2ccPA had suppressing effect of cartilage degrading enzymes expression on SFs and chondrocytes, supports the hypothesis that 2ccPA might have played direct role to suppress inflammation and also protect articular cartilage in arthritic condition. Disclosure of Interest I. Masuda Grant/research support from: SANSHO, K. Okada: None declared, H. Yamanaka: None declared, S. Momohara: None declared

Background Patients with rheumatoid arthritis (RA) have a higher risk of comorbidities such as infections1, cardiovascular diseases2, and fractures3 than general population. To understand the risk of these comorbidities in RA more precisely, it is needed to compare the risk between RA and other chronic diseases. A Dutch study4 showed that patients with RA had comparable risk of cardiovascular diseases to diabetes mellitus (DM). Because of possible racial or ethnic difference of risks of comorbidities, it is warranted to compare the risk between RA and DM in Asian countries. Objectives To compare risk of hospitalized infections (HIs), cardiovascular diseases and stroke (CVDs), and fractures between RA and DM cases using Japanese health insurance database. Methods This retrospective longitudinal population-based study was conducted using claims data provided by the Japan Medical Data Center Co., Ltd. We defined individuals as RA cases if they met all of the following: 1) had at least 6 months of continuous enrollment in the health insurance database; 2) had at least one RA diagnostic code and at least one prescription of disease-modifying antirheumatic drugs between January 2005 and December 2013; and 3) were ≥50 years old (RA group, n=3,607). Among individuals who met above criteria 1) and had at least DM diagnostic code and at least one prescription of drugs for DM, but did not meet 2), we selected age- (±5 years), gender-, calendar year of the observation start, and observation length-matched DM cases at 1:3 ratio (RA: DM) (DM group, n=10,821). Each comorbidity was defined as follows: HIs, at least one ICD10 code and one prescription of drugs for infections with hospitalization; CVDs, at least one ICD10 code and one prescription of drugs or medical procedures for CVDs with hospitalization; fractures, at least one ICD10 code for fractures. We calculated incidence rates (IR) with 95% confidence interval (CI) of each comorbidity in the two groups up to 10 years and adjusted odds ratio (OR) of RA compared with DM for each comorbidity using generalized estimating equation. Results The median age was 58, and 75.1% were female in the both groups. The IR [95% CI] of HIs, CVDs, and fractures was 2.8 [2.5–3.2]/100 patient years (PY), 9.2 [7.4–11.4]/1,000 PY, 16.7 [14.2–19.6]/1,000 PY in the RA group, 2.8 [2.6–3.0]/100PY, 26.3 [24.4–28.3]/1,000PY, 10.3 [9.1–11.6]/1,000PY in the DM group respectively. The OR [95% CI] of RA (vs. DM) for HIs, CVDs, fractures was 0.9 [0.8–1.1], 0.4 [0.3–0.6], 1.3 [1.0–1.7] after adjusting for baseline characteristics. Conclusions This study revealed that patients with RA had significantly lower risk of CVDs than and similar risk of HIs and fractures to those with DM using health insurance database for the first time in Asia. References Arthritis Rheum, 2002;46:2287–93. Ann Rheum Dis, 2012:71:1524–29. Arthritis Res Ther, 2010;12:R154. Arthritis Rheum, 2009;61:1571–9. Acknowledgements This work was supported by the research grant from the Ministry of Health, Labour, and Welfare, Japan. Disclosure of Interest R. Sakai Grant/research support from: Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., and Teijin Pharma Ltd.,Bristol-Meyers Squibb, S. Kasai: None declared, M. Tsutsumino Grant/research support from: Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., and Teijin Pharma Ltd., H. Yamanaka Grant/research support from: Chugai Pharmaceutical Co. Ltd., Astellas Pharma Inc., Bristol-Meyers Squibb, AbbVie Japan Co. Ltd., Daiichi-Sankyo, Mitsubishi-Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., UCB Japan., Consultant for: Chugai Pharmaceutical Co. Ltd., Astellas, Bristol-Meyers Squibb, AbbVie Japan Co. Ltd., Daiichi-Sankyo, Mitsubishi-Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., UCB Japan., Speakers bureau: Chugai Pharmaceutical Co. Ltd., Astellas, Bristol-Meyers Squibb, AbbVie Japan Co. Ltd., Daiichi-Sankyo, Mitsubishi-Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., UCB Japan., N. Miyasaka: None declared, M. Harigai Grant/research support from: Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., and Teijin Pharma Ltd.,Eisai

