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.

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.

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.

A comparison of three strategies to reduce the burden of osteoarthritis: A population-based microsimulation study.

OBJECTIVES: The purpose of this study was to compare three strategies for reducing population health burden of osteoarthritis (OA): improved pharmacological treatment of OA-related pain, improved access to joint replacement surgery, and prevention of OA by reducing obesity and overweight. METHODS: We applied a validated computer microsimulation model of OA in Canada. The model simulated a Canadian-representative open population aged 20 years and older. Variables in the model included demographics, body mass index, OA diagnosis, OA treatment, mortality, and health-related quality of life. Model parameters were derived from analyses of national surveys, population-based administrative data, a hospital-based cohort study, and the literature. We compared 8 what-if intervention scenarios in terms of disability-adjusted life years (DALYs) relative to base-case, over a wide range of time horizons. RESULTS: Reductions in DALYs depended on the type of intervention, magnitude of the intervention, and the time horizon. Medical interventions (a targeted increase in the use of painkillers) tended to produce effects quickly and were, therefore, most effective over a short time horizon (a decade). Surgical interventions (increased access to joint replacement) were most effective over a medium time horizon (two decades or longer). Preventive interventions required a substantial change in BMI to generate a significant impact, but produced more reduction in DALYs than treatment strategies over a very long time horizon (several decades). CONCLUSIONS: In this population-based modeling study we assessed the potential impact of three different burden reduction strategies in OA. Data generated by our model may help inform the implementation of strategies to reduce the burden of OA in Canada and elsewhere.

Risk of Incident Chronic Obstructive Pulmonary Disease in Rheumatoid Arthritis: A Population-Based Cohort Study.

OBJECTIVE: Studies have demonstrated a link between chronic obstructive pulmonary disease (COPD) and inflammation, raising the question whether chronic inflammatory conditions, such as rheumatoid arthritis (RA), predispose to COPD. Our objective was to evaluate the risk of incident COPD hospitalization in RA compared to the general population. METHODS: We studied a population-based incident RA cohort with matched general population controls, using administrative health data. All incident RA cases in British Columbia who first met RA definition between January 1996 and December 2006 were selected using previously published criteria. General population controls were randomly selected, matched 1:1 to RA cases on birth year, sex, and index year. COPD outcome was defined as hospitalization with a primary COPD code. Incidence rates, 95% confidence intervals (95% CIs), and incidence rate ratios (IRRs) were calculated for RA and controls. Multivariable Cox proportional hazards models estimated the risk of COPD in RA compared to the general population after adjusting for potential confounders. Sensitivity analyses were performed to test the robustness of the results to the possible confounding effect of smoking, unavailable in administrative data, and to COPD outcome definitions. RESULTS: The cohorts included 24,625 RA individuals and 25,396 controls. The incidence of COPD hospitalization was greater in RA than controls (IRR 1.58, 95% CI 1.34-1.87). After adjusting for potential confounders, RA cases had a 47% greater risk of COPD hospitalization than controls. The increased risk remained significant after modeling for smoking and with varying COPD definitions. CONCLUSION: In our population-based cohort, individuals with RA had a 47% greater risk of COPD hospitalization compared to the general population.

Association of Knee Effusion Detected by Physical Examination With Bone Marrow Lesions: Cross-Sectional and Longitudinal Analyses of a Population-Based Cohort.

