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Supplemental Digital Content is available in the text., Background: Blood pressure (BP) increase cardiovascular disease (CVD) risk. Indigenous Canadians experience slightly higher CVD compared with nonIndigenous Canadians. This study examined the role of polychlorinated biphenyls (PCBs), other organic compound concentrations (OCs), and toxic metals on blood pressure measures among Indigenous Canadians. Methods: Using data from the Environment-and-Health Study, the sample was restricted to adults with valid BP measures and detectable body burden mixtures. In total, n = 759 participants were eligible, of which, n = 447(59%) were females. Principal Component Analysis (PCA) was used to reduce the complexity of the contaminant data. Orthogonal principal component (PC) variables, and sum (∑) of contaminant compounds were used as independent predictors in modified Poisson regression models with robust variance estimation, deriving prevalence ratios (PR) for hypertension, that is, systolic BP (SBP) ≥140 ml of mercury (mmHg), or diastolic BP ≥90 mm Hg. Additionally, using multivariable generalized linear regression, sex-stratified continuous SBP measure was regressed on ∑ contaminant compounds. Results: Two PCs were extracted from the PCA analysis. PCBs and OCs positively highly loaded on the first axis (PC-1). Lead loaded positively on the second (PC-2) axis. Hypertension was consistently associated with PC-1 across models, PR = 1.08 (95% confidence intervals = 1.003 to 1.172) fully adjusted model. Examining ∑ of contaminants, the strength of association with hypertension was strongest for ∑OCs compared with ∑PCBs. The measure of effect for continuous SBP measures with ∑ dichlorodiphenyltrichloroethane(p,p'-DDT) and dichlorodiphenyldichloroethylene(p,p’-DDE) concentrations although small was similar for both females and males, β = 0.04 (95% confidence intervals = 0.005 to 0.075) among females; however, for males the estimate is imprecise after adjusting for body mass index. Conclusion: This cross-sectional analysis found that PCBs and OCs were associated with associated prevalent hypertension; and exposure to OC pesticides, particularity DDT/DDE were found to be associated with prevalent SBP measures among females and not males.

Scientifically robust selections of epidemiological studies and assessments of the dose-response of inorganic arsenic in the low-dose range must consider key issues specific to arsenic in order to reduce risk of bias. The abundance of toxicological, mechanistic, and epidemiological evidence on arsenic enables a nuanced assessment of risk of bias in epidemiological studies of low-level arsenic, as opposed to a generic evaluation based only on standard principles. Important concepts in this context include 1) arsenic metabolism and mode of action for toxicity and carcinogenicity; 2) effects of confounding factors such as diet, health status including nutritional deficiencies, use of tobacco and other substances, and body composition; 3) strengths and limitations of various metrics for assessing relevant exposures consistent with the mode of action; and 4) the potential for bias in the positive direction for the observed dose-response relationship as exposure increases in the low-dose range. As an example, evaluation of a recent dose-response modeling using eight epidemiological studies of inorganic arsenic and bladder cancer demonstrated that the pooled risk estimate was markedly affected by the single study that was ranked as having a high risk of bias, based on the above factors. The other seven studies were also affected by these factors to varying, albeit lesser, degrees that can influence the apparent dose-response in the low-dose range (i.e., drinking water concentration of 65 µg/L or dose of approximately ≤1 µg/kg-day). These issues are relevant considerations for assessing health risks of oral exposures to inorganic arsenic in the U.S. population, and setting evidence-based regulatory limits to protect human health.

Traditional physical activities have numerous physiological and psychosocial benefits for Indigenous youth around the world. Little is known about the positive health and wellness impacts of traditional physical activity experiences on Indigenous youths. The aim of this systematic review is to explore the holistic health and wellness impacts of traditional physical activities on Indigenous youth from certain North American and Oceania geographic areas. A systematic search of four electronic databases (PubMed, ERIC, Scopus and Web of Science) was conducted to identify peer-reviewed publications of qualitative research exploring the diverse health experiences of traditional physical activities for Indigenous youth in Canada, the United States of America, New Zealand and Australia. A qualitative synthesis of studies between 2006 and 2018 were included, and findings were synthesized using an integrated Indigenous-ecological model, which broadly captures health and wellness impacts under intrapersonal, interpersonal, organizational, community and policy level outcomes using medicine wheel teachings. In total, nine studies were identified via this search. Overall, the literature described numerous emotional, mental and spiritual benefits of traditional physical activity, and youth experiences were affected by familial and communal relationships, and systemic factors. Among Indigenous youth, this research shows the importance of including traditional physical activity in future programs and partnerships with community expertise.

By breaking down barriers that impacted the ability of subarctic First Nations people to harvest waterfowl, the Sharing-the-Harvest program provided a safe, nutritious, and culturally appropriate food (i.e., geese) to James Bay Cree communities while also helping to protect the environment by harvesting overabundant geese. However, the impacts extend beyond those described above. Thus, the objectives of the present paper are twofold: to document the food sharing networks of the Sharing-the-Harvest program, and to examine the benefits associated with the harvest program beyond food security and environmental sustainability issues, as revealed through semi-directed interviews. In the regional initiative, harvested geese were shared with all James Bay communities, sharing is an important part of Cree culture. Where detailed information was collected, the goose-sharing network reached 76% of the homes in one of the communities. Likewise, in the local initiative, the goose-sharing network had a 76% coverage rate of the homes in the community. Although decreasing food insecurity was an important focus of the harvest-sharing programs, there were other benefits, from an Indigenous perspective, of being on the land, as identified by the Cree harvesters through semi-directed interviews (e.g., the transmission of Indigenous knowledge, the strengthening of social networks, and the feeling of wellness while out on-the-land). Thus, by participating in the on-the-land harvest programs, the Cree gained benefits beyond those solely related to strengthening food security and contributing in part to environmental sustainability. The Sharing-the-Harvest protocol has the potential to be adapted and employed by other Indigenous (or marginalized) groups worldwide, to help improve health and wellness, while, also protecting the environment from overabundant and/or invasive species.

Diabetes mellitus is a growing public health problem affecting persons in both developed and developing nations. The prevalence of type 2 diabetes mellitus (T2DM) is reported to be several times higher among Indigenous populations compared to their non-Indigenous counterparts. Discriminant function analysis (DFA) is a potential tool that can be used to quantitatively evaluate the effectiveness of Indigenous health-and-wellness programs (e.g., on-the-land programs, T2DM interventions), by creating a type of pre-and-post-program scoring system. As the communities of the Eeyou Istchee territory, subarctic Quebec, Canada, have varying degrees of isolation, we derived a DFA tool for point-of-contact evaluations to aid in monitoring and assessment of health-and-wellness programs in rural and remote locations. We developed several DFA models to discriminate between those with and without T2DM status using age, fasting blood glucose, body mass index, waist girth, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, and total cholesterol in participants from the Eeyou Istchee. The models showed a ~97% specificity (i.e., true positives for non-T2DM) in classification. This study highlights how varying risk factor models can be used to discriminate those without T2DM with high specificity among James Bay Cree communities in Canada.

BackgroundUpadacitinib is a Janus kinase inhibitor under evaluation for the treatment of psoriatic arthritis (PsA). We evaluated upadacitinib in patients with PsA and prior inadequate response or intolerance to at least one biologic disease-modifying antirheumatic drug (DMARD).MethodsIn this 24-week randomised, placebo-controlled, double-blind, phase 3 trial, 642 patients were randomised (2:2:1:1) to once per day upadacitinib 15 mg or 30 mg, placebo followed by upadacitinib 15 mg or placebo followed by upadacitinib 30 mg at week 24. The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 12. Achievement of minimal disease activity (MDA) was assessed at week 24. Treatment-emergent adverse events are reported for all patients who received at least one dose of trial drug.ResultsAt week 12, significantly more patients receiving upadacitinib 15 mg and 30 mg versus placebo achieved ACR20 (56.9% and 63.8% vs 24.1%; pConclusionIn this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA.Clinical trial registration numberNCT03104374

Fishing is part of the traditional activities of Indigenous people in Canada. However, it is also a route of exposure to methylmercury, a known neurotoxicant, and this is a concern for those who rely on fish as part of their diet. The probable weekly intake (PWI) of methylmercury from six species of fish was calculated for Indigenous community members (N = 1406), grouped by age and sex, and compared to Canadian and international provisional reference doses to assess exposure. Mixed-effects regression models were also used to estimate the input of methylmercury into the blood, and Hazard Quotients (HQ) were used to assess potential effects. Of the species of fish in our study, walleye and lake trout contributed the most to methylmercury intake. There was a positive association between the consumption of walleye and the total blood mercury concentrations of mercury in women and men (R2A = 0.40 and 0.47, respectively), and to a lesser extent, children. Similar results were observed for the consumption of lake trout. The 95th-percentile HQ for girls (3.16) and boys (3.18) from the consumption of lake trout was relatively high, and to a lesser extent, so was the HQ for walleye and pike. The consumption of some species of fish increases the exposure to methylmercury, however, taking a balanced approach, there are health benefits associated with the consumption of fish that must be considered. To mitigate future exposure to methylmercury, we recommend follow-up blood monitoring and local-geospatial-based assessments.

