Risk of venous thromboembolism in patients with rheumatoid arthritis: a meta-analysis of observational studies.

BACKGROUND: Thrombotic events, such as venous thromboembolism (VTE) are a major health complication linked to rheumatoid arthritis (RA). We performed a meta-analysis to evaluate the risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in adults with RA compared to the general population. METHODS: MEDLINE and EMBASE databases were searched from inception to April 2022 to identify publications meeting the following criteria: (1) prospective and retrospective original data from cohort or case-control studies; (2) pre-specified RA definition; (3) clearly defined VTE outcomes; (4) reported risk estimate and 95% confidence intervals (95% CIs); (5) at least sex- and age-matched to comparison group; and (6) English language. Of 372 studies screened, 14 were included (602,760 RA patients, 123,076 VTE events) and their quality was assessed by an adaptation of the STROBE quality scoring scale. RESULTS: The pooled risk ratios of VTE, DVT and PE in patients with RA were 1.57 (95% CI 1.41-1.76), 1.58 (95% CI 1.26-1.97) and 1.57 (95% CI 1.30-1.88), respectively. The I2 value of 92%, 94% and 92% for VTE, DVT and PE analyses, suggesting considerable heterogeneity. There were no significant differences in risk estimates among the five subgroup analyses: quality score (P = 0.35, I2 = 0%); sex (P = 0.31, I2 = 1.7%); study year (P = 0.81, I2 = 0%); population source (P = 0.35, I2 = 0%); study design (P = 0.62, I2 = 0%). CONCLUSIONS: Results show that patients with RA are at a higher risk of VTE, DVT and PE compared to the general population.

Effect of Immunosuppressive or Immunomodulatory Agents on Severe COVID-19 Outcomes: A Population-Based Cohort Study.

OBJECTIVE: We estimated the association between immunosuppressive and immunomodulatory agent (IIA) exposure and severe COVID-19 outcomes in a population-based cohort study. METHODS: Participants were 18 years or older, tested positive for SARS-CoV-2 between February 6, 2020, and August 15, 2021, and were from administrative health data for the entire province of British Columbia, Canada. IIA use within 3 months prior to positive SARS-CoV-2 test included conventional disease-modifying antirheumatic drugs (antimalarials, methotrexate, leflunomide, sulfasalazine, individually), immunosuppressants (azathioprine, mycophenolate mofetil/mycophenolate sodium [MMF], cyclophosphamide, cyclosporine, individually and collectively), tumor necrosis factor inhibitor (TNFi) biologics (adalimumab, certolizumab, etanercept, golimumab, infliximab, collectively), non-TNFi biologics or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) (rituximab separately from abatacept, anakinra, secukinumab, tocilizumab, tofacitinib and ustekinumab collectively), and glucocorticoids. Severe COVID-19 outcomes were hospitalizations for COVID-19, ICU admissions, and deaths within 60 days of a positive test. Exposure score-overlap weighting was used to balance baseline characteristics of participants with IIA use compared with nonuse of that IIA. Logistic regression measured the association between IIA use and severe COVID-19 outcomes. RESULTS: From 147,301 participants, we identified 515 antimalarial, 573 methotrexate, 72 leflunomide, 180 sulfasalazine, 468 immunosuppressant, 378 TNFi biologic, 49 rituximab, 144 other non-TNFi biologic or tsDMARD, and 1348 glucocorticoid prescriptions. Risk of hospitalizations for COVID-19 was significantly greater for MMF (odds ratio [95% CI]): 2.82 [1.81-4.40], all immunosuppressants: 2.08 [1.51-2.87], and glucocorticoids: 1.63 [1.36-1.96], relative to nonuse. Similar outcomes were seen for ICU admission and MMF: 2.52 [1.34-4.74], immunosuppressants: 2.88 [1.73-4.78], and glucocorticoids: 1.86 [1.37-2.54]. Only glucocorticoids use was associated with a significant increase in 60-day mortality: 1.58 [1.21-2.06]. No other IIAs displayed statistically significant associations with severe COVID-19 outcomes. CONCLUSION: Current use of MMF and glucocorticoids were associated with an increased risk of severe COVID-19 outcomes compared with nonuse. These results emphasize the variety of circumstances of patients taking IIAs.

