Search

To evaluate a stratified screening process for the early identification of axial spondyloarthritis (SpA) with consideration of the following: 1) wait times from primary care to rheumatology screen, 2) incremental precision and accuracy from primary care to rheumatology screening, and 3) diagnostic delay.Adults with low back pain attending primary care at low back pain clinics prospectively underwent a primary standardized clinical screening. Patients with low back pain of3 months who experienced symptom onset at age50 years were referred for a comprehensive secondary screening by a physical therapist with advanced rheumatology training. At secondary screening, patients with features of inflammation were classified as being at a low, medium, or high risk for axial SpA versus no risk for axial SpA. Precision and accuracy of this screening strata were measured against a rheumatologist with expertise in axial SpA.Overall, 405 patients underwent primary and secondary screening in the present study. The study cohort had a mean ± SD age of 36.9 ± 9.9 years, and 55% were women. HLA-B27 was present in 14.4% of patients. Median wait time from primary screening to secondary screening was 15 days. Axial SpA risk assignment by rheumatologist was 64.9% for no risk or low risk for axial SpA and 35.1% for medium risk or high risk for axial SpA. The best combination of sensitivity (68%), specificity (90%), positive predictive values (80%), and negative predictive values (84%) was evident in the secondary screening. In this cohort, 15.6% of patients received a final diagnosis of axial SpA. Median low back pain duration from symptom onset to diagnosis was 2 years for nonradiographic axial SpA and 7 years for ankylosing spondylitis.A stratified interprofessional screening process can facilitate rapid diagnosis of persistent low back pain with high precision and accuracy in patients who have axial SpA.

Objective To determine the contribution of rheumatoid arthritis (RA) to conditions and medical events. A secondary objective is to quantify this association before and after the introduction of biologic medications. Methods All data were collected as health administrative data in Ontario, Canada. Patients with RA (n = 136 678) matched 1:1 to a pool of possible controls without RA from 1995 to 2016. The study was a retrospective longitudinal observational administrative data-based cohort study with cases (RA) and controls (two non-RA comparator groups). The main exposure was new-onset RA identified by a validated diagnosis algorithm. The secondary exposure was the calendar year, which provided a natural experiment to compare years in which biologics were unavailable (pre-2001) to increasing utilization over time. The main outcomes were counts of 27 Johns Hopkins Expanded Diagnostic Cluster Comorbid Conditions. Outcomes were reported as counts and percentage differences between cases and matched controls. Results Patients experienced increases in conditions and medical events up to 5 years before RA disease incidence-4.9 conditions per patient-year compared with 4.6 conditions per patient-year in matched controls. Comorbidities increased to 8.7 conditions per patient-year in the year of RA incidence but were lower in the years after diagnosis-6.9 conditions per patient-year at 5 years postdiagnosis. Conclusion This study reframes the clinical manifestations of RA with detailed data on the marginal contribution of RA to conditions and medical events. These results show that a large portion of disease burden is due to the indirect effects of RA.

Background Tophi develop in untreated or uncontrolled gout. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the benefits and harms of non-surgical and surgical treatments for the management of tophi in gout. Search methods We updated the search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases to 28 August 2020. Selection criteria We included all published randomised controlled trials (RCTs) or controlled clinical trials examining interventions for tophi in gout in adults. Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We included one trial in our original review. We added four more trials (1796 participants) in this update. One had three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Two studies looked at lesinurad 200 mg or 400 mg in combination with allopurinol. One trial studied lesinurad 200 mg or 400 mg in combination with febuxostat. One trial compared febuxostat 80 mg and 120 mg to allopurinol. Two trials were at unclear risk of performance and detection bias due to lack of information on blinding of participants and personnel. All other trials were at low risk of bias. Moderate-certainty evidence (downgraded for imprecision; one study; 79 participants) showed that biweekly pegloticase resolved tophi in 21/52 participants compared with 2/27 on placebo (risk ratio (RR) 5.45, 95% confidence interval (CI) 1.38 to 21.54; number needed to treat for a benefit (NNTB) 3, 95% CI 2 to 6). Similar proportions of participants receiving biweekly pegloticase (80/85) had an adverse event compared to placebo (41/43) (RR 0.99, 95% CI 0.91 to 1.07). However, more participants on biweekly pegloticase (15/85) withdrew due to an adverse event compared to placebo (1/43) (RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for a harm (NNTH) 7, 95% CI 4 to 16). More participants on monthly pegloticase (11/52) showed complete resolution of tophi compared with placebo (2/27) (RR 2.86, 95% CI 0.68 to 11.97; NNTB 8, 95% CI 4 to 91). Similar numbers of participants on monthly pegloticase (84/84) had an adverse event compared to placebo (41/43) (RR 1.05, 95% CI 0.98 to 1.14). More participants on monthly pegloticase (16/84) withdrew due to adverse events compared to placebo (1/43) (RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Infusion reaction was the most common reason for withdrawal. Moderate-certainty evidence (2 studies; 103 participants; downgraded for imprecision) showed no clinically significant difference for complete resolution of target tophus in the lesinurad 200 mg plus allopurinol arm (11/53) compared to the placebo plus allopurinol arm (16/50) (RR 0.40, 95% CI 0.04 to 4.57), or in the lesinurad 400 mg plus allopurinol arm (12/48) compared to the placebo plus allopurinol arm (16/50) (RR 0.79, 95% CI 0.42 to 1.49). An extension study examined lesinurad 200 mg or 400 mg in combination with febuxostat, or placebo (low-certainty evidence, downgraded for indirectness and imprecision). Participants on lesinurad in the original study continued (CONT) on the same dose. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution; 43/65 in the lesinurad 400 mg CONT arm compared to 38/64 in the lesinurad 200 mg CONT arm had tophi resolution (RR 1.11, 95% CI 0.85 to 1.46). Lesinurad 400 mg plus febuxostat may result in no difference in adverse events; 57/65 in the lesinurad 400 mg CONT arm had an adverse event compared to 50/64 in lesinurad 200 mg CONT arm (RR 1.12, 95% CI 0.96 to 1.32). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events; 10/65 participants in the lesinurad 400 mg CONT arm withdrew due to an adverse event compared to 10/64 participants in the lesinurad 200 mg CONT arm (RR 0.98, 95% CI 0.44 to 2.20). Lesinurad 400 mg plus febuxostat may result in no difference in mean serum uric acid (sUA), which was 3 mg/dl in the lesinurad 400 mg CONT group compared to 3.9 mg/dl in the lesinurad 200 mg CONT group (mean difference -0.90, 95% CI -1.51 to -0.29). Participants who were not on lesinurad in the original study were randomised (CROSS) to lesinurad 200 mg or 400 mg, both in combination with febuxostat. Low-certainty evidence downgraded for indirectness and imprecision showed that lesinurad 400 mg (CROSS) may result in tophi resolution (17/34) compared to lesinurad 200 mg (CROSS) (14/33) (RR 1.18, 95% CI 0.70 to 1.98). Lesinurad 400 mg in combination with febuxostat may result in no difference in adverse events (33/34 in the lesinurad 400 mg CROSS arm compared to 27/33 in the lesinurad 200 mg (CROSS); RR 1.19, 95% CI 1.00 to 1.41). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events, 5/34 in the lesinurad 400 mg CROSS arm withdrew compared to 2/33 in the lesinurad 200 mg CROSS arm (RR 2.43, 95% CI 0.51 to 11.64). Lesinurad 400 mg plus febuxostat results in no difference in sUA (4.2 mg/dl in lesinurad 400 mg CROSS) compared to lesinurad 200 mg (3.8 mg/dl in lesinurad 200 mg CROSS), mean difference 0.40 mg/dl, 95% CI -0.75 to 1.55. Authors' conclusions Moderate-certainty evidence showed that pegloticase is probably beneficial for resolution of tophi in gout. Although there was little difference in adverse events when compared to placebo, participants on pegloticase had more withdrawals due to adverse events. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution compared with lesinurad 200 mg plus febuxostat; there was no difference in adverse events between these groups. We were unable to determine whether lesinurad plus febuxostat is more effective than placebo. Lesinurad (400 mg or 200 mg) plus allopurinol is probably not beneficial for tophi resolution, and there was no difference in adverse events between these groups. RCTs on interventions for managing tophi in gout are needed, and the lack of trial data is surprising given that allopurinol is a well-established treatment for gout.

