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Hunting, trapping, and fishing are part of an Indigenous lifestyle in subarctic Canada. However, this lifestyle may be a route of exposure to contaminants and may pose a risk for the people who rely on a subsistence diet. Monte Carlo simulations for the chemical concentration of eight game species and one fish species were carried out by randomly sampling 10,000 samples from the contaminant measures for each species. We then calculated a probabilistic non-carcinogenic hazard quotient or carcinogenic risk values to estimate the human health risk of exposure to contaminants. Of the species examined, ducks were of concern for potential carcinogenic risk. There was a modeled probabilistic 95th-percentile risk associated with the consumption of ducks and polybrominated biphenyl (PBB) congener 153 in boys, women, and men (1.09 × 10−6, 1.57 × 10−6, and 2.17 × 10−6, respectively) and, to a lesser extent, with geese and polychlorinated biphenyl (PCB) congener 153 in men (1.19 × 10−6). Contaminant concentration in the intake rate (food consumption) for PBB congener 153 exposure risk was more important than that for PCB congener 153, where intake rate had greater relevance. The consumption of waterfowl may increase the exposure to organohalogens; however, there are health and wellness benefits associated with the harvesting and consumption of subsistence foods that must also be considered. We recommend follow-up species-specific studies focused on ducks to clarify and elucidate the results in the present study.

Type 2 diabetes mellitus (T2DM) disproportionately affects Indigenous populations. It is possible that exposure to complex mixtures of environmental contaminants contribute to T2DM development. This study examined the association between complex environmental contaminant mixtures and T2DM among Canadian Indigenous communities from the Eeyou Istchee territory, Quebec, Canada. Using data from the cross-sectional Multi-Community Environment-and-Health Study (2005–2009) Principal Component Analysis (PCA) was used to reduce the dimensionality of the following contaminants: 9-polychlorinated biphenyl congeners; 7-organic pesticides; and 4-metal/metalloids. Following this data reduction technique, we estimated T2DM prevalence ratios (PR) and 95% confidence intervals using modified Poisson regression with robust error variance across derived principal components, adjusting for a priori covariates. For both First Nation adult males (n = 303) and females (n = 419), factor loadings showed dichlorodiphenyltrichloroethane (DDT) and lead (Pb) highly loaded on the second principal component (PC) axis: DDT negatively loaded, and Pb positively loaded. T2DM was significantly associated with PC-2 across all adjusted models. Because PCA produces orthogonal axes, increasing PC-2 scores in the fully adjusted model for females and males showed (PR = 0.84; 95% CI 0.72, 0.98) and (PR = 0.78; 95% CI 0.62, 0.98), respectively. This cross-sectional study suggests that our observed association with T2DM is the result of DDT, and less likely the result of Pb exposure. Further, detectable levels of DDT among individuals may possibly contribute to disease etiology.

Indigenous populations are disproportionately affected by type 2 diabetes (T2DM) compared to non-Indigenous people. Of importance, the prevalence of T2DM is greater amongst females than males in First Nations communities, in contrast to higher male prevalence reported in non-Indigenous Canadians. Therefore, in this study we extend our previously published work with respect to females, and the potential association between environmental exposures to organochlorine pesticides, such as dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE) to explain the greater prevalence of T2DM among Indigenous females compared to males. Using data from the Multi-Community Environment-and-Health Study, Principal Component Analysis (PCA), examined 9-polychlorinated biphenyl congeners, 7-organic pesticides, and 4-metal/metalloids. Modified Poisson regression with robust error variance estimated adjusted prevalence ratios (PR) and corresponding 95% confidence intervals (95% CI), regressing prevalent T2DM on the newly derived principal components (PC), adjusting for a priori covariates, including parity. We further examined the relationship between high detection concentrations of DDT and tertials of categorized DDE exposures on T2DM among Indigenous Cree women. Among 419 female participants, 23% (n = 95) had physician-diagnosed T2DM. PCA analysis show that DDT and Lead (Pb) loaded highly on the second axis (PC-2), although in opposite directions, indicating the different exposure sources. As previously published, T2DM was significantly associated with PC-2 across adjusted models, however, after further adjusting for parity in this analysis, T2DM was no longer significantly associated with increasing PC-2 scores (PR = 0.88, 95% 0.76, 1.03). Furthermore, we found that the highest detectable levels of DDT, and tertiles of DDE were significantly associated with prevalent T2DM in the fully adjusted model (PR = 1.93, 1.17, 3.19), and (PR = 3.58, 1.10, 11.70), respectively. This cross-sectional analysis suggests organochlorines, specifically, detectable high exposure concentrations of DDT and DDE are associated with prevalent type 2 diabetes, signifying a possible important link between parity and environmental organochlorines pesticides among Indigenous Cree women.

Indoor concentrations of black carbon (BC) were measured when wood was burned for traditional cultural activities in a study in a Cree community located in subarctic Canada. The study also included an intervention using a propane-fuelled heater to mitigate in situ BC. Mass concentrations of BC were measured in a game-smoking tent for 39 days and in hunting cabins on the west coast of James Bay, Canada, for 8 days. Five-minute averaged BC mass concentration (N = 12,319) data were recorded and assessed using optimised noise-reduction averaging. Mean BC mass concentrations were lower in hunting cabins (mean = 8.25 micrograms per cubic metre (µg m−3)) and higher in the game-smoking tent (mean = 15.46 µg m−3). However, excessive BC peaks were recorded in the game-smoking tent (maximum = 3076.71 µg m−3) when the fire was stoked or loaded. The intervention with the propane heater in a hunting cabin yielded a 90% reduction in measured BC mass concentrations. We do not presume that exposure to BC is of concern in hunting cabins with appropriate wood-burning appliances that are well-sealed and vent outside. In game-smoking tents, we advise that persons take intermittent breaks outside of the tent for fresh air.