Relationship Between Fruit and Vegetables Intake and Common Mental Disorders in Youth: A Systematic Review.

Objective: Recent evidence suggests that adequate fruit and vegetables intake (FVI) might be associated with lower risk of common mental disorders (CMDs) in adults, but studies in youth are also beginning to emerge and are synthesized in this systematic review. Methods: Online databases were searched from inception to 30 October 2020 to locate cross-sectional, cohort, and case-control studies focusing on the FVI and CMDs in youth (i.e., 10-18 years old). The risk of bias of studies was assessed using Joanna Briggs Institute Critical Appraisal Tool and the Newcastle-Ottawa quality assessment scale. Results: Among 3,944 records identified, 12 studies (8 cross-sectional, 1 case-control, and 3 prospective cohort studies) were included in the final synthesis. None of the prospective cohort studies identified a statistically significant association between FVI and CMDs in youth, although inconsistent associations were reported in cross-sectional and case-control studies. Conclusion: The lack of associations between FVI and CMDs in youth, along with consistent associations in adults, might be explained by the accumulation of risk theoretical model and methodological challenges.

Increased risk of venous thromboembolism in patients with granulomatosis with polyangiitis: A population-based study.

We assessed the risk and time trends of venous thromboembolism (VTE) including pulmonary embolism (PE) and deep venous thrombosis (DVT) in new granulomatosis with polyangiitis (GPA) cases compared to the general population. Using a population-level database from the entire province of British Columbia, Canada, we conducted a matched cohort study of all patients with incident GPA with up to ten age-, sex-, and entry time-matched individuals randomly selected from the general population. We compared incidence rates of VTE, PE, and DVT between the two groups, and calculated hazard ratios (HR), adjusting for relevant confounders. Among 549 individuals with incident GPA (57.6% female, mean age 55.4 years), the incidence rates for VTE, PE, and DVT were 7.22, 2.73, and 6.32 per 1,000 person-years, respectively; the corresponding rates were 1.36, 0.74, and 0.81 per 1,000 person-years among the 5,490 non-GPA individuals. Compared with the non-GPA cohort, the fully adjusted HRs among GPA patients were 2.90 (95% CI, 1.10-7.64), 4.70 (95% CI, 1.74-12.69), and 1.66 (95% CI, 0.52-5.27) for VTE, PE, and DVT, respectively. The risks of VTE, PE, and DVT were highest during the first year after GPA diagnosis with HR (95% CI) of 11.04 (1.37-88.72), 26.94 (4.56-159.24), and 2.68 (0.23-31.21), respectively. GPA patients are at significantly increased risk of PE, but not DVT. Monitoring for these complications is particularly warranted in this patient population, especially early after diagnosis.

Association of tramadol with all-cause mortality, cardiovascular diseases, venous thromboembolism, and hip fractures among patients with osteoarthritis: a population-based study.