Background While the results of several observational studies suggest that light-to-moderate alcohol consumption may decrease the risk for susceptibility to or severity of rheumatoid arthritis (RA) (1–3), findings regarding the effect of alcohol consumption on RA disease activity are conflicting. Furthermore, there are few reports of longitudinal studies regarding the effect of alcohol consumption on RA disease activity. In addition, although alcohol consumption in the Japanese general population was lower than that in European countries, according to the 2011 World Health Organization9s Global Status Report on Alcohol and Health, there are few reports specifically concerning alcohol consumption in Japanese RA patients. Objectives To examine the longitudinal relationship between alcohol consumption and changes in disease activity in patients with RA using the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort database. Methods Subjects were RA patients who participated in the IORRA cohort study between October 2014 and October 2015. Patients were assigned to one of 5 groups according to alcohol-drinking status at baseline: the non-drinking group, drinking group 1 (0 g Results Data from a total of 4,695 Japanese patients with RA (female: 86.6%, mean age: 61.3 years old, mean disease duration: 15.2 years, and mean DAS28: 2.5) were analyzed. The number of patients and their characteristics (% female, mean age, mean disease duration, mean DAS28 at baseline/after 1 year) in the non-drinking group, and drinking groups 1, 2, 3, and 4 were 2,735 (92.8%, 64.0 years old, 16.1 years, 2.7/2.7); 646 (89.9%, 58.7 years old, 14.8 years, 2.4/2.5), 497 (82.5%, 56.7 years old, 13.8 years, 2.3/2.3), 444 (71.6%, 56.4 years old, 13.0 years, 2.3/2.3), and 373 (58.2%, 57.5 years old, 13.7 years, 2.2/2.3), respectively. Baseline DAS28 in drinking groups 2 (p=0.02), 3 (p Conclusions Although moderate-to-heavy alcohol consumption was associated with lower baseline DAS28 in patients, alcohol drinking status was not associated with change in disease activity, as measured by DAS28, at 1-year follow-up. References Di Giuseppe D. BMJ, 2012 Jul 10;345:e4230. Kallberg H. Ann Rheum Dis, 2009;68:222–7. Maxwell JR. Rheumatology (Oxford), 2010;49:2140–6. Disclosure of Interest Y. Shimizu: None declared, E. Tanaka Consultant for: Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Pfizer, Takeda Pharmaceutical, and Ayumi Pharmaceutical., E. Inoue: None declared, M. Ochiai: None declared, R. Yamaguchi: None declared, N. Sugimoto Speakers bureau: Takeda Pharmaceutical and Bristol Myers Squibb., A. Nakajima Consultant for: Bristol-Meyers, Mitsubishi Tanabe Pharma, Nippon Kayaku Co. Ltd., Novartis Pharma, Pfizer, Siemens Healthcare Diagnostics K.K. and Takeda Pharmaceutical Company., Speakers bureau: Bristol-Meyers, Mitsubishi Tanabe Pharma, Nippon Kayaku Co. Ltd., Novartis Pharma, Pfizer, Siemens Healthcare Diagnostics K.K. and Takeda Pharmaceutical Company., K. Ikari Grant/research support from: Astellas, UCB, Bristol-Meyers, Pfizer, Eisai, Tanabe-Mitsubishi, Chugai, AbbVie, Janssen Pharmaceutical, Otsuka, Kaken, Asahi-Kasei, Hisamitsu and Takeda., Speakers bureau: Astellas, UCB, Bristol-Meyers, Pfizer, Eisai, Tanabe-Mitsubishi, Chugai, AbbVie, Janssen Pharmaceutical, Otsuka, Kaken, Asahi-Kasei, Hisamitsu and Takeda., A. Taniguchi Grant/research support from: AbbVie, Eisai, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Pfizer., Speakers bureau: AbbVie, Eisai, Takeda, Tanabe-Mitsubishi, Teijin Pharma, Pfizer., H. Yamanaka Grant/research support from: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi- Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers., Consultant for: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers., Speakers bureau: MSD, Ayumi, AbbVie, Eisai, Ono, Astellas, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, Nippon Shinyaku, Pfizer. UCB. Nippon Kayaku, YL biologics, Bayer and Bristol-Meyers.