Background Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers that can predict RPILD development remain unclear. Objectives To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM-ILD. Methods In total, 49 patients with PM/DM-ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti-MDA5 antibody, compared them between the RPILD (n = 23) and non-RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL-15 expression in lung tissues. The IL-15 production was also investigated using A549 and BEAS-2B cells. Results The RPILD group had significantly higher IL-15, IL-1RA, IL-6, CXCL10, VCAM-1, anti-MDA5 antibody and ferritin serum levels than the non-RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti-MDA5 antibody, IL-15, CXCL8, CCL22, IL-1RA and ferritin were the best combination to distinguish the two groups. IL-15 and CCL22 were also predictive marker for RPILD development in anti-MDA5 antibody-positive patients. Additionally, the RPILD group had significantly high IL-15 levels in BALF. The lung tissues expressed IL-15, which increased after cytokine stimulation in the A549 cells. Conclusion This study identified a combination of biomarkers predicting PM/DM-RPILD progression, and IL-15 is an important cytokine for predicting RPILD development and reflecting ILD severity.

The late Pleistocene mylodontine sloth Glossotherium wegneri (Spillmann, 1931) (Interandean ­region, Ecuador) has been assigned to Glossotherium Owen, 1839 and Oreomylodon Hoffstetter, 1949 (the latter ranked as a subgenus or genus), and synonymized with G. robustum (Owen, 1842). However, the phylogenetic and comparative analyses conducted here, which include previously undescribed remains, strongly suggest specific distinction for G. wegneri and that there is little, if any, support for generic or subgeneric distinction for Oreomylodon. Among the notable features of this species are the ­presence of an internasal element, marked expansion of the rostrum anteriorly, and dorsoventrally and the palatal region transversely, increased separation of the caniniform tooth from the anterior edge of maxilla, increased relative braincase width, relatively enlarged hypoglossal foramen, and greatly elongated zygomatic process of the squamosal. The resulting single MPT recovered a monophyletic Glossotherium, with the following phylogenetic arrangement of the species of this genus (G. robustum + ((G. wegneri + G. tropicorum Hoffstetter, 1952) + (G. phoenesis Cartelle, De Iuliis, Boscaini & Pujos, 2019 + G. tarijense Ameghino, 1902))).

High latitude communities are cultivating crops to adapt to global warming, and thereby reduce dependency on food importation. To minimize the dependency of imported soil nutrient amendments for crop production, the Indigenous subarctic community of Fort Albany First Nation generated compost using by‐products from the traditional activities of goose harvesting along with other organic waste within the community. The compost was evaluated in a single growing season pot experiment as an amendment for bush beans (Phaseolus vulgaris L.) by being mixed with the local Terric Haplosaprist edaphic soil that was P and K deficient. Twelve pots growing bush beans were amended with compost at rates ranging from 3 to 30% and with unamended controls. All eight plant metrics (height, aboveground, leaf and bean biomass, quantity of leaves and pods, and individual and summed leaf surface area) showed a significant positive relationship with increasing compost amendments (p ≤ .0025, r2 = .66–.86), suggesting soils with compost attain greater bean yields than unamended soil. A threshold of bean growth was not reached, implying that compost amendments >30% may provide even greater bean yield. However, the application of P and K with the 30% compost addition exceeds recommended rates, suggesting that nutrient availability was hindered. Notwithstanding logistical issues in scaling‐up to amend all gardens in the community, such as improving the compost quality and quantity, composting using Indigenous harvest by‐products and local organic wastes is a promising adaptive food security strategy.

OBJECTIVES In this study, we investigated whether monocyte CD64 (mCD64) expression is correlated with disease activity in patients with adult-onset Still disease (AOSD) and whether it could be used to distinguish between active and inactive disease states. METHODS We reviewed a series of 10 patients with a definite diagnosis of AOSD, recruited from January 2013 to December 2016. We used flow cytometry to quantitatively measure mCD64 expression levels in patients presenting with active and inactive disease states and statistically analyzed the corresponding changes. RESULTS The mean ± SD values of mCD64 expression levels in patients with active and inactive disease states were 77,148.3 ± 39,066.3 and 19,225.8 ± 7006.2 molecules/cell, respectively, indicating significantly higher mCD64 expression in the active state than in the inactive state (p = 0.005). Receiver operating characteristic analysis with a cutoff value of 31,796.0 molecules/cell was applied to distinguish active from inactive disease states; the sensitivity and specificity were both 100%. In these patients, only the mCD64 expression levels changed in parallel with disease activity under tocilizumab treatment; other conventional biomarkers measured showed no changes. CONCLUSIONS Monocyte CD64 expression could be used to clearly distinguish between active and inactive AOSD. Thus, mCD64 could be a promising biomarker for evaluating the disease activity of AOSD, even in patients receiving tocilizumab treatment.

Understanding climate change impacts on winter road systems in Ontario’s Far North is critical due to the high dependence on such seasonal corridors by local residences, particularly among remote First Nations communities. In recent years, a warmer climate has resulted in a shorter winter road season and an increase in unreliable road conditions, thus limiting access among remote communities. This study focused on examining the future freezing degree day (FDD) accumulations during the preconditioning period of the winter roads at five locations using the multi-model ensembles of general circulation models (GCMs) and regional climate models (RCMs), under the representative concentration pathway (RCP) scenarios. The Statistical DownScaling Model Decision Centric Version 5 (SDSM-DC) was applied to validate the baseline climate. The results from the CMIP5 showed that by mid-century, the trends of FDDs under RCP4.5 for Moosonee and Kapuskasing were projected to decrease below the lowest threshold with the mean FDDs at 376 and 363, respectively. Under RCP8.5, the mean FDDs for Lansdowne House and Red Lake were projected to be below the lowest threshold, at 356 and 305, respectively, by the end of the century. Results of the FDD threshold measure indicated that climate conditions would possibly be unfavorable during the winter road construction period by mid-century for Moosonee and Kapuskasing and for Lansdowne House and Red Lake by the end of the century. For Big Trout Lake, on the other hand, climate conditions are expected to remain favorable for the winter road construction through the end of 2100.

A network of winter roads that consists of snow-ice roads over land, muskeg, and frozen lakes and rivers has been and continues to be a critical seasonal lifeline in remote-northern First Nation (FN) communities in Ontario’s Far North. This study examines current vulnerability of the Fort Albany community to physical, social, and economic impacts associated with the changing of the viability and longevity of winter roads and its seasons, as well as the river ice regimes. Semi-directive interviews with key informants (n = 8) and structured surveys with winter road users (n = 54) were conducted to gather local knowledge about the evolution of winter roads and climatic and environmental changes in winter road conditions and seasons. Trends in the river ice breakup and flood events for the Moose River, Albany River, and Attawapiskat River were also examined. The results of this study indicate that climatic factors, particularly air temperature and snowfall, have directly affected the construction and maintenance of the James Bay Winter Road. Trend analyses of spring flooding for the three rivers exhibit statistically significant increases (p ≤ 0.01) over the past few decades; thus, flooding in nearby communities has become a more significant threat in recent years. A few short- and medium-term adaptation strategies have been initiated in response to the impacts of climate change on winter roads; however, developing long-term planning and feasible adaptation for remote-northern communities in Ontario’s Far North is necessary.

Off-gassed compounds emitted from various materials can, in some instances, present health risks. In order to assess the potential health risks, off-gassed compounds must be identified, quantified, and evaluated relative to known health-based exposure guidance levels. We present a simple screening method for doing this that combines thermogravimetric analysis with thermal desorption–gas chromatography–mass spectrometry. The masses of particular volatile compounds are estimated over the course of a short-term, acute exposure. Assumptions (or measurements) of a room size can be used to convert these mass estimates to estimated concentrations, which can then be compared with readily available health-based exposure thresholds.

While policies to decrease lead in the environment have been implemented to reduce human exposure to various lead sources, the use of lead ammunition to harvest wild game may continue to contribute significantly to human blood lead levels (BLLs). As part of a multi-community environment-and-health study, BLLs representing all age groups were evaluated in the nine Cree Nations located in the James and Hudson Bay regions of Quebec, Canada. Personal, market food, traditional food and 24-h recall questionnaires were administered. Predictor variables were assessed for various exposure sources, including diet and hunting practices. Elevated BLLs were observed in association with increased hunting status, use of firearms and leaded ammunition, and consumption of traditional foods. Significant differences were observed between all communities, age groups and sexes. Recommendations include educational campaigns that promote switching to non-lead ammunition and, if lead ammunition continues to be used, careful removal from tissues of pellets, bullet fragments and ammunition paths.

This study aimed to investigate the frequency of hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) and to verify the guidelines relating to HBV reactivation in Japan.We retrospectively investigated 1351 RA patients who were treated with antirheumatic drugs at our hospital.Fifty patients (3.7%; 50/1351) were determined to be HBV carriers and 360 patients (26.7%; 360/1351) had resolved infections. HBV reactivation occurred in six cases (1.7%: 6/360) with resolved infections, of whom, two cases (0.6%; 2/360) developed de novo HBV infections. Eleven of the patients who were HBV carriers received a nucleoside analogue (NA) prophylactically. In all of the cases, the HBV-DNA levels became undetectable and the patients' liver function normalized. Sixteen patients, who had lower titers of the HBV surface antigen and undetectable HBV-DNA levels, did not show HBV reactivation in the absence of NA therapy.The results from this study suggest that HBV reactivation might not be so frequent among RA patients, and that reliable indicators for prescribing a NA should be clarified for RA patients.

