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Objective In the face of the ongoing circulation of SARS‐CoV‐2, the durability of neutralization post–COVID‐19 vaccination in immune‐mediated inflammatory disease (IMID) is a key issue, as are the effects of medications. Methods Adults (n = 112) with inflammatory bowel disease, psoriasis/psoriatic arthritis, rheumatoid arthritis, spondylarthritis, and systemic lupus were recruited from participating Canadian medical centers from 2021 to 2023. We focused on log‐transformed neutralization (lentivirus methods) as a continuous outcome, with separate models for wild‐type and Omicron strains BA.1 and BA.5. Results Compared with 30 to 120 days postvaccination, subsequent periods were associated with greater neutralization in unadjusted models for wild‐type, BA.1, and BA.5 strains and against the BA.1 strain in adjusted models. Rituximab was associated with lower neutralization for the BA.1 strain in adjusted models, with a similar trend for BA.5. In methotrexate users, there were trends for less neutralization of BA.1 and BA.5 in all unadjusted models, whereas in adjusted models, there was significantly lower neutralization only for the wild type. Three or more doses and Omicron‐specific vaccines were both independently associated with better neutralization ability for all three strains. A COVID‐19 infection within six months before sampling was associated with higher neutralization of wild type and BA.1 in adjusted analyses. Anti–tumor necrosis factor agents were associated with lower neutralization ability for BA.5 in adjusted analyses. Conclusion Neutralization responses in immunosuppressed individuals with IMID were durable over time and were augmented by more than three doses and Omicron‐specific vaccines. Less neutralization was seen with certain medications. Our work clarifies the joint effects of vaccine history, infection, and medications on COVID‐19 immunity.

Abstract Background Safety remains a significant concern for biologic drugs, and studies are needed to ensure a comparable safety profile for biosimilars and their legacy treatments. Using Canadian administrative health data from 2015–2019, we compared the incidence of serious infection between biosimilars and bio-originators initiators for etanercept and infliximab, two of the most commonly used biologics during this time. Methods We performed a retrospective cohort study using pan-Canadian data (except Quebec) from the National Prescription Drug Utilization Information System linked to hospitalization data. We studied new users of infliximab or etanercept (January/2015-December/2019) and compared incidence rates of serious infection, defined as those which required hospitalization, by using Cox regression models adjusted by biological sex, age at treatment initiation, prior corticosteroid or biologic, province, and calendar year. Results We studied 6,583 etanercept users (mean age 62) and 7,202 infliximab users (mean age 45). Hospitalization with infections occurred in 7% of infliximab and 2% of etanercept users. Comparing the risk of infection between biosimilar to bio-originator, the adjusted hazard ratio (95% confidence interval) was 1.33 (0.77, 2.30) for etanercept and 0.93 (0.72, 1.18) for infliximab. Conclusions Our study found no clear difference between etanercept and infliximab biosimilars and their bio-originators for infection incidence, suggesting a similar safety profile.

Abstract Background and aims There is an incomplete understanding of the full safety profiles of repeated COVID-19 vaccinations in patients with inflammatory bowel disease (IBD). Among individuals with IBD, we assessed whether COVID-19 vaccines were associated with serious adverse events of special interest (AESI) and health care utilization [all-cause hospitalizations, Emergency Department (ED) visits, gastroenterology visits, IBD-related visits]. Methods Using comprehensive administrative health data from Ontario, Canada, adults with IBD who received at least one COVID-19 vaccine from December 2020-January 2022 were included. Self-controlled case series analyses were conducted to evaluate the relative incidence rates of AESI and health care utilization outcomes across post-vaccination risk and control periods. Results Among 88,407 IBD patients, 99.7% received mRNA vaccines and 75.9% received ≥ 3 doses. Relative to control periods, we did not detect an increase in AESI. IBD patients had fewer all-cause hospitalizations during post-vaccination risk periods. Patients experienced more all-cause ED visits after dose 2 [Relative Incidence (RI):1.08(95%CI:1.04–1.12)] but fewer visits after doses 3 [RI:0.85 (95%CI:0.81–0.90)] and 4 [RI:0.73 (95%CI:0.57–0.92)]. There was no increase in gastroenterologist visits or IBD-related health care utilization post-vaccination. There were fewer IBD-related hospitalizations after dose 1 [RI:0.84 (95%CI:0.72–0.98)] and 3 [RI:0.63 (95%CI:0.52–0.76)], fewer IBD-related ED visits after dose 3 [RI:0.81 (95%CI:0.71–0.91)] and 4 [RI:0.55 (95%CI:0.32–0.96)], and fewer outpatient visits after dose 2 [RI:0.91 (95%CI:0.90–0.93)] and 3 [RI:0.87 (95%CI:0.86–0.89)]. Conclusion This population-based study did not detect increased AESI, all-cause or IBD-related health care utilization following COVID-19 vaccination, suggesting a lack of association between vaccination and increased disease activity.

Abstract We estimated the operating characteristics of ICD-10 code U07.1, introduced by the World Health Organization in 2020, to identify lab-confirmed SARS-CoV-2. CCEDRRN is a national research registry of adults (March 2020–August 2021) with suspected/confirmed SARS-CoV-2 identified in Canadian emergency departments (EDs) using chart review (symptoms, clinical information, and lab test results including SARS-CoV-2 polymerase chain reaction, PCR results). CCEDRRN data were linked to administrative hospitalization discharge and ED ICD-10 diagnostic codes (accessed centrally via the Canadian Institute for Health Information). We identified ICD-10 diagnostic codes in CCEDRRN participants. We defined lab-confirmed SARS-CoV-2 based on at least one positive PCR in the 0–14 days before the ED presentation and/or during hospitalization (in those admitted from ED). We performed separate analyses for CCEDRRN participants discharged from ED and those hospitalized from the ED. Additional analyses were stratified by province, sex, age, and (for hospitalized patients) timing of the first PCR test. The sensitivity of ICD-10 code U07.1 for a positive SARS-CoV-2 test was 93.6% (95% CI 93.0–94.1%) in those hospitalized from ED and 83.0% (95% CI 82.1–83.9%) in those discharged from the ED. Sensitivity was similar across provinces and demographics, but in each stratified analysis, values were higher in those hospitalized versus those discharged from ED. The ICD-10 diagnostic code for U07.1 within administrative data identified most lab-confirmed SARS-CoV-2 within persons hospitalized from ED, although a significant number of cases discharged from ED were missed. This should be considered when using administrative data for research and public health planning.

