Reporting of determinants of health inequities and participant characteristics in randomized controlled trials of systemic lupus erythematosus in Canada: A scoping review.

OBJECTIVE: To report participant characteristics relevant to identifying health inequities in systemic lupus erythematosus (SLE) randomized controlled trials conducted in Canada. METHODS: We conducted a scoping review by searching MEDLINE (Ovid) and Embase (1990 to June 2023), and CENTRAL (inception to June 2023). Eligible studies: used an RCT design; evaluated interventions (pharmacologic and non-pharmacologic) among SLE patients aged ≥18 years; and were conducted in Canada. Data extraction was guided by the Campbell and Cochrane Equity Methods Group's PROGRESS-Plus framework on 11 factors leading to health inequities (Place of residence; Race, culture, ethnicity, and language; Occupation; Gender and sex; Religion; Education; Socioeconomic status; Social capital; Plus: Personal characteristics associated with discrimination; Features of relationships; and Time-dependent relationships). RESULTS: Of 1901 unique records, 6 met the inclusion criteria. Sex and age were the only PROGRESS factors that were reported in all studies. The majority of participants were female (84.4% to 100%), and mean ages of participants ranged from 42 to 52.3 years. Place of residence, race, education, and social capital were reported in three studies. Socioeconomic status was reported in two studies, and occupation was reported in one study. Religion, features of relationships, and time-dependent relationships were not reported in any included studies. CONCLUSION: Limited reporting of determinants of health inequities in RCTs for SLE in Canada suggests the need for reporting standards to support equity, diversity, and inclusion practices in research.

Antimalarial Adherence and Risk of Cardiovascular Events in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus: A Population-Based Study.

OBJECTIVE: We aimed to assess the association between antimalarial adherence and cardiovascular events between incident rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) population-based cohorts. METHODS: All patients with incident RA/SLE and incident antimalarial use in British Columbia, Canada, between January 1997 and March 2015 were identified using provincial administrative databases. The outcomes were incident cardiovascular events, including myocardial infarction (MI), stroke, or venous thromboembolism (VTE). The exposure was antimalarial adherence with levels: discontinuation (proportion of days covered [PDC = 0]), nonadherence (0 < PDC < 0.90), and adherence (PDC ≥ 0.90). We used marginal structural models to estimate the effect of antimalarial adherence on the rate of cardiovascular events, accounting for potential confounders. RESULTS: We identified 16,538 individuals with incident RA/SLE and incident antimalarial use without any cardiovascular event before the index date. Over nine years mean follow-up, 2,174 incident cardiovascular events (13.2%) were observed. The adjusted hazard ratio (aHR) for incident cardiovascular events for antimalarial adherence relative to discontinuation was 0.72 (95% confidence interval [CI] 0.64-0.81) and 1.01 (95% CI 0.90-1.14) for nonadherence. Additionally, the aHRs for all cardiovascular events, MI, stroke, and VTE for adherence relative to nonadherence was 0.71 (95% CI 0.61-0.82), 0.62 (95% CI 0.51-0.75), 0.45 (95% CI 0.36-0.58), and 0.65 (95% CI 0.46-0.93), respectively. We found older age modified the association between antimalarial adherence and cardiovascular events (P = 0.02). CONCLUSION: When people newly diagnosed with RA or SLE take their antimalarial regularly as prescribed (PDC ≥ 0.90), they have a 29% lower risk of sustaining a cardiovascular event than patients with a lower degree of adherence (PDC < 0.90) and a 28% lower risk than if they discontinue antimalarials.

Effect of digital monitoring and counselling on self-management ability in patients with rheumatoid arthritis: a randomised controlled trial.