Background:Upadacitinib (UPA) has shown efficacy and safety in patients (pts) with active PsA in the Phase 3 SELECT-PsA 1 and SELECT-PsA 2 clinical trials.1,2 Historically efficacy has been lower with second- and third-line therapy compared with first-line anti-TNF therapy in PsA;3,4 however, clinical trial data that describe efficacy in pts who have had an inadequate response (IR) to multiple biologic DMARDs (bDMARDs) are limited.Objectives:This analysis assessed the effects of prior bDMARD failure on UPA efficacy in the SELECT-PsA 2 trial.Methods:The SELECT-PsA 2 study enrolled pts with prior IR or intolerance to ≥1 bDMARD (N=642). Pts were randomized to placebo (PBO), UPA 15 mg once daily (QD, UPA15), or UPA 30 mg QD (UPA30). Stable background treatment of ≤2 non-bDMARDs was permitted; background therapy was not required. Only the pts who had IR to ≥1 bDMARD were included in this analysis; pts were subgrouped based on the number of bDMARDs failed prior to enrollment (1, 2, or ≥3). This analysis includes assessment of proportion of pts achieving ACR20/50/70, and change in HAQ-DI, FACIT-Fatigue, and SF-36 Physical Component Summary at Wk 12; static Investigator Global Assessment of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline, PASI75, and change in Self-Assessment of Psoriasis Symptoms at Wk 16; and proportion of pts achieving minimal disease activity (MDA) at Wk 24. Non-responder imputation was used for binary endpoints. Mixed-effects model for repeated measures was used for continuous endpoints. Point estimates and 95% confidence intervals (CIs) of the PBO subtracted treatment effect were calculated.Results:641 pts were randomized and received study drug; 92% were bDMARD-IR: 391 (61%) of pts failed 1 bDMARD, 116 (18%) failed 2 bDMARDs, and 83 (13%) failed ≥3 bDMARDs. In the overall study population, UPA15 and UPA30 demonstrated superiority vs placebo for all endpoints evaluated. In this post hoc analysis, the PBO subtracted treatment effect demonstrates generally consistent efficacy as compared to the overall study population for UPA15 and UPA30 across efficacy endpoints in the subgroups of pts with IR to 1, 2, or ≥3 prior bDMARDs (Figure 1). Due to limited sample sizes for pts with IR to >1 bDMARD and the pt subsets analyzed for psoriasis-related endpoints, results should be interpreted with caution.Conclusion:Upadacitinib demonstrated consistent efficacy in treating clinical manifestations of PsA including musculoskeletal symptoms, psoriasis, physical function, fatigue, and quality of life in pts with IR to 1 or multiple prior bDMARDs. In addition, comprehensive disease control as measured by MDA, was generally consistently achieved with upadacitinib regardless of number of prior bDMARDs tried.References:[1]McInnes IB, et al. Ann Rheum Dis, 2020; 79:12.[2]Genovese MC, et al. Ann Rheum Dis, 2020; 79:139.[3]Costa L, et al. Drugs R D. 2017;17:509-522.[4]Reddy SM, et al. 2016;35:2955-2966.Acknowledgements:AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea, PhD of AbbVie Inc.Disclosure of Interests:Philip J Mease Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers, Celgene, Galapagos, Genentech, Gilead, GlaxosmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB., Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers, Celgene, Galapagos, Genentech, Gilead, GlaxosmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB., Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers, Celgene, Galapagos, Genentech, Gilead, GlaxosmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB., Apinya Lertratanakul Shareholder of: AbbVie, Employee of: AbbVie, Bruce Strober Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Consultant of: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Boehringer Ingelheim, Bristol-Myers-Squibb, Cara, Celgene, Dermavant, Dermira, Janssen, Leo, Eli Lilly, Meiji Seika Pharma, Novartis, Pfizer, GlaxoSmithKline, UCB Pharma, Sun Pharma, Ortho Dermatologics, Regeneron, Sanofi-Genzyme, Shigeyoshi Tsuji Speakers bureau: AbbVie Inc., Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB, Consultant of: AbbVie Inc., Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB, Pascal Richette Speakers bureau: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Consultant of: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Charles Lovan Shareholder of: AbbVie, Employee of: AbbVie, Dai Feng Shareholder of: AbbVie, Employee of: AbbVie, Jaclyn Anderson Shareholder of: AbbVie, Employee of: AbbVie, Filip van den Bosch Speakers bureau: AbbVie Inc., Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB, Consultant of: AbbVie Inc., Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB.

Introduction L’efficacite et la tolerance d’upadacitinib (UPA) ont ete demontrees chez des patients (pts) ayant un RP actif dans les etudes de phase 3 SELECT-PsA1 et SELECT-PsA2 [1] , [2] . Historiquement, l’efficacite des anti-TNF en 2eet 3e lignes etait inferieure a celle de la 1ere ligne dans le RP [3] , [4] . Toutefois, les donnees des essais cliniques chez les pts ayant eu une reponse inadequate (IR) a plusieurs bDMARDs sont limitees. Cette analyse a evalue l’impact d’un echec a un bDMARD anterieur sur l’efficacite d’UPA dans l’etude SELECT-PsA2. Patients et methodes SELECT-PsA2 a inclus des pts ayant une IR ou une intolerance a ≥ 1 bDMARD (n= 642). Les pts ont ete randomises pour recevoir un PBO, UPA15 mg 1x/j ou UPA 30 mg 1x/j. Un ttt de fond a dose stable avec ≤ 2 non-bDMARDs etait autorise, mais pas obligatoire. Seuls les pts ayant eu une IR a ≥1 bDMARD ont ete inclus dans cette analyse. Les pts etaient repartis en sous-gpes en fonction du nbre de bDMARDs anterieurs a BL (1, 2 ou ≥ 3). Cette analyse inclut les repondeurs ACR20/50/70 ainsi que la variation du HAQ-DI, du FACIT-F et du SF-36 PCS a S12 ; l’evaluation globale par l’investigateur du pso (sIGA) de 0/1 avec une amelioration ≥2 pts par rapport a BL, le PASI75 et la variation du score d’auto-evaluation des symptomes du pso a S16 ; et la proportion de pts en MDA a S24. L’imputation des non-repondeurs a ete utilisee pour les variables binaires ; un modele a effets mixtes pour mesures multiples pour les variables continues. Les estimations ponctuelles et les IC a 95 % ont ete calcules pour l’effet du traitement diminue de la valeur du PBO (delta vs. PBO) Resultats 641 pts ont ete randomises et ont recu le traitement ; 92 % etaient bDMARD-IR : 391 (61 %) des pts etaient en echec a 1 bDMARD, 116 (18 %) en echec a 2 bDMARDs et 83 (13 %) en echec a ≥ 3 bDMARDs. Dans cette etude, UPA15 et UPA30 ont demontre une superiorite vs. PBO pour tous les criteres evalues. Dans cette analyse post-hoc, delta vs. PBO demontre une efficacite coherente avec celle obtenue dans la population generale de l’etude pour UPA15 et UPA30 sur les differents criteres d’evaluation de l’efficacite dans les sous-groupes de pts ayant eu une IR a 1, 2 ou ≥ 3 bDMARDs anterieurs ( Fig. 1 ). Compte tenu de la taille limitee des echantillons de pts en IR a >1 bDMARD et des sous-groupes de pts analyses pour les criteres lies au psoriasis, les resultats doivent etre interpretes avec prudence. Conclusion UPA a demontre une efficacite similaire dans le ttt des manifestations cliniques du RP, y compris les symptomes musculosquelettiques, le psoriasis, la fonction physique, la fatigue et la qualite de vie chez les pts en IR a 1 ou plusieurs bDMARDs anterieurs. De plus, un controle de la maladie mesure par la MDA, generalement similaire a ete obtenu avec UPA, quel que soit le nombre de bDMARDs anterieurs.

Background Early onset hypertension among youth has important cardiovascular health implications later in life. Persistent organochlorine pollutants, polybrominated diphenyl ethers (PBDEs), and toxic metals have been associated with adverse cardiovascular outcomes. Objectives This study examined body burdens of environmental contaminants and blood pressure measurements (BP) among adolescents. Methods We used data collected from the Multi-Community Environment-and-Health Study. First Nation adolescents with valid contaminant and BP measures were eligible. Principal Component Analysis (PCA) produced orthogonal principal component (PC) axes that were subsequently used as independent predictors in modified Poisson regression models, with robust variance estimation. Prevalence ratios (PR) with corresponding 95% confidence intervals (95% CI) were derived for elevated blood pressure (EBP), which was defined as systolic (SBP≥120 mm Hg or diastolic DBP)≥80 mm Hg according to new clinical practice guidelines for BP screening among adolescents between 13 and 19 years of age. Bayesian Kernel Machine Regression (BKMR) further examined individual contaminant contributions on continuous BP measures. Results In total there were (n=148; 47 % females) First Nation adolescents. Prevalence of EBP, was 29%. Four PCs were extracted from the PCA analysis. The first axis (PC-1) explained 45% of the total variance, showing positive, primarily high loadings from polychlorinated biphenyl congeners (PCB). PBDEs loaded highly on PC-2, explaining 18% of the variation. Toxic metals (i.e., lead and mercury), and cadmium highly and positively loaded on PC-3 and PC-4, accounting for 11% and 10% of the variation, respectively. EBP was significantly associated with increasing PC-2 (i.e., PBDEs) across all adjusted models, fully adjusted model (PR=1.21; 95% 1.05, 1.40). Results from BKMR bolster the findings from the PCA and regression models. Conclusion In this cross-sectional analysis, exposure to PBDE, specifically, PBDE-47 may adversely affect BP measures among young First Nation adolescents in Canada.