Objective Quality measurement for rheumatoid arthritis (RA) patients has largely focused on care provided by rheumatologists. Our aim was to develop and assess quality measures related to the screening and management of comorbidity in RA patients in primary care. Methods We used the primary care Electronic Medical Record Administrative data Linked Database in Ontario, Canada. We harmonized Canadian general population and RA clinical recommendations to develop and assess screening, process, and outcome measures. For each RA patient, 10 non-RA patients were matched by age and sex. Stratified analyses were performed, comparing patients with RA to those without RA, to assess the performance of quality measures. Results We compared 1,405 RA patients to 14,050 matched non-RA patients (72.8% female; mean age 62.5 years). Compared to non-RA patients, RA patients more frequently had influenza (44.9% versus 40.0%) and pneumococcal (40.4% versus 34.1%) vaccinations and bone mineral density testing (67.4% versus 58.1%). Herpes zoster vaccinations were less frequent among RA patients (13.8% versus 19.5%), as was screening for cervical cancer (58.6% versus 64.0%). No significant differences were observed between RA and non-RA patients in screenings for breast (70.7% versus 73.8%) or colorectal (31.7% versus 34.5%) cancers. Only a quarter of RA patients had a comprehensive cardiovascular risk assessment. No definitive differences were detected in the management of patients who had co-occurring cardiovascular disease or diabetes mellitus. Conclusion For both RA and non-RA patients, compliance with Canadian recommendations for preventive medical services and screening for comorbid conditions in primary care was less than optimal. This indicates key targets for improvement.

Objective Our aim was to characterize referrals to rheumatologists, the early care management of patients with rheumatic diseases, and timeliness of care and treatment. Methods We conducted a retrospective observational study involving patients with first-time rheumatology referrals between 2000 and 2013 in the primary care Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Referrals were characterized in terms of diagnoses, patient demographics, diagnostic tests, treatment initiated by family physicians and rheumatologists, and other specialists seen prior to rheumatology consultation. Timeliness of referrals, rheumatologist consultations, and treatment were determined overall and for each diagnostic category. Results Among 2,430 patients referred to a rheumatologist, 69% were female, with an average age of 53 years. The principal diagnosis associated with the referral included osteoarthritis (32%), systemic inflammatory rheumatic diseases (31%), regional musculoskeletal conditions (16%), chronic pain conditions (14%), osteoporosis (2%), and other/miscellaneous (5%). Family physicians most frequently prescribed nonsteroidal antiinflammatory drugs/cyclooxygenase 2 inhibitors (38%), and their pre-referral diagnostic testing practice varied considerably. The duration of time from symptom onset to rheumatology consultation varied by diagnoses, with the shortest being for patients with systemic rheumatic diseases; for rheumatoid arthritis (RA), the median time to consultation was 327 days. Most of the delay occurred prior to referral; 36% of RA patients initiated a disease-modifying antirheumatic drug within 6 months of symptom onset. Conclusion Approximately 1 in 3 referrals to rheumatologists were for a systemic inflammatory rheumatic disease. We observed substantial delays to rheumatology consultations and variations in patterns of care that could be amenable to quality improvement interventions.