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.

Objective: High blood pressure (BP) is a risk factor for cardiovascular disease. Examining the role of inflammatory mediators on BP is important since vitamin D (VD) is a modifiable risk factor, which possibly modulates inflammatory cytokines. This study simulated what are known as average 'controlled direct effects (CDE)' of inflammatory markers, C reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interlukin-6 (IL-6) on continuous BP measures, while fixing VD, an intermediate variable to specific level. Design: Cross-sectional study. Setting: We analysed data from the Multi-Community Environment-and-Health Study, 2005-2009, conducted in Eeyou Istchee, Quebec, Canada. Participants: This study recruited 1425 study Indigenous Cree participants from seven Cree communities. Only adults with serum VD levels, inflammatory markers and BP measures were included in this data analysis. Primary and secondary outcomes measures: Inflammatory markers examined the top 25th exposure percentiles. VD 'insufficiency' (ie, 25-hydroxyvitamin-D levels Results: Among 161 participants, 97 (60 %) were female. The prevalence of VD insufficiency was 32%. CDE estimates show in the presence and absence of population vitamin D insufficiency, inflammatory markers have a slightly different association on BP. TNF-α significantly and inversely associated with SBP in the presence of vitamin D insufficiency, fully adjusted model β = -13.61 (95% CI -24.42 to -2.80); however, TNF-α was not associated with SBP in the absence of vitamin D insufficiency. CRP, IL-6 were also not significantly associated with BP measures, although the magnitude of association was greater for those with elevated inflammation and VD insufficiency. Conclusion: This novel analysis shows in the presence of VD insufficiency, inflammation (particularly TNF-α) may affect SBP. Additional research is needed to elucidate these findings, and the temporal relationship between these variables.

The James Bay Treaty-Treaty No. 9 was unique among the numbered treaties of Canada in that there was a need for the concurrence of the Province of Ontario. Last-minute negotiations by the Dominion of Canada to gain said concurrence led to an agreement with the Province of Ontario, and this agreement became part of the Treaty No. 9 package at Ontario’s insistence. However, since the agreement was not executed until after the Treaty No. 9 expedition had left for the field, an incomplete Treaty No. 9 package that lacked the agreement was presented to and signed by the First Nation groups in 1905. Furthermore, spaces had been left in the vellum copies of Treaty No. 9 and the agreement to add in the date of the agreement when fully executed. In the spaces that were left for this purpose, the date of the agreement was backdated to 3 July. This act of deception was suggested by the Treasurer of the Government of Ontario, A. Matheson in order to date of the agreement earlier than the date in the Treaty. Thus, the common law legality of the Treaty No. 9 package must be questioned, especially since officials of the Governments of Canada and Ontario left documentation of their deception. Without the agreement being attached as specified in the Treaty No. 9 document that left Ottawa in 1905, consideration of the terms of the agreement by the First Nation signatories of the treaty could not have occurred prior to signing. It follows that there exists a question of whether the land south of the Albany River was ever ceded in Treaty No. 9 from a common law perspective, unless documentation can be presented indicating that the complete Treaty No. 9 package was presented to the First Nation signatories; the written record indicates otherwise. In the end, the courts will have to decide the legality of Treaty No. 9 from a common law perspective.

This study investigated the effectiveness of treatment with Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA) assessed by ultrasonography (US) activity, and the influence of patient characteristics and previous treatments.This prospective study assessed 60 treatment initiations among 53 Japanese patients diagnosed with RA who underwent treatment with JAK inhibitors during June 2013 to February 2020. Of the 53 patients, seven patients were enrolled in duplicate because they were treated with two different JAK inhibitors at different periods. For each case, the improvement rate on the power Doppler (PD) score was assessed at 6 month follow-up. Median improvement rate of PD score was used to classify cases as either US responders or non-responders, and patient characteristics were compared between the two groups.All indicators of clinical disease activity and US activity showed a significant improvement at 3 months compared with baseline. Although the JAK inhibitor-cycler group and the interleukin-6 (IL-6) inhibitor inadequate response (IR) group tended to show a later improvement for US activity, all indicators of clinical disease activity and US activity showed a significant improvement at 6 months compared with baseline for both groups. Multivariate analysis showed that concomitant methotrexate use and an IR to the previous biologic or targeted-synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) treatment were independently and significantly associated with US responders.Use of a JAK inhibitor in combination with methotrexate and an absence of IR to any previous b/tsDMARDs demonstrated superior effectiveness for patients with RA.

Worker-specific Biological Exposure Action Levels (BEALs) for nickel (Ni) exposure are a urinary Ni concentration that reflects a dose that can be experienced on a daily basis without adverse syste...