Addressing food security with local and sustainable food production is a key requirement for supporting a globally sustainable agricultural system. Food insecurity is prevalent in Indigenous commun...

Background: this article constitutes a report on the comprehensive Nituuchischaayihtitaau Aschii multi-community environment-and-health study conducted among the Cree peoples (Eeyouch) of northern Quebec, Canada. Objectives: to interpret observed concentrations of a suite of chemical elements in a multi-media biological monitoring study in terms of sources and predictors. Methods: the concentrations of 5 essential and 6 toxic chemical elements were measured in whole blood, and/or in urine or hair by ICP-MS. Concentrations of essential elements are compared to those considered normal (i.e., required for good health) and, when toxic, deemed acceptable at specified concentrations in public health guidelines. Their dependence on age, sex, the specific community lived-in and diet were explored employing multivariate analysis of variance (MANOVA) involving new variables generated by principle component analysis (PCA) and correspondence analysis (CA). Results: the 5 most prominent PCA axes explained 67.7% of the variation, compared to 93.0% by 6 main CA factors. Concentrations of the essential elements in whole blood (WB) and iodine(I) and arsenic (As) in urine were comparable to those reported in the recent Canadian Health Measures survey and are assigned to dietary sources. By contrast, WB cadmium (Cd) was elevated even when smoking was considered. Mercury (Hg) concentrations in WB and hair were also higher in adults, although comparable to those observed for other indigenous populations living at northern latitudes. Fish consumption was identified as the prominent source. Of the 5 coastal communities, all but one had lower Hg exposures than the four inland communities, presumably reflecting the type of fish consumed. Use of firearms and smoking were correlated with WB-lead (Pb). The concentrations of both Hg and Pb increased with age and were higher in men, while WB-Cd and smoking prevalence were higher in women when considering all communities. Hg and Pb were low in children and women of reproductive age, with few exceedances of health guidelines. Although individuals with T2D had somewhat lower WB-Cd, there is some indication that Cd may potentiate renal dysfunction in this subgroup. Plots of selected CA axes grouped those elements expected to be in a normal diet and distinguished them from those with well-known unique sources (especially Hg and As in hair; and Hg, Pb and Cd in WB). Conclusions: the use of multiple biological media in conjunction with the complementary PCA and CA approaches for constructing composite variables allowed a more detailed understanding of both the sources of the essential and toxic elements in body fluids and the dependencies of their observed concentrations on age, sex, community and diet.

Objectives: To assess the incidence of reactive lymph node hyperplasia (RLH) and the diagnostic characteristics that can help differentiate it from lymphoproliferative disorders (LPD) in patients w...

Background The antimalarial drug hydroxychloroquine (HCQ) is used worldwide to control the disease activity of systemic lupus erythematosus (SLE). In Japan, HCQ was not approved until September 2015 due to the problem of retinopathy induced by chloroquine. There is insufficient evidence of the effects of HCQ or adverse events linked to HCQ treatment. Objectives Here, we evaluated adverse events and the relapse risk of SLE during HCQ treatment. Methods We retrospectively analyzed the data of 109 patients diagnosed with SLE and treated with HCQ for ≥12 months at Nagasaki University Hospital and community hospitals. The demographic data included the patient‘s age at the onset of SLE, gender, the disease duration of SLE (the time from the diagnosis of SLE until the renal biopsy), comorbidities of Sjogren syndrome (SS)/anti-phospholipid syndrome (APS), and the treatment for induction. We identified the risk of adverse events and relapse at 12 months after the introduction of HCQ. Decision tree models predicting relapse were built with the Classification and Regression Trees (CART) algorithm. The data of the length of time between a patient‘s HCQ induction to the first observation of relapse was analyzed by the Kaplan-Meier method with a log-rank test. Results Most of the patients were female (88.1%). The median age at the introduction of HCQ was 40.0 years (interquartile range [IQR] 30.5–50.0 years), and the SLE disease duration was 95 months (IQR 38.0–184.5 months). The mean observation period after HCQ introduction was 12 months. The comorbidity rates of SS and APS were 25.7% and 20.2%, respectively. The SELENA-SLEDAI scores were significantly decreased at 3 months post-HCQ introduction. The dose of oral prednisolone was significantly decreased at 6 months post-HCQ introduction. Eighty-six patients (78.9%) were continuing HCQ at 12 months post-introduction. Adverse events occurred in 27 patients (24.8%), including skin rashes (n=11, 10.1%) and gastrointestinal symptoms (n=6, 5.5%). The sole predictive factor for adverse events was the white blood cell (WBC) count at baseline (odds ratio: 0.9997, 95%CI: 0.9994–0.9999, p=0.0285). Twelve of 86 patients (14.0%) experienced relapse that required the start of prednisolone or an immunosuppressant or an increased prednisolone dose. The multivariate analysis revealed that the C4 value at baseline was a predictive factor of relapse (odds ratio: 0.841, 95%CI: 0.718–0.984, p=0.0097). The cut-off point determined by the CART algorithm showed that C4 ≥9.3 mg/dl at baseline provides the best performance for predicting relapse. The Kaplan-Meier analysis showed that compared to C4 Conclusion A lower C4 value at HCQ introduction was a predictive factor for the relapse of SLE, and a lower WBC count was a predictive factor for adverse events. References [1] Ponticelli C, Moroni G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf. 2017 Mar;16(3):411-419. doi: 10.1080/14740338.2017.1269168. Disclosure of Interests None declared

Background Systemic lupus erythematosus (SLE) is multisystem disorder that is caused by tissue damage resulting from antibody and complement-fixing immune complex deposition. Lupus nephritis (LN) is frequent complication and one of the most serious manifestations of SLE. The expression of nephrin, as podocyte marker, is reduced in various renal diseases that develop into nephrotic syndrome1). The alteration of the structural protein in podocytes is known as a mechanism of proteinuria in LN. Objectives The signaling lymphocyte activation molecule family (the SLAM family) of type I transmembrane receptors consists of nine related members of the immunoglobulin superfamily and has been reported to mediate important regulatory signals between immune cells through their homophilic and heterophilic interactions2).The 1q23 region (Sle1b region in mouse) on human chromosome 1 including the SLAMF cluster of genes, containing SLAMF6 has been identified as a lupus susceptibility locus3).It has been shown that the expression of signaling lymphocyte activation molecule family 6 (SLAMF6) is enhanced in CD4+T cells of SLE patients and is involved in IL-17 production4). We sought to examine the functional role of SLAMF6 in lupus podocytes. Methods We evaluated the co-expression of nephrin, a podocyte marker and SLAMF6 in kidney of normal controls and LN patients, also in B6 and MRL/lpr mice at the age of 8wk and 16wk by immunofluorescence analysis. We also examined nephrin positive SLAMF6 expression in isolated podocytes from B6 and MRL/lpr kidneys. Then, we analyzed the expression of SLAMF6 in CD4+T cells of isolated kidney and spleen in B6 and MRL/lpr mice. We treated human podocytes with IgG from healthy individuals and LN patients for 24 h and 48h and analyzed the expression of SLAMF6 by real-time PCR. Results In the histopathology, the expression of SLAMF6 was increased in nephrin positive area in LN patients and MRL/lpr mice compared to each control groups. Although the expression of nephrin in MRL/lpr mice kidney at 16 wk old decreased compared to B6 mice at same age, the expression of SLAMF6 in podocytes increased in diseased MRL/lpr mice compared to B6 mice. Similarly, the expression of SLAMF6 in CD4+ T cells increased in diseased MRL/lpr mice kidney and spleen compared to B6 mice. The level of SLAMF6 mRNA elevated in human podocytes exposed to LN-derived IgG compared to healthy individuals-derived IgG. Conclusion The expression of SLAMF6 is enhanced in LN podocytes, suggesting that the possibility of cooperating with CD4+T cells contributing to its dysfunction. Further examination is needed to investigate in detail how SLAMF6 is involved in the development of LN in the future. References [1] J Am Soc Nephrol. 2003Aug;14(8):2063-71., [2] Nat Rev Immunol. 2003Oct;3(10):813-21., [3] Nat Rev Rheumatol. 2010Jun;6(6):348-57., [4] J Immunol2012; 188:1206-1212. Disclosure of Interests Takashi Igawa: None declared, Kunihiro Ichinose: None declared, Mizuna Eguchi: None declared, Momoko Okamoto: None declared, Yushiro Endo: None declared, Sousuke Tsuji: None declared, Ayuko Takatani: None declared, Toshimasa Shimizu: None declared, Remi Sumiyoshi: None declared, Tomohiro Koga: None declared, Shin-ya Kawashiri: None declared, Naoki Iwamoto: None declared, Mami Tamai: None declared, Hideki Nakamura: None declared, Tomoki Origuchi: None declared, Atsushi Kawakami Grant/research support from: Astellas Pharma, Consultant for: Astellas Pharma, Speakers bureau: Astellas Pharma

We report the case of a 40-year-old patient with systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) overlap syndrome with pulmonary arterial hypertension (overlap-PAH) that was successfully treated with a combination of immunosuppressive therapy and the soluble guanylate cyclase stimulator riociguat. She was diagnosed with mixed connective tissue disease (MCTD) two years prior to admission. She was admitted to our hospital with dyspnea on exertion and progressive skin sclerosis. She fulfilled both SLE and SSc classification criteria and was re-diagnosed with overlap syndrome. The tricuspid valve pressure gradient (TRPG) on echocardiography was 64 mmHg at admission. On right heart catheterization, mean pulmonary arterial pressure (mPAP) was 43 mmHg and pulmonary capillary wedge pressure was 15 mmHg. We diagnosed her with SSc-SLE overlap-PAH and started treatment with corticosteroids and intravenous cyclophosphamide. We also started treatment with riociguat because we speculated she had a component of SSc-PAH and that immunosuppressive therapy alone may be insufficient. We chose riociguat because of its favorable treatment effect on SSc-PAH. Two months after treatment, her TRPG improved to 33 mmHg and the skin sclerosis improved dramatically, suggesting the efficacy of multi-drug treatment and the importance of early intervention.