Objective To evaluate excess mortality over time, comparing rheumatoid arthritis (RA) patients with the general population. Methods We computed all-cause mortality rates among Ontario residents age ≥15 years with RA versus without RA from 1996 to 2009. Age- and sex-standardized mortality rates were expressed as the number of deaths per 1,000 population. Excess mortality rates were calculated as the difference between death rates among RA patients and those in the general population. We estimated standardized mortality ratios (SMRs) and mortality rate ratios (MRRs) to assess relative excess mortality over time. Results From 1996 to 2009, SMRs in RA ranged from 13.0 (95% confidence interval [95% CI] 12.2, 13.9) to 9.2 deaths per 1,000 RA patients (95% CI 8.4, 10.0); and for those without RA from 8.7 (95% CI 8.6, 8.7) to 6.0 deaths (95% CI 5.9, 6.0) per 1,000 general population. Over the study period, the excess mortality rate among RA patients was approximately 3 excess deaths per 1,000 population. Relative reductions in standardized mortality rates occurred over time for those with and without RA (−21.4% versus −13.4%). The SMRs for RA patients in 1996–1997, 2000–2001, 2004–2005, and 2008–2009 were 1.51 (95% CI 1.43, 1.59), 1.50 (95% CI 1.43, 1.57), 1.43 (95% CI 1.37, 1.50), and 1.41 (95% CI 1.35, 1.47), respectively. We did not find a significant change in the MRR by calendar time. Conclusion Mortality for RA patients has decreased over time but remains elevated compared to the general population, with 40–50% more deaths among RA patients. The relative excess mortality over time (mortality gap) remains unchanged in our sample.

The ability to interpret scores from patient-reported outcome measures at the individual patient level depends on the availability of valid, clinically meaningful benchmarks of response and state attainment. The goal was to develop multinational estimates for minimal clinically important improvement (MCII) and patient acceptable symptomatic state (PASS). A multinational sample of patients with osteoarthritis (OA) was evaluated before and 4 weeks after treatment with nonsteroidal antiinflammatory drugs. Patients completed either the Western Ontario and McMaster Osteoarthritis Index (WOMAC) numerical rating scale 3.1 (hip and knee OA) or the Australian/Canadian Index (AUSCAN) numerical rating scale 3.1 (hand OA) before and after treatment. Patients rated the clinical importance of their response to treatment and their satisfaction with the health state achieved, from which multinational MCII and PASS estimates were calculated for both the WOMAC and AUSCAN indices. A total of 609 patients from 7 countries participated in the study. MCII and PASS estimates varied slightly by instrument and subscale. Absolute (percentage) change for MCII ranged 6-9 (10% to 17%) for WOMAC and 4-9 (8% to 15%) for AUSCAN. PASS estimates ranged 39-48 for WOMAC and 38-45 for AUSCAN. Some between-country variation was observed in MCII and PASS. Preliminary multinational estimates for MCII and PASS have been developed for several countries. Further research is required to evaluate the robustness, temporal consistency, and age- and sex-dependency of the preliminary estimates as well as their generalizability to other countries, languages, cultures, regions, and other condition-specific outcome measures.

Objective Epidemiologic assessments of sufficiently large populations are required in order to obtain robust estimates of disease prevalence and incidence, particularly when exploring the influence of various factors (age, sex, calendar time). We undertook this study to describe the epidemiology of rheumatoid arthritis (RA) over the past 15 years. Methods We used the Ontario Rheumatoid Arthritis administrative Database (ORAD), a validated population-based research database of all Ontarians with RA. The ORAD records were linked with census data to calculate crude and age and sex–standardized prevalence and incidence rates from 1996 to 2010. Vital statistics were used to estimate annual all-cause mortality during the study period. Results As of 2010, there were 97,499 Ontarians with RA, corresponding to a cumulative prevalence of 0.9%. Age and sex–standardized RA prevalence increased steadily over time from 473 (95% confidence interval [95% CI] 469–478) per 100,000 population (0.49%) in 1996 to 784 (95% CI 779–789) per 100,000 population (0.9%) in 2010. Age and sex–standardized incidence per 100,000 population ranged from 62 (95% CI 60–63) in 1996 to 54 (95% CI 52–55) in 2010. All-cause mortality decreased by a relative 21.4% since 1996. Conclusion Over a 15-year period, we observed an increase in RA prevalence over time. This rise may be attributed to the increasing time to ascertain cases (which may have been latent in the population during earlier years of the study), increasing survival, and/or an increase in the aging background population. Incidence appears to be stable.

Objective To determine if low-risk elderly patients with rheumatoid arthritis (RA) who screen positive for latent tuberculosis (TB) infection prior to anti–tumor necrosis factor (anti-TNF) therapy should be given isoniazid (INH). Methods A Markov model was developed. The base case was a patient age 65 years with RA starting anti-TNF therapy with a positive tuberculin skin test (TST) finding of 5–9 mm, who was born in a country with low TB prevalence and had no other TB risk factors. The decision was 9 months of INH or not. The primary outcome was quality-adjusted life expectancy. Multiple sensitivity analyses were performed. Results No prophylaxis was favored, with a gain of 1.1 quality-adjusted life days, but the decision was sensitive to several variables. Prophylaxis was favored for patients ages 2.5, if the RR with anti-TNF therapy was >5.8, or if the utility associated with INH therapy was >0.98. Prophylaxis was also preferred for patients with a TST result >10 mm and for patients from higher risk countries. If 6 months of INH or 4 months of rifampin were used, prophylaxis was preferred, providing that therapy reduced the risk of TB reactivation by >47% and >27%, respectively. Conclusion Withholding prophylaxis prior to anti-TNF therapy may be reasonable for low-risk elderly RA patients with a TST finding of 5–9 mm, although the decision is sensitive to patient preferences. For patients age 10 mm, prophylaxis is preferred.