Background Denosumab is a fully human monoclonal antibody (IgG2 subclass) that inhibits bone resorption by inhibiting RANKL, a key mediator of osteoclast formation, function, and survival. Objectives To evaluate the effect of denosumab 60 mg every 6 months (Q6M) or every 3 months (Q3M) on the progression of joint damage in Japanese patients with RA on csDMARD background treatment. Methods DESIRABLE is a 12-month randomized, double-blind, placebo-controlled, parallel-group study in patients with RA receiving csDMARD treatment. Subjects fulfilling the 1987 ACR criteria or 2010 ACR-EULAR criteria were randomized (1:1:1) to denosumab 60 mg Q6M, denosumab 60 mg Q3M, or placebo. The primary endpoint is the change from baseline to 12 months in the van der Heijde modified total Sharp score (mTSS). Radiographs of hands and feet at baseline, 6 months and 12 months were scored with blinded time order by 2 readers independently. Average score of the 2 readers is used for the analysis. Comparisons of each denosumab group with placebo for the change from baseline were performed using van Elteren stratified rank test adjusting for baseline glucocorticoid use. Missing scores were imputed using linear extrapolation/interpolation. Results Among 679 patients randomized, 667 (placebo, n=223; Q6M, n=222; Q3M, n=222) received at least one dose of study drug, and 60 (placebo n=15; Q6M, n=23; Q3M, n=22) were discontinued during the study. Demographic and baseline characteristics were similar across the groups (Table 1). Mean change from baseline in mTSS and erosion score (ES) at 12 months was significantly lower with both denosumab 60 mg Q6M and Q3M compared with placebo, with no obvious evidence of an effect on joint space narrowing (JSN) score for denosumab. (Table 2). Consistently, the percent of nonprogressors (ie, mTSS change ≤0.5) at 12 months was significantly greater with denosumab 60 mg Q6M (75.6%, p=0.010) and Q3M (78.1%, p=0.001) compared with placebo (64.2%). Incidence of adverse events (AEs), serious AEs, and AEs leading to discontinuation of study drug were similar across treatment groups. No events of osteonecrosis of the jaw or atypical femoral fracture were observed. Conclusions Denosumab inhibited the progression of joint destruction significantly more than placebo and was generally well tolerated in Japanese patients with RA on csDMARDs. Denosumab has potential to be a new therapeutic option to inhibit structural progression for patients with RA. Disclosure of Interest T. Takeuchi Grant/research support from: Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, AYUMI Pharmaceutical, Takeda, Teijin Pharma, AbbVie, Asahi Kasei Pharma, and Taisho Toyama, Consultant for: AstraZeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, Asahi Kasei Pharma, AbbVie, Daiichi Sankyo, Bristol-Myers Squibb, Nipponkayaku, Janssen, Merck Serono, Takeda, Astellas, and Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, Takeda, Astellas, Daiichi Sankyo, Celtrion, and Nipponkayaku, Y. Tanaka Grant/research support from: BMS, MSD, Chugai, Mitsubishi Tanabe, Astellas, AbbVie, and Daiichi Sankyo, Speakers bureau: UCB Pharma, Mitsubishi Tanabe, Abbott, AbbVie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, and Asahi Kasei Pharma, S. Soen Grant/research support from: Eisai, Daiichi Sankyo, and Takeda, Speakers bureau: Asahi Kasei Pharma, Astellas, Eisai, MSD, Ono Pharmaceutical, Daiichi Sankyo, Takeda, Chugai, Teijin Pharma, and Pfizer, H. Yamanaka Grant/research support from: UCB Pharma, AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, Consultant for: UCB Pharma, AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, T. Yoneda Consultant for: Daiichi Sankyo, S. Tanaka Consultant for: Amgen inc, Amgen Astellas, KYOCERA Medical, Daiichi Sankyo, Teijin Pharma, Asahi Kasei Pharma, Ono Pharmaceutical, Eli Lilly, and Pfizer, T. Nitta Employee of: Daiichi Sankyo, N. Okubo Shareholder of: Daiichi Sankyo, Employee of: Daiichi Sankyo, H. K. Genant Consultant for: Daiichi Sankyo, Pfizer, Amgen, BioClinica, Eli-Lilly, Janssen, Servier, Novartis, Takeda, Merck, Biomarin, Clemencia, Agnovos, and Regeneron, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB Pharma, Employee of: Imaging Rheumatology bv