In an exploratory study we compared a new regimen of low-volume polyethylene glycol plus ascorbic acid (PEG-Asc) with the standard regimen for same-day bowel cleansing in constipated patients.Between January and June 2015 we studied consecutive patients with constipation (Rome III constipation criteria) scheduled for colonoscopy. The initial group received the standard regimen of PEG-Asc. The subsequent group received the new regimen. The new regimen involved ingestion of 10 mL of sodium picosulfate and 50g of magnesium citrate dissolved in 0.2 L of water followed by 0.2 L of PEG-Asc +0.2 L of water given 6 or 7 times over 3 hours. Bowel cleansing was prospectively evaluated using the Boston bowel preparation scale (BBPS). Bowel cleansing, adenoma detection rates and adverse events were reviewed using electronic medical records and endoscopic filing system.Sixty-two patients used the standard regimen and sixty used the new regimen. The basic characteristics of the two groups were similar. The mean volume of PEG-Asc and total liquid intake was less with the new regimen compared to the standard regimen (1.3 L vs. 2.0 L, P0.001; 2.6 L vs. 3.0 L, P0.001). The proportion of patients with a BBPS score ≥ 6 was significantly greater with the new than the standard regimen (93% vs. 76%, P=0.008). Nausea and/or vomiting was also significantly less frequent than with the standard regimen (5% vs. 16%, P=0.046).The new regimen of PEG-Asc gave improved same-day bowel cleansing for colonoscopy in constipated patients.

The biologic effects of inorganic arsenic predominantly involve reaction of the trivalent forms with sulfhydryl groups in critical proteins in target cells, potentially leading to various toxicologic events including cancer. This mode of action is a threshold process, requiring sufficient concentrations of trivalent arsenic to disrupt normal cellular function. Nevertheless, cancer risk assessments for inorganic arsenic have traditionally utilized various dose-response models that extrapolate risks from high doses assuming low-dose linearity without a threshold. We present here an approach for a cancer risk assessment for inorganic arsenic in drinking water that involves considerations of this threshold process. Extensive investigations in mode of action analysis, in vitro studies (>0.1 µM), and in animal studies (>2 mg/L in drinking water or 2 mg/kg of diet), collectively indicate a threshold basis for inorganic arsenic-related cancers. These studies support a threshold for the effects of arsenic in humans of 50–100 µg/L in drinking water (about 65 µg/L). We then evaluate the epidemiology of cancers of the urinary bladder, lung, and skin and non-cancer skin changes for consistency with this calculated value, focusing on studies involving low-level exposures to inorganic arsenic primarily in drinking water (approximately

Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment. Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation. Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months. Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.

Lesser snow geese (Chen caerulescens caerulescens) that breed in subarctic and arctic Canada are overabundant due to a number of anthropogenic influences, including climate change. In 2011, First Nations Cree from subarctic Ontario, Canada, participated in a regional spring harvest of overabundant snow geese—these geese have caused desertification of the environment—using only steel shotshell, as part of a food security initiative. Benefits included the procurement and sharing of an uncontaminated, nutritious source of game birds, while also helping to protect the environment for future generations. However, in 2012, the spring was unusually warm which disrupted the timing and routes of waterfowl migration. Thus, we adapted our intervention to be locally focused, allowing for quick response to changes in timing and migration routes of waterfowl due to climate change. Although global warming can present a challenge to food security, the warming climate also offers opportunities for the growth of vegetables and fruits in subarctic Canada, previously beyond their distributional range. In 2012, we initiated a pilot, agroforestry intervention in subarctic Ontario, to foster adaptive capacity and resilience. Agroforestry is a stewardship practice that combines woody perennials with crops in beneficial arrangements and can increase food security. At a site that met agricultural-soil-contamination guidelines, an agroforestry plot was established between rows of willows, while a non-treed site acted as a control. Findings indicate that the agroforestry site is more productive with respect to potato and bean yields. In the present initiative, the subarctic food system is now viewed as a whole with our main objective being the harmonization of traditional harvesting and agroforestry activities into one locally, sustainable food system by utilizing by-products of the game bird harvest to nutrient enrich the soil. Adaptation to climate change and import substitution of fruits and vegetables are the end goals.

Background:Upadacitinib (UPA) is an oral Janus kinase inhibitor currently under evaluation for the treatment of psoriatic arthritis (PsA). Previous 24-week results from the SELECT-PsA 2 study in patients with PsA and prior inadequate response to ≥1 biologic disease-modifying antirheumatic drug (bDMARD) demonstrated UPA efficacy with a safety profile consistent with that observed in rheumatoid arthritis.1Objectives:To evaluate the 56-week efficacy and safety of UPA in the SELECT-PsA 2 study.Methods:Patients were randomized to 56 weeks of blinded treatment with UPA 15 or 30 mg once daily (QD), or placebo (PBO) switched to UPA 15 or 30 mg QD at Week 24. Efficacy endpoints included proportions of patients achieving 20/50/70% improvement in American College of Rheumatology (ACR) criteria (ACR20/50/70), 75/90/100% improvement in the Psoriasis Area and Severity Index (PASI75/90/100), resolution of dactylitis and enthesitis, and minimal disease activity (MDA). Non-responder imputation was used for missing data. Treatment-emergent adverse events (TEAEs) were summarized for events occurring while on UPA and ≤30 days after last dose (for those who discontinued).Results:Of 641 patients who received ≥1 dose of study drug, 74.7% completed 56 weeks of treatment. Clinical improvements based on the proportion of patients achieving ACR20/50/70 and MDA (Figure 1), PASI75/90/100, and resolution of dactylitis and enthesitis were generally maintained through 56 weeks of UPA treatment. Week 56 results for patients who switched from PBO to UPA at Week 24 had a similar trajectory to those for patients originally randomized to UPA. Overall, improvements observed with UPA 15 mg were similar to or approached those with UPA 30 mg over 56 weeks. Dose-dependent increases were observed for exposure-adjusted event rates (EAERs) of serious infections, herpes zoster (HZ), hepatic disorders, hematologic lab-related adverse events, and creatine phosphokinase (CPK) elevations, but not for exposure-adjusted incidence rates (EAIRs) of major adverse cardiovascular events (MACE), venous thromboembolic events (VTEs), or malignancies (Table 1). Generally, rates of TEAEs were lower with UPA 15 mg versus 30 mg.Conclusion:In patients with PsA and prior inadequate response to ≥1 bDMARD, UPA efficacy was maintained over 56 weeks with no new safety signals.References:[1]Mease PJ, et al. Ann Rheum Dis 2020. Epub ahead of print.Table 1.Safety through Week 56EventUPA 15 mg QD(n=290; PY=419.4)UPA 30 mg QD(n=308; PY=423.5)EAER, events/100 PY (95% CI)Infection89.7 (81.0–99.2)113.6 (103.9–124.2) Serious infection2.6 (1.5–4.7)6.1 (4.2–9.0) Opportunistic infectiona0.7 (0.2–2.2)0.9 (0.4–2.5) HZ3.8 (2.3–6.2)8.5 (6.1–11.8) Active TB00Gastrointestinal perforation (adjudicated)00Hepatic disorder4.8 (3.1–7.4)17.7 (14.1–22.2)Anemia2.1 (1.1–4.1)5.4 (3.6–8.2)Neutropenia1.0 (0.4–2.5)3.1 (1.8–5.3)Lymphopenia0.7 (0.2–2.2)2.4 (1.3–4.4)CPK elevation5.2 (3.5–8.0)8.7 (6.3–12.1)Renal dysfunction0.5 (0.1–1.9)0.2 (0.0–1.7)EAIR, n/100 PY (95% CI)NMSCb1.2 (0.5–2.9)1.0 (0.4–2.5)Malignancy other than NMSCc1.2 (0.5–2.9)1.2 (0.5–2.9)Lymphomad0.5 (0.1–1.9)0MACE (adjudicated)0.2 (0–1.7)0.2 (0–1.7)VTE (adjudicated)0.2 (0–1.7)0.2 (0–1.7)aExcludes TB and HZ. bUPA 15 mg: 4 cases of BCC and 1 case of SCC of the skin; UPA 30 mg: 3 cases of BCC and 3 cases of SCC of the skin. cUPA 15 mg: 2 cases of prostate cancer, and single cases of malignant melanoma, ovarian cancer, and rectal cancer; UPA 30 mg: single cases of basosquamous carcinoma (considered NMSC after medical review), malignant melanoma, oropharyngeal SCC, and rectal adenocarcinoma, as well as endometrial cancer and ovarian cancer (in the same patient). dUPA 15 mg: 2 events of treatment-emergent abnormal lymphocyte morphology; abnormal lymphocytes were not reported in subsequent laboratory testingBCC, basal cell carcinoma; CI, confidence interval; NMSC, non-melanoma skin cancer; PY, patient-years; SCC, squamous cell carcinoma; TB, tuberculosisAcknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Russell Craddock, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Philip J Mease Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Apinya Lertratanakul Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Kim Papp Speakers bureau: AbbVie, Akros, Allergan, Almirall, Amgen, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Consultant of: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, GSK, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Grant/research support from: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, GSK, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Filip van den Bosch Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Shigeyoshi Tsuji Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, and UCB., Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, and UCB., Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, and UCB., Eva Dokoupilova Grant/research support from: AbbVie, Affibody AB, Eli Lilly, Galapagos, Gilead, GSK, Hexal AG, MSD, Novartis, Pfizer, R-Pharm, Sanofi-Aventis, and UCB, MAURO KEISERMAN Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Xianwei Bu Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Liang Chen Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Reva McCaskill Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Patrick Zueger Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Erin McDearmon-Blondell Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Aileen Pangan Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, and Janssen