Hunting, trapping, and fishing are part of an Indigenous lifestyle in subarctic Canada. However, this lifestyle may be a route of exposure to contaminants and may pose a risk for the people who rely on a subsistence diet. Monte Carlo simulations for the chemical concentration of eight game species and one fish species were carried out by randomly sampling 10,000 samples from the contaminant measures for each species. We then calculated a probabilistic non-carcinogenic hazard quotient or carcinogenic risk values to estimate the human health risk of exposure to contaminants. Of the species examined, ducks were of concern for potential carcinogenic risk. There was a modeled probabilistic 95

Introduction Upadacitinib is a Janus kinase inhibitor under investigation in patients with psoriatic arthritis (PsA). This study assessed the 56-week efficacy and safety of upadacitinib in patients with PsA and an inadequate response or intolerance to biologic therapy. Methods In the phase 3 SELECT-PsA 2 study, patients were randomized to 56 weeks of blinded treatment with oral upadacitinib 15 or 30 mg once daily, or placebo switched to upadacitinib 15 or 30 mg once daily at week 24. Efficacy endpoints included the proportion of patients achieving 20/50/70% improvement in American College of Rheumatology criteria (ACR20/50/70), 75/90/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), and minimal disease activity. Safety was assessed throughout the study. Results Of 641 patients who received ≥ 1 dose of study drug, 479 (74.7%) completed 56 weeks of treatment. Improvements in the proportion of patients achieving ACR20/50/70, PASI75/90/100, and minimal disease activity were maintained with both doses of upadacitinib through 56 weeks. Week 56 results for patients who switched from placebo to upadacitinib at week 24 were similar to those for patients originally randomized to the upadacitinib groups. The exposure-adjusted event rate for serious infections was 2.6 and 6.1 events/100 patient-years in the upadacitinib 15 and 30 mg groups, respectively. Herpes zoster occurred more frequently with upadacitinib 30 versus 15 mg; most cases were non-serious. Conclusion In patients with PsA who had an inadequate response or intolerance to biologic therapy, the efficacy of upadacitinib was maintained over 56 weeks with no new significant safety signals observed. Trial registration NCT03104374. Electronic supplementary material The online version of this article (10.1007/s40744-021-00305-z) contains supplementary material, which is available to authorized users.

Objectives: Using multicentre ultrasound (US) cohort data among patients with rheumatoid arthritis (RA), we aimed to identify baseline factors that permit differentiation between two patient cohort...

Background Participation in on-the-land programs that encourage traditional cultural activities may improve health and well-being. The Income Security Program (ISP) − a financial incentive-based on-the-land program − for Eeyouch (Cree) hunters and trappers in Eeyou Istchee was created as a result of the 1975 James Bay and Northern Quebec Agreement to help mitigate the effects of hydroelectric development on the Cree people of northern Quebec, Canada. Beyond the ISP’s financial incentives, little is known about the health measures of those who are eligible to participate in the ISP (i.e. spent ≥120 days on-the-land during the previous year). Therefore, this paper’s objective was to assess the health measures of northern Quebec Cree, who were eligible for participation in the ISP. Methods Using participant data (n = 545) compiled from the Nituuchischaayihtitaau Aschii Multi-Community Environment-and-Health Study, we assessed 13 different health measures in generalized linear models with the independent variable being the eligibility to participate in the ISP. Results Participants in the present study who were eligible for the ISP had significantly higher levels of vigorous and moderate activity per week, and higher concentrations of omega-3 polyunsaturated fatty acids in the blood compared to those ineligible for the ISP (i.e. spent ≤119 days on-the-land during the previous year). Encouragingly, following model adjustment for age and sex, participants eligible for the ISP did not have higher blood concentrations of mercury than those who were not eligible for the ISP. Conclusions Our results suggest that the participants eligible for participation in the ISP are likely to be healthier than those who are ineligible to participate − and are promising for on-the-land programs for Indigenous peoples beyond a financial incentive − with no apparent higher risk of increasing contaminant body burden through traditional on-the-land-activities (e.g. fish consumption).

On 1 April 1999, Akimiski Island of the western James Bay region of northern Ontario, Canada, was included in the newly formed territory of Nunavut, Canada—an Inuit-dominated territory—even though the Inuit had never asserted Aboriginal title to the island. By contrast, the Omushkegowuk Cree of the western James Bay region have asserted Aboriginal title to Akimiski Island. The Government of Canada by their action (or inaction) has reversed the onus of responsibility for proof of Aboriginal title from the Inuit to the Cree. In other words, the Government of Canada did not follow their own guidelines and the common-law test for proof of Aboriginal title. In this paper, we documented and employed Cree oral history as well as a sea-level retrodiction (based on state-of-the-art numerical modeling of past sea-level changes in James Bay), which incorporated a modified ICE-6G ice history and a 3-D model of Earth structure, to establish that criterion 2 of the test for Aboriginal title has now been fully met. In other words, Cree traditional use and occupancy of Akimiski Island was considered sufficiently factual at the time of assertion of sovereignty by European nations. As all the criteria of the common-law test for proof of Aboriginal title in Canada, with respect to Akimiski Island, have now been addressed, the Cree have sufficient basis to initiate the process of a formal land claim.