Background and aims Autoantibodies to M-type phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (MN). It has also been suggested that anti-PLA2R antibody is associated with disease activity and prognosis but more solid evidence is needed. We aimed to establish quantitative measurement of anti-PLA2R antibodies and further investigate its clinical usefulness. Methods Using stable cell line expressing PLA2R, we developed a quantitative cell-based enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) for anti-PLA2R antibodies. The usefulness of these tests and the commercial solid phase ELISA were retrospectively studied in sera from 23 patients with biopsy-proven primary MN, and 16 patients with lupus MN. Repeated sera were also available in 9 patients with primary MN. Results Anti-PLA2R antibodies were detected in 12, 6, and 12 out of 23 patients with primary MN by the WB, the cell-based ELISA, and the commercial solid phase ELISA, respectively. Conversely, all of the samples from the lupus MN patients were negative. The levels of proteinuria were moderately correlated with titers of anti-PLA2R antibodies by the 3 methods (r=0.39 to 0.47). Anti-PLA2R antibodies were significantly associated with physicians’ decision on immunosuppressive therapy without prior knowledge of anti-PLA2R antibody positivity (p Conclusions This study showed that anti-PLA2R antibody is clinically useful as diagnostic and surrogate biomarkers in primary MN. In addition, the 3 methods are all reliable measurement methods for anti-PLA2R antibodies but demonstrated different performance.

Background and aims Programmed cell death protein 1 (PD-1/CD279) is a cell surface receptor that belongs to the extended CD28/CTLA-4 family and is expressed on T cells and pro-B cells. PD-1 plays an important role in down regulating the immune system by preventing the activation of T-cells. Soluble PD-1 (sPD-1), which is produced by the alternative splicing, can functionally block the regulatory effect of membrane-bound PD-1 on T cell activation. We aimed to retrospectively evaluate the usefulness of sPD-1 in patients with systemic lupus erythematosus (SLE). Methods We measured the levels of sPD-1 by enzyme-linked immunosorbent assay (ELISA) kit in sera of patients with SLE (n=59) and systemic sclerosis, and healthy controls, and compared them. We also analysed the association between the levels of sPD-1 and clinical information in patients with SLE. Results The levels of sPD-1 in SLE patients with SLEDAI-2K≥6 were significantly higher than those in SLE patients with SLEDAI-2K Conclusions The present study suggested that sPD-1 can serve as a new biomarker reflecting disease activity in patients with SLE.

Despite improvements in rheumatoid arthritis disease activity of in the past 10 years, the incidence of self-reported non-vertebral fractures did not decrease in our cohort of 9,987 patients. This study may indicate that osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the rheumatoid arthritis disease activity. Although rheumatoid arthritis (RA) is a risk factor for osteoporosis and fractures, few studies have described the association between disease activity and the fracture incidence in patients with RA. This study aimed to investigate changes in the non-vertebral fracture incidence between 2001 and 2010 in our Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort. The IORRA is a prospective observational cohort study of Japanese RA patients. A total of 9,987 patients with RA were enrolled in this cohort from 2000 to 2010. The clinical parameter and non-vertebral fracture occurrence data were collected biannually through self-reported questionnaires. Incidences of self-reported non-vertebral fractures were also analyzed via standardization according to gender, age, and disease activity during each 2-year period. From 2001 to 2010, the percentage of patients with 28-joint disease activity score remission increased from 7.8 to 39.7 %, prednisolone intake decreased from 51.4 to 41.3 %, and bisphosphonate intake increased from 5.0 to 23.4 %. The non-vertebral fracture incidence rates were 24.6/1,000 person-years in 2001 and 35.5/1,000 person-years in 2010, with no apparent change even after standardization. The overall non-vertebral fracture incidence was significantly higher in the autumn/winter than in the spring/summer (p = 0.02). Despite improvements in disease activity and functional disability, the non-vertebral fracture incidence exhibited no apparent change between 2001 and 2010 in our patients with RA. Osteoporosis treatment and non-vertebral fracture prevention remain important regardless of the disease control in patients with RA.