Worry is influenced by environmental pollution and affects individual health and well-being; however, little is known about this association in Indigenous communities. Using logistic regression models, we examined self-reported responses among Cree adults to the question “Are you worried about the pollution of the environment (land, water or air) in Iiyiyiu Aschii?” to assess if increased worry was associated with proximity to industrial and hydroelectric development, whether increased worry was associated with self-reported behavioural changes of water consumption type in the community or bush, and days spent on-the-land. Proximity to multiple industrial and hydroelectric development sites was associated with increased worry about pollution. Notably, the decreased consumption of tap water in the community was significantly associated with increased worry, but time-on-the land was not. Overall, our study provides new findings concerning development in a Cree territory in northern Quebec, Canada, and the worry about pollution's association with self-reported behavioural changes.

Introduction: Heart rate variability (HRV) is a measure of cardiac autonomic regulation that examines the variation in beat-to-beat fluctuations in heart rate. While many exposure-based studies have examined the effects of single or similar groups of contaminants on HRV parameters, none have examined the association between complex environmental mixtures, including organic and elemental contaminants, and HRV. Methods: Using data collected from the Multi-Community Environment-and-Health Study in Eeyou Istchee (Quebec, Canada), we assessed HRV in two time domain measures: root mean square of successive differences (RMSSD) and standard deviation of the N-N (RR) intervals (SDNN); and in three frequency domains: high frequency (HF), low-frequency (LF), and very-low frequency (VLF) in 443 participants. We first examined mixture effects of nineteen organic and metal contaminants in blood using principal component analysis (PCA) and a multivariable general linear regression on HRV responses, adjusting for age, sex, body mass index, smoking status, and kidney disease covariates. We subsequently assessed HRV outcome response variables using Bayesian kernel machine regression (BKMR) to further examine individual contaminant contribution and overall mixture effects. Results: In the PCA, a significant positive association was observed between RMSSD and principal component (PC) axis 2, which was highly positively-loaded for nickel and moderately negatively-loaded for mercury. A negative association between SDNN and PC-1, which was highly positively-loaded for all PCBs (polychlorinated biphenyls) and organochlorines and moderately positively-loaded for mercury, was observed. Additionally, a significant and positive association was observed between PC-2 and SDNN and a significant and negative association between PC-3 (negatively loaded for cadmium) and LF. Associations with contaminants were not observed for HF or VLF. BKMR results suggest that trans-nonachlor and cis-nonachlor are primarily responsible for reductions in HRV; however, their contributions to HRV deficits was non-significant when examined as a complete mixture. Conclusions: While PCA results suggested that organochlorines, mercury, nickel, and cadmium may all play a role in altering various HRV, subsequent BKMR analysis illustrated the individual components driving these effects may be trans- and cis-nonachlor and nickel and likely not mercury or cadmium. However, other contaminants appear to temper this effect when the entire mixture of chemicals is assessed as a whole. This study expands our knowledge of the effects of environmental contaminant mixtures on HRV, which is especially important in exposed populations such as those in the Eeyou Istchee territory, whilst utilizing novel statistical methods such as PCA and BKMR to examine co-exposures concurrently.

Background Obesity incidence and prevalence is of increasing concern in First Nations communities around Canada. In addition to diet and physical activity, environmental pollutants have been suggested as a potential contributory factor to obesity associated morbidity. Owing to the exposure of Cree First Nations people to various persistent organic pollutants (POPs) and toxic metals, it is important to examine the association between obesity in these communities, and contaminant body burdens. Objective To determine whether selected morphometry measures (body mass index [BMI], waist circumference [WC] and body fat percentage) are associated with body burdens of 10 POPs and toxic metals. Methods Using data from the Nituuchischaayihtitaau Aschii Multi-community Environment-and-Health study in the eastern James Bay (Eeyou Istchee) Cree communities, this cross-sectional study examined morphometric and contaminant measures of 695 eligible participants. Sex stratified principal component analysis was conducted on blood plasma concentrations of 10 POPs and toxic metals. BMI, WC, body fat percent, and resultant contaminant components were used to create generalized linear models, and adjusted for covariates (age, total lipids, smoking, and n-3 fatty acids). Results Two principal components (PCs; PC-1 and PC-2) were extracted for both males and females. For females, PC-1 explained 73.3% and PC-2 explained 10.5%, and for males, PC-1 explained 71.6% and PC-2 explained 11.2% of the variance in contaminant burden. For both sexes, PC-1 loaded highly for polychlorinated biphenyl (PCB) congeners, organochlorine pesticides and, to a lesser extent, mercury and lead. PC-2 loaded highly for cadmium for females, and cadmium and lead for males. After adjusting for covariates, the generalized linear model showed that PC-2 was significantly and negatively associated with BMI, body fat percent, and WC in males and females. Conclusions Our cross-sectional analysis indicates a negative association between cadmium with various obesity measures in both males and females. Null associations were found between PCBs and organochlorine pesticides and morphometry.

Exposure to methylmercury is a concern for those who rely on fish as a traditional food in the Eeyou Istchee territory of James Bay, Quebec, Canada, because industrial land uses overlap with community water bodies where fish are harvested. Consequently, this study assessed if traditional practices, particularly fishing, increased the risk of exposure to methylmercury from the consumption of locally harvested fish. We designed a geographic information system (GIS) that included land use and fish methylmercury tissue concentrations to assess clustering of potential hot spots. We also used generalized linear models to assess the association of fish consumption to blood organic-mercury concentrations, and logistic regression models to assess the probability of fish exceeding the safety threshold for methylmercury tissue concentrations in areas of high intensity land use. The GIS demonstrated significant clustered hot spots around regions of hydroelectric and mining land use. Our results also revealed that adult consumption of pike, lake trout and/or walleye, and child consumption of pike or walleye were significantly associated with blood organic-mercury concentrations. Further, large fish harvested in a community with high intensity land use yielded a 77% probability that the fish exceeded the safety threshold. From a human exposure perspective, our study highlights the need for further research on children who consume fish from this region.

In northern Canada, winter roads are essential for communities. The duration of the winter road season depends on particular meteorological conditions. In this study, we investigated whether there is a temporal relationship between seasonal weather trends and the historical opening dates of the James Bay Winter Road in Ontario’s Far North. The statistical significance of the temporal trends and their magnitude are determined by the Mann-Kendall test and the Theil-Sen method. Results showed that decreasing trends in the freezing degree-days (FDDs) are statistically significant, along with the statistically significant increasing trends of monthly averages of both T min and T mean during the winter months in the western James Bay region for the 1961–2014 period. However, there were no statistically significant linkages between opening dates and FDDs detected, perhaps due to the paucity of opening dates data, although early opening dates in the last 10 years may be the result of larger FDDs. The FDDs during the months of October through December were more closely linked to opening dates than FDDs that were calculated up the opening date (including January dates), suggesting the key role of preconditioning during late fall and early winter. The lowest FDDs for the months of October to December that resulted in a viable winter road were 380 degree-days (°C). This threshold can be potentially used as a lower threshold for winter roads.

Dietary arsenic exposure and chronic health outcomes are of interest, due in part to increased awareness and data available on inorganic arsenic levels in some foods. Recent concerns regarding levels of inorganic arsenic, the primary form of arsenic of human health concern, in foods are based on extrapolation from adverse health effects observed at high levels of inorganic arsenic exposure; the potential for the occurrence of these health effects from lower levels of dietary inorganic arsenic exposure has not been established. In this review, longitudinal cohort studies are evaluated for their utility in estimating dietary inorganic arsenic exposure and quantifying statistically reliable associations with health outcomes. The primary limiting factor in longitudinal studies is incomplete data on inorganic arsenic levels in foods combined with the aggregation of consumption of foods with varying arsenic levels into a single category, resulting in exposure misclassification. Longitudinal cohort studies could provide some evidence to evaluate associations of dietary patterns related to inorganic arsenic exposure with risk of arsenic-related diseases. However, currently available data from longitudinal cohort studies limit causal analyses regarding the association between inorganic arsenic exposure and health outcomes. Any conclusions should therefore be viewed with knowledge of the analytical and methodological limitations.