OBJECTIVES: To assess a remote physiotherapist (PT) counselling intervention using self-monitoring tools for improving self-management ability, physical activity participation, and health outcomes in people with rheumatoid arthritis (RA). METHODS: Eligible participants were randomly assigned to receive group education, a Fitbit®, a self-monitoring app, and PT counselling phone calls (Immediate Group). The Delayed Group received a monthly e-newsletter until week 26, and then the intervention. The primary outcome was Patient Activation Measure (PAM-13). Participants were assessed at baseline, 27 weeks (the primary end point) and 53 weeks. Secondary outcomes included disease activity, pain, fatigue, depression, sitting/walking habits, daily physical activity time, and daily awake sedentary time. Generalized Linear Mixed-effect Models (GLMMs) were used to assess the effect of the intervention on the change of each outcome measure from the initiation to 27 weeks after the intervention. RESULTS: Analysis included 131 participants (91.6% women; 80.2% completed during the COVID-19 pandemic). The mean change of PAM-13 at 27 weeks was 4.6 (SD = 14.7) in the Immediate Group vs -1.6 (SD = 12.5) in the Delayed Group. The mean change in Delayed Group at 53 weeks (after the 26-week intervention) was 3.6 (SD = 14.6). Overall, the intervention improved PAM-13 at 27 weeks post-intervention from the GLMM analysis (adjusted coefficient: 5.3; 95% CI: 2.0, 8.7; p = <0.001). Favourable intervention effects were also found in disease activity, fatigue, depression, and self-reported walking habit. CONCLUSION: Remote counselling paired with self-monitoring tools improved self-management ability in people with RA. Findings of secondary outcomes indicate that the intervention had a positive effect on symptom management.

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.

T1Gd is reduced in bone marrow lesions overlying cartilage in the hip.

OBJECTIVE: Bone Marrow Lesions (BMLs) are areas in bone with high fluid signal on MRI associated with painful and progressive OA. While cartilage near BMLs in the knee has been shown to be degenerated, this relationship has not been investigated in the hip. RESEARCH QUESTION: is T1Gd lower in areas of cartilage overlying BMLs in the hip? DESIGN: 128 participants were recruited from a population-based study of hip pain in 20-49-year-olds. Proton-density weighted fat-suppressed and delayed Gadolinium Enhanced MR Imaging of Cartilage (dGEMRIC) images were acquired to locate BMLs and quantify hip cartilage health. BML and cartilage images were registered and cartilage was separated into BML overlying and surrounding regions. Mean T1Gd was measured in 32 participants with BMLs in both cartilage regions and in matched regions in 32 age- and sex-matched controls. Mean T1Gd in the overlying cartilage was compared using linear mixed-effects models between BML and control groups for acetabular and femoral BMLs, and between cystic and non-cystic BML groups. RESULTS: Mean T1Gd of overlying cartilage was lower in the BML group compared to the control group (acetabular: -105 ms; 95% CI: -175, -35; femoral: -8 ms; 95% CI: -141, 124). Mean T1Gd in overlying cartilage was lower in cystic compared to non-cystic BML subjects, but the confidence interval is too large to provide certainty in this difference (-3 [95% CI: -126, 121]). CONCLUSIONS: T1Gd is reduced in overlying cartilage in hips from a population-based sample of adults aged 20-49, which suggests BMLs are associated with local cartilage degeneration in hips.

Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: a population-based interrupted time-series analysis.

OBJECTIVES: To determine the impact of the introduction of biologic DMARDs (bDMARDs) on severe infections among people newly diagnosed with RA compared with non-RA individuals. METHODS: In this population-based retrospective cohort study using administrative data (from 1990-2015) for British Columbia, Canada, all incident RA patients diagnosed between 1995 and 2007 were identified. General population controls with no inflammatory arthritis were matched to RA patients based on age and gender, and were assigned the diagnosis date (i.e. index date) of the RA patients they were matched with. RA/controls were then divided into quarterly cohorts according to their index dates. The outcome of interest was all severe infections necessitating hospitalization or occurring during hospitalization after the index date. We calculated 8-year severe infection rates for each cohort and conducted interrupted time-series analyses to compare severe infection trends in RA/controls with index date during pre-bDMARDs (1995-2001) and post-bDMARDs (2003-2007) periods. RESULTS: A total of 60 226 and 588 499 incident RA/controls were identified. We identified 14 245 severe infections in RA, and 79 819 severe infections in controls. The 8-year severe infection rates decreased among RA/controls with increasing calendar year of index date in the pre-bDMARDs period, but increased over time only among RA, not controls, with index date in the post-bDMARDs period. The adjusted difference between the pre- and post-bDMARDs secular trends in 8-year severe infection rates was 1.85 (P = 0.001) in RA and 0.12 (P = 0.29) in non-RA. CONCLUSION: RA onset after bDMARDs introduction was associated with an elevated severe infection risk in RA patients compared with matched non-RA individuals.

Investigating Associations Between Access to Rheumatology Care, Treatment, Continuous Care, and Healthcare Utilization and Costs Among Older Individuals With Rheumatoid Arthritis.