BACKGROUND: The use of tramadol among osteoarthritis (OA) patients has been increasing rapidly around the world, but population-based studies on its safety profile among OA patients are scarce. We sought to determine if tramadol use in OA patients is associated with increased risks of all-cause mortality, cardiovascular diseases (CVD), venous thromboembolism (VTE), and hip fractures compared with commonly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) or codeine. METHODS: Using administrative health datasets from British Columbia, Canada, we conducted a sequential propensity score-matched cohort study among all OA patients between 2005 and 2013. The tramadol cohort (i.e., tramadol initiation) was matched with four comparator cohorts (i.e., initiation of naproxen, diclofenac, cyclooxygenase-2 [Cox-2] inhibitors, or codeine). Outcomes are all-cause mortality, first-ever CVD, VTE, and hip fractures within the year after the treatment initiation. Patients were followed until they either experienced an event, left the province, or the 1-year follow-up period ended, whichever occurred first. Cox proportional hazard models were used to estimate hazard ratios after adjusting for competing risk of death. RESULTS: Overall, 100,358 OA patients were included (mean age: 68 years, 63% females). All-cause mortality was higher for tramadol compared to NSAIDs with rate differences (RDs/1000 person-years, 95% CI) ranging from 3.3 (0.0-6.7) to 8.1 (4.9-11.4) and hazard ratios (HRs, 95% CI) ranging from 1.2 (1.0-1.4) to 1.5 (1.3-1.8). For CVD, no differences were observed between tramadol and NSAIDs. Tramadol had a higher risk of VTE compared to diclofenac, with RD/1000 person-years (95% CI) of 2.2 (0.7-3.7) and HR (95% CI) of 1.7 (1.3-2.2). Tramadol also had a higher risk of hip fractures compared to diclofenac and Cox-2 inhibitors with RDs/1000 person-years (95% CI) of 1.9 (0.4-3.4) and 1.7 (0.2-3.3), respectively, and HRs (95% CI) of 1.6 (1.2-2.0) and 1.4 (1.1-1.9), respectively. No differences were observed between tramadol and NSAIDs for all events. CONCLUSIONS: OA patients initiating tramadol have an increased risk of mortality, VTE, and hip fractures within 1 year compared with commonly prescribed NSAIDs, but not with codeine.

RetINal Toxicity And HydroxyChloroquine Therapy (INTACT): protocol for a prospective population-based cohort study.

PURPOSE: Hydroxychloroquine (HCQ) is an important medication for patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other rheumatic diseases. Although it is well-tolerated and cost-effective, the risk of HCQ retinal toxicity is of increasing concern. The aim of this study is to re-examine the HCQ retinal toxicity incidence rate, risk factors and clinical course after discontinuation. METHODS: We designed a prospective population-based cohort study in adult patients with SLE or RA, currently receiving HCQ for five or more years, who are residents of British Columbia (BC), Canada. Based on administrative data, we identified 5508 eligible participants (1346 SLE and 4162 RA). They will participate in annual or biannual retinal screening over 5 years in alignment with the recently revised American Academy of Ophthalmology guidelines. To standardise procedures for retinal screening, imaging, diagnostic criteria, severity staging and data transfer, a consensus meeting was convened in December 2019 with participation of BC retinal specialists and the research team. Agreement was attained on: use of spectral domain-optical coherence tomography as the primary objective screening modality; classification of images into categories of normal, equivocal or abnormal; and transferring the equivocal and abnormal images plus corresponding subjective test results via cloud-based server from each clinic to a reading centre. Confirmation of HCQ retinal toxicity diagnoses and severity staging will be performed by three independent and masked reviewers. The incidence of HCQ retinal toxicity will be calculated, accounting for the competing risk of death. Hazard ratios for each risk factor will be calculated for the risk of HCQ retinopathy, after adjusting for confounders. We will also estimate the risk of HCQ retinal toxicity progression over 5 years. ETHICS AND DISSEMINATION: This study has received approval from the University of British Columbia Clinical Research Ethics Board (H20-00736) and the Vancouver Coastal Health Research Institute.

Immunosuppression and COVID-19 infection in British Columbia: Protocol for a linkage study of population-based administrative and self-reported survey data.