Locally harvested food consumption is declining among Canadian First Nations (FN) youth. The objective of this study was to investigate, among youth in 2 FN communities, the frequency of lesser snow goose (Chen caerulescens caerulescens) consumption, its contribution to nutritional intake, and the nutritional outcomes of a harvest sharing program. A cross-sectional survey and pre–posttest design was used. Food intakes were assessed via 24-hour recall and food frequency questionnaire. At baseline (n = 84, 12.38 ± 1.07 years, 49% male) 48% of participants consumed snow goose. Consumption frequency was associated with meat and alternatives (P = .019), protein (P = .004), vitamin B12 (P = .004), iron (P = .011), and zinc (P = .006). At postprogram (n = 73, 12.34 ± .99 years, 44% male), consumption prevalence increased, significantly for girls (P = .015). Harvest sharing supports snow goose consumption, which imparts nutritional benefits.

Persistent organohalogens (POHs) and metals have been linked to alterations in menstrual cycle function and fertility in humans. The Cree First Nations people living near James Bay in Ontario and Quebec, Canada, have elevated levels of POHs, mercury and lead compared to other Canadians. The present study examines the interrelationships between selected POHs and elements on menstrual cycle function in these Cree women. Menstrual cycle characteristics were derived from structured daily diaries and endocrine measurements from daily urine samples collected during one cycle for 42 women age 19-42. We measured 31 POHs in blood plasma and 18 elements in whole blood, for 31 of the participants. POHs and elements detected in ≥ 70% of the participants were transformed by principal component (PC) analysis to reduce the contaminant exposure data to fewer, uncorrelated PCA variables. Multiple regression analysis revealed that, after adjusting for confounders, PC-3 values showed significant negative association with cycle length, after adjusting for confounders (p = 0.002). PC-3 accounted for 9.2% of the variance and shows positive loadings for cadmium, selenium, and PBDE congeners 47 and 153, and a negative loading for copper. Sensitivity analysis of the model to quantify likely effect sizes showed a range of menstrual cycle length from 25.3 to 28.3 days using the lower and upper 95% confidence limits of mean measured contaminant concentrations to predict cycle length. Our observations support the hypothesis that the menstrual cycle function of these women may be altered by exposure to POHs and elements from their environment.

A 27-year-old woman with complete placenta previa was referred at 22 weeks of gestation because of vaginal bleeding and fetal growth restriction. At 24 weeks, sudden fetal death occurred, but bleeding continued and transvaginal sonography revealed abundant periplacental blood flow in the uterine wall. To avoid cesarean section, the authors performed uterine artery embolization (UAE) be- fore vaginal delivery of the fetus. Subsequently, there was little bleeding when laminaria was inserted for cervical ripening and the fetus was delivered vaginally by using vaginal gemeprost. Total blood loss was only 149 ml. The present case suggests that UAE may be an option for patients with placenta previa who desire vaginal delivery after intrauterine fetal death (IUFD) in a second-trimester pregnancy.

Background:Osteoporosis is one of the major comorbidities in patients with psoriasis and psoriatic arthritis (PsA). It has been reported that PsA induces fragility bone structure1and high risk of osteoporosis2. However, there is no report about relationship between psoriatic arthritis and osteoporosis in Japanese patients and its mechanism has not been elucidated.Objectives:The objective of this study is to investigate influence of PsA on bone mineral density (BMD) and its mechanism including analysis between axial and peripheral PsA in Japanese patients.Methods:This study was retrospective study. We examined 58 cases of PsA and 29 cases of RA that underwent DXA tests at our facility from January 2017 to July 2019 (Table 1). The axial PsA was classified as axial SpA using the ASAS classification criteria. First, we investigated influence of PsA containing both axial (n=30,19 males, 11 females, mean age: 50.6 years) and peripheral (n=28, 19 males, 9 females, mean age: 58.0 years) subtypes on BMD measured by dual-energy X-ray absorptiometry. Second, we measured serum bone metabolism markers (P1NP: type I procollagen-N-propeptide, TRACP-5b: tartrate-resistant acid phosphatase 5b) and bone remodeling effector molecules (Dkk1: Dickkopf1, sclerostin, 25(OH)D: 25-hydroxyvitamin D) to elucidate differences in BMD between axial and peripheral PsA. Furthermore, rheumatoid arthritis (RA) (n=29, 2 males, 27 females, mean age: 66.2 years), as a reference disease, was also evaluated for comparison with axial and peripheral PsA.Osteoporosis and Osteopenia were defined as T-score ≤ -2.5 or %YAM ≤70%., -1.0< T-score >-2.5 or 80>%YAM >70% respectively.Results:58 patients with PsA indicated low T-score, Z-score and %YAM in both lumbar spine and proximal femur (Table 1). Axial PsA and peripheral PsA showed osteoporosis in 16.7% and 35.7%, and osteopenia in 20.0% and 32.1%, respectively, despite the fact that there were many middle-aged men. Comparison between axial and peripheral PsA, axial PsA showed higher BMDthan peripheral PsA. In bone remodeling makers, P1NP in both PsA were almost same, but TRACP-5b, bone resorption marker, in axial PsA was lower than that in peripheral PsA(Table 2). In bone remodeling influencer molecules, Dkk1, and sclerostin in axial PsA was slightly higher than those in peripheral PsA, whereas 25(OH)D is almost same as the both PsA. On the other hand, RA also indicated low T-score and %YAM in both lumbar spine. P1NP in RA showed slightly lower, but TRACP-5b and Homocysteine in RA higher than those in axial and peripheral PsA. Dkk1 and sclerostin in RA were slightly lower than those in both PsA.Conclusion:Peripheral PsA indicated more severe bone loss than axial PsA in our study. There were some differences in bone remodeling markers and bone remodeling effector molecules between axial and peripheral PsA, but the relationships between BMD and these parameters were not confirmed. Further studies are needed to elucidate bone loss mechanism in these PsA.References:[1]Zhu TY, et al. Osteoporosis Int. 2015; 26:261–272.[2]Kathuria R, et al. J Am Acad Dermatol. 2017;76:1045-53.Disclosure of Interests:Shigeyoshi Tsuji Grant/research support from: Eli Lilly, Speakers bureau: AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K., Tetsuya Tomita Consultant of: Eli Lilly and Company, Mari Higashiyama: None declared, Takaaki Noguchi: None declared, Toshikazu Mouri: None declared, Jun Hashimoto Speakers bureau: AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K.

Background:In IgG4-related diseases (IgG4-RD), usefulness of18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging for detecting the organ involvement of IgG4-RD have been shown and,18FDG PET/CT was more accurate and appeared to be more sensitive as compared to other imaging technics1,2. However, until now, the studies regarding about quantitative analysis of PET/CT imaging in IgG4-RD were few. To avoid unnecessary biopsy and select suitable lesion for biopsy on multi-organ involvement disease such as IgG4-RD, the information which lesion is suspected as disease-involvement lesion in a non-invasive test is important.Objectives:The purpose of this work is to evaluate the usefulness of18FDG-PE/CT imaging in management of IgG4-RD using quantitative analysis of PET/CT imaging.Methods:21 patients with IgG4-RD, in whom PET/CT was undertaken at the time of diagnosis between December 2009 and July 2018, were enrolled. We retrospectively investigated the association between histological findings in which biopsy was performed for diagnosis of IgG4-RD and findings of PET/CT.18FDG uptake was assessed in site of major organ involvement of IgG4-RD which could be differentiated from the normal uptake of background tissue with18FDG-PET/CT. For quantitative analysis, we measured the highest standardized uptake value (SUV) of the pixels within the region of interest (ROI) (SUVmax) and the average SUV within ROI (SUVmean). We also measured SUVmeanof liver as reference tissue. Then, we calculated ratio between SUVmeanof ROI and SUVmean/liver.Results:The age at diagnosis was 64.5 ± 11.9 years, serum IgG4 was 743.8 ± 584.1 mg/dl, and biopsy was performed at 24 sites (Submandibular gland 10, prostate gland 4, pancreas 2, thyroid gland 1, lung 1, retroperitoneum 1, kidney 1). Histological findings were consistent with IgG4RD (positive) at 19 sites.Although SUVmaxat the biopsy site was not correlated with the biopsy results, SUVmeanat the biopsy site were significantly higher in the biopsy-positive group (figure 1). As similar, SUVmean/liver SUVmeanwere also higher in the biopsy-positive group (2.17 vs 1.52, respectively Pmeanto consider biopsy, A receiver operating characteristics (ROC) curve was constructed. ROC curve analysis indicated SUVmean=4.074 as cut-off value which discriminate IgG4-RD related lesion.Conclusion:Our present study suggested that quantitative analysis of18FDG-PET/CT imaging is useful for selecting the biopsy site in IgG4-related disease.Figure 1.XXXXXReferences:[1]Ebbo M, Grados A, Guedj E, et al. Usefulness of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography for staging and evaluation of treatment response in IgG4-related disease: a retrospective multicenter study. Arthritis Care Res (Hoboken) 2014; 66(1): 86-96.[2]Zhang J, Chen H, Ma Y, et al. Characterizing IgG4-related disease with (1)(8)F-FDG PET/CT: a prospective cohort study. Eur J Nucl Med Mol Imaging 2014; 41(8): 1624-34.Disclosure of Interests:None declared