The act of decolonizing knowledge systems involves recovering and renewing traditional, non-commodified cultural patterns, such as the sustenance of intergenerational relationships and traditional practices. A decline in beaver harvesting, which was once an integral part of the

Objective: To determine whether the positivity of baseline anti-Ro/Sjögren’s syndrome antigen A (SSA) antibodies influences the response to abatacept, we compared therapeutic responses between anti-Ro/SSA antibody-negative and -positive patients with rheumatoid arthritis (RA) using a multicentre RA ultrasonography prospective cohort. Method: We reviewed Japanese patients with RA who started abatacept as the first biological disease-modifying anti-rheumatic drug between June 2013 and April 2018. We assessed 28-joint Disease Activity Score–erythrocyte sedimentation rate (DAS28-ESR) change between baseline and 6 or 12 months after treatment in RA patients treated with abatacept, and European League Against Rheumatism (EULAR) response at 6 and 12 months. The Global OMERACT-EULAR Synovitis Score (GLOESS) was calculated at baseline and at 6 and 12 months. Results: Overall, 51 patients were enrolled and divided into anti-Ro/SSA antibody-negative and -positive groups of 35 and 16, respectively. Median age at baseline was significantly higher in the anti-Ro/SSA antibody-negative group (p = 0.04). The retention rate and percentage of EULAR good responders at 12 months were significantly higher in the anti-Ro/SSA antibody-negative group (both p = 0.02). Anti-Ro/SSA antibody-negative patients exhibited larger decreases in both DAS28-ESR and DAS28-C-reactive protein at 12 months than anti-Ro/SSA antibody-positive patients (p = 0.02 and 0.04, respectively). GLOESS decreased significantly at 6 months in anti-Ro/SSA antibody-negative patients (p = 0.03). Multivariate analyses showed that anti-Ro/SSA antibody positivity was an independent factor associated with change in the DAS28-ESR at 6 months (p Conclusion: Anti-Ro/SSA antibody positivity predicts a poor response to abatacept and low retention rate.

A 54-year-old woman developed drop head syndrome (DHS), Raynaud's phenomenon and creatine kinase (CK) elevation. She did not meet the international classification criteria of dermatomyositis/polymyositis, as we observed no muscle weakness, grasping pain or electromyography abnormality in her limbs, and antiaminoacyl tRNA synthetase (ARS) antibody was negative. Cervical magnetic resonance imaging and a muscle biopsy of the trapezius muscle revealed myositis findings as the only clinical observations in muscle. These findings, along with her anti-U1-ribonucleoprotein (RNP) antibody positivity and leukopenia, resulted in a diagnosis of mixed connective tissue disease (MCTD). Prednisolone treatment significantly improved her myositis. To our knowledge, this is the first report of DHS as the only muscle complication of MCTD., Internal medicine, 59(5), pp.729-732; 2020

To retrospectively analyze the differences in musculoskeletal ultrasound (MSUS) findings to distinguish patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome and patients with elderly-onset rheumatoid arthritis (EORA). We consecutively recruited patients with RS3PE syndrome (n = 7) and EORA (n = 22) who underwent pre-treatment MSUS of both hands. Synovial hypertrophy and vascularity of articular synovitis and those of tenosynovitis of the digital flexor tendons and the carpal extensor tendon were evaluated by gray-scale and power Doppler, respectively on a semi-quantitative scale (0–3). The presence/absence of intra-articular synovial effusion, bone erosion, peritendinitis of the digital extensor tendon, and subcutaneous edema were noted. Compared to the EORA group, mild articular synovitis was observed more extensively, and the frequency of intra-articular synovial effusion was significantly higher in the RS3PE syndrome group. Severe articular synovial hypertrophy was more frequent in the EORA group compared to the RS3PE syndrome group, and bone erosion was observed in some EORA cases. Tenosynovitis of the digital flexor tendon was more frequent and severe in the RS3PE syndrome group compared to the EORA group. Although the frequency and severity of tenosynovitis of the carpal extensor tendon were similar in the two groups, digital extensor tendon peritendinitis was more frequent in the RS3PE syndrome group. To distinguish patients with RS3PE syndrome from those with EORA, it is important to evaluate not only intra-articular lesions but also extra-articular lesions by MSUS.

The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) database, the authoritative source of U.S. risk assessment toxicity factors, currently lacks an oral reference dose (RfD) for copper. In the absence of such a value, various health-based reference values for copper are available for use in risk assessment. We summarize the scientific bases and differences in assumptions among key reference values for ingested copper to guide selection of appropriate values for risk assessment. A comprehensive review of the scientific literature best supports the oral RfD of 0.04 mg/kg body weight/day derived by EPA from their Drinking Water Action Level. This value is based on acute gastrointestinal effects but is further supported by broader analysis of copper deficiency and toxicity.

Historically, goose harvesting provided a source of culturally significant, safe, and nutritious food for the Omushkego Cree of subarctic Ontario, Canada. Disruptions stemming from colonization and climate change have led to a decrease in harvesting, resulting in higher rates of food insecurity. The aim of the Niska program was to reconnect Elders and youth to revitalize goose harvesting activities and associated Indigenous knowledge within the community. The program and evaluation were built using a two-eyed seeing (Etuaptmumk) and community-based participatory research approach. Salivary cortisol, a biomedical measure of stress, was collected before (n = 13) and after (n = 13) participation in the spring harvest. Likewise, cortisol samples were collected before (n = 12) and after (n = 12) the summer harvest. Photovoice and semi-directed interviews were employed after the spring (n = 13) and summer (n = 12) harvests to identify key elements of well-being from an Indigenous perspective. The changes observed in cortisol levels for the spring (p = 0.782) and summer (p = 0.395) harvests were not statistically significant. However, there was a noteworthy increase in the subjective well-being observed through the qualitative measures (semi-directed interviews and photovoice), highlighting the importance of using multiple perspectives when assessing well-being, especially in Indigenous peoples. Future programs should incorporate multiple perspectives when addressing complex environmental and health issues, such as food security and environmental conservation, especially in Indigenous homelands worldwide.