OBJECTIVE: To examine the association between rheumatologist access, early treatment, and ongoing care of older-onset rheumatoid arthritis (RA) and healthcare utilization and costs following diagnosis. METHODS: We analyzed data from a population-based inception cohort of individuals aged > 65 years with RA in Ontario, Canada, diagnosed between 2002 and 2014 with follow-up to 2019. We assessed 4 performance measures in the first 4 years following diagnosis, including access to rheumatology care, yearly follow-up, timely treatment, and ongoing treatment with a disease-modifying antirheumatic drug. We examined annual healthcare utilization, mean direct healthcare costs, and whether the performance measures were associated with costs in year 5. RESULTS: A total of 13,293 individuals met inclusion criteria. The mean age was 73.7 (SD 5.7) years and 68% were female. Total mean direct healthcare cost per individual increased annually and was CAD $13,929 in year 5. All 4 performance measures were met for 35% of individuals. In multivariable analyses, costs for not meeting access to rheumatology care and timely treatment performance measures were 20% (95% CI 8-32) and 6% (95% CI 1-12) higher, respectively, than where those measures were met. The main driver of cost savings among individuals meeting all 4 performance measures were from lower complex continuing care, home care, and long-term care costs, as well as fewer hospitalizations and emergency visits. CONCLUSION: Access to rheumatologists for RA diagnosis, timely treatment, and ongoing care are associated with lower total healthcare costs at 5 years. Investments in improving access to care may be associated with long-term health system savings.

Hydroxychloroquine Use and Cardiovascular Events Among Patients With Systemic Lupus Erythematosus and Rheumatoid Arthritis.

OBJECTIVE: We evaluated the potential temporal association between hydroxychloroquine (HCQ) use and cardiovascular (CV) events among patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). METHODS: We conducted a nested case-control study within inception cohorts of SLE and RA patients using administrative health databases including the entire population of British Columbia, Canada. We identified cases with incident CV events, including myocardial infarction (MI), stroke, or venous thromboembolism (VTE). We matched each case with up to 3 controls on age, sex, and rheumatic disease. HCQ exposure was categorized by the time between the last HCQ prescription date covered and the index date as current use, recent use, remote use, or never used. We used conditional logistic regression to assess the association between HCQ exposure and CV events, using remote use as the reference group. RESULTS: We identified 10,268 cases and 29,969 controls. Adjusted conditional odd ratios (cORs) and 95% confidence intervals (95% CIs) for current HCQ use relative to remote use were 0.86 (0.77-0.97) for combined CV events, 0.88 (0.74-1.05) for MI, 0.87 (0.74-1.03) for stroke, and 0.74 (0.59-0.94) for VTE. Recent HCQ users and nonusers had similar odds of combined CV events as remote users (cORs 0.93, 95% CI 0.77-1.13 and 0.96, 95% CI 0.88-1.04, respectively). CONCLUSION: In this nested case-control study of patients with SLE and RA, we found a reduced risk of overall CV events associated with current HCQ use, including reductions in VTE and trends toward reductions in MI and stroke. These findings suggest a possible cardiovascular preventative benefit of HCQ use.

Risk of Arrhythmia Among New Users of Hydroxychloroquine in Rheumatoid Arthritis and Systemic Lupus Erythematosus: A Population-Based Study.

OBJECTIVES: We assessed the association between hydroxychloroquine (HCQ) initiation and risk of arrhythmia among patients with incident rheumatoid arthritis (RA) or with incident systemic lupus erythematosus (SLE). METHODS: All patients with incident RA or SLE and no arrhythmic events, not receiving antiarrhythmic medications, and not receiving HCQ prior to the index date of disease in British Columbia, Canada, between January 1996 and December 2014 were identified from administrative databases. We identified patients who were dispensed HCQ prescriptions (HCQ initiators) or were not dispensed HCQ prescriptions (HCQ noninitiators) during each study year; groups were matched 1:1 by propensity scores using baseline confounders on demographics, comorbidities, medications, and health care utilization. Outcomes were any new arrhythmias, atrial fibrillation, abnormal electrocardiograms, including long QT syndrome and conduction disorder, and other unspecified arrhythmias during follow-up. We used cause-specific Cox proportional hazards models with death as a competing event to assess the association between HCQ initiation and the outcomes. RESULTS: We identified 11,518 propensity score-matched patients with RA or SLE in each group. Over the mean follow-up of 8 years, there were 1,610 and 1,646 incident arrhythmias in the HCQ initiator group and the noninitiator group, respectively, with crude incidence rates of arrhythmia of 17.5 and 18.1 in 1,000 persons per year, respectively. The adjusted cause-specific hazard ratio (cHR) for patients who received HCQ was 0.96 (95% confidence interval [95% CI] 0.89-1.03) compared with HCQ noninitiators, and the cHRs for patients who took HCQ and had arrhythmia subtypes of atrial fibrillation, abnormal electrocardiograms, and other unspecified arrhythmias were 0.93 (95% CI 0.83-1.04), 0.98 (95% CI 0.87-1.11), and 0.95 (95% CI 0.84-1.07), respectively. CONCLUSION: Risk of any type of arrhythmia was not increased among new users of HCQ.