For the realization of the ITER neutral beam (NB) system, a measure to achieve the acceleration voltage of 1 MV for the vacuum insulated beam source (VIBS) has been developed. In addition, the design basis for 1 MV vacuum insulation has also been developed by integrating previous empirical scaling of the voltage holding capability for plane and coaxial electrodes and new scaling for corner region where locally-concentrated electric field is generated. The scaling clarified that a product of electric field and voltage obtained by the electric field analysis in the beam source vessel was much higher than the allowable level. Therefore, in order to improve the voltage holding capability, electrostatic shields having intermediate potential have been proposed. Consequently, it was found that the VIBS needs to be surrounded by more than three intermediate shields instead of a single gap insulation of 1 MV. Reliability of the design basis of the developed intermediated shields has been experimentally verified by improving the 1.3 m single gap insulation in the voltage holding test. As a result, the sustainable voltage has been significantly improved from 0.7 MV with the single gap to 1 MV with the shields up to the power supply limit. This result ensures the realization of the 1 MV VIBS in the ITER NB system.

The HV bushing has a function of a bulk head between insulation gas (SF6) of 0.6 MPa and vacuum, which is needed to insulate −1 MV in vacuum in ITER heating neutral beam (NB) injection system. Mechanical analyses were carried out to verify the mechanical integrity of the HV bushing composed of five-stage double-layered insulator columns with large brazed ceramic ring and fiber reinforced plastic (FRP) ring of which non-metallic material is required to satisfy a safety factor of ≥3.5. As for the FRP ring required sustaining the pressure load, seismic load and dead weight, it was confirmed that isotropic fiber cloth FRP rings having sufficient strength against shear stress should be used. The shape and fixation area of the Kovar sleeve were modified to lower the stress at the brazing area having vacuum leak tightness and pressure tightness against the air filled at 0.6 MPa. As a result, a design of the insulator for the HV bushing was established satisfying the requirement.

The realization of the ITER Neutral Beam Test Facility (NBTF) and the start the experimental phase are important tasks of the fusion roadmap, since the target requirements of injecting to the plasma a beam of Deuterium atoms with a power up to 16.5 MW, at 1MeV of energy and with a pulse length up to 3600s have never been reached together before. The ITER NBTF, called PRIMA (Padova Research on ITER Megavolt Accelerator), is hosted in Padova, Italy; it includes two experiments: MITICA, the full-scale prototype of the ITER injector and SPIDER, the full-size negative ion source. The realization promoted by the ITER organization is carried out with the contribution of the European Union, channeled through the Joint Undertaking for ITER (F4E), of the Consorzio RFX which hosts the Test Facility, the Japanese and the Indian ITER Domestic Agencies (JADA and INDA) and several European laboratories, such as IPP-Garching, KIT-Karlsruhe, CCFECulham, CEA-Cadarache. The early start of operation of PRIMA experiments is urgent because sufficient experimental time is necessary to face and solve the issues related to the achievement of the desired performance in time for the ITER operation, requiring NBI since the beginning. Substantial progresses have been recently achieved: the buildings construction, begun in October 2012, has been completed by the end of 2015 and the installation of some components has been started since the end of 2014. The SPIDER realization is well advanced: the installation phase is proceeding in good agreement with the general plan; it is expected to be almost completed by the end of 2016. In parallel, the commissioning of the SPIDER power supply (PS) and auxiliary plant systems is being proceeding. Tests at full power and remote control are planned, including also those addressed to reproduce the grid breakdowns and to test the relevant protections. The design of the MITICA injector components was completed in 2015their procurement is being made through a number of tenders, some of them already launched. The HV Power Supply system of the MITICA 1MV accelerator, provided by JADA, was delivered on site in December 2015. The challenging installation of these components, including the step-up transformers and the SF6 gas insulated transmission line, started soon after and will go on throughout 2016. The present phase, with the PRIMA buildings continuously filled with new components, with the installation activities progressing and with also the commissioning and testing phase starting represents a substantial step forward toward the main target. The paper will describe the main challenges the Project Team has dealt during this phase and the important feedback derived for the ITER HNB systems both from the technical and the organizational standpoints.