OBJECTIVE: To determine the association of effusion detected by physical examination with the prevalence of bone marrow lesions (BMLs) on magnetic resonance imaging (MRI), and the incidence/progression of BMLs over 3 years in subjects with knee osteoarthritis. METHODS: A population-based cohort with knee pain (n = 255) was assessed for effusion on physical examination. On MRI, BMLs were graded 0-3 (none, mild, moderate, severe), and incidence/progression was defined as a worsening of the sum of BML scores over 6 surfaces by ≥1 grade. We analyzed the full cohort and a mild disease subsample with a Kellgren/Lawrence (K/L) grade <3. Cross-sectional logistic and longitudinal exponential regression analyses were performed, adjusted for age, sex, body mass index (BMI) and pain. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for effusion detected by physical examination versus BMLs (prevalence and incidence/progression). RESULTS: The weighted mean age was 56.7 years, the mean BMI was 26.5, 56.3% were women, 20.1% had effusion on physical examination, and 80.7% had a K/L grade <3. Effusion on physical examination was significantly associated with prevalent BMLs in the full cohort (odds ratio [OR] 6.10 [95% confidence interval (95% CI) 2.77-13.44]) and in the K/L grade <3 cohort (OR 6.88 [95% CI 2.76-17.15]). In the full cohort, sensitivity, specificity, PPV, and NPV were 34.6, 92.5, 79.9, and 62.1%, respectively, and in the K/L <3 cohort 31.7, 94.0, 75.5, and 70.1%, respectively. Longitudinally, effusion on physical examination was not significantly associated with BML incidence/progression in the full cohort (hazard ratio [HR] 1.83 [95% CI 0.95-3.52]) or in the K/L grade <3 cohort (HR 1.73 [95% CI 0.69-4.33]). In the two cohorts, sensitivity, specificity, PPV, and NPV were 32.0, 82.2, 42.2, and 74.9%, respectively, and 21.2, 85.6, 30.1, and 78.8% respectively. CONCLUSION: BMLs on MRI can be predicted from physical examination effusion cross-sectionally, with a high PPV of 79.9%. Assessment for knee effusion on physical examination is useful for determining potential candidates with BMLs before costly MRI screening for recruitment into clinical trials.

All-Cause and Cause-Specific Mortality in Patients With Granulomatosis With Polyangiitis: A Population-Based Study.

OBJECTIVE: To investigate all-cause and cause-specific mortality in patients with newly diagnosed granulomatosis with polyangiitis (GPA) between 2 calendar time periods, 1997-2004 and 2005-2012. METHODS: Using an administrative health database, we compared all patients with incident GPA with non-GPA controls matched for sex, age, and time of entry into the study. The study cohorts were divided into 2 subgroups based on the year of diagnosis ("early cohort [1997-2004] and "late cohort" [2005-2012]). The outcome was death (all-cause, cardiovascular disease [CVD]-related cancer-related, renal disease-related, and infection-related) during the follow-up period. Hazard ratios (HR) were estimated using Cox proportional hazards models, first adjusted for age, sex, and time of entry and then adjusted for selected covariates based on a purposeful selection algorithm. RESULTS: Three hundred seventy patients with GPA and 3,700 non-GPA controls were included in this study, contributing 1,624.8 and 1,8671.3 person-years of follow-up, respectively. Sixty-eight deaths occurred in the GPA cohort, and 310 deaths occurred in the non-GPA cohort. Overall, the age-, sex-, and entry time-adjusted all-cause mortality HR in the GPA cohort was 3.12 (95% confidence interval CI 2.35-4.14). There was excess mortality due to CVD-related causes, but not cancer, in the GPA cohort. Reports of death due to infection or renal disease was not permitted, because the numbers of death were insufficient (<6 deaths for each outcome). All-cause mortality significantly improved between the early cohort and late cohort time periods (HR 5.61 and 2.33, respectively; P for interaction = 0.017). CONCLUSION: This population-based study showed increased all-cause and CVD-related mortality risks in patients with GPA. There was significant improvement in the all-cause mortality risk over time, but the risk remained increased compared with that in the general population.

Cardiovascular Disease Prevention in Rheumatoid Arthritis: Compliance with Diabetes Screening Guidelines.