The coarsening of austenite grains produced through a massive-like transformation from the ferrite to the austenite phase during/after solidification in Fe–0.45mass%C steel was examined through time-resolved X-ray diffraction measurements using time-resolved computed tomography. The δ phase solidification resulted in a single δ grain in the observation region (0.6 mm in diameter, 0.1 mm in height). The massive-like transformation produced multiple γ grains, and coarsening immediately followed the transformation. The coarsening in the observation region was completed even within 200 s. A correlation of crystallographic orientation between the γ grains was found in the γ grain structure. The massive-like transformation frequently produced fcc (111) twinned grains, and the twinned austenite grains tended to remain during coarsening because the twin interface energy is lower than the grain boundary energy. The massive-like transformation following the solidification contributed to the texture formation in the γ grain structure.

Decades of study indicate that copper oral exposures are typically not a human health concern. Ingesting high levels of soluble copper salts can cause acute gastrointestinal symptoms and, in uncommon cases, liver toxicity in susceptible individuals with repeated exposure. This focused toxicological review evaluated the current literature since the last comprehensive reviews (2007–2010). Our review identified limitations in the existing United States and international guidance for determining an oral reference dose (RfD) for essential metals like copper. Instead, an alternative method using categorical regression analysis to develop an optimal dose that considers deficiency, toxicity, and integrates information from human and animal studies was reviewed for interpreting an oral RfD for copper. We also considered subchronic or chronic toxicity from genetic susceptibility to copper dysregulation leading to rare occurrences of liver and other organ toxicity with elevated copper exposure. Based on this approach, an oral RfD of 0.04 mg Cu/kg/day would be protective of acute or chronic toxicity in adults and children. This RfD is also protective for possible genetic susceptibility to elevated copper exposure and allows for background dietary exposures. This dose is not intended to be protective of patients with rare genetic disorders for copper sensitivity within typical nutritional intake ranges, nor is it protective for those with excessive supplement intake. Less soluble mineral forms of copper in soil have reduced bioavailability as compared with more soluble copper in water and diet, which should be considered in using this RfD for risk assessments of copper.

Globally, mortality of Indigenous persons is greater than that of their non-Indigenous counterparts, which has been shown to be disproportionately attributable to non-communicable diseases. The historically subordinate position that Indigenous Knowledge (IK) held in comparison to Western science has shifted over the last several decades, with the credibility and importance of IK now being internationally recognized. Herein, we examine how Marsahall’s (2014) Two-Eyed Seeing can foster collaborative and culturally relevant Developmental Origins of Health and Disease (DOHaD) studies for health and well-being by using ‘..the best in Indigenous ways of knowing…[and] the best in Western (or mainstream) ways of knowing…and learn to use both these eyes for the benefit of all.’ At its core, Two-Eyed Seeing also includes the principles of ownership, control, access and possession, and Community-Based Participatory Research, which further reinforces the critical role of Indigenous peoples taking active roles in DOHaD research. Additionally, we also present a partnership model for working with Indigenous communities that includes the principles of respect, equity and empowerment. As researchers begin to fill the gap in Indigenous health, we outline how Two-Eyed Seeing should form the basis of DOHaD studies involving Indigenous communities. This model can be used to develop and guide projects that result in robust and meaningful participatory partnerships that have impactful uptake of research findings.

BackgroundThe achievement of disease control has been shown to be associated with improved prognosis in PsA, though no single measure of low disease activity or remission is currently universally accepted. Patient-reported outcomes (PROs) have been well-established in PsA and are important indicators of patient improvement while on treatment. To date, the association between PROs and disease control in PsA has not been fully characterized.ObjectivesWe examined the association between clinically meaningful improvement in PROs and stringent measures of disease control among patients with PsA enrolled in the Phase 3 SELECT-PsA 1 trial.MethodsPatients with active PsA and an inadequate response to ≥1 non-biologic DMARDs were randomized to receive upadacitinib (UPA) 15 mg once daily (QD), UPA 30 mg QD, adalimumab (ADA) 40 mg every other week, or PBO for 24 weeks. PROs included: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), 36-Item Short-Form Health Survey (SF-36), and Work Productivity and Activity Impairment (WPAI). Measures of stringent disease control included achievement of minimal disease activity (MDA), ACR70 response, and remission based on Disease Activity Index in PsA (DAPSA ≤4.0) or PsA Disease Activity Score (PASDAS ≤1.9). The percentage of patients achieving stringent disease control was determined among patients reporting vs not reporting PRO improvements ≥ minimal clinically important differences (MCID) in the combined active treatment and PBO group at Week 24.ResultsA total of 1704 patients were included in the SELECT PsA 1 trial, of whom 59.2%, 72.4%, 51.3%, 62.3%, 64.6%, and 63.9% reported improvements ≥ MCID (MCID responders) in FACIT-F, SF-36 physical component summary score, SF-36 mental component summary (MCS) score, WPAI activity impairment, WPAI overall work impairment, and WPAI presenteeism, respectively, at week 24. The percentage of patients achieving MDA, ACR70 or DAPSA remission at week 24 was significantly higher (nominal P≤0.01) among patients who reported improvements ≥ MCID for all PROs vs those who did not (Figures 1, 2). Similar results were seen in patients achieving PASDAS remission except for SF-36 MCS score (Figure 2). Among patients reporting improvements ≥ MCID across all PROs, more patients achieved ACR70 and MDA responses (29%-49%) with fewer patients achieving DAPSA or PASDAS remission (14%-19%).ConclusionPsA patients who reported clinically meaningful improvements in key PROs: fatigue, quality of life, and work productivity were more likely to achieve stringent measures of disease control. These results suggest a close association between meaningful improvements in patient-centric outcomes and achievement of stringent disease control.AcknowledgementsThis work/study was funded by AbbVie Inc. AbbVie participated in the study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication. All authors had access to the data results, and participated in the development, review, and approval of this abstract. No honoraria or payments were made for authorship.Disclosure of InterestsLaure Gossec Consultant of: AbbVie, Amgen, BMS, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, and UCB, Grant/research support from: Lilly, Pfizer, Sandoz, Sanofi, Nemanja Damjanov Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Grant/research support from: AbbVie, Pfizer, and Roche, 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, Apinya Lertratanakul Shareholder of: Formerly of AbbVie, Employee of: former employee of AbbVie, Ralph Lippe Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jayeshkumar Patel Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Patrick Zueger Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kurt de Vlam Speakers bureau: Celgene Eli Lilly, Galapagos, Novartis, and UCB, Consultant of: Eli Lilly, Galapagos, Novartis, and UCB, Grant/research support from: Celgene and Galapagos

BackgroundUpadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥1 biologic disease-modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study.1ObjectivesTo evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2.MethodsPts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks; PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104.ResultsA total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks1 (Table 1). Similarly, mean change from baseline in HAQ-DI, patient’s assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 (Figure 1) were consistent with that reported at wk 56.1 Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information; however, the patient had recently been diagnosed with ovarian cancer) and 2 with UPA30 (pancytopenia and COVID-19 pneumonia).Table 1.Efficacy Endpoints at Week 104EndpointUPA15 (n=211)UPA30 (n=218)Proportion of Pts (%)aNRIAONRIAOACR2055.580.354.681.8ACR5044.562.939.959.4ACR7023.232.221.631.5Minimal Disease Activity (MDA)29.441.333.949.3PASI75b47.769.852.781.1PASI90b37.755.244.367.8PASI100b23.135.435.955.6Resolution of enthesitis by LEIc39.867.837.568.4Resolution of dactylitis by LDId54.597.452.096.9Change from BLeMMRMAOMMRMAOHealth Assessment Questionnaire - Disability Index (HAQ-DI)-0.36-0.39-0.50-0.53Patient’s assessment of pain (numeric rating scale)-2.7-3.0-2.9-3.1Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)f-2.6-3.0-2.6-2.9Ankylosing Spondylitis Disease Activity Score (ASDAS)f-1.4-1.7-1.3-1.5ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; AO, as observed; BL, baseline; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MMRM, mixed effect model repeated measurement; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; pts, patients; UPA, upadacitinib.aData shown as NRI and AO for binary endpoints.bFor pts with psoriasis affecting ≥3% of body surface area at BL.cFor pts with LEI >0 at BL; resolution LEI=0.dFor pts with LDI >0 at BL; resolution LDI=0.eData shown as MMRM (LS mean) and AO (mean) for continuous endpoints.fFor pts with psoriatic spondylitis at BL.ConclusionIn PsA pts with prior inadequate response or intolerance to ≥1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to 2 years of treatment. No new safety signals were identified in this long-term extension.References[1]Mease PJ, et al. Rheumatol Ther. 2021;8:903-19.AcknowledgementsAbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial (NCT03104374). AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie.Disclosure of InterestsPhilip 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, Arathi Setty Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of 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, 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: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Liang Chen Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Reva McCaskill Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Erin McDearmon-Blondell Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of AbbVie, Peter Wung Shareholder of: Employee of AbbVie and may hold stock options, Employee of: Employee of 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

The etiology of Kawasaki Disease (KD), the most common cause of acquired heart disease in children in developed countries, remains elusive, but could be multifactorial in nature as suggested by the numerous environmental and infectious exposures that have previously been linked to its epidemiology. There is still a lack of a comprehensive model describing these complex associations. We present a Bayesian disease model that provides insight in the spatiotemporal distribution of KD in Canada from 2004 to 2017. The disease model including environmental factors had improved Watanabe-Akaike information criterion (WAIC) compared to the base model which included only spatiotemporal and demographic effects and had excellent performance in recapitulating the spatiotemporal distribution of KD in Canada (98% and 86% spatial and temporal correlations, respectively). The model suggests an association between the distribution of KD and population composition, weather-related factors, aeroallergen exposure, pollution, atmospheric concentration of spores and algae, and the incidence of healthcare encounters for bacterial pneumonia or viral intestinal infections. This model could be the basis of a hypothetical data-driven framework for the spatiotemporal distribution of KD. It also generates novel hypotheses about the etiology of KD, and provides a basis for the future development of a predictive and surveillance model.