INTRODUCTION: Cases of the novel coronavirus disease (COVID-19) continue to spread around the world even one year after the declaration of a global pandemic. Those with weakened immune systems, due to immunosuppressive medications or disease, may be at higher risk of COVID-19. This includes individuals with autoimmune diseases, cancer, transplants, and dialysis patients. Assessing the risk and outcomes of COVID-19 in this population has been challenging. While administrative databases provide data with minimal selection and recall bias, clinical and behavioral data is lacking. To address this, we are collecting self-reported survey data from a randomly selected subsample with and without COVID-19, which will be linked to administrative health data, to better quantify the risk of COVID-19 infection associated with immunosuppression. METHODS AND ANALYSIS: Using administrative and laboratory data from British Columbia (BC), Canada, we established a population-based case-control study of all individuals who tested positive for SARS-CoV-2. Each case was matched to 40 randomly selected individuals from two control groups: individuals who tested negative for SARS-CoV-2 (i.e., negative controls) and untested individuals from the general population (i.e., untested controls). We will contact 1000 individuals from each group to complete a survey co-designed with patient partners. A conditional logistic regression model will adjust for potential confounders and effect modifiers. We will examine the odds of COVID-19 infection according to immunosuppressive medication or disease type. To adjust for relevant confounders and effect modifiers not available in administrative data, the survey will include questions on behavioural variables that influence probability of being tested, acquiring COVID-19, and experiencing severe outcomes. ETHICS AND DISSEMINATION: This study has received approval from the University of British Columbia Clinical Research Ethics Board [H20-01914]. Findings will be disseminated through scientific conferences, open access peer-reviewed journals, COVID-19 research repositories and dissemination channels used by our patient partners.

All-cause and cause-specific mortality in systemic lupus erythematosus: a population-based study.

OBJECTIVE: To investigate all-cause and cause-specific mortality in SLE patients between two time periods, 1997-2005 and 2006-14. METHODS: We used an administrative health database from the province of British Columbia, Canada to match all incident SLE patients to 10 non-SLE individuals on sex, age and index date. Cohorts were divided into two subgroups, according to diagnosis year: early cohort 1997-2005 and late cohort 2006-14. The outcome was death [all-cause, renal disease, cancer, infection, cardiovascular disease (CVD) and other]. Hazard ratios (HR) and 95% CIs were estimated using univariate and multivariable Cox models. RESULTS: Among 6092 SLE patients and 60 920 non-SLE individuals, there were 451 and 1910 deaths, respectively. The fully adjusted all-cause mortality HR (95% CI) in the overall SLE cohort was 1.85 (1.66, 2.06), with no statistically significant improvement between early and late cohorts [1.95 (1.69, 2.26) vs 1.74 (1.49, 2.04)]. There was excess mortality from renal disease [3.04 (2.29, 4.05)], infections [2.74 (2.19, 3.43)] and CVD [2.05 (1.77, 2.38)], but not cancer [1.18 (0.96, 1.46)], in the overall SLE cohort. There was no statistically significant improvement in cause-specific mortality between early and late cohorts for renal disease [3.57 (2.37, 5.36) vs 2.65 (1.78, 3.93)], infection [2.94 (2.17, 3.98) vs 2.54 (1.84, 3.51)] and CVD [1.95 (1.60, 2.38) vs 2.18 (1.76, 2.71)]. There was no increase in cancer-related mortality in either cohort [1.27 (0.96, 1.69) vs 1.10 (0.82, 1.48)]. CONCLUSION: This population-based study demonstrates a persisting mortality gap in all-cause and cause-specific deaths in SLE patients, compared with the general population.

Diet Quality and Health Service Utilization for Depression: A Prospective Investigation of Adults in Alberta's Tomorrow Project.

Depression is a leading cause of disability and economic burden worldwide. Primary prevention strategies are urgently needed. We examined the association of diet quality with depression in a large provincial cohort of adults. A past year food frequency questionnaire was completed by Alberta's Tomorrow Project (ATP) participants enrolled between 2000-2008 (n = 25,016; average age 50.4 years) and used to calculate Healthy Eating Index-Canada (HEI-C) 2015 scores. The number of physician visits for depression 2000-2015 was obtained via linkage with administrative health records. Negative binomial regression models assessed the relationship between HEI-C 2015 scores and physician visits for depression, adjusting for confounders. Every 10-unit increase in HEI-C 2015 scores was associated with 4.7% fewer physician visits for depression (rate ratio (RR): 0.95; 95% Confidence Interval (CI): 0.92-0.98). This relationship persisted when participants with physician visits for mental illness prior to cohort enrollment were excluded. Higher quality diets were associated with a lower number of physician visits for depression. Results highlight diet may be an important prevention strategy for reducing the burden of health service utilization for depression.