OBJECTIVE: To evaluate compliance with diabetes screening guidelines for cardiovascular disease (CVD) prevention in rheumatoid arthritis (RA) compared to the general population. METHODS: We conducted the first longitudinal study of a population-based RA cohort including all prevalent RA cases in British Columbia between 1996 and 2006 and followed until 2010, with matched general population comparators. Using administrative data, we measured compliance with general population guidelines [i.e., testing plasma glucose (PG) at least once every 3 years after age 45] after excluding individuals with previous diabetes. Followup was divided into 3-year eligibility periods. Compliance was measured as the proportion of periods with ≥ 1 PG test performed. OR (95% CI) of compliance in RA (vs general population) was calculated using generalized estimating equation models, adjusting for age and sex. Mean compliance rate per patient was also calculated and compared using the Mann-Whitney U test. RESULTS: Analysis included 22,624 individuals with RA, contributing 48,724 three-year eligibility periods; and 22,579 people in a general population group, contributing 51,081 three-year eligibility periods. PG was measured in 72.3% (SD 37%) of the eligible time periods in the RA sample and in 70.4% (SD 38%) for the general population (OR 1.05, 95% CI 1.02-1.09, p < 0.0001). RA individuals met recommended screening guidelines in 71.4% of their eligible periods, compared to 70.6% (p < 0.001). Screening improved over time in RA relative to the general population. Family physicians ordered nearly all the PG tests. CONCLUSION: Compliance with general population guidelines for diabetes screening in RA was suboptimal, with little difference relative to the general population, despite a higher risk of CVD and diabetes.

Hydroxychloroquine prescription trends and predictors for excess dosing per recent ophthalmology guidelines.

BACKGROUND: Hydroxychloroquine (HCQ) retinopathy may be more common than previously recognized; recent ophthalmology guidelines have revised recommendations from ideal body weight (IBW)-based dosing to actual body weight (ABW)-based dosing. However, contemporary HCQ prescribing trends in the UK remain unknown. METHODS: We examined a UK general population database to investigate HCQ dosing between 2007 and 2016. We studied trends of excess HCQ dosing per ophthalmology guidelines (defined by exceeding 6.5 mg/kg of IBW and 5.0 mg/kg of ABW) and determined their independent predictors using multivariable logistic regression analyses. RESULTS: Among 20,933 new HCQ users (78% female), the proportions of initial HCQ excess dosing declined from 40% to 36% using IBW and 38% to 30% using ABW, between 2007 and 2016. Among these, 47% of women were excess-dosed (multivariable OR 12.52; 95% CI 10.99-14.26) using IBW and 38% (multivariable OR 1.98; 95% CI,1.81-2.15) using ABW. Applying IBW, 37% of normal and 44% of obese patients were excess-dosed; however, applying ABW, 53% of normal and 10% of obese patients were excess-dosed (multivariable ORs = 1.61 and 0.1 (reference = normal); both p < 0.01). Long-term HCQ users showed similar excess dosing. CONCLUSION: A substantial proportion of HCQ users in the UK, particularly women, may have excess HCQ dosing per the previous or recent weight-based guidelines despite a modest decline in recent years. Over half of normal-BMI individuals were excess-dosed per the latest guidelines. This implies the potential need to reduce dosing for many patients but also calls for further research to establish unifying evidence-based safe and effective dosing strategies.

Quality of care for cardiovascular disease prevention in rheumatoid arthritis: compliance with hyperlipidemia screening guidelines.

Objective: To evaluate compliance with hyperlipidaemia screening guidelines for cardiovascular disease prevention in RA compared with the general population. Methods: We conducted a longitudinal study of a population-based RA cohort including all prevalent cases in British Columbia between 1996 and 2006, followed up until 2010, with matched general population controls. Using administrative data, we measured compliance with general population guidelines (testing lipids every 5 years for women ⩾50 and men ⩾40), after excluding individuals with previous diabetes, coronary artery disease or hyperlipidaemia. Compliance was measured as the proportion of 5-year eligibility periods with one or more lipid test. Compliance rates in RA and controls were compared by Chi-square test. Odds ratio (95% CI) of compliance in RA (vs controls) was estimated using generalized estimating equation models, adjusting for age and sex. Mean compliance rate per patient was also calculated and compared using Mann-Whitney U test. Results: Analyses included 5587 RA individuals and 5613 controls, contributing 6993 and 7208 5-year eligibility periods, respectively. Lipids were measured in 56.6 and 59.5% of eligibility periods in RA and controls, respectively [adjusted odds ratio (95% CI): 0.97 (0.90, 1.06)]. Screening improved over time in RA relative to the general population, but remained suboptimal even after 2003, at 65.8%. Mean (s.d.) compliance rate per patient was 56.6 (47.2)% for RA and 59.5 (46.6)% for controls. Family physicians ordered almost all the lipid tests. Conclusion: Compliance with general population guidelines for hyperlipidaemia screening in RA was poor and did not differ from the general population, despite a higher risk of cardiovascular diseases.