Abstract Understanding the efficacy of SARS-CoV-2 vaccination in people on immunosuppressive drugs, including those with rheumatoid arthritis (RA), is critical for their protection. Vaccine induced protection requires antibodies, CD4+ T cells, and CD8+ T cells, but it is unclear if these are equally affected by immunomodulatory drugs. Here, we determined how humoral and cellular SARS-CoV-2 vaccination responses differed between people with RA and controls, and which drug classes impacted these responses. Blood was collected from participants with RA on immunomodulatory drugs and controls after their second, third, and fourth SARS-CoV-2 vaccinations. Receptor binding domain (RBD)-specific antibodies were quantified by ELISA. Spike-specific memory T cells were quantitated using flow cytometry. Linear mixed models assessed the impact of age, sex, and immunomodulatory drug classes on SARS-CoV-2 vaccination responses. Compared to non-RA controls (n = 35), participants with RA on immunomodulatory drugs (n = 62) had lower anti-RBD IgG and spike-specific CD4+ T cell levels, but no deficits in spike-specific CD8+ T cells, following SARS-CoV-2 vaccination. Use of costimulation inhibitors was associated with lower humoral responses. JAK inhibitors were associated with fewer spike-specific CD4+ T cells. Participants with RA on immunomodulatory drugs mounted weaker responses to SARS-CoV-2 vaccination, with different drug classes impacting the cellular and humoral compartments.

Abstract Background Due to the paucity of paediatric rheumatologists in Kenya, it is paramount that we explore strategies to bridge clinical care gaps for paediatric rheumatology patients in order to promote early diagnosis, prompt referral, and optimal management. Purpose To identify proposed interventions which can improve the ability of non-specialist healthcare workers to care for paediatric rheumatology patients across Kenya. Methods We conducted 12 focus group discussions with clinical officers (community physician assistants), nurses, general practitioners and paediatricians across six regions in Kenya. Interviews were conducted, audio-recorded, transcribed verbatim, and analysed using MAXQDA 2022.2 software. Results A total of 68 individuals participated in the study; 11 clinical officers, 12 nurses, 10 general practitioners, 27 paediatricians and eight other healthcare workers. Proposed patient interventions included patient education and psychosocial support. Community interventions were outreach awareness campaigns, mobilising financial support for patients’ care, mobilising patients to access diagnostic and therapeutic interventions. Healthcare worker interventions include diagnostic, management, and referral guidelines, as well as research and educational interventions related to symptom identification, therapeutic strategies, and effective patient communication skills. In addition, it was highlighted that healthcare systems should be bolstered to improve insurance coverage and access to integrated multi-disciplinary clinical care. Conclusions Study participants were able to identify potential initiatives to improve paediatric rheumatology care in Kenya. Additional efforts are underway to design, implement and monitor the impact of some of these potential interventions,

We were tasked by Canada’s COVID-19 Immunity Task Force to describe severe adverse events (SAEs) associated with emergency department (ED) visits and/or hospitalizations in individuals with immune-mediated inflammatory diseases (IMIDs). At eight Canadian centres, data were collected from adults with rheumatoid arthritis (RA), axial spondyloarthritis (AxS), systemic lupus (SLE), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). We administered questionnaires, analyzing SAEs experienced within 31 days following SARS-CoV-2 vaccination. About two-thirds (63%) of 1556 participants were female; the mean age was 52.5 years. The BNT162b2 (Pfizer) vaccine was the most common, with mRNA-1273 (Moderna) being second. A total of 49% of participants had IBD, 27.4% had RA, 14.3% had PsA, 5.3% had SpA, and 4% had SLE. Twelve (0.77% of 1556 participants) SAEs leading to an ED visit or hospitalization were self-reported, occurring in 11 participants. SAEs included six (0.39% of 1556 participants) ED visits (including one due to Bell’s Palsy 31 days after first vaccination) and six (0.39% of 1556 participants) hospitalizations (including one due to Guillain-Barré syndrome 15 days after the first vaccination). Two SAEs included pericarditis, one involved SLE (considered a serious disease flare), and one involved RA. Thus, in the 31 days after SARS-CoV-2 vaccination in our IMID sample, very few serious adverse events occurred. As SARS-CoV2 continues to be a common cause of death, our findings may help optimize vaccination acceptance.

Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied the effects of methotrexate and tumor necrosis factor inhibitor (TNFi) on neutralization responses after COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Methods: Prospective data and sera of adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and systemic lupus (SLE) were collected at six academic centers in Alberta, Manitoba, Ontario, and Quebec between 2022 and 2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between five laboratories, and each lab’s results were analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for the effects of methotrexate and TNFi were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID-19 vaccinations (number/type), and infections in the 6 months prior to sampling. The adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for the ancestral strains and the Omicron BA1 and BA5 strains). Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) were RA, and the remainder were PsA, SpA, and SLE. The mean age was 57 (62.2% female). For both the individual labs and the meta-analyses, the adjusted ORs suggested independent negative effects of TNFi and methotrexate on neutralization. The meta-analysis adjusted ORs for TNFi were 0.56 (95% confidence interval (CI) 0.39, 0.81) for the ancestral strain and 0.56 (95% CI 0.39, 0.81) for BA5. The meta-analysis adjusted OR for methotrexate was 0.39 (95% CI 0.19, 0.76) for BA1. Conclusions: SARS-CoV-2 neutralization in vaccinated IMID was diminished independently by TNFi and methotrexate. As SARS-CoV-2 circulation continues, ongoing vigilance regarding optimized vaccination is required.

Background Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort.Methods Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up.Results Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1).Conclusion Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis.

Abstract Background Antibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX). Methods We identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011–2020). TMP-SMX prophylaxis was defined as a $$\ge$$ ≥ 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities. Results Among 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83–248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX ( $$\ge$$ ≥ 20 mg/day vs none, OR 3.96; 95% CI 3.0–5.2; 1–19 mg/day vs none, OR 2.63; 95% CI 1.8–3.8), and methotrexate use (OR 1.48, 95% CI 1.04–2.1), intensive care (OR 1.95; 95% CI 1.4–2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2–2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5–0.8) was negatively associated with TMP-SMX use. Conclusions TMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV.

Objective To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease.Methods We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed.Results Frequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2–53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection.Conclusion In COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.

Abstract Background Delay in diagnosis and access to specialist care is a major problem for many children and young people with rheumatic disease in sub-Saharan Africa. Most children with symptoms of rheumatic disease present to non-specialists for care. There is an urgent need to understand and scale-up paediatric rheumatology knowledge and skills amongst non-specialist healthcare workers to promote early diagnosis, prompt referral, and management. Purpose We evaluated the knowledge, attitudes and practices towards diagnosis and care of paediatric rheumatology patients among health care workers in Kenya. Methods We conducted 12 focus group discussions with clinical officers (third-tier community health workers) nurses, general practitioners and paediatricians across 6 regions in Kenya. Interviews were conducted on zoom, audio-recorded, transcribed, and analysed using NVIVO software. Results A total of 68 individuals participated; 11 clinical officers, 12 nurses, 10 general practitioners, 27 paediatricians and 7 others. Most (n = 53) were female, and the median age was 36 years (range 31–40 years). Fifty per cent of the participants (34 of 68) worked in public health facilities. Our study revealed gaps in knowledge of paediatric rheumatology amongst healthcare workers which contributes to delayed diagnosis and poor management. Healthcare workers reported both positive and negative attitudes towards diagnosis and care of paediatric rheumatology patients. Perceived complexity and lack of knowledge in diagnosis, management and lack of health system clinical pathways made all cadres of healthcare workers feel helpless, frustrated, inadequate and incompetent to manage paediatric rheumatology patients. Positive attitudes arose from a perceived feeling that paediatric rheumatology patients pose unique challenges and learning opportunities. Conclusion There is an urgent need to educate healthcare workers and improve health systems to optimize clinical care for paediatric rheumatology patients.

Abstract Introduction Although short-term clinical trials have demonstrated that switching from infliximab (INF) bio-originator to its biosimilar is safe with no significant loss of efficacy, there are limited real-world data comparing their patterns of use and adherence. Methods Using 2015–2018 IBM Marketscan data, we established 4 cohorts of patients with at least one administration or pharmacy claim for INF bio-originator or biosimilar in 2017, including INF naïve biosimilar users, INF prevalent biosimilar users, INF naïve bio-originator users, and INF prevalent bio-originator users, defined according to their prior use of INF from 2015 to their first INF administration in 2017. The proportion of days covered (PDC) was calculated for patients with at least 6, 12, or 18 months of follow-up time. Factors associated with optimal adherence (PDC > 80%) were evaluated using log-binomial models. Results We identified 96 INF naïve biosimilar users, 223 INF prevalent biosimilar users, 2,149 INF naïve bio-originator users, and 10,970 INF prevalent bio-originator users. At the end of 18 months of follow-up, 64% of INF prevalent bio-originators, 48% of INF naïve biosimilars, 41% of INF naïve bio-originators, and 36% of INF prevalent biosimilars had optimal adherence. Depression, previous hospitalization, and greater use of prior biologics were negatively associated with adherence, whereas IBD diagnoses (referent to RA) and age 55–64 (referent to

Abstract Background Individuals living with a rheumatic pain condition can face delays in accessing pain clinics, which prevents them from receiving timely treatment. Little is known regarding their specific healthcare utilization in order to alleviate pain while waiting to obtain services in pain clinics. Hence, the aim of this study was to explore the perceptions and experiences of persons living with rheumatic conditions regarding healthcare utilization while waiting to access a pain clinic. Methods In this qualitative descriptive study, semi-structured interviews were conducted with adults living with a painful rheumatic condition that reported either being waiting for admission in a pain clinic, having been referred but then denied pain clinic services, or having received services during the previous six months, in the province of Quebec, Canada. The interviews were transcribed verbatim, and an inductive thematic analysis was performed. Results Twenty-six individuals were interviewed (22 women and 4 men; mean age 54 ± 10 years). Three themes were identified: 1) lacking guidance in identifying solutions to their complex and multidimensional needs, 2) struggling to obtain and maintain services due to systemic access barriers, and 3) displaying resilience through a search for accessible and sustainable self-management strategies. Conclusions The current approaches and structures of health services fail to adequately answer the service needs of individuals experiencing painful rheumatic conditions. Important shifts are required in pain education, in increasing access to multidisciplinary approaches at the primary care level and in breaking down barriers individuals with chronic pain face to receive appropriate and timely care.

Abstract Objectives To estimate associations between fine particulate matter (PM2.5) and ozone and the onset of systemic autoimmune rheumatic diseases (SARDs). Methods An open cohort of over 6 million adults was constructed from provincial physician billing and hospitalization records between 2000 and 2013. We defined incident SARD cases (SLE, Sjogren’s syndrome, scleroderma, polymyositis, dermatomyositis, polyarteritis nodosa and related conditions, polymyalgia rheumatic, other necrotizing vasculopathies, and undifferentiated connective tissue disease) based on at least two relevant billing diagnostic codes (within 2 years, with at least 1 billing from a rheumatologist), or at least one relevant hospitalization diagnostic code. Estimated PM2.5 and ozone concentrations (derived from remote sensing and/or chemical transport models) were assigned to subjects based on residential postal codes, updated throughout follow-up. Cox proportional hazards models with annual exposure levels were used to calculate hazard ratios (HRs) for SARDs incidence, adjusting for sex, age, urban-versus-rural residence, and socioeconomic status. Results The adjusted HR for SARDS related to one interquartile range increase in PM2.5 (3.97 µg/m3) was 1.12 (95% confidence interval 1.08–1.15), but there was no clear association with ozone. Indirectly controlling for smoking did not alter the findings. Conclusions We found associations between SARDs incidence and PM2.5, but no relationships with ozone. Additional studies are needed to better understand interplays between the many constituents of air pollution and rheumatic diseases.

Background: Past investigations of air pollution and systemic autoimmune rheumatic diseases (SARDs) typically focused on individual (not mixed) and overall environmental emissions. We assessed mixtures of industrial emissions of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and sulfur dioxide (SO2) and SARDs onset in Ontario, Canada. Methods: We assembled an open cohort of over 12 million adults (without SARD diagnoses at cohort entry) based on provincial health data for 2007–2020 and followed them until SARD onset, death, emigration, or end of study (December 2020). SARDs were identified using physician billing and hospitalization diagnostic codes for systemic lupus, scleroderma, myositis, undifferentiated connective tissue disease, and Sjogren’s. Rheumatoid arthritis and vasculitis were not included. Average PM2.5, NO2, and SO2 industrial emissions from 2002 to one year before SARDs onset or end of study were assigned using residential postal codes. A quantile g-computation model for time to SARD onset was developed for the industrial emission mixture, adjusting for sex, age, income, rurality index, chronic obstructive pulmonary disease (as a proxy for smoking), background (environmental overall) PM2.5, and calendar year. We conducted stratified analyses across age, sex, and rurality. Results: We identified 43,931 new SARD diagnoses across 143,799,564 person-years. The adjusted hazard ratio for SARD onset for an increase in all emissions by one decile was 1.018 (95% confidence interval 1.013–1.022). Similar positive associations between SARDs and the mixed emissions were observed in most stratified analyses. Industrial PM2.5 contributed most to SARD risk. Conclusions: Industrial air pollution emissions were associated with SARDs risk.

Objective Patients with rheumatic disease (RD) have an increased risk of influenza and its complications. Despite inactivated influenza vaccine (IIV) recommendations, IIV uptake in patients with RD is suboptimal, a problem of increasing importance in the COVID‐19 era. We estimated the frequency of IIV hesitancy and associated factors among Canadian patients with RD. Methods A cross‐sectional vaccine hesitancy survey was completed by rheumatology clinic patients (November 2019 to January 2020). Patients rated their likelihood of receiving the influenza vaccine (scale of 0‐10). We categorized these as follows: likely to refuse (scale of 0‐2), uncertain (scale of 3‐7), or likely to accept (scale of 8‐10). Multivariate logistical regression was used to evaluate factors associated with vaccine hesitancy. Results A total of 282 patients (63.5% of those approached) completed the survey, with 165 (58.5%) being likely to accept, 67 (23.8%) being likely to refuse, and 50 (17.7%) uncertain. Uncertain patients were younger and more likely to be employed than those in the other two groups. No previous influenza vaccination (odds ratio [OR] 36.6, 95% confidence interval [CI] 5.3‐252.9), belief that vaccination should not be mandatory (OR 0.1, 95% CI 0.0‐0.7), unwillingness to take time off work to be vaccinated (OR 6.8, 95% CI 1.5‐30.6), and distrust in pharmaceutical companies (OR 41.0, 95% CI 5.6‐301.5) predicted likeliness to refuse. Reluctance to pay for vaccination (OR 2.8, 95% CI 1.1‐7.5) and no previous influenza vaccination (OR 18.9, 95% CI 3.3‐109.7) predicted uncertainty. Conclusion More than 40% of rheumatology patients are either likely to refuse or uncertain about receiving IIV. This contributes to suboptimal vaccine coverage in this population. Interventions addressing these concerns are needed, particularly in the COVID‐19 era.

Objective To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.Methods Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity.Results We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09).Conclusions This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.

Abstract Influenza immunization protects seniors against influenza and its potentially serious complications. It is uncertain whether standard-dose (SD) quadrivalent vaccine offers better protection over other formulations in the elderly. In this study, we compared the effectiveness of SD-trivalent, high-dose (HD) trivalent, SD-quadrivalent, and adjuvanted trivalent vaccines in seniors (≥65 years) in a real-world setting. We selected over 200,000 individuals in each of 6 influenza seasons from 2012 to 2018 using MarketScan® databases. The two outcomes were hospitalization or emergency room (ER) visit due to (1) influenza or (2) pneumonia. Here, SD-quadrivalent was associated with higher risk of influenza-related hospitalization/ER visit (adjusted hazard ratio (aHR) 1.14 and 95% confidence interval (95% CI) 1.05–1.24) and of pneumonia-related hospitalization/ER visit (aHR 1.04 and 95% CI 1.01–1.07) vs. HD-trivalent. SD-trivalent followed similar trends compared to HD-trivalent (aHR 1.16 and 95% CI 1.06–1.27 for hospitalized/ER visit influenza; aHR 1.07 and 95% CI 1.05–1.10 for hospitalized/ER visit pneumonia). We could not demonstrate risk differences between SD vaccine formulations and between adjuvanted trivalent and one of the other three vaccines. Risk estimates slightly varied across seasons. These findings suggest that SD vaccine formulations vs. HD-trivalent were associated with higher risk of hospitalization/ER visit for influenza and pneumonia in seniors.

Objective We conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic.Methods Patients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources.Results Surveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference −8.3%, 95% CI −10.2% to −6.5%; family physicians: 57.1% pre vs 50.0% post, difference −7.1%, 95% CI −9.2% to −5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted.Conclusions Physicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation.

Abstract Background Extensive waiting times before receiving services is a major barrier to adequate pain management. Waiting times may have a detrimental impact on patients’ conditions and quality of life. However, there remains a lack of knowledge on the actual experiences of patients waiting to receive services, especially for those with rheumatic conditions. The present study aimed to gain an in-depth understanding of perceptions and experiences of patients with rheumatic conditions regarding access to pain clinic services. The secondary objective was to identify possible solutions to improve this access according to patients’ perspectives. Methods This qualitative study based on semi-structured interviews was conducted with adults with rheumatic conditions waiting to access pain clinics in the province of Quebec, Canada. Interviews were transcribed verbatim and analyzed using thematic content analysis. Results Twenty-six participants were interviewed (22 women and 4 men; mean age 54 ± 10 years). Four main themes were identified: 1) the perception that waiting time is unacceptably long; 2) how the lack of information affects patients’ experiences of waiting; 3) patients’ various expectations towards the pain clinic, from high hopes to disillusionment and 4) carrying an emotional, physical and financial burden resulting from the wait. Participants reported several solutions to improve the experience of waiting, including providing information to patients, increasing resources, improving prioritization processes and care coordination, and providing alternative interventions to patients during the wait. Conclusions For patients with rheumatic conditions, access to pain clinic services is challenging due to extensive waiting times. The burden it imposes on them adds to the existing challenge of living with a chronic rheumatic condition. The solutions identified by participants could serve as building blocks to develop and implement measures to improve patients’ experience of accessing pain-related services.

Abstract Background Access to multidisciplinary pain treatment facilities (MPTF) is limited by extensive waiting time in many countries. However, there is a lack of knowledge about the impact of waiting time on clinical outcomes, particularly for patients with rheumatic conditions. This study examined the association between waiting time for MPTF and clinical outcomes in patients with rheumatic conditions. Methods Data were extracted from the Quebec Pain Registry, a large database of patients who received services in MPTF. The associations between waiting time (classified as 6 months) and change in pain interference, pain intensity and health-related quality of life, from the initial visit at the MPTF to the 6-month follow-up, were tested using generalized estimating equations. Results A total of 3230 patients with rheumatic conditions (mean age: 55.8 ± 14.0 years; 66% were women) were included in the analysis. Small significant differences in improvement between waiting time groups were revealed, with patients waiting less than 2 months having a larger improvement in all clinical outcomes compared to patients who waited 2–6 months or over 6 months before their initial visit (adjusted time X group effect p ≤ 0.001). Only patients waiting less than 2 months reached a clinically important improvement in pain interference (1.12/10), pain intensity (1.3/10) and physical and mental quality of life (3.9 and 3.7/100). Conclusions Longer delays experienced by patients before receiving services in MPTF were associated with statistically significant smaller improvements in pain interference, pain intensity and health-related quality of life; these differences were, however, not clinically significant. Based on these results, we advise that strategies are developed not only to reduce waiting times and mitigate their impacts on patients with rheumatic conditions, but also to improve treatment effectiveness in MPTF.

Abstract Background Studies of associations between industrial air emissions and rheumatic diseases, or diseases-related serological biomarkers, are few. Moreover, previous evaluations typically studied individual (not mixed) emissions. We investigated associations between individual and combined exposures to industrial sulfur dioxide (SO2), nitrogen dioxide (NO2), and fine particles matter (PM2.5) on anti-citrullinated protein antibodies (ACPA), a characteristic biomarker for rheumatoid arthritis (RA). Methods Serum ACPA was determined for 7600 randomly selected CARTaGENE general population subjects in Quebec, Canada. Industrial SO2, NO2, and PM2.5 concentrations, estimated by the California Puff (CALPUFF) atmospheric dispersion model, were assigned based on residential postal codes at the time of sera collection. Single-exposure logistic regressions were performed for ACPA positivity defined by 20 U/ml, 40 U/ml, and 60 U/ml thresholds, adjusting for age, sex, French Canadian origin, smoking, and family income. Associations between regional overall PM2.5 exposure and ACPA positivity were also investigated. The associations between the combined three industrial exposures and the ACPA positivity were assessed by weighted quantile sum (WQS) regressions. Results Significant associations between individual industrial exposures and ACPA positivity defined by the 20 U/ml threshold were seen with single-exposure logistic regression models, for industrial emissions of PM2.5 (odds ratio, OR = 1.19, 95% confidence intervals, CI: 1.04–1.36) and SO2 (OR = 1.03, 95% CI: 1.00–1.06), without clear associations for NO2 (OR = 1.01, 95% CI: 0.86–1.17). Similar findings were seen for the 40 U/ml threshold, although at 60 U/ml, the results were very imprecise. The WQS model demonstrated a positive relationship between combined industrial exposures and ACPA positivity (OR = 1.36, 95% CI: 1.10–1.69 at 20 U/ml) and suggested that industrial PM2.5 may have a closer association with ACPA positivity than the other exposures. Again, similar findings were seen with the 40 U/ml threshold, though 60 U/ml results were imprecise. No clear association between ACPA and regional overall PM2.5 exposure was seen. Conclusions We noted positive associations between ACPA and industrial emissions of PM2.5 and SO2. Industrial PM2.5 exposure may play a particularly important role in this regard.

BackgroundGiven that pregnant women taking medications are excluded from clinical trials, real-world evidence is essential. We aimed to build a Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO) and compare frequency of prematurity, low-birth-weight (LBW), major malformations, multiplicity, and gestational medication use across four provinces.MethodsCAMCCO is a collaborative research infrastructure that uses real-world data from large provincial health care databases in Canada; developed with standardized methods to similarly construct population-based pregnancy/child cohorts with longitudinal follow-up by linking administrative/hospital/birth databases. CAMCCO also includes a common repository to i) share algorithms and case definitions based on diagnostic and procedural codes for research/training purpose, and ii) download aggregate data relevant to primary care providers, researchers, and decision makers. For this study, data from Quebec (1998-2015), Manitoba (1995-2019), Saskatchewan (1996-2020), and Alberta (2005-2018) are compared (Chi-square tests, p-values), and trends are calculated using Cochran-Armitage trend tests.ResultsAlmost two-thirds (61%) of women took medications during pregnancy, mostly antibiotics (26%), asthma drugs (8%), and antidepressants (4%). Differences in the prevalence of prematurity (5.9-6.8%), LBW (4.0-5.2%), and multiplicity (1.0-2.5%) were statistically significant between provinces (pInterpretationMedications are often used among Canadian pregnancies but adverse pregnancy outcomes vary across provinces. Digitized health data may help researchers and care providers understand the risk-benefit ratios related to gestational medication use, as well as province-specific trends.

Objective Hypertension (HTN) is common in systemic lupus erythematosus (SLE), representing a key risk factor for cardiovascular and renal disease. We described HTN treatment patterns in SLE, evaluated uncontrolled HTN according to Canadian and American guidelines and identified factors associated with uncontrolled HTN.Methods We performed a cross-sectional study, identifying all McGill Lupus Clinic registry patients with an annual visit between January 2017 and May 2019 who were taking HTN medications. We excluded those taking medications only for another indication (eg, Raynaud’s). We determined the frequency of uncontrolled HTN according to Canadian and American College of Cardiology/American Heart Association guidelines. Multivariate logistic regression (adjusted for age, sex and race/ethnicity) evaluated if uncontrolled HTN was more common with high body mass index (BMI), longer SLE duration, high disease activity, renal damage, multiple concomitant antihypertensives, prednisone and non-steroidal anti-inflammatory drugs.Results Of 442 patients with SLE, 108 were taking medications to treat HTN, and 38 took multiple medications concurrently. Angiotensin-receptor blockers were most common, followed by calcium channel blockers, diuretics, angiotensin-converting enzyme inhibitors and beta blockers. Among the 108 patients, 39.8% (n=43) had blood pressure (BP) >140/90 mm Hg, while 66.7% (n=72) had BP >130/80 mm Hg. In multivariate analyses, uncontrolled HTN (>130/80 mm Hg) was more likely in Caucasians (OR 2.72, 95% CI 1.12 to 6.78) and patients with higher BMI (OR 1.08, 95% CI 1.00 to 1.19). Patients with renal damage had better HTN control (OR 0.39, 95% CI 0.16 to 0.97). We could not draw definitive conclusions regarding other variables.Conclusion Caucasians and patients with higher BMI had more uncontrolled HTN. The negative association with renal damage is reassuring, as controlled BP is key for renal protection.

We assessed the frequency and correlates of COVID-19 vaccine hesitancy before Canada’s vaccine rollout. A cross-sectional vaccine hesitancy survey was completed by consecutive patients/family members/staff who received the influenza vaccine at McGill University affiliated hospitals. Based on the self-reported likelihood of receiving a future vaccine (scale 0–10), the following three groups were defined: non-hesitant (score 10), mildly hesitant (7.1–9.9), and significantly hesitant (0–7). Factors associated with vaccine hesitancy were assessed with multivariate logistic regression analyses and binomial logistic regression machine learning modelling. The survey was completed by 1793 people. Thirty-seven percent of participants (n = 669) were hesitant (mildly: 315 (17.6%); significantly: 354 (19.7%)). Lower education levels, opposition and uncertainty about vaccines being mandatory, feelings of not receiving enough information about COVID-19 prevention, perceived social pressure to get a future vaccine, vaccine safety concerns, uncertainty regarding the vaccine risk-benefit ratio, and distrust towards pharmaceutical companies were factors associated with vaccine hesitancy. Vaccine safety concerns and opposition to mandatory vaccinations were the strongest correlates of vaccine hesitancy in both the logistic regressions and the machine learning model. In conclusion, in this study, over a third of people immunized for influenza before the COVID-19 vaccine rollout expressed some degree of vaccine hesitancy. Effectively addressing COVID-19 vaccine safety concerns may enhance vaccine uptake.

Introduction: Chloroquine (CQ) and hydroxychloroquine (HCQ) are currently used for the prevention/treatment of malaria, and treatment of systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Although present data do not show their efficacy to treat COVID-19, they have been used as potential treatments for COVID-19. Given that pregnant women are excluded from randomized controlled trials, and present evidence are inconsistent and inconclusive, we aimed to investigate the safety of CQ or HCQ use in a large pregnancy cohort using real-world evidence.Methods: Using Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn, 1998–2015, (n = 233,748). The exposure time window for analyses on prematurity and low birth weight (LBW) was the second/third trimesters; was any time during pregnancy; only first trimester exposure was considered for analyses on major congenital malformations (MCM). The risk of prematurity, LBW, and MCM (overall and organ-specific) were quantified using generalized estimation equations.Results: We identified 288 pregnancies (0.12%) exposed to CQ (183, 63.5%) or HCQ (105, 36.5%) that resulted in liveborn singletons; CQ/HCQ was used for RA (17.4%), SLE (16.3%) or malaria (0.7%). CQ/HCQ was used for 71.8 days on average [standard-deviation (SD) 70.5], at a dose of 204.3 mg/d (SD, 155.6). We did not observe any increased risk related to CQ/HCQ exposure for prematurity (adjusted odds ratio [aOR] 1.39, 95%CI 0.84–2.30), LBW (aOR 1.11, 95%CI 0.59–2.06), or MCM (aOR 1.01, 95%CI 0.67–1.52).Conclusion: in this large CQ/HCQ exposed pregnancy cohort, we saw no clear increased risk of prematurity, LBW, or MCM, although number of exposed cases remained low.

The original coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country’s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world’s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada’s first 118 COVID-19 cases were related to travelers from China. The most commonly reported travel history among the 118 cases related to the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may have helped control global COVID-19 spread.

Abstract Background Good communication is central to a high-quality consultation process. We assessed the quality of referral information from primary care physicians (PCPs) to rheumatologists and the quality and timeliness of consultation letters from rheumatologists back to PCPs. Methods We sampled referral letters between 2000 and 2013 from 168 PCPs and performed a retrospective chart review of 2430 patients referred to 146 rheumatologists. We assessed the completeness and timeliness of referral and consultation letters. Results Osteoarthritis (n = 787, 32%) and systemic inflammatory rheumatic diseases (n = 745, 31%) comprised the top reasons for referral. Only 55% of referral letters summarized the patients’ medical history. Referral letters provided some details of diagnostic tests (51% labs, 34% imaging) but there was underreporting of this information on referral letters. Almost all referral letters (92%) contained details of at least one patient symptom, with the most common complaint being joint pain (54%). Only half of all referral letters provided symptom duration. The PCP only stressed an urgent consultation among 211 patients (9%). Overall, 69% of consultation letters were returned to PCPs within 30 days of consultation visit. Conclusion We found that basic items necessary for appropriate triage, including a description of symptoms or other relevant history and results of investigations were often lacking in referral letters. The delay of receipt of consultation letters may further represent a lost opportunity for coordination and continuity of care, and may affect the quality of care patients receive.

Obesity and related metabolic complications represent an important health burden. Here the authors carry out a methylC-capture sequencing-based epigenome-wide association study to link circulating plasma lipid levels, CpG methylation and cardiometabolic risk across adipose and blood tissues.

Objective In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence.Methods We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966–October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with

BackgroundMedications already available to treat other conditions are presently being studied in clinical trials as potential treatments for COVID-19. Given that pregnant women are excluded from these trials, we aimed to investigate their safety when used during pregnancy within a unique population source.MethodsUsing the population-based Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn (1998-2015). Taking potential confounders into account including indications for use, the risk of prematurity, low birth weight (LBW), small for gestational age (SGA), and major congenital malformation (MCM) associated with COVID-19 repurposed drug use during pregnancy were quantified using generalized estimation equations.ResultsOf the 231,075 eligible pregnancies, 107 were exposed to dexamethasone (0.05%), 31 to interferons (0.01%), 1,398 to heparins (0.60%), 24 to angiotensin-receptor blockers (ARB) (0.01%), 182 to chloroquine (0.08%), 103 to hydroxychloroquine (0.05%), 6,206 to azithromycin (2.70%), 230 to oseltamivir (0.10%), and 114 to HIV medications (0.05%). Adjusting for potential confounders, we observed an increased risk of prematurity related to dexamethasone (aOR 1.92, 95%CI 1.11-3.33; 15 exposed cases), anti-thrombotics (aOR 1.58, 95%CI 1.31-1.91; 177 exposed cases), and HIV medications (aOR 2.04, 95%CI 1.01-4.11; 20 exposed cases) use. An increased risk for LBW associated with anti-thrombotics (aOR 1.72, 95%CI 1.41-2.11; 152 exposed cases), and HIV medications (aOR 2.48, 95%CI 1.25-4.90; 21 exposed cases) use were also found. Gestational exposure to anti-thrombotics (aOR 1.20, 95%CI 1.00-1.44; 176 exposed cases), and HIV medications (aOR 2.61, 95%CI 1.51-4.51; 30 exposed cases) were associated with SGA. First-trimester dexamethasone (aOR 1.66, 95%CI 1.02-2.69; 20 exposed cases) and azithromycin (aOR 1.10, 95%CI 1.02-1.19; 747 exposed cases) exposures were associated with MCM.ConclusionsMany available medications considered as treatments for COVID-19 are associated with adverse pregnancy outcomes. Caution is warranted when considering these medications during the gestational period.

Summary: Objective: To estimate the 1) accuracy of algorithms for identifying osteoarthritis (OA) using health administrative data; and 2) population-level OA prevalence and incidence over time in Ontario, Canada. Method: We performed a retrospective chart abstraction study to identify OA patients in a random sample of 7500 primary care patients from electronic medical records. The validation sample was linked with several administrative data sources. Accuracy of administrative data algorithms for identifying OA was tested against two reference standard definitions by estimating the sensitivity, specificity and predictive values. The validated algorithms were then applied to the Ontario population to estimate and compare population-level prevalence and incidence from 2000 to 2017. Results: OA prevalence within the validation sample ranged from 10% to 23% across the two reference standards. Algorithms varied in accuracy depending on the reference standard, with the sensitivity highest (77%) for patients with OA documented in medical problem lists. Using the top performing administrative data algorithms, the crude population-level OA prevalence ranged from 11% to 25% and standardized prevalence ranged from 9 to 22% in 2017. Over time, prevalence increased whereas incidence remained stable (~1% annually). Conclusion: Health administrative data have limited sensitivity in adequately identifying all OA patients and appear to be more sensitive at detecting OA patients for whom their physician formally documented their diagnosis in medical problem lists than individuals who have their diagnosis documented outside of problem lists. Irrespective of the algorithm used, OA prevalence has increased over the past decade while annual incidence has been stable.

Background: Air pollution has many adverse health effects, but the combined or synergistic effects of multiple ambient air pollutants on anti-nuclear antibodies (ANA, a serologic marker of systemic autoimmune rheumatic disease, SARDs) have never been assessed. Objective: To flexibly model ANA and individual and joint associations of long-term exposures to nitrogen dioxide (NO2), ozone (O3), and fine particles matter (PM2.5) using a Bayesian Kernel machine regression (BKMR) approach and to compare the results to those from individual logistic regressions. Methods: Serum ANA positivity was determined for randomly selected CARTaGENE general population subjects in Quebec, Canada. CARTaGENE is a public research platform created for investigating the associations of environmental, genomic, and lifestyle factors on chronic diseases. Ambient NO2, O3, and PM2.5 estimates, derived from ground-measurement and chemical-transport-model simulated concentrations, were assigned to subjects based on residential postal codes at the time of blood collection. Our models adjusted for age, sex, French Canadian origin, smoking, and family income. Results: Concentrations of NO2, O3, and PM2.5 were closely correlated in space. In the 5485 CARTaGENE subjects studied, we did not see clear associations between NO2, PM2.5 or O3 and ANA positivity, with either the BKMR or logistic models. Conclusions: BKMR did not uncover associations between ANA positivity and individual levels or combined exposures of NO2, O3, and PM2.5; neither did simpler logistic models. Additional studies (in younger populations, in distinct race/ethnicity groups, and/or in jurisdictions with high air pollution levels) would be helpful to reinforce current findings. Keywords: Anti-nuclear antibodies (ANAs), Nitrogen dioxide (NO2), Ozone (O3), Fine particles matter (PM2.5), Bayesian kernel machine regression (BKMR)

Background Population health studies often use existing databases that are not necessarily constituted for research purposes. The question arises as to whether different data sources such as in administrative health data (AHD) and self-report questionnaires are equivalent and lead to similar information. Objectives The main objective of this study was to assess the level of agreement between self-reported medical conditions and medical diagnosis captured in AHD. A secondary objective was to identify predictors of agreement among medical conditions between the two data sources. Therefore, the purposes of the study were to explore the extent to which these two methods of commonly used public health data collection provide concordant records and identify the main predictors of statistical variations. Methods Data was extracted from CARTaGENE, a population-based cohort study in Québec, Canada, which was linked to the provincial health insurance records of the same individuals, namely the MED-ÉCHO database from the Régie de l’assurance maladie du Québec (RAMQ) and the fee-for-service billing records provided by the physician, for the time period 1998-2012. Agreement statistics (kappa coefficient) along with sensitivity, specificity and predictive positive value were calculated for 19 chronic conditions and 12 types of cancers. Logistic regressions were used to identify predictors of concordance between self-report and AHD from significant covariates (sex, age groups, education, region, income, heavy utilization of health care system and Charlson comorbidity index). Results Agreement between self-reported data and AHD across diseases ranged from kappa of 0.09 for chronic renal failure to 0.86 for type 2 diabetes. Sensitivity of self-reported data was higher than 50% for 14 out of the 31 medical conditions studied, especially for myocardial infarction (88.62%), breast cancer (86.28%), and diabetes (85.06%). Specificity was generally high with a minimum value of 89.70%. Lower concordance between data sources was observed for higher frequency of health care utilization and higher comorbidity scores. Discussion Overall, there was moderate agreement between the two data sources but important variations were found depending on the type of disease. This suggests that CARTaGENE’s participants were generally able to correctly identify the kind of diseases they suffer from, with some exceptions. These results may help researchers choose adequate data sources according to specific study objectives. These results also suggest that Québec’s AHD seem to underestimate the prevalence of some chronic conditions, which might result in inaccurate estimates of morbidity with consequences for public health surveillance.

Background Randomized controlled trials showed that newer glucose‐lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women. Methods and Results Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium‐glucose‐like transport‐2 inhibitors (SGLT‐2i), glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), dipeptidyl peptidase‐4 inhibitors, initiated as second‐line agents relative to sulfonylureas (reference‐group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas, SGLT‐2i, GLP‐1RA, or dipeptidyl peptidase‐4 inhibitors (Marketscan‐Database: 2011–2017). We used multivariable Cox proportional hazards models with time‐varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex–drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5‐year follow‐up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000‐person‐year). Compared with sulfonylureas, hazard ratios (HRs) for cardiovascular events were lower with GLP‐1RA (adjusted HR‐women: 0.57, 95% CI: 0.48–0.68; aHR‐men: 0.82, 0.71–0.95), dipeptidyl peptidase‐4 inhibitors (aHR‐women: 0.83, 0.77–0.89; aHR‐men: 0.85, 0.79–0.91) and SGLT‐2i (aHR‐women: 0.58, 0.46–0.74; aHR‐men: 0.69, 0.57–0.83). A sex‐by‐drug interaction was statistically significant only for GLP‐1RA (P=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for GLP‐1RA (aHR‐women: 0.81, 0.73–0.89; aHR‐men: 0.80, 0.71–0.89), dipeptidyl peptidase‐4 inhibitors (aHR‐women: 0.82, 0.78–0.87; aHR‐men: 0.83, 0.78–0.87) and SGLT‐2i (aHR‐women: 0.68, 0.59–0.78; aHR‐men: 0.67, 0.59–0.78) (all sex–drug interactions for adverse events P>0.05). Conclusions Newer glucose‐lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of GLP‐1RA in women than men. Overall, they appeared safe, with a better safety profile for SGLT‐2i than for GLP‐1RA regardless of sex.

Abstract Background Tofacitinib is the first oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA). We compared the effectiveness and safety of tofacitinib, disease-modifying antirheumatic drugs (DMARDs), tumor necrosis factor inhibitors (TNFi), and non-TNF biologics in patients with RA previously treated with methotrexate. Methods We used MarketScan® databases (2011–2014) to study methotrexate-exposed patients with RA who were newly prescribed tofacitinib, DMARDs other than methotrexate, and biologics. The date of first prescription was defined as the cohort entry. The therapy was considered effective if all of the following criteria from a claims-based algorithm were achieved at the first year of follow-up: high adherence, no biologic or tofacitinib switch or addition, no DMARD switch or addition, no increase in dose or frequency of index drug, no more than one glucocorticoid joint injection, and no new/increased oral glucocorticoid dose. The safety outcome was serious infections requiring hospitalization. Non-TNF biologics comprised the reference group. Results We included 21,832 patients with RA, including 0.8% treated with tofacitinib, 24.7% treated with other DMARDs, 61.2% who had started therapy with TNFi, and 13.3% treated with non-TNF biologics. The rates of therapy effectiveness were 15.4% for tofacitinib, 11.1% for DMARDs, 18.6% for TNFi, and 19.8% for non-TNF biologics. In adjusted analyses, tofacitinib and non-TNF biologics appeared to have similar effectiveness rates, whereas DMARD initiators were less effective than non-TNF biologics. We could not clearly establish if tofacitinib was associated with a higher rate of serious infections. Conclusions In patients with RA previously treated with methotrexate, our comparisons of tofacitinib with non-TNF biologics, though not definitive, did not demonstrate differences with respect to hospitalized infections or effectiveness.

Abstract Background In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE. Methods We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort. This included 216 patients with NP events and two matched controls with SLE but no NP events for each of these patients. For the NP patients we tested samples taken before, during and after the NP event. Results Twenty-six patients had events attributed to SLE according to the most stringent SLICC attribution rule. In these patients there was no association between onset of event and elevated serum NN. In 190 patients in whom events were not attributed to SLE by the SLICC rules, median serum NN was elevated at the onset of event (P = 0.006). The predominant clinical features in this group of 190 patients were headache, mood disorders and anxiety. Conclusions Serum NN levels rise at the time of an NP event in a proportion of patients with SLE. Further studies are needed to determine the value of serum NN as a biomarker for NPSLE.