For many Indigenous communities, decreased participation in traditional land-based activities has led to higher rates of chronic disease and a decrease in well-being. This systematic review explores how traditional land-based activities impact self-reported health and well-being of Indigenous adults, using Indigenous and Western perspectives. A search of three electronic databases (PubMed, Scopus, and Web of Science) identified nine studies which explored the experiences and perspectives of Indigenous adults taking part in land-based subsistence and ceremonial activities. A thematic analysis of these studies identified many interconnected physical, spiritual, mental, emotional, and community benefits. Community engagement throughout all stages of the interventions was an important factor in effectively addressing challenges and barriers stemming from colonization, decreased knowledge transfer, and increased use of technology. Participants reported developing more effective stress management techniques, a greater awareness of modifiable risk factors along with increased engagement with Elders. Ultimately, land-based subsistence and ceremonial activities were identified as playing an influential role in the lives of Indigenous adults. The involvement of community members allowed for the development of more culturally relevant interventions. Future community-specific research is needed to increase engagement in traditional physical-activities, improve well-being and overall reduce the risk of chronic disease.

To address food insecurity in northern Canada, some isolated communities started gardening initiatives to reduce dependencies on expensive foods flown in to communities. From 2012–2014, soils in northern Ontario James Bay lowlands were cultivated with bush beans and potatoes, grown in sole and intercropping configurations, in an open field and an agroforestry system enclosed by willow trees. The objective of this study was to compare the supply rates of 15 plant-available nutrients in these soils using in situ ion exchange membranes. After three years of cultivation, the agroforestry site had significantly greater supply of PO4, Ca, and Zn and these nutrients had positive correlations with yield. By contrast, the open site had significantly greater supply of Mg, SO4, and B, these nutrients, and Al, had negative correlations with yield. Whilst there were no differences between sole and intercropping configurations, significantly greater supply of NO3, Ca, Cu, Fe, and Zn occurred early in the growing season, compared to significantly greater supply of K, SO4, B, and Al later in the season. Significantly greater yields have been harvested in the agroforestry site and it is suspected that the presence of a willow shelterbelt improves the microclimate and plant-available PO4, Ca, and Zn.

Summary Inorganic arsenic (iA) in the drinking water is a human carcinogen (bladder, lung, and skin). The mode of action involves metabolism to trivalent arsenicals that react with sulfhydryl groups in critical proteins, leading to cytotoxicity with regenerative proliferation, involving a threshold at in vitro concentrations >0.1 μM. Adverse biologic effects at such tissue concentrations in rodents occur with ≥10 ppm of iAs in diet or drinking water. On the basis of mode of action, in vitro, and in vivo studies, anticipated drinking water exposures of 50–150 μg/L exceed a tissue concentration of >0.1 μM in humans. Epidemiologic investigations evaluating populations exposed at levels

BackgroundLupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE).MethodsWe retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993–2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares.ResultsOf the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5–154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01–1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44–0.90, p = 0.00048) and serum β2 microglobulin (MG) (OR 0.26, 95% CI 0.06–0.74, p = 0.00098) levels.ConclusionsAmong LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum β2MG levels were negative predictive factors of CR at 12 months.

Introduction Dans le rhumatisme psoriasique (RP), l’obtention d’un controle de la maladie est associee a une amelioration du pronostic, bien qu’il n’existe pas de mesure unique universellement acceptee de faible activite de la maladie ou de remission. Les resultats rapportes par le patient (PRO) constituent des indicateurs majeurs d’amelioration clinique durant le traitement. A ce jour, la correlation entre PRO et controle de la maladie n’est pas pleinement decrite dans le RP. Nous avons etudie cette correlation chez des patients atteints de RP inclus dans l’etude de phase III SELECT-PsA 1. Patients et methodes Des patients atteints de RP actif et ayant une reponse inadequate a ≥ 1 DMARD biologique ont ete randomises pour recevoir upadacitinib (UPA) 15 mg une fois par jour (1×/j), UPA 30 mg 1×/j, adalimumab (ADA) 40 mg toutes les 2 semaines ou un placebo (PBO) pendant 24 semaines. Les questionnaires de PRO etaient les suivants : Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), 36-Item Short-Form Health Survey (SF-36), et Work Productivity and Activity Impairment (WPAI). Les mesures de controle strict de la maladie comprenaient l’observation d’une activite minimale de la maladie (MDA), la reponse ACR70 et la remission basee le score DAPSA [Disease Activity Index in PsA] ou PASDAS [PsA Disease Activity Score]. La proportion de patients ayant atteint un controle strict de la maladie a ete determine chez les patients ayant vs n’ayant pas decrit d’ameliorations des PRO ≥ a des differences minimales cliniquement importantes (MCID) dans la population traitement actif et PBO a la semaine 24. Resultats Au total, 1 704 patients ont ete inclus dans l’etude SELECT PsA 1, dont respectivement 59,2 %, 72,4 %, 51,3 %, 62,3 %, 64,6 % et 63,9 % ont decrit des ameliorations ≥ MCID (repondeurs MCID) dans les questionnaires FACIT-F, SF-36-PCS, SF-36-MCS, WPAI Limitation des activites, WPAI Limitation globale de l’activite professionnelle et WPAI Presenteisme, a la semaine 24. La proportion de patients ayant atteint la MDA, une reponse ACR70 ou la remission DAPSA a la semaine 24 etait significativement plus elevee (p nominal ≤ 0,01) chez les patients ayant decrit des ameliorations ≥ MCID pour tous les PRO ( Figure 1 , Figure 2 ). Des resultats comparables ont ete observes chez les patients en remission PASDAS, sauf pour le score SF-36-MCS ( Fig. 2 ). Les patients ayant decrit des ameliorations ≥ MCID pour tous les PRO ont ete plus nombreux a atteindre une reponse ACR70 et la MDA (29 %–49 %) que la remission DAPSA ou PASDAS (14 %-19 %). Conclusion Les patients atteints de RP ayant decrit des ameliorations cliniquement significatives des principaux PRO (fatigue, qualite de vie, productivite au travail) etaient plus susceptibles de repondre a des criteres stricts de controle de la maladie. Ces resultats suggerent une etroite correlation entre l’amelioration significative des criteres orientes sur le patient et l’obtention d’un controle strict de la maladie.