Magnetic resonance imaging predictors (cartilage, osteophytes and meniscus) of prevalent and 3-year incident medial and lateral tibiofemoral knee joint tenderness and patellofemoral grind.

OBJECTIVE: To identify magnetic resonance imaging (MRI) predictors (cartilage [C], osteophytes [O] and meniscus [M] scores) of prevalent and 3-year incident medial tibiofemoral (MTF) and lateral tibiofemoral (LTF) knee joint tenderness and patellofemoral (PF) grind.  METHODS: Population-based knee pain cohort aged 40-79 was assessed at baseline (N = 255), 3- and 7-year follow-up (N = 108 × 2 = 216). COM scores were measured at 6/8/6 subregions respectively. Age-sex-BMI adjusted logistic models predicted prevalence versus relevant COM predictors (medial, lateral or patellar / trochlear groove scores). Fully adjusted models also included all relevant COM predictors. Binary generalized estimating equations models predicting 3-year incidence were also adjusted for individual follow-up time between cycles. RESULTS: Significant predictors of prevalent MTF tenderness: medial femoral cartilage (fully adjusted odds ratio [aOR] 1.84; 95% confidence interval [CI] 1.11, 3.05), female (aOR = 3.05; 1.67, 5.58), BMI (aOR = 1.53 per 5 units BMI; 1.10, 2.11). Predictors of prevalent LTF tenderness: female (aOR = 2.18; 1.22, 3.90). There were no predictors of prevalent PF grind in the fully adjusted model. However, medial patellar osteophytes was predictive in the age-sex-BMI adjusted model. There were no predictors of 3-year incident MTF tenderness. Predictors of 3-year incident LTF tenderness: female (aOR = 3.83; 1.25, 11.77). Predictors of 3-year incident PF grind: lateral patellar osteophytes (aOR = 4.82; 1.69, 13.77). In the age-sex-BMI adjusted model, patellar cartilage was also a predictor. CONCLUSION: We explored potential MRI predictors of prevalent and 3-year incident MTF/LTF knee joint tenderness and PF grind. These findings could guide preemptive strategies aimed at reducing these symptoms in the present and future (3-year incidence).

System-level performance measures of access to rheumatology care: a population-based retrospective study of trends over time and the impact of regional rheumatologist supply in Ontario, Canada, 2002-2019.

OBJECTIVE: To determine whether there were improvements in rheumatology care for rheumatoid arthritis (RA) between 2002 and 2019 in Ontario, Canada, and to evaluate the impact of rheumatologist regional supply on access. METHODS: We conducted a population-based retrospective study of all individuals diagnosed with RA between January 1, 2002 and December 31, 2019. Performance measures evaluated were: (i) percentage of RA patients seen by a rheumatologist within one year of diagnosis; and (ii) percentage of individuals with RA aged 66 years and older (whose prescription drugs are publicly funded) dispensed a disease modifying anti-rheumatic drug (DMARD) within 30 days after initial rheumatologist visit. Logistic regression was used to assess whether performance improved over time and whether the improvements differed by rheumatology supply, dichotomized as < 1 rheumatologist per 75,000 adults versus ≥1 per 75,000. RESULTS: Among 112,494 incident RA patients, 84% saw a rheumatologist within one year: The percentage increased over time (adjusted odds ratio (OR) 2019 vs. 2002 = 1.43, p < 0.0001) and was consistently higher in regions with higher rheumatologist supply (OR = 1.73, 95% CI 1.67-1.80). Among seniors who were seen by a rheumatologist within 1 year of their diagnosis the likelihood of timely DMARD treatment was lower among individuals residing in regions with higher rheumatologist supply (OR = 0.90 95% CI 0.83-0.97). These trends persisted after adjusting for other covariates. CONCLUSION: While access to rheumatologists and treatment improved over time, shortcomings remain, particularly for DMARD use. Patients residing in regions with higher rheumatology supply were more likely to access care but less likely to receive timely treatment.