Mortality in ANCA-associated vasculitis: ameta-analysis of observational studies.

OBJECTIVE: To determine the magnitude of all-cause mortality risk in patients with antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) compared with the general population through a meta-analysis of observational studies. METHODS: We searched Medline and Embase databases from their inception to April 2015. Observational studies that met the following criteria were assessed by two researchers: (1) clearly defined AAV identified by either the American College of Rheumatology 1990 classification criteria or the 2012 Chapel Hill Consensus Conference disease definitions, and (2) reported standardised mortality ratios (SMR) and 95% CI. We calculated weighted-pooled summary estimates of SMRs (meta-SMRs) for all-cause mortality using random-effects model, tested for publication bias and heterogeneity. RESULTS: Ten studies met the inclusion criteria, comprising 3338 patients with AAV enrolled from 1966 to 2009, and a total of 1091 observed deaths. Overall, we found a 2.7-fold increased risk of death in patients with AAV when compared with the general population (meta-SMR: 2.71 (95% CI 2.26 to 3.24)). Analysis on studies that included only granulomatosis with polyangiitis cases also indicated a similar mortality risk (meta-SMR: 2.63 (95% CI 2.02 to 3.43)). There was no significant publication bias or small-study effect. Subgroup analyses showed that mortality risks were higher in older cohorts, with a trend towards improvement over time (ie, those with their midpoint of enrolment periods that were between 1980-1993 and 1994-1999, vs 2000-2005). CONCLUSION: Published data indicate there is a 2.7-fold increase in mortality among patients with AAV compared with the general population.

Associations between MRI features versus knee pain severity and progression: Data from the Vancouver Longitudinal Study of Early Knee Osteoarthritis.

OBJECTIVE: To determine associations between features of osteoarthritis (OA) on MRI and knee pain severity and knee pain progression. DESIGN: Baseline, 3.3- and 7.5-year assessments were performed for 122 subjects with baseline knee pain (age 40-79), sample-weighted for population (with knee pain) representativeness. MRIs were scored for: osteophytes (0:absent to 3:large); cartilage (0:normal to 4:full thickness defect; 0/1 collapsed); subchondral sclerosis (0:none to 3:>50% of site), subchondral cyst (0:absent to 3:severe), bone marrow lesions (0:none to 3:≥50% of site); and meniscus (0:normal to 3:maceration/resection), in 6-8 regions each. Per feature, scores were averaged across regions. Effusion/synovitis (0:absent to 3:severe) was analyzed as ≥2 vs. <2. Linear models predicted WOMAC knee pain severity (0-100), and binary models predicted 10+ (minimum perceptible clinical improvement [MPCI]) and 20+ (minimum clinically important difference [MCID]) increases. Models were adjusted for age, sex, BMI (and follow-up time for longitudinal models). RESULTS: Pain severity was associated with osteophytes (7.17 per unit average; 95% CI = 3.19, 11.15) and subchondral sclerosis (11.03; 0.68, 21.39). MPCI-based pain increase was associated with osteophytes (odds ratio per unit average 3.20; 1.36, 7.55), subchondral sclerosis (5.69; 1.06, 30.44), meniscal damage (1.68; 1.08, 2.61) and effusion/synovitis ≥2 (2.25; 1.07, 4.71). MCID-based pain increase was associated with osteophytes (3.79; 1.41, 10.20) and cartilage defects (2.42; 1.24, 4.74). CONCLUSIONS: Of the features investigated, only osteophytes were consistently associated with pain cross-sectionally and longitudinally in all models. This suggests an important role of bone in early knee osteoarthritis.

Medication Nonadherence in Systemic Lupus Erythematosus: A Systematic Review.

OBJECTIVE: Medication nonadherence has not been well characterized in systemic lupus erythematosus (SLE). Our objective was to a conduct a systematic review of the literature, examining the burden and determinants of medication nonadherence in SLE. METHODS: We conducted a systematic search of Medline (1946-2015), Embase (1974-2015), and Web of Science (1900-2015) databases and selected original studies of SLE patients that evaluated nonadherence to SLE therapies as the primary study outcome. We extracted information on study design, sample size, length of followup, data sources, type of nonadherence problem examined, adherence measures and reported estimates, and determinants of adherence reported in multivariable analyses. RESULTS: After screening 4,111 titles, 11 studies met the inclusion criteria. Study sample sizes ranged from 32 to 246 patients, and studies were categorized according to data source: self-report (5), electronic monitoring devices (1), clinical records from rheumatology clinics (3), and refill information from pharmacy records (2). Overall, the percentage of nonadherent patients ranged from 43% to 75%, with studies consistently reporting that over half of patients are nonadherent. Studies also showed that up to 33% of patients discontinue therapy after 5 years. Determinants of nonadherence included having depression, rural residence, lower education level, and polypharmacy. CONCLUSION: Overall, synthesis of current evidence suggests that the burden of medication nonadherence is substantial in SLE. Findings highlight the importance of developing interventions to support adherence and improve outcomes among patients.

Gaps in Addressing Cardiovascular Risk in Rheumatoid Arthritis: Assessing Performance Using Cardiovascular Quality Indicators.

OBJECTIVE: Cardiovascular disease (CVD) is a major comorbidity for patients with rheumatoid arthritis (RA). This study sought to determine the performance of 11 recently developed CVD quality indicators (QI) for RA in clinical practice. METHODS: Medical charts for patients with RA (early disease or biologic-treated) followed at 1 center were retrospectively reviewed. A systematic assessment of adherence to 11 QI over a 2-year period was completed. Performance on the QI was reported as a percentage pass rate. RESULTS: There were 170 charts reviewed (107 early disease and 63 biologic-treated). The most frequent CVD risk factors present at diagnosis (early disease) and biologic start (biologic-treated) included hypertension (26%), obesity (25%), smoking (21%), and dyslipidemia (15%). Performance on the CVD QI was highly variable. Areas of low performance (< 10% pass rates) included documentation of a formal CVD risk assessment, communication to the primary care physician (PCP) that patients with RA were at increased risk of CVD, body mass index documentation and counseling if overweight, communication to a PCP about an elevated blood pressure, and discussion of risks and benefits of antiinflammatories in patients at CVD risk. Rates of diabetes screening and lipid screening were 67% and 69%, respectively. The area of highest performance was observed for documentation of intent to taper corticosteroids (98%-100% for yrs 1 and 2, respectively). CONCLUSION: Gaps in CVD risk management were found and highlight the need for quality improvements. Key targets for improvement include coordination of CVD care between rheumatology and primary care, and communication of increased CVD risk in RA.

Development of Cardiovascular Quality Indicators for Rheumatoid Arthritis: Results from an International Expert Panel Using a Novel Online Process.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have a high risk of premature cardiovascular disease (CVD). We developed CVD quality indicators (QI) for screening and use in rheumatology clinics. METHODS: A systematic review was conducted of the literature on CVD risk reduction in RA and the general population. Based on the best practices identified from this review, a draft set of 12 candidate QI were presented to a Canadian panel of rheumatologists and cardiologists (n = 6) from 3 academic centers to achieve consensus on the QI specifications. The resulting 11 QI were then evaluated by an online modified-Delphi panel of multidisciplinary health professionals and patients (n = 43) to determine their relevance, validity, and feasibility in 3 rounds of online voting and threaded discussion using a modified RAND/University of California, Los Angeles Appropriateness Methodology. RESULTS: Response rates for the online panel were 86%. All 11 QI were rated as highly relevant, valid, and feasible (median rating ≥ 7 on a 1-9 scale), with no significant disagreement. The final QI set addresses the following themes: communication to primary care about increased CV risk in RA; CV risk assessment; defining smoking status and providing cessation counseling; screening and addressing hypertension, dyslipidemia, and diabetes; exercise recommendations; body mass index screening and lifestyle counseling; minimizing corticosteroid use; and communicating to patients at high risk of CVD about the risks/benefits of nonsteroidal antiinflammatory drugs. CONCLUSION: Eleven QI for CVD care in patients with RA have been developed and are rated as highly relevant, valid, and feasible by an international multidisciplinary panel.

Association of smoking with cutaneous manifestations in systemic lupus erythematosus.

OBJECTIVE: To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE). METHODS: We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data. RESULTS: In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials. CONCLUSION: Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.

Pharmacist-initiated intervention trial in osteoarthritis: a multidisciplinary intervention for knee osteoarthritis.

OBJECTIVE: Knee osteoarthritis (OA) is a commonly undiagnosed condition and care is often not provided. Pharmacists are uniquely placed for launching a multidisciplinary intervention for knee OA. METHODS: We performed a cluster randomized controlled trial with pharmacies providing either intervention care or usual care (14 and 18 pharmacies, respectively). The intervention included a validated knee OA screening questionnaire, education, pain medication management, physiotherapy-guided exercise, and communication with the primary care physician. Usual care consisted of an educational pamphlet. The primary outcome was the pass rate on the Arthritis Foundation's quality indicators for OA. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Lower Extremity Function Scale (LEFS), the Paper Adaptive Test-5D (PAT-5D), and the Health Utilities Index Mark 3 (HUI3). RESULTS: One hundred thirty-nine patients were assigned to the control (n = 66) and intervention (n = 73) groups. There were no differences between the groups in baseline measures. The overall quality indicator pass rate was significantly higher in the intervention arm compared to the control arm (difference of 45.2%; 95% confidence interval 34.5, 55.9). Significant improvements were observed for the intervention care group as compared to the usual care group in the WOMAC global, pain, and function scores at 3 and 6 months (all P < 0.01); the PAT-5D daily activity scores at 3 and 6 months (both P < 0.05); the PAT-5D pain scores at 6 months (P = 0.05); the HUI3 single-attribute pain scores at 3 and 6 months (all P < 0.05); and the LEFS scores at 6 months (P < 0.05). CONCLUSION: Pharmacists can launch a multidisciplinary intervention to identify knee OA cases, improve the utilization of treatments, and improve function, pain, and quality of life.

Frequency of bone marrow lesions and association with pain severity: results from a population-based symptomatic knee cohort.

OBJECTIVE: To evaluate the prevalence of bone marrow lesions (BML) and their association with pain severity in a population-based cohort of symptomatic early knee osteoarthritis (OA). METHODS: Subjects with knee pain (n = 255), age 40-79 years, were evaluated by radiograph and magnetic resonance imaging (MRI) and classified into OA stages: no OA (NOA), preradiographic OA (PROA), and radiographic OA (ROA). BML were graded 0-3 (none, mild, moderate, severe) in 6 regions and defined as (1) BMLsum = the sum of 6 scores; and (2) BMLmax = the worst score at any region. Pain was assessed by the Western Ontario and McMaster Universities OA Index (WOMAC). Linear regression analysis was completed to assess the association of Total WOMAC Pain (primary outcome) versus BMLsum or BMLmax. Secondary outcomes were WOMAC Pain on Walking and WOMAC Pain on Climbing Stairs. All analyses were adjusted for age, sex, body mass index, OA stage, joint effusion, and meniscal damage. RESULTS: BML were present in 11% of NOA, 38% of PROA, and 71% of ROA subjects (p < 0.001). No association was seen for BMLsum or BMLmax versus Total WOMAC Pain or Pain on Walking. However, BMLsum was associated with Pain on Climbing Stairs [regression coefficients (RC) = 0.09, 95% CI 0.00-0.18]. BMLmax was associated with Pain on Climbing Stairs, with the strongest association for severe BML (RC 0.60, 95% CI 0.04-1.17). CONCLUSION: BML were present in 38% of PROA and 71% of ROA subjects in this symptomatic knee cohort. BML were significantly associated with Pain on Climbing Stairs but not Total WOMAC or Pain on Walking.