Objective To evaluate the quality of the methods and reporting of published studies that validate administrative database algorithms for rheumatic disease case ascertainment. Methods We systematically searched MEDLINE, Embase, and the reference lists of articles published from 1980 to 2011. We included studies that validated administrative data algorithms for rheumatic disease case ascertainment using medical record or patient-reported diagnoses as the reference standard. Each study was evaluated using published standards for the reporting and quality assessment of diagnostic accuracy, which informed the development of a methodologic framework to help critically appraise and guide research in this area. Results Twenty-three studies met the inclusion criteria. Administrative database algorithms to identify cases were most frequently validated against diagnoses in medical records (83%). Almost two-thirds of the studies (61%) used diagnosis codes in administrative data to identify potential cases and then reviewed medical records to confirm the diagnoses. The remaining studies did the reverse, identifying patients using a reference standard and then testing algorithms to identify cases in administrative data. Many authors (61%) described the patient population, but few (26%) reported key measures of diagnostic accuracy (sensitivity, specificity, and positive and negative predictive values). Only one-third of studies reported disease prevalence in the validation study sample. Conclusion The methods used in administrative data validation studies of rheumatic diseases are highly variable. Few studies reported key measures of diagnostic accuracy despite their importance for drawing conclusions about the validity of administrative database algorithms. We developed a methodologic framework and recommendations for validation study conduct and reporting.

Objective To conduct a systematic review to identify and describe the scope and nature of the research evidence on the effectiveness of interventions to improve health care quality or reduce disparities in the care of disadvantaged populations with osteoarthritis (OA) as an example of a common chronic disease. Methods We searched electronic databases from 1950 through February 2010 and grey literature for relevant articles using any study design. Studies with interventions designed explicitly to improve health care quality or reduce disparities in the care of disadvantaged adult populations with OA and including an evaluation were eligible. We used the PROGRESS-Plus framework to identify disadvantaged population subgroups. Results Of 4,701 citations identified, 10 met the inclusion criteria. Eight were community based and 6 targeted race/ethnicity/culture. All 10 studies evaluated interventions aimed at people with OA; 2 studies also targeted the health care system. No studies targeted health care providers. Nine of 10 studies evaluated arthritis self-management interventions; all showed some benefit. Only 1 study compared the difference in effect between the PROGRESS-Plus disadvantaged population and the relevant comparator group. Conclusion There are few studies evaluating the effectiveness of interventions to improve health care quality in disadvantaged populations with OA. Further research is needed to evaluate interventions aimed at health care providers and the health care system, as well as other patient-level interventions. Gap intervention research is also needed to evaluate whether interventions are effective in reducing documented health care inequities.

Objective Among people with arthritis, the need for work transitions may signal a risk for more adverse work outcomes in the future, such as permanent work loss. Our aim was to evaluate the ability of the Work Instability Scale for Rheumatoid Arthritis (RA-WIS) to predict arthritis-related work transitions within a 12-month period. Methods Workers with osteoarthritis or rheumatoid arthritis (n = 250) from 3 clinical sites participated in self-administered surveys that assessed the impact of health on employment at multiple time points over 12 months. Multivariable logistic regressions were conducted to assess the ability of the RA-WIS (range 0–23, where 23 = highest work instability) to predict 4 types of work transition: reductions in work hours, disability leaves of absence, changes in job/occupation, or temporary unemployment, assembled as a composite outcome. Covariates assessed include age, sex, education, marital status, income, pain intensity, disease duration, and the Health Assessment Questionnaire. Areas under the receiver operating characteristic curves (AUROCCs) were also assessed to further examine the predictive ability of the RA-WIS and to determine optimal cut points for predicting specific work transitions. Results After 12 months, 21.7% (n = 50 of 230) of the participants had indicated at least one arthritis-related work transition. Higher baseline RA-WIS was predictive of such an outcome (relative risk [RR] 1.05 [95% confidence interval (95% CI) 1.00–1.11]), particularly at >17 (RR 2.30 [95% CI 1.11–4.77]). The RA-WIS cut point of >13 was found to be most accurate for prediction (AUROCC 0.68 [95% CI 0.58–0.78]). Conclusion The RA-WIS demonstrated the ability to predict arthritis-related work transitions within a short timeframe, and could be a promising measurement candidate for risk prognostication where work disability outcomes are of concern.

Objective To compare the primary therapist model (PTM), provided by a single rheumatology-trained primary therapist, with the traditional treatment model (TTM), provided by a physical therapy (PT) and/or occupational therapy (OT) generalist, for treating patients with rheumatoid arthritis (RA). Methods Eligible patients were adults requiring rehabilitation treatment who had not received PT/OT in the past 2 years. Participants were randomized to the PTM or TTM group. The primary outcome was defined as the proportion of clinical responders who experienced a ≥20% improvement in 2 of the following measures from baseline to 6 months: Health Assessment Questionnaire, pain visual analog scale, and Arthritis Community Research and Evaluation Unit RA Knowledge Questionnaire. Results Of 144 consenting patients, 33 (10 PTM participants, 23 TTM participants) dropped out without completing any followup assessment, leaving 111 for analysis (63 PTM participants, 48 TTM participants). The majority were women (PTM 87.3%, TTM 79.2%), with a mean age of 54.2 years and 56.8 years for the PTM and TTM groups, respectively. Average disease duration was 10.6 years and 13.2 years for each group, respectively. At 6 months, 44.4% of patients in the PTM group were clinical responders versus 18.8% in the TTM group (χ2 = 8.09, P = 0.004). Conclusion Compared with the TTM, the PTM was associated with better outcomes in patients with RA. The results, however, should be interpreted with caution due to the high dropout rate in the TTM group.