A high power density and a long pulse negative ion beam accelerator has been developed in QST to realize the ITER neutral beam accelerator. A main target was the H− ion beam acceleration up to 1 MeV with 200 A/m2 for 60 s. After the achievement of 1 MeV at a short pulse, the pulse length has been gradually extended by modifications of grid configurations to suppress grid heat loads due to negative ions and electrons. However, the beam energy was limited up to 0.7 MeV at 60 s operation. One issue was an unstable negative ion production for a long time due to arcing and excess temperature rise of a plasma grid for optimum negative ion production. To suppress arcing, a cathode filament shape was modified. The plasma grid was modified to have a large heat capacitance in order to suppress temperature rise for 60 s operation at high discharge power required for 1 MeV operation. Another issue is to optimize beam optics more precisely. Fine tuning of the 1st acceleration stage was carried to improve beam optics f...

Vacuum insulation of −1 MV is a common issue for the HV bushing and the accelerator for the ITER neutral beam injector (NBI). The HV bushing as an insulating feedthrough has a five-stage structure and each stage consists of double-layered insulators. To sustain −1 MV in vacuum, reduction of electric field at several triple points existing around the double-layered insulators is a critical issue. To reduce electric field simultaneously at these points, three types of stress ring have been developed. In a voltage holding test of a full-scale mockup equipped with these stress rings, 120% of rated voltage was sustained and the voltage holding capability required in ITER was verified. In the MeV accelerator, whose target is the acceleration of a H− ion beam of 1 MeV, 200 A/m2, the gap between the grid support was extended to suppress breakdowns triggered by electric field concentration at the edge and corner of the grid support. This modification improved the voltage holding capability in vacuum, and the MeV accelerator succeeded in sustaining −1 MV stably. Furthermore, it appeared that the H− ions beam was deflected and a part of the beam was intercepted at the acceleration grid. This causes high heat load on the grids and breakdowns during beam acceleration. To suppress the direct interception, a new grid was designed with proper aperture displacement based on a three dimensional beam trajectory analysis. As a result, 980 keV, 185 A/m2 H− ion beam acceleration has been demonstrated, which is close to the ITER requirement.

SummaryObjective: Development of a clinical sensor network system that automatically collects vital sign and its supplemental data, and evaluation the effect of automatic vital sensor value assignment to patients based on locations of sensors.Methods: The sensor network estimates the data-source, a target patient, from the position of a vital sign sensor obtained from a newly developed proximity sensing system. The proximity sensing system estimates the positions of the devices using a Bluetooth inquiry process. Using Bluetooth access points and the positioning system newly developed in this project, the sensor network collects vital sign and its 4W (who, where, what, and when) supplemental data from any Blue-tooth ready vital sign sensors such as Continua-ready devices. The prototype was evaluated in a pseudo clinical setting at Kyoto University Hospital using a cyclic paired comparison and statistical analysis.Results: The result of the cyclic paired analysis shows the subjects evaluated the proposed system is more effective and safer than POCS as well as paper-based operation. It halves the times for vital signs input and eliminates input errors. On the other hand, the prototype failed in its position estimation for 12.6% of all attempts, and the nurses overlooked half of the errors. A detailed investigation clears that an advanced interface to show the system’s “confidence”, i.e. the probability of estimation error, must be effective to reduce the oversights.Conclusions: This paper proposed a clinical sensor network system that relieves nurses from vital signs input tasks. The result clearly shows that the proposed system increases the efficiency and safety of the nursing process both subjectively and objectively. It is a step toward new generation of point of nursing care systems where sensors take over the tasks of data input from the nurses.