Reducing the burden of low back pain: results from a new microsimulation model.

BACKGROUND: Low back pain (LBP) causes the highest morbidity burden globally. The purpose of the present study was to project and compare the impact of three strategies for reducing the population health burden of LBP: weight loss, ergonomic interventions, and an exercise program. METHODS: We have developed a microsimulation model of LBP in Canada using a new modeling platform called SimYouLate. The initial population was derived from Cycle 1 (2001) of the Canadian Community Health Survey (CCHS). We modeled an open population 20 years of age and older. Key variables included age, sex, education, body mass index (BMI), type of work, having back problems, pain level in persons with back problems, and exercise participation. The effects of interventions on the risk of LBP were obtained from the CCHS for the effect of BMI, the Global Burden of Disease Study for occupational risks, and a published meta-analysis for the effect of exercise. All interventions lasted from 2021 to 2040. The population health impact of the interventions was calculated as a difference in years lived with disability (YLDs) between the base-case scenario and each intervention scenario, and expressed as YLDs averted per intervention unit or a proportion (%) of total LBP-related YLDs. RESULTS: In the base-case scenario, LBP in 2020 was responsible for 424,900 YLDs in Canada and the amount increased to 460,312 YLDs in 2040. The effects of the interventions were as follows: 27,993 (95% CI 23,373, 32,614) YLDs averted over 20 years per 0.1 unit change in log-transformed BMI (9.5% change in BMI) among individuals who were overweight and those with obesity, 19,416 (16,275, 22,557) YLDs per 1% reduction in the proportion of workers exposed to occupational risks, and 26,058 (22,455, 29,661) YLDs averted per 1% increase in the proportion of eligible patients with back problems participating in an exercise program. CONCLUSIONS: The study provides new data on the relationship between three types of interventions and the resultant reductions in LBP burden in Canada. According to our model, each of the interventions studied could potentially result in a substantial reduction in LBP-related disability.

The Impact of 51 Risk Factors on Life Expectancy in Canada: Findings from a New Risk Prediction Model Based on Data from the Global Burden of Disease Study.

The aims of this study were (1) to develop a comprehensive risk-of-death and life expectancy (LE) model and (2) to provide data on the effects of multiple risk factors on LE. We used data for Canada from the Global Burden of Disease (GBD) Study. To create period life tables for males and females, we obtained age/sex-specific deaths rates for 270 diseases, population distributions for 51 risk factors, and relative risk functions for all disease-exposure pairs. We computed LE gains from eliminating each factor, LE values for different levels of exposure to each factor, and LE gains from simultaneous reductions in multiple risk factors at various ages. If all risk factors were eliminated, LE in Canada would increase by 6.26 years for males and 5.05 for females. The greatest benefit would come from eliminating smoking in males (2.45 years) and high blood pressure in females (1.42 years). For most risk factors, their dose-response relationships with LE were non-linear and depended on the presence of other factors. In individuals with high levels of risk, eliminating or reducing exposure to multiple factors could improve LE by several years, even at a relatively advanced age.

A Population-Based Study Evaluating Retention in Rheumatology Care Among Patients With Rheumatoid Arthritis.

OBJECTIVE: The study objective was to assess adherence to system-level performance measures measuring retention in rheumatology care and disease modifying anti-rheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). METHODS: We used a validated health administrative data case definition to identify individuals with RA in Ontario, Canada, between 2002 and 2014 who had at least 5 years of potential follow-up prior to 2019. During the first 5 years following diagnosis, we assessed whether patients were seen by a rheumatologist yearly and the proportion dispensed a DMARD yearly (in those aged ≥66 for whom medication data were available). Multivariable logistic regression analyses were used to estimate the odds of remaining under rheumatologist care. RESULTS: The cohort included 50,883 patients with RA (26.1% aged 66 years and older). Over half (57.7%) saw a rheumatologist yearly in all 5 years of follow-up. Sharp declines in the percentage of patients with an annual visit were observed in each subsequent year after diagnosis, although a linear trend to improved retention in rheumatology care was seen over the study period (P < 0.0001). For individuals aged 66 years or older (n = 13,293), 82.1% under rheumatologist care during all 5 years after diagnosis were dispensed a DMARD annually compared with 31.0% of those not retained under rheumatology care. Older age, male sex, lower socioeconomic status, higher comorbidity score, and having an older rheumatologist decreased the odds of remaining under rheumatology care. CONCLUSION: System-level improvement initiatives should focus on maintaining ongoing access to rheumatology specialty care. Further investigation into causes of loss to rheumatology follow-up is needed.

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.

Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage Values in Hips With Bone Marrow Lesions.

OBJECTIVE: Bone marrow lesions (BMLs) are associated with painful and progressive osteoarthritis (OA). Quantitative magnetic resonance imaging (MRI) has been used to study early cartilage degeneration in knees with BML, but similar work has not been done in hips. The purpose of this study was to compare mean delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) relaxation values (T1Gd) in hips with BML to hips without BML in a population-based study. Reduced T1Gd suggests depleted glycosaminoglycan. Our hypothesis was that mean T1Gd is lower in hips with BML compared to hips without BML. METHODS: Study participants (n = 128) were recruited from a cross-sectional population-based study of people ages 20-49 years with and without hip pain. dGEMRIC and proton density (PD)-weighted MRI scans of 1 hip from each participant were used for this analysis. BMLs were identified from PD-weighted fat-suppressed images. We applied a sampling-weighted linear regression model to determine the association of the presence of BMLs with mean cartilage T1Gd (significance: P < 0.05). The model was adjusted for age, sex, body mass index (BMI), hip pain, cam/pincer deformity, and physical activity. RESULTS: Thirty-two (25%) of the 128 participants had at least 1 BML. Subjects with at least 1 BML, compared to those without, had similar weighted characteristics of age, BMI, physical activity levels, and frequency of hip pain. Mean T1Gd was 75.25 msec lower (95% confidence interval -149.69, -0.81; P = 0.048) (9%) in the BML compared to the no-BML group. CONCLUSION: Our results suggest that hips with BMLs are associated with hip cartilage degeneration early in the OA disease process.

Has the incidence of total joint arthroplasty in rheumatoid arthritis decreased in the era of biologics use? A population-based cohort study.

OBJECTIVES: To determine whether the introduction of biological DMARDs (bDMARDs) was associated with reduced incidences of total hip and knee arthroplasty (THA/TKA) among patients with RA compared with OA. METHODS: Using a population-based cohort in British Columbia, Canada, RA and OA patients diagnosed between 1995 and 2007 were divided into semi-annual cohorts according to diagnosis date. For each cohort, we calculated 8-year incidence rates of THA and TKA. We compared levels and trends of THA/TKA incidence in RA/OA patients diagnosed during pre-bDMARDs (1995-2001) and post-bDMARDs (2003-2007) periods using interrupted time-series analysis, adjusting for baseline characteristics. Adjusted 8-year total joint arthroplasty incidence estimated for RA/OA cohorts diagnosed five years after bDMARDs introduction were compared with expected rates assuming no bDMARDs introduction, based on extrapolation of pre-bDMARDs trends. RESULTS: We identified 60 227 RA and 288 260 OA incident cases. For cohorts diagnosed pre-bDMARDs, 8-year THA/TKA incidence rates increased over time in both RA and OA. For cohorts diagnosed post-bDMARDs, these rates decreased over time in RA but continued to increase for OA. For RA, differences between the post- and pre-bDMARDs secular trends in incidence rates were -0.49 (P = 0.002) for THA and -0.36 (P = 0.003) for TKA, compared with +0.40 (P = 0.006) and +0.54 (P < 0.001), respectively, for OA. For RA cohorts diagnosed five years after bDMARDs introduction, 8-year incidences were 26.9% and 12.6% lower for THA and TKA, respectively, than expected rates. In contrast, corresponding rates in OA were higher by 11.7% and 16.6%, respectively. CONCLUSION: Arthritis onset after bDMARDs introduction is associated with a significant reduction in THA/TKA incidence in RA, but not in OA. The reduction reflects a significant improvement in RA treatment during the biological era.