Objective To examine the association between HLA–DRB1 alleles and the production of anti–cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) autoantibodies in patients with rheumatoid arthritis (RA). Methods We studied 1,723 Caucasian RA patients enrolled in the North American Rheumatoid Arthritis Consortium (NARAC) family cohort and the Study of New Onset Rheumatoid Arthritis (SONORA) cohort. All patients were tested for anti-CCP antibodies (by enzyme-linked immunosorbent assay), RF (by nephelometry), and HLA–DR genotype (by polymerase chain reaction and sequence-specific oligonucleotide hybridization). Results When controlled for the presence of RF, anti-CCP positivity was strongly associated with the HLA–DRB1 shared epitope (SE). In RF+ patients, the presence of the SE was very significantly associated with anti-CCP positivity, with an odds ratio (OR) of 5.8 and a 95% confidence interval (95% CI) of 4.1–8.3. This relationship was also seen in RF– patients (OR 3.1 [95% CI 1.8–5.3]). In contrast, RF positivity was not significantly associated with presence of the SE independently of anti-CCP antibodies. Strikingly, HLA–DRB1*03 was strongly associated with reduced anti-CCP titers, even after controlling for the presence of the SE and restricting the analysis to anti-CCP+ patients. HLA–DR3 was also associated with anti-CCP– RA in our population. Conclusion The HLA–DRB1 SE is strongly associated with the production of anti-CCP antibodies, but not RF. In contrast, HLA–DR3 alleles are associated with anti-CCP– disease and with lower levels of anti-CCP antibodies, even when controlling for the SE. These data emphasize the complexity of the genetic effects of the major histocompatibility complex on the RA phenotype.

Objective To examine the use of nonpharmacologic treatment by patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods Patients were recruited from physicians' offices in Ontario, Canada. All participants completed questionnaires that asked about their health status, use of medications and nonpharmacologic treatments, and use of health care resources. Results A total of 326 patients with OA and 253 patients with RA completed the survey on the use of nonpharmacologic treatment. Only 73% of patients with OA had been told to use nonpharmacologic modalities, but 98.8% had tried at least 1 type of treatment. About 97% of those with RA had been told to use and had tried at least 1 type of treatment. Most patients continued to use a treatment once they had tried it. Conclusion The use of nonpharmacologic modalities is common among patients with arthritis. It is important that clinicians address with their patients the appropriate use of and barriers to continuing these treatments.

Purpose Research into the meaning of illness has often focused on an individual's transition into a state of being ill, for example the adoption of a sick role. The question “Are you better?” addresses the transition out of this state and is fundamental to the patient–clinician relationship, guiding decisions about treatment. However, the question assumes that all patients have the same meaning for “being better.” The purpose of this study was to explore the meaning of the concept of recovery (getting better) in a group of people with upper limb musculoskeletal disorders. Methods Qualitative (grounded theory) methods were used. Individual interviews were conducted with 24 workers with work-related musculoskeletal disorders of the upper limb. The audiotaped interviews were transcribed and coded for content. Categories were linked, comparisons made, and a theory built about how people respond to the question “Are you better?” Results The perception of “being better” is highly contextualized in the experience of the individual. Being better is not only reflected in changes in the state of the disorder (resolution) but could be an adjustment of life to work around the disorder (readjustment) or an adaptation to living with the disorder (redefinition). The experience of the disorder can be influenced by factors such as the perceived legitimacy of the disorder, the comparators used to define health and illness, and coping styles, which in turn can influence being better. Conclusion Two patients could mean very different things when saying that they are better. Some may not actually have a change in disease state as measured by symptoms, impairments, or function.

Objective. To assess the efficacy of leflunomide or methotrexate compared with placebo in improving function and health-related quality of life in patients with active rheumatoid arthritis (RA), and to examine correlations between response status (as defined by the American College of Rheumatology [ACR] response criteria) and improvement in these measures. Methods. This 52-week, multicenter, doubleblind, controlled trial compared responses to the Health Assessment Questionnaire (HAQ), modified Health Assessment Questionnaire (MHAQ), Problem Elicitation Technique (PET), Medical Outcomes Study Short Form 36 (SF-36), and questions regarding work productivity among 3 treatment groups (leflunomide, methotrexate, and placebo). Improvement in the PET top 5 and SF-36 scales and component scores were compared with ACR response rates. Results. Clinically meaningful and statistically significant (P 20% and >50% improvement. Conclusion. Significant improvements in function and health-related quality of life occurred in patients with RA during treatment with leflunomide or methotrexate. These findings were clinically meaningful and correlated with the ACR response status.

Objective To investigate whether 3 disease activity indices commonly used to evaluate systemic lupus erythematosus (SLE) in adults are sensitive to clinical change in children, and thus suitable for the use in the management of childhood-onset SLE. Methods Thirty-five SLE patients who were newly diagnosed between 1993 and 1997, had an age at onset of 6–16 years (26 female and 9 male), and were currently being followed up at The Hospital for Sick Children (followup of 9 months to 4 years) were reviewed. The SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), BILAG (British Isles Lupus Assessment Group index), and SLAM (Systemic Lupus Activity Measure) were applied at up to 4 occasions during the disease course: at the time of diagnosis, 6 months postdiagnosis, at the time of a flare (a deterioration in clinical presentation or laboratory results requiring initiation or increase of either corticosteroids or “second-line” drugs), and 6 months postflare. The sensitivity of the 3 measures to change, as gauged by the effect size (ES), effect size index (ESI), standard response mean (SRM), responsiveness statistic (RS), and relative efficiency index (REI), were compared. Results All 3 tools were very sensitive to change in disease activity (ES >0.8, ESI >2.3, SRM >0.6, RS >0.86, REI >0.72), but were ranked differently depending on the statistic used for comparison. Conclusion All 3 measures of disease activity are highly sensitive to clinical change in children; none showed an overall superiority. The SLEDAI, BILAG, and SLAM can all be used to study response to treatment in children with SLE.

Introduction. The relationship between the effectiveness of health care interventions and their costs is of increasing interest. The goal of the present study was to summarize the economic evaluations (EEs) published in the field of rheumatology and related disciplines, and to focus in particular on methodologic issues. Methods. MEDLINE was searched in order to identify all relevant EEs published between 1966 and February 1995. Titles and abstracts of 1,435 articles were retrieved and independently reviewed by 2 assessors. Overall, 63 articles were identified by either assessor as being definite or possible full EEs (defined as an analysis comparing 2 or more strategies involving the assessment of both costs and consequences), and were assessed independently. Results. Thirty-six articles were determined to be full EEs (33 cost-effectiveness and 3 cost-utility analyses). Most were published in the periods 1984–1990 (31%) and 1991–1995 (61%). Main areas covered were methods of prevention (44%), treatment (31%), and treatment-prevention (22%). Disorders most frequently studied were osteoarthritis (36%), osteoporosis (22%), and rheumatoid arthritis (14%). Direct and indirect costs were measured or estimated in 100% and 28% of the EEs, respectively. The viewpoint of the analysis was stated explicitly in 12 studies (33%). Incremental and sensitivity analyses were presented in 17 (47%) and 23 (64%), respectively. Inadequate use of economic terms was also documented. Conclusion. The EE articles reviewed adhered partially to basic analytic methods. Economic evaluations in the field of rheumatology need to be improved to comply with current standards for the evaluation of health care interventions.

Objective Health administrative data can be a valuable tool for disease surveillance and research. Few studies have rigorously evaluated the accuracy of administrative databases for identifying rheumatoid arthritis (RA) patients. Our aim was to validate administrative data algorithms to identify RA patients in Ontario, Canada. Methods We performed a retrospective review of a random sample of 450 patients from 18 rheumatology clinics. Using rheumatologist-reported diagnosis as the reference standard, we tested and validated different combinations of physician billing, hospitalization, and pharmacy data. Results One hundred forty-nine rheumatology patients were classified as having RA and 301 were classified as not having RA based on our reference standard definition (study RA prevalence 33%). Overall, algorithms that included physician billings had excellent sensitivity (range 94–100%). Specificity and positive predictive value (PPV) were modest to excellent and increased when algorithms included multiple physician claims or specialist claims. The addition of RA medications did not significantly improve algorithm performance. The algorithm of “(1 hospitalization RA code ever) OR (3 physician RA diagnosis codes [claims] with ≥1 by a specialist in a 2-year period)” had a sensitivity of 97%, specificity of 85%, PPV of 76%, and negative predictive value of 98%. Most RA patients (84%) had an RA diagnosis code present in the administrative data within ±1 year of a rheumatologist's documented diagnosis date. Conclusion We demonstrated that administrative data can be used to identify RA patients with a high degree of accuracy. RA diagnosis date and disease duration are fairly well estimated from administrative data in jurisdictions of universal health care insurance.

The purpose of this study was to compare the measurement properties of five generic health status measures in a cross-sectional study of injured workers. One hundred twenty-seven injured workers participated in the study. Forty-seven percent had disorders of the upper limb, 12% neck and upper back, and 27% lower back (14% unspecified). All participants completed a package containing: SF-36 (Acute), Nottingham Health Profile (NHP), Duke Health Profile (Duke), Health status section of the Ontario Health Survey (OHS), and the Sickness Impact Profile (SIP). Frequency distributions were examined, correlations carried out, and the ability to discriminate between part of body and overall health state evaluated using analysis of variance. The results showed a ceiling (healthy) effect in the OHS, NHP, and SIP. Correlations were moderate to good. Upper limb subjects appeared “healthier” than low back pain subjects. The instruments were able to discriminate between health states (p < 0.05) except the OHS-Physical function (p = 0.51). Different questionnaires give a different impression of health. Clinicians and researchers should be thoughtful in their selection of outcome measures as different instruments may alter the description, intervention, and priorization of a particular disorder. © 1996 Wiley-Liss, Inc.

This paper describes the development of an evaluative outcome measure for patients with upper extremity musculoskeletal conditions. The goal is to produce a brief, self-administered measure of symptoms and functional status, with a focus on physical function, to be used by clinicians in daily practice and as a research tool. This is a joint initiative of the American Academy of Orthopedic Surgeons (AAOS), the Council of Musculoskeletal Specialty Societies (COMSS), and the Institute for Work and Health (Toronto, Ontario). Our approach is consistent with previously described strategies for scale development. In Stage 1, Item Generation, a group of methodologists and clinical experts reviewed 13 outcome measurement scales currently in use and generated a list of 821 items. In Stage 2a, Initial Item Reduction, these 821 items were reduced to 78 items using various strategies including removal of items which were generic, repetitive, not reflective of disability, or not relevant to the upper extremity or to one of the targeted concepts of symptoms and functional status. Items not highly endorsed in a survey of content experts were also eliminated. Stage 2b, Further Item Reduction, will be based on results of field testing in which patients complete the 78-item questionnaire. This field testing, which is currently underway in 20 centers in the United States, Canada, and Australia, will generate the final format and content of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Future work includes plans for validity and reliability testing.

The aim of this study is to determine the validity of the ICD-9 for diagnostic classification of soft tissue disorders of the neck and upper limb, using routinely collected data at a large steel company. The documentation in the clinical chart served as the gold standard. First, the overall accuracy of identifying these disorders from the ICD-9 was examined. Second, we examined whether the codes themselves, on an individual basis, accurately reflected the underlying problems as documented in the medical records. There were 1,267 new cases identified in 1991 by inclusion of all potentially applicable ICD-9 codes. Only 805 (63.5%) fulfilled the definition of a soft tissue disorder of the neck or upper limb as determined by chart review. A more restrictive strategy that only included cases coded by those ICD-9 codes that specifically pertain to these disorders yielded a higher proportion of true cases 458/480 cases (95.4%), but failed to identify the other 347 cases. The anatomical site of the problem could not be identified from the codes describing 651/1,267 cases (51.4%). There was poor agreement between the diagnostic labels recorded in the medical records and the ICD-9 codes, suggesting that many of the terms are being used interchangeably. Our results suggest that conclusions about these disorders drawn from analysis of administrative data which rely upon the ICD-9 for diagnostic classification must be interpreted cautiously. For these soft tissue disorders, researchers will need to develop strategies which would improve upon and supplement the ICD-9. © 1996 Wiley-Liss, Inc.

Objective. To determine the discriminant validity of the core set of outcome measures proposed by the American College of Rheumatology (ACR) and the Outcome Measures in Clinical Trials (OMERACT) conference committee to be used in clinical trials of rheumatoid arthritis (RA). Methods. Utilizing data from a multicenter randomized double-blind clinical trial of low-dose cyclosporine and placebo in RA, we estimated the relative efficiency (RE) of measures to detect a treatment effect (relative to tender joint count, which was assigned a value of 1). Four pain measures (10-cm visual analog scale [VAS], 5-point categorical scale, Health Assessment Questionnaire [HAQ] pain index, Arthritis Impact Measurement Scales [AIMS] pain score) and 3 quality-of-life measures (Problem Elicitation Technique [PET], HAQ, AIMS) were compared. Results. Physician and patient global measures were the most responsive instruments, although neither was statistically superior to tender joint count. Swollen joint count, grip strength, pain measured on a 10-cm VAS, and functional status as measured by the PET and HAQ were all of intermediate responsiveness. Morning stiffness, 5-point pain scale, and erythrocyte sedimentation rate were the least responsive instruments. Conclusion. This study provides further evidence to support the core set of outce measures proposed by the ACR and OMERACT.

Objective. Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. Methods. Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. Results. The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acutephase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. Conclusion. We present a definition of improvement which we hope will be used widely in RA trials.

Objective. To examine the importance of renal biopsy as a predictor of death due to any cause in patients with systemic lupus erythematosus (SLE). Methods. The study included 123 SLE patients who had a renal biopsy between 1970 and 1984 and were followed up as part of a prospective study. Data were initially analyzed to identify clinical and laboratory features that were significantly associated with the risk of dying. Renal biopsy variables were then examined to determine whether they contributed additional information about prognosis. Results. The clinical and laboratory factors most closely associated with the risk of dying in multivariate analyses were the serum creatinine level and the SLE Disease Activity Index score. The presence of chronic renal lesions on biopsy contributed significantly to the prognostic information offered by clinical and laboratory factors in the subset of patients who had normal serum creatinine levels—the majority (85%) of patients in this study. Conclusion. These results indicate that renal biopsy serves an important role in the assessment of prognosis in patients who do not have advanced renal disease.

Criteria sets formalize our approach to studying the etiology, course, and management of rheumatic diseases, and provide a conceptual base for measuring future improvements in clinical care. They focus our clinical objectives and improve our clinical research activities. They are dynamic, evolving, and will certainly undergo major changes. Understanding the purposes of specific criteria sets and the differences between different criteria categories is crucial for understanding the rheumatic disease literature and for the design and conduct of clinical and epidemiologic investigations.

Objective. To develop a set of disease activity measures for use in rheumatoid arthritis (RA) clinical trials, as well as to recommend specific methods for assessing each outcome measure. This is not intended to be a restrictive list, but rather, a core set of measures that should be included in all trials. Methods. We evaluated disease activity measures commonly used in RA trials, to determine which measures best met each of 5 types of validity: construct, face, content, criterion, and discriminant. The evaluation consisted of an initial structured review of the literature on the validity of measures, with an analysis of data obtained from clinical trials to fill in gaps in this literature. A committee of experts in clinical trials, health services research, and biostatistics reviewed the validity data. A nominal group process method was used to reach consensus on a core set of disease activity measures. This set was then reviewed and finalized at an international conference on outcome measures for RA clinical trials. The committee also selected specific ways to assess each outcome. Results. The core set of disease activity measures consists of a tender joint count, swollen joint count, patient's assessment of pain, patient's and physician's global assessments of disease activity, patient's assessment of physical function, and laboratory evaluation of 1 acute-phase reactant. Together, these measures sample the broad range of improvement in RA (have content validity), and all are at least moderately sensitive to change (have discriminant validity). Many of them predict other important long-term outcomes in RA, including physical disability, radiographic damage, and death. Other disease activity measures frequently used in clinical trials were not chosen for any one of several reasons, including insensitivity to change or duplication of information provided by one of the core measures (e.g., tender joint score and tender joint count) The committee also proposes specific ways of measuring each outcome. Conclusion. We propose a core set of outcome measures for RA clinical trials. We hope this will decrease the number of outcomes assessed and standardize outcomes assessments. Further, we hope that these measures will be found useful in long-term studies.

Objective. To compare, in a Canadian health care setting, the costs and consequences of 3 strategies of misoprostol prophylaxis for osteoarthritis patients: prophylaxis for all patients taking nonsteroidal antiinflammatory drugs (NSAIDs), for no patients taking NSAIDs, and for only elderly patients (age ≥60) taking NSAIDs. Methods. We designed a decision-analysis model which incorporated costs (estimated with ulcer patient profiles and medical records), review, and probabilities (estimated from a companion metaanalysis, selected literature review, and Ontario Ministry of Health Statistics). Effectiveness was defined as the number of episodes of gastric ulceration requiring hospitalization or outpatient management that were averted by each strategy. Results. On average, prophylaxis cost an additional $650 for every additional gastrointestinal event prevented. Prophylaxis for elderly NSAID users was cost saving if the ulcer complication rate in this group exceeds 1.2%, or if either the charges for outpatient ulcer treatment exceed $2,000, or the 3-month price of misoprostol is ≤90. Conclusion. Our results demonstrate that, in this setting, misoprostol prophylaxis may be highly cost effective.

Objective. To standardize outcome measures in systemic lupus erythematosus (SLE). Three indices were identified which could adequately describe outcome (disease activity, damage from disease, and health status); we describe here the development of the Disease Activity Index. Methods. Twenty-four variables were identified as important factors in a disease activity index. These were used to generate 574 patient profiles, which were rated on a disease activity scale of 0–10 by 14 rheumatologists. A second rating of 10 of the profiles yielded scores that were not significantly different from the first, indicating that experienced clinicians can reliably make global estimates of disease activity. Multiple regression models were used to estimate the relative importance of the 24 clinical variables in the physicians' global rating of disease activity. These were estimated on a ‘training set’ of 75% of physicians' ratings, and then validated on a ‘testing set,’ consisting of the remaining 25% of physicians' ratings. Results. The explanatory power of the models in the training set was high (R2 = 0.93). The models' regression coefficients for the organ systems were simplified for easier use in clinical practice. This generated a ‘weighted’ index of 9 organ systems for disease activity in SLE, the SLEDAI, as follows: 8 for central nervous system and vascular, 4 for renal and musculoskeletal, 2 for serosal, dermal, immunologic, and 1 for constitutional and hematologic. The maximum theoretical score is 105, but in practice, few patients have scores greater than 45. The SLEDAI predicted well the physicians' ratings in the testing set (Pearson's correlation coefficients = 0.64–0.79). Conclusion. The SLEDAI is a validated model of experienced clinicians' global assessments of disease activity in lupus. It represents the consensus of a group of experts in the field of lupus research.

In 40 years of development in the area of quality of life, the goal of applicability to the individual patient has not been accomplished. During the 1980s, we strived to improve the applicability of these instruments by refining disease-specific measures and developing patient-specific measures so that the sensitivity of these tools to clinically important change could be increased and comparative indices across conditions could be established. Finding the balance between brevity, reliability, and comprehensiveness will improve practicality. The reliability of serial measurements using the various instruments in individual patients and in small groups of patients needs to be established. In the absence of a gold standard, validity will continue to be derived from testing new measures against accepted clinical measures. The ideal tool for use in clinical practice has not yet been developed. At this time, the clinician may choose among the many reliable and valid questionnaires assessing functional status, health status, and utility, according to his or her purpose. The information gathered from these instruments may help identify patients' problems, set treatment priorities, direct interventions, monitor the longitudinal course of disease, and assist in program evaluation and policy planning.

To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary-concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left- and right-sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in greater than or equal to 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary-concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary-concomitant fibromyalgia (as defined in the text) is abandoned.

Objective To examine correlations between clinical improvement as defined by the American College of Rheumatology (ACR) responder analysis and clinical improvement as determined by 4 function and/or health-related quality of life measures, and to estimate the sensitivity and relative efficiency of these measures compared with changes in the tender joint count in patients with rheumatoid arthritis (RA). Methods A 52-week, multicenter, double-blind controlled trial was conducted to compare treatment with leflunomide (n = 182), methotrexate (n = 180), or placebo (n = 118) in patients with active RA. ACR response rates and improvement in scores on the Health Assessment Questionnaire (HAQ), Problem Elicitation Technique (PET), and Medical Outcomes Survey Short Form 36 (SF-36) were compared in 438 of the patients. Results In comparing leflunomide with placebo, the patient global assessment, HAQ disability index, and SF-36 bodily pain scale were most responsive to treatment group differences. The modified HAQ (M-HAQ), PET Top 5, SF-36 physical component score, physician global assessment, pain intensity scale, and SF-36 physical functioning scale were more responsive to treatment group differences than was the tender joint count. In comparing methotrexate with placebo, the patient and physician global assessments were most responsive. These 2 measures, as well as the pain intensity scale and the C-reactive protein level, were more responsive to treatment group differences than was the tender joint count, while the SF-36 mental health component score was least responsive. A close correlation between changes in the M-HAQ and HAQ scores indicated that the M-HAQ was similarly responsive to change over time. Improvements in the PET, SF-36 physical component score, bodily pain, and physical functioning scales correlated with the ACR responder status. Conclusion Both disease-specific and generic measures of function and health-related quality of life detect improvements in RA patients. Using both types of measures for evaluating therapies will identify discernible changes that are important to patients, and will facilitate comparisons across different disease states.

Women with active rheumatoid arthritis who were judged to be in need of hospitalization were assigned at random to receive inpatient therapy (n = 35) or intensive outpatient therapy (n = 36). All relevant costs of treatment were measured. At 19 weeks, clinical outcomes, as summarized in a pooled index, were significantly better in the inpatient group (pooled index units: inpatient 0.72, outpatient 0.25; F[1,69] = 10.9, P = 0.002). Inpatient therapy produced a sustained three-fold increase in efficacy, at a 2.5-fold increase in cost to society.

We describe 2 patients who had coexistent rheumatoid arthritis and sickle cell disease. Both patients developed sickle cell crises following intraarticular injection of corticosteroids to control their arthritis. The mechanism of this phenomenon is not clear, but it is suggested that intraarticular steroids be used with caution in patients with sickle cell disease.