Background:Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) is a rare disease involving skin and skeleton, with a potentially complicated and severe course, optimal management of which seems to require a collaborative rheumatology and dermatology care. Diagnostic criteria for SAPHO remain preliminary and lack validation. There are no evidence-based treatment algorithms in SAPHO due to lack of clinical trials in this rare medical condition.Objectives:This study aimed to investigate the current practice in the diagnosis and treatment of SAPHO syndrome among the international rheumatology and dermatology communities.Methods:We conducted a survey among the members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) combining international rheumatologists and dermatologists as well as members of the Japanese and Israeli Societies of Rheumatology.Results:A total of 78 physicians participated in the survey: rheumatologists (83%, n=65), dermatologists (11.5%, n=9), and orthopedics (3.8%, n=3). SAPHO was considered a subtype of spondylarthritis by 48.7% (n=38), a subtype of psoriatic arthritis by 19.2% (n=15), a separate entity by 25.6% (n=20), and a subtype of reactive arthritis by 6.4% (n=5). Palmoplantar pustulosis was the most prevalent cutaneous manifestation (n=44, 56.4%) and anterior chest pain - the most prevalent osteoarticular manifestation (n=66, 84.6%). The majority (84.6%, n=66) voted for the update of the present diagnostic criteria by Khan 1994. Magnetic resonance imaging was considered the preferred imaging modality for the diagnosis of SAPHO by 41% (n=32). Conduction of bone biopsy for diagnosis of non-infectious osteitis was supported only by 10.3% (n=8). Patient-reported outcomes were considered the most appropriate measure for the assessment of disease activity by 47.4% (n=37). The treatment approach was overall similar among the rheumatology and dermatology communities, including non-steroidal anti-inflammatory drugs, bisphosphonates, conventional disease-modifying anti-inflammatory drugs, and biologics (Table 1).Table 1.Preferences in the treatment choice of SAPHOTreatment% of respondersNSAIDs76.6%Glucocorticoids32.5%Conventional DMARDs57.1%Bisphosphonates48.1%Anti-TNF biologic therapy75.3%Other biologic therapy20.8%Antibiotic14.3%Tonsillectomy5.1%Isotretinoin5.2%Topical therapy10.4%Intra-articular steroid injection7.8%Legend: NSAIDs – non-steroidal anti-inflammatory drugs; DMARDs – disease modifying anti-rheumatic drugsConclusion:Our study underlines the controversy on diagnosis and treatment of SAPHO syndrome among specialists in rheumatology and dermatology and emphasizes an unmet need for update and validation of diagnostic criteria and treatment approach.Acknowledgments:GRAPPA, Japanese Society of Rheumatology, Israeli Society of RheumatologyDisclosure of Interests:Victoria Furer: None declared, Mitsumasa Kishimoto: None declared, Shigeyoshi Tsuji Grant/research support from: Eli Lilly, Speakers bureau: AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K., Yoshinori Taniguchi: None declared, Yoko Ishihara: None declared, Tetsuya Tomita Consultant of: Eli Lilly and Company, Ori Elkayam Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Novartis, Jansen

Background:Recently, the relation between M2 macrophage and fibrosis have been reported in several diseases including systemic sclerosis (SSc). Similar with macrophages, monocytes can be classified into M1 and M2 subset, and the relation of imbalance of these monocytes with disease such as rheumatoid arthritis have been reported1,2.Objectives:In this study, we attempted to investigate relationship among M1 or M2 monocytes in SSc.Methods:This study included 23 SSc patients and 20 healthy donors. Using fluorescence-activated cell sorting, we defined CD14, CD68 and CCR2 positive cells as M1 monocytes and CD14, CX3CR1 and CD163 positive cells as M2 monocytes. We examined the ability of cytokines/chemokines secretion of CD14 positive cells from SSc by multiplex bead array assay using MAP human cytokine/chemokine Magnetic Bead Panel which can measure 38 cytokines/chemokines. We next extracted M2 monocytes from CD14-positive cells using FACS, and we used the rest of the CD14 positive cells as M1-dominant monocytes. Then, we evaluated their ability of TGF-β production by multiplex bead array assay.Results:SSc patients had higher M2/M1 ratio as compared with healthy control (7.00 vs 1.63, PM1 (M2/M1 ratio>1) were higher than that from CD14 positive cells which consists M2Conclusion:Our present study suggested that the imbalance of M1/M2 monocytes might contribute to pathogenesis of SSc.References:[1]Fadini GP, Simoni F, Cappellari R, et al. Pro-inflammatory monocyte-macrophage polarization imbalance in human hypercholesterolemia and atherosclerosis.Atherosclerosis2014;237(2): 805-8.[2]Fukui S, Iwamoto N, Takatani A, et al. M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis.Front Immunol2017;8: 1958.Disclosure of Interests:None declared

Background:Upadacitinib (UPA) is an oral, reversible, JAK inhibitor approved for treatment of moderate to severe rheumatoid arthritis (RA) and currently under evaluation for treatment of psoriatic arthritis (PsA).Objectives:To assess the efficacy and safety of UPA versus placebo (PBO) in patients (pts) with PsA and prior inadequate response or intolerance to ≥1 biologic disease-modifying anti-rheumatic drug (bDMARD).Methods:In SELECT-PsA-2, pts were randomized 1:1:1 to once daily UPA 15 mg (UPA15), UPA 30 mg (UPA30), or PBO. Pts were stratified by baseline DMARD use, number of prior failed bDMARDs, and extent of psoriasis. The primary endpoint was the proportion of pts achieving ACR20 response at Wk 12. Multiplicity controlled secondary endpoints included change in HAQ-DI, FACIT-Fatigue (FACIT-F), and SF-36 Physical Component Summary (PCS) at Wk 12; static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline, PASI75, and change in Self-Assessment of Psoriasis Symptoms (SAPS) at Wk 16; and proportion of pts achieving MDA at Wk 24. Additional key secondary endpoints were ACR50 and ACR70 at Wk 12, and ACR20 at Wk 2. Treatment-emergent adverse events (TEAEs) are reported for pts who received ≥1 dose of study drug.Results:641 pts were randomized and received study drug; 54.3% were female with mean age of 53.4 years, and mean duration since PsA diagnosis of 10.1 years. 61% of pts failed 1 bDMARD, 18% failed 2 bDMARDs, and 13% failed ≥3 bDMARDs. 543 (84.6%) pts completed Wk 24 study drug.At Wk 12, a significantly greater proportion of pts receiving UPA15 and UPA30 vs PBO achieved ACR20 (56.9% and 63.8% vs 24.1%; p < .0001 for both comparisons). Statistically significant improvements were observed in the UPA15 and UPA30 arms vs PBO in all multiplicity controlled secondary endpoints, including ΔHAQ-DI (PBO, -0.10; UPA15, -0.30; UPA30, -0.41), ΔSF-36 PCS (PBO, 1.6; UPA15, 5.2; UPA30, 7.1), ΔFACIT-F (PBO, 1.3; UPA15, 5.0; UPA30, 6.1), and ΔSAPS (PBO, -1.5; UPA15, -24.4; UPA30, -29.7; p < .0001 for all endpoints;Figure 1). In addition, a greater proportion of pts achieved ACR50 and ACR70 at Wk 12 with UPA vs PBO. Generally, TEAEs were reported at similar frequencies in the PBO and UPA15 arms and at a higher frequency in the UPA30 arm (Figure 2). Numerically higher rates of serious AEs were reported in the UPA arms. Herpes zoster was more frequent with UPA30. Three malignancies occurred in each of the UPA arms. One adjudicated non-fatal myocardial infarction and one adjudicated pulmonary embolism were reported with UPA15.Conclusion:In this bDMARD-IR PsA population, UPA15 and UPA30 demonstrated significant improvements across PsA domains including improvements in joint and skin signs and symptoms vs PBO through Wk 24 with improvement observed by Wk 2. A greater percentage of pts treated with UPA achieved MDA and ACR50/70, stringent composite measures of disease control. No new safety signals were identified compared to what has been observed with UPA in RA.Disclosure of Interests:Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Apinya Lertratanakul Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jaclyn Anderson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kim Papp Grant/research support from: AbbVie, Amgen, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Takeda, UCB, and Valeant., Consultant of: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Speakers bureau: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Shigeyoshi Tsuji Grant/research support from: Eli Lilly, Speakers bureau: AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K., Eva Dokoupilova Grant/research support from: Eli Lilly, AbbVie, Novartis, MAURO KEISERMAN Speakers bureau: Pfizer, Abbott, Actelion, AstraZeneca, Amgen, Roche, Bristol Myers Squibb, and Janssen and has received clinical trial honoraria from Pfizer, Amgen, AstraZeneca, Anthera Pharmaceuticals, Bristol-Myers Squibb, Biogen Idec Inc, Celltrion Inc., Eli Lilly, Human Genome Sciences, Novartis, Roche, Sanofi, UCB Inc., xin wang Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Sheng Zhong Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Patrick Zueger Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Aileen Pangan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau