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Background There is limited information about mortality rates among patients with psoriasis and psoriatic arthritis (PsA) in North America and their change over the past 2 decades. Objective To compare all-cause and cause-specific mortality rates in patients with psoriasis to the general population in Ontario, Canada, from 1996 to 2016. Methods We conducted a population-based, retrospective cohort study of adult residents using administrative health data. All-cause and cause-specific standardized mortality rates, standardized mortality ratios, and excess mortality rates were calculated. Results 176,858 (2,524 deaths) patients with psoriasis and 15,430 (221 deaths) patients with PsA were identified in 2016. Patients with psoriasis and PsA had standardized excess mortality rates of 1.44 and 2.43 per 1000 population, respectively. Standardized mortality rates decreased by approximately 30% over the study period in both disease groups but remained significantly elevated compared to the general population. The leading causes of death in psoriasis and PsA patients were cancer, circulatory disease, and respiratory conditions. Limitations We were unable to classify patients according to disease severity. Conclusions Despite improvements in psoriasis treatment, the relative excess mortality, which may be related to risk factors for psoriatic disease, remained unchanged, with an average of approximately 1 to 2 extra deaths per 1,000 patients in 2016.

Background Recent randomized control trials have described a protective cardiovascular effect of novel glucose lowering drugs in patients at high cardiovascular risk. Whether these second-line agents have similar effects in the general population is unknown. We aimed to compare the risk of major cardiovascular and adverse events in new users of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitor (DPP-4i), glucagon-like peptide 1 agonist (GLP-1a), and sulfonylurea in T2DM patients not controlled on metformin therapy. Methods Retrospective cohort study using the MarketScan database (2011–2015). We selected T2DM individuals who were newly dispensed sulfonylureas, SGLT-2i, DPP-4i, or GLP-1a, as second-line therapy, added to metformin. Cohort entry was defined by date of first prescription of the second-line agent. Time to first non-fatal cardiovascular or adverse event was compared using Cox regression models adjusted for confounders. Results Among 118,341 T2DM patients using metformin (mean age: 56), most were at low cardiovascular risk (4% with previous cardiovascular or cerebrovascular event). During a median follow-up of 10 months compared with sulfonylureas users, cardiovascular risk was lower in users of SGLT-2i (aHR = 0.61; 95% CI: 0.40–0.97), DPP-4i (aHR = 0.79; 95% CI: 0.69–0.90) and GLP-1a (aHR = 0.65; 95% CI: 0.48–0.89). Serious adverse events were rare but compared with sulfonylurea, the risk was lower in new users of novel glucose lowering agents. Conclusion In our analyses, which included patients with and without prior cardiovascular disease, initiating novel glucose lowering drugs as second-line therapy for T2DM was associated with a lower risk of cardiovascular and adverse events than sulfonylurea initiation.

Summary Background Patients with rheumatoid arthritis have increased risk of seasonal influenza and influenza-related complications but have reduced vaccine immunogenicity. It is unknown whether patients with rheumatoid arthritis would benefit from more immunogenic vaccine formulations. This study investigated the immunogenicity and safety of a high-dose trivalent inactivated influenza vaccine (HD-TIV) in patients with rheumatoid arthritis compared to a standard-dose quadrivalent influenza vaccine (SD-QIV). Methods This study was a treatment-stratified, randomised, double-blind trial to compare the immunogenicity and safety of SD-QIV (15 μg of haemagglutinin [HA] per strain) versus HD-TIV (60 μg of HA per strain) in adults with rheumatoid arthritis who are positive for rheumatoid factor or anti-cyclic citrullinated peptide, or both, recruited during the 2016–17 and 2017–18 influenza seasons at three hospitals affiliated with McGill University (Montreal, QC, Canada). Participants had received treatment for rheumatoid arthritis with conventional or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) or biological DMARDs, or combinations of them, were still on treatment at the time of enrolment, and their treatment had not been modified during the 3 months before enrolment. They were stratified into one of three groups according to treatment. Patients who, at enrolment, were taking conventional or targeted synthetic DMARDs (methotrexate, hydroxychloroquine, and sulfasalazine) as monotherapy or in combination were stratified to group 1; those who were taking a biological DMARD (anti-tumour necrosis factor or anti-interleukin 6), with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 2; and those who were taking abatacept, tofacitinib, or rituximab, with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 3. Participants were randomly allocated (1:1) to receive the SD-QIV or HD-TIV vaccine. Randomisation was based on a computer-generated allocation sequence, and participants, investigators, and research nurses responsible for safety assessments were masked to vaccine assignment. The primary outcome was the seroconversion rate (as measured by haemagglutination-inhibition assay) per strain at day 28. Analysis was done in the modified intention-to-treat population, which included all randomly assigned participants for whom seroconversion status was available. Safety was assessed throughout the surveillance period (day 0–186). This trial is registered at ClinicalTrials.gov , number NCT02936180 . Findings Between Oct 24, 2016, and Dec 6, 2017, 696 patients with rheumatoid arthritis were invited to participate in the study and 279 were randomly assigned and vaccinated (140 [50%] received SD-QIV and 139 [50%] HD-TIV). 136 patients who received SD-QIV and 138 who received HD-TIV were included in the modified intention-to-treat anaysis. Patients who received HD-TIV were more likely to seroconvert than those who received SD-QIV: the odds ratio was 2·99 (95% CI 1·46–6·11) for seroconversion to strain A/H3N2, 1·95 (1·19–3·22) for seroconversion to strain B/Bris, 3·21 (1·57–6·56) for seroconversion to strain A/H1N1 (in 2016–2017), and 2·44 (1·18–5·06) for seroconversion to strain A/H1N1 (in 2017–2018). Similar results were observed in patients from groups 1 and 2; the number of individuals in group 3 was insufficient to draw conclusions. Local and systemic adverse events were similar in both vaccine groups, no serious adverse events were reported between days 0 and 28 in any group, and neither vaccine increased rheumatoid arthritis disease activity. Interpretation Our data suggest that in patients with seropositive rheumatoid arthritis, HD-TIV is safe and more immunogenic than SD-QIV. These results are the first evidence to support the use of the HD-TIV in these patients. Funding The Arthritis Society-Canada.

Objectives The aim of the study was to quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics. Study Design and Setting Using the Quebec Pregnancy Cohort (1998–2015), first-trimester doxylamine–pyridoxine, metoclopramide, and ondansetron exposures were assessed for their association with MCM. Generalized estimating equations were used to estimate odds ratios (OR), adjusting for potential confounders (aOR). Results Within 17 years of follow-up, the prevalence of antiemetic use during pregnancy increased by 76%. Within our cohort, 45,623 pregnancies were exposed to doxylamine–pyridoxine, 958 to metoclopramide, and 31 to ondansetron. Doxylamine–pyridoxine and metoclopramide use were associated with an increased risk of overall MCM (aOR 1.07, 95% confidence interval [CI]: 1.03–1.11; 3,945 exposed cases) and (aOR 1.27, 95% CI: 1.03–1.57; 105 exposed cases), respectively. Doxylamine–pyridoxine exposure was associated with increased risks of spina bifida (aOR 1.87, 95% CI: 1.11–3.14; 23 exposed cases), nervous system (aOR 1.25, 95% CI: 1.06–1.47; 225 exposed cases), and musculoskeletal system defects (aOR 1.08, 95% CI: 1.02–1.14; 1,735 exposed cases). Metoclopramide exposure was associated with an increased risk of genital organ defects (aOR 2.26, 95% CI: 1.14–4.48; 10 exposed cases). No statistically significant association was found between ondansetron exposure and the risk of overall MCM. Conclusion First-trimester doxylamine–pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall and specific MCM.

Introduction Mental health regional differences during pregnancy through the COVID-19 pandemic is understudied. Objectives We aimed to quantify the impact of the COVID-19 pandemic on maternal mental health during pregnancy. Methods A cohort study with a web-based recruitment strategy and electronic data collection was initiated in 06/2020. Although Canadian women, >18 years were primarily targeted, pregnant women worldwide were eligible. The current analysis includes data on women enrolled 06/2020-11/2020. Self-reported data included mental health measures (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7)), stress. We compared maternal mental health stratifying on country/continents of residence, and identified determinants of mental health using multivariable regression models. Results Of 2,109 pregnant women recruited, 1,932 were from Canada, 48 the United States (US), 73 Europe, 35 Africa, and 21 Asia/Oceania. Mean depressive symptom scores were lower in Canada (EPDS 8.2, SD 5.2) compared to the US (EPDS 10.5, SD 4.8) and Europe (EPDS 10.4, SD 6.5) (p Conclusions In this first international study on the impact of the COVID-19 pandemic, CONCEPTION has shown significant country/continent-specific variations in depressive symptoms during pregnancy, whereas severe anxiety was similar regardless of place of residence. Strategies are needed to reduce COVID-19’s mental health burden in pregnancy. Disclosure No significant relationships.

Objective To determine the association of anti-citrullinated antibodies (ACPA) with the ambient air pollutants fine particulate matter (PM2.5) and sulfur dioxide (SO2). Methods The CARTaGENE first-wave cohort includes 20,000 general population subjects from Quebec (Canada). On a sample of unselected 1586 subjects, we determined serum, ACPA and performed multivariable logistic regression, for the outcome of positive ACPA, assessing for independent effects of our air pollution variables, adjusting for age, sex, smoking, and French Canadian origin. Two models assessed distance to main industrial emitters of PM 2.5 , and of SO2, and two models assessed tons of SO2 and of PM 2.5 annual emissions. We also assessed associations with PM2.5 regional ambient concentrations estimated with satellite imagery. Results Adjusted analyses suggested a positive association between annual industrial PM 2.5 and SO2 emissions and the presence of ACPA antibodies (OR: 1.02, 95%CI 1.00–1.04 per 10 t of PM2.5 and 100 t of SO2). The data were also consistent with a negative association between the presence of ACPA, and distance to a major industrial emitter of both PM 2.5 and SO 2 . We found no association with PM2.5 estimates of ambient levels. Conclusions These analyses suggest that exposure to industrial emissions of air pollutants is related to ACPA positivity.

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)

In many autoimmune rheumatic diseases, there is an increased risk of cancer compared to the general population. While reasons for this increased risk have not been elucidated, it has been hypothesized that the link between cancer and autoimmunity may be bidirectional. For instance, chronic inflammation and damage from the rheumatic disease or its therapies may trigger malignant transformation; conversely, antitumor immune responses targeting cancers may become cross-reactive resulting in autoimmunity. In rare rheumatic diseases, longitudinal observational studies can play a critical role in studying these complex relationships, thereby enabling investigators to quantify the extent of cancer risk, identify unique clinical phenotypes associated with cancer, investigate the biological link between these conditions, and define optimal strategies for screening and treatment of the underlying cancer. In this review, we discuss recent data on cancer in the rheumatic diseases and suggest a research agenda to address several gaps in our current knowledge base.

The systemic lupus erythematosus (SLE) population has a unique cancer risk profile. This article presents the most recent data on risk of cancer in lupus and discusses possible contributing factors. The risk of lymphoma is particularly increased in SLE and may be mediated by immunosuppressive medication. Lung cancer risk is also increased in SLE. There is a high rate of cervical dysplasia in women with SLE. A similar pathophysiology could be responsible for the trend seen in vulvovaginal and hepatic carcinomas. There is a decreased risk in SLE for some hormone-sensitive cancers, but the cause of this remains unclear.

To determine the validity of the diagnostic algorithms for osteoporosis and fractures in administrative data.A systematic search was conducted to identify studies that reported the validity of a diagnostic algorithm for osteoporosis and/or fractures using administrative data.Twelve studies were reviewed. The validity of the diagnosis of osteoporosis in administrative data was fair when at least 3 years of data from hospital and physician visit claims were used (area under the receiver operating characteristic [ROC] curve [AUC]=0.70) or when pharmacy data were used (with or without the use of hospital and physician visit claims data, AUC0.70). Nonetheless, the positive predictive values (PPVs) were low (0.60). There was good evidence to support the use of hospital data to identify hip fractures (sensitivity: 69-97%; PPV: 63-96%) and the addition of physician claims diagnostic and procedural codes to hospitalization diagnostic codes improved these characteristics (sensitivity: 83-97%; PPV: 86-98%). Vertebral fractures were difficult to identify using administrative data. There was some evidence to support the use of administrative data to define other fractures that do not require hospitalization.Administrative data can be used to identify hip fractures. Existing diagnostic algorithms to identify osteoporosis and vertebral fractures in administrative data are suboptimal.

Background It is recommended that persons recently diagnosed with heart failure consult with a specialist in heart failure. Objectives To determine whether patients who were diagnosed with new-onset chronic heart failure (CHF) by a noncardiologist consulted with a cardiologist, and identify the factors associated with delayed consultation. Methods Physician reimbursement administrative data were obtained for all adults with suspected new-onset CHF in the year 2000 in Quebec, defined operationally as a physician visit for CHF (based on the International Classification of Diseases, 9th Revision diagnostic codes), with no previous physician visit code for CHF in the preceding three years. Among those first diagnosed by a noncardiologist, Cox regression modelling was used to identify patient and physician characteristics associated with time to cardiology consultation. Results Of the 13,523 persons coded as having incident CHF, 54.9% consulted a cardiologist within the next 2.5 to 3.5 years, and 67.4% were seen by an internist or cardiologist. Older patients, women, and those with lower comorbidity and socioeconomic status had significantly longer times to cardiology consultation. Conclusion The data suggest that many patients with suspected new-onset CHF do not receive prompt cardiology care, as stipulated by current recommendations. Equity of access for women and those with lower socioeconomic status appears to be problematic.

What have we learnt about cancer risk in systemic lupus erythematosus (SLE) over the past decade? One important lesson is that data do confirm a slightly increased risk in SLE for all cancers combined, compared to that in the general population. However, it is clear that this is largely driven by an increased risk for haematological malignancies, particularly non-Hodgkin's lymphoma (NHL), although Hodgkin's lymphoma may be increased as well. In addition, there is evidence for a moderately increased risk of lung cancer, and possibly for rarer cancer types such as hepatobiliary and vulvar/vaginal malignancies. Unfortunately, the most clinically relevant question--the mechanism underlying the association between cancer and SLE--remains largely unanswered. Key issues remaining relate to the links between cancer risk, SLE disease activity, and medication exposures. Much of the recent data suggest that disease-related factors may be at least as important as medication exposures for certain cancers, such as NHL. The independent effects of drug exposures versus disease activity in mediating cancer risk in SLE remain unknown. Work is in progress to further elucidate these important issues. Meanwhile, there is good evidence that cervical dysplasia is increased in women with SLE. This may be mediated by decreased clearance of the human papilloma virus, which some suggest is an innate characteristic of SLE patients. However, an increased risk of cervical dysplasia is also associated with immunosuppressive medication exposures, particularly cyclophosphamide. For these reasons, it is important that women with SLE follow established guidelines for cervical cancer screening.

To assess the construct validity of the Self-Administered Comorbidity Questionnaire (SCQ) in patients with systemic sclerosis (SSc) and systemic lupus erythematosus (SLE).The SCQ was modified for the SSc cohort to emphasize the objective of recording problems other than the patients' scleroderma. It was administered to 406 SSc and 147 SLE patients. Construct validity of the SCQ was evaluated separately in the SSc and SLE cohorts by testing the hypotheses that a valid comorbidity index should correlate with age and health-related quality of life (Medical Outcomes Trust Short Form 36 [SF 36]) but not with disease-specific variables.The SCQ score correlated with age in the SSc patients only (Tau B=0.37, P0.001) and not in the SLE patients. It correlated with the SF 36 in both SSc and SLE. However, it also correlated with several disease-related variables. There was significant overlap between reports of comorbidities and disease-related problems in the SSc cohort.Patients with systemic autoimmune diseases cannot distinguish true comorbidities from conditions related to their index disease and, as such, a self-administered comorbidity questionnaire does not appear useful in these diseases.

Summary Objective To assess the effects of disease modifying anti-rheumatic drugs (DMARDs) on lung cancer risk in a large rheumatoid arthritis (RA) cohort. Methods We assembled a cohort of RA patients ( N =23,810) from population-based administrative healthcare databases. We ascertained cases of lung cancer in the cohort using physician billing and hospitalization records. Each lung cancer case was age and sex matched to 10 controls. We used conditional logistic regression to determine the effects of DMARDs on lung cancer risk, calculating the adjusted rate ratio (RR) attributable to each DMARD. Results Subjects were followed for a total of 157,204 person-years. During this time, 960 cases of lung cancer were recorded. The frequency of exposures to various DMARDs was similar in cases and controls; our adjusted RR estimates, reflecting the independent effects of each DMARD exposure, did not associate any of the drugs with an increased risk of lung cancer. Conclusions Our data do not suggest that DMARD exposures are the primary mediator of lung cancer risk in RA. An increased risk of lung cancer in RA patients may be related to other determinants, including shared risk factors for the development of both RA and lung cancer.

Background: Evidence points to a link between systemic lupus erythematosus (SLE) and an increased risk of lung cancer. Our objective was to provide a brief report of the lung cancer cases from an SLE cohort, with respect to demographics, histology, and exposures to smoking and immunosuppressive medications. Methods: Data were obtained from a multi-site international cohort study of over 9500 SLE patients from 23 centres. Cancer cases were ascertained through linkage with regional tumor registries. Results: We analyzed information on histology subtype for 30 lung cancer cases that had occurred across five countries. Most (75%) of these 30 cases were female, with a median age of 61 (range 27-91) years. In eight cases, the histological type was not specified. In the remainder, the most common histological type reported was adenocarcinoma (N = 8; two of the adenocarcinomas were bronchoalveolar carcinoma) followed by small cell carcinoma (N = 6), and squamous cell carcinoma (N = 6) with one case each of large cell carcinoma and carcinoid tumor. Most (71%) of the lung cancer cases were smokers; only the minority (20%) had been previously exposed to immunosuppressive agents. Conclusions: The histological distribution of the lung cancers from the SLE sample appeared similar to that of lung cancer patients in the general population, though the possibility of a higher proportion of more uncommon tumors (such as bronchoalveolar and carcinoid) cannot be excluded. A large proportion of the cancer cases were smokers, which is also not surprising. However, only a minority appeared to have been exposed to immunosuppressive agents. A large case-cohort study currently in progress should help shed light on the relative importance of these exposures in lung cancer risk for SLE patients. (c) 2007 Elsevier Ireland Ltd. All rights reserved. (Less)

For decades, concern has been mounting that individuals with systemic lupus erythematosus (SLE) have increased susceptibility to cancer. Recent data confirm that certain cancers, particularly hematologic, occur more frequently in SLE than in the general population. Numerous pathogenic mechanisms are possible, but hypotheses remain largely speculative. In particular, data are inadequate on how cancer risk in SLE may be related to medication exposures. To evaluate the impact of medication exposures on cancer risk in SLE, cooperative efforts of Systemic Lupus International Collaborating Clinics and Canadian Network for Improved Outcomes in Systemic Lupus are currently in progress. This should provide much-needed insight into the pathogenesis of the association between cancer and SLE.