Background/Aims Upadacitinib (UPA) is a selective JAK inhibitor licensed for moderate-severe rheumatoid arthritis (RA), under evaluation for treating psoriatic arthritis (PsA). We aim to assess the efficacy and safety of UPA versus placebo (PBO) in PsA patients with prior inadequate response or intolerance to ≥ 1 biologic disease-modifying anti-rheumatic drug (bDMARD). This research was previously presented at EULAR; published in Annals of Rheumatic Diseases. Methods In SELECT-PsA-2, patients were randomised 1:1:1 to once-daily UPA 15mg (UPA15), UPA 30mg (UPA30), or PBO. Patients were stratified by baseline DMARD use, number of prior failed bDMARDs, and extent of psoriasis. Primary endpoint: the proportion of patients achieving ACR20 response at Wk12. Multiplicity controlled secondary endpoints: change in HAQ-DI, FACIT-Fatigue (FACIT-F), SF-36 Physical Component Summary (PCS) at Wk12, static Investigator Global Assessment (sIGA) of Psoriasis of 0/1 and at least a 2-point improvement from baseline, PASI75, change in Self-Assessment of Psoriasis Symptoms (SAPS) at Wk16 and proportion of patients achieving MDA at Wk24. Additional secondary endpoints: ACR50 and ACR70 at Wk12, ACR20 at Wk2. Treatment-emergent adverse events (TEAEs) reported for patients receiving ≥1 dose of study drug. Results 641 patients 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%,18%, 13% of patients failed 1, 2, ≥3 bDMARD respectively. 543 (84.6%) patients completed Wk24 study drug. At Wk12, a significantly greater proportion of patients receiving UPA15 and UPA30 vs PBO achieved ACR20 (56.9% and 63.8% vs 24.1%; p < 0.0001 for both comparisons). Statistically significant improvements were observed in 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). In addition, a greater proportion of patients achieved ACR50 and ACR70 at Wk12 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. Numerically higher rates of serious AEs were reported in the UPA arms. Herpes zoster was more frequent with UPA30. Three malignancies occurred in each UPA arm. 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 Wk24, with improvement observed by Wk2. A greater percentage of patients treated with UPA achieved MDA and ACR50/70, stringent composite measures of disease control. No new safety signals were identified compared to those with UPA in RA. Disclosure M.C. Genovese: Consultancies; M.G. is a consultant for AbbVie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme. Grants/research support; M.G. has received grants/research support from AbbVie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme. A. Lertratanakul: Shareholder/stock ownership; A.L. is a stock/shareholder of AbbVie Inc. J. Anderson: Shareholder/stock ownership; J.A. may be a stock/ shareholder of AbbVie Inc. K. Papp: Consultancies; K.P. is a consultant for AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, *. Member of speakers’ bureau; K.P. is a member of the speakers bureau for AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma *. Grants/research support; K.P. has received grants/research support from AbbVie, Amgen, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma *. Other; * & 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. W. Tillett: Consultancies; W.T. is a consultant of AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc. & UCB. Member of speakers’ bureau; W.T. is a member of the speakers bureau for AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc. & UCB. Grants/research support; W.T. has received grants/research support from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB. F. van den Bosch: Consultancies; F.vdB. is a consultant of AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB. Member of speakers’ bureau; F.vdB. is a member of the speakers bureau for AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB. S. Tsuji: Member of speakers’ bureau; S.T. is a member of the speakers bureau for AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K. Grants/research support; S.T. has received grants/research support from Eli Lilly. E. Dokoupilova: Grants/research support; E.D. has received grants/research support from Eli Lilly, AbbVie, Novartis, MAURO KEISERMAN. M. Keiserman: Honoraria; M.K. has received honoraria from Pfizer, Amgen, AstraZeneca, Anthera Pharmaceuticals, Bristol-Myers Squibb, Biogen Idec Inc, Celltrion Inc., Eli Lilly, Human Genome Sciences, Novartis, Roche, Sanofi,. Member of speakers’ bureau; M.K. is a member of the speakers bureau for Pfizer, Abbott, Actelion, AstraZeneca, Amgen, Roche, Bristol Myers Squibb, and Janssen. X. Wang: Shareholder/stock ownership; X.W. may be a shareholder of AbbVie Inc. S. Zhong: Shareholder/stock ownership; S.Z. may be a stock/ shareholder of AbbVie Inc. P. Zueger: Shareholder/stock ownership; P.Z. may be a stock/shareholder of AbbVie Inc. A. Pangan: Shareholder/stock ownership; A.P. may be a stock/shareholder of AbbVie Inc. P. Mease: Consultancies; P.M. is a consultant of Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB. Member of speakers’ bureau; P.M. is a member of the speakers bureau for Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB. Grants/research support; P.M. has received grants/research support from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB.

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.