The erratic C-reactive protein: a novel outcome measure for longitudinal disease activity in rheumatoid arthritis.

OBJECTIVES: There is a relationship between both the magnitude and variability of C-reactive protein (CRP) levels and disease activity level in rheumatoid arthritis (RA). It seems that CRP levels remain low and stable in clinical remission then increase and become erratic in active disease. The purpose of this research was to determine if there is a difference in the variability of CRP levels over time in patients in clinical remission versus those with active disease. METHODS: Patients with a diagnosis of RA with a minimum of 3 CRP readings in the previous 12-month period were included at a single site. At each visit the patient was evaluated by an experienced rheumatologist to determine current disease activity - remission versus active disease. The primary outcome measure was the difference between the coefficient of variation of the CRP (CRP-COV) in patients in remission versus those with active disease. RESULTS: 272 patients were enrolled into the study. The mean CRP and CRP-COV was significantly smaller for patients in clinical remission versus active disease, for patients in CDAI remission (<2.6), and for those who did not require a change in treatment. Smokers, on average, had higher mean CRP readings regardless of clinical status. CONCLUSIONS: We have identified a new clinical outcome measure of disease activity in RA that captures longitudinal variability in disease activity and identifies those patients with clinically active disease despite a "normal" CRP level due to the higher variability of CRP if not in remission.

Health Literacy Rates in a Population of Patients with Rheumatoid Arthritis in Southwestern Ontario.

OBJECTIVE: To determine the rate of low health literacy in the rheumatoid arthritis (RA) population in southwestern Ontario. METHODS: For the study, 432 patients with RA were contacted, and 311 completed the assessment. The health literacy levels of the participants were estimated using 4 assessment tools administered in the following order: the Single Item Literacy Screener (SILS), the Medical Term Recognition Test (METER), the Rapid Estimate of Adult Literacy in Medicine (REALM), and the Shortened Test of Functional Health Literacy in Adults (STOFHLA). RESULTS: The rates of low literacy as estimated by STOFHLA, REALM, METER, and SILS were 14.5%, 14.8%, 14.1%, and 18.6%, respectively. All 4 assessment tools were statistically significantly correlated. STOFHLA, REALM, and METER were strongly correlated with each other (r = 0.59-0.79), while SILS only demonstrated moderate correlations with the other assessment tools (r = 0.33-0.45). Multiple linear regression and binary logistic regression analyses revealed that low levels of education and a lack of daily reading activity were common predictors of low health literacy. Using a non-English primary language at home was found to be a strong predictor of low health literacy in STOFHLA, REALM, and METER. Male sex was found to be a significant predictor of poor performance in REALM and METER, but not STOFHLA. CONCLUSION: Low health literacy is an important issue in the southwestern Ontario RA population. About 1 in 7 patients with RA may not have the necessary skills to become involved in making decisions regarding their personal health. Rheumatologists should be aware of the low health literacy levels of patients with RA and should consider identifying patients at risk of low health literacy.

Response to Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis for Function and Pain is Affected by Rheumatoid Factor.

OBJECTIVES: To investigate differences in response to tumor necrosis factor inhibitor treatment (TNFi) in seropositive (rheumatoid factor positive; RF+) versus seronegative (RF-) patients with established RA as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain. METHODS: RA patients from an established RA cohort were studied according to rheumatoid factor (RF) status for change in HAQ-DI and pain (0-3 VAS) one year after starting treatment with a TNFi. RESULTS: There were 238 patients treated with TNFi who had follow-up data (178 RF+ and 60 RF-). Disease duration was longer in RF+ vs RF- (12+8 vs 8+8 years) but the proportion of females (82% vs 72%, P=0.7), baseline HAQ-DI (1.44+0.63 vs 1.41+0.63, P=0.8) and pain (1.92+0.67 vs 1.93+0.67, P=0.9) were not different. The mean duration of treatment of first TNFi was 2.8 vs 2.3 years, P=0.1 and 68% of RF+ vs 62% of RF- were still receiving first TNFi at last visit (P=0.5). For patients with data at baseline and one year, the one-year HAQ-DI change was significantly greater in 90 RF+ patients (-0.356) versus 38 RF- patients (-0.126; P=0.04). The mean pain improvement was also greater in 77 RF+ vs 32 RF- patients (-0.725 vs -0.332 respectively; P=0.03). Numbers are small, data are missing and comorbidities, DAS28 and anti-CCP were not collected. CONCLUSION: Despite limitations in the data, in established RA after failure of DMARDs, RF+ patients may be more responsive to TNFi therapy as measured by changes in HAQ-DI and pain. INNOVATION: There may be a better response to TNFi in RA if RF positive for function and pain.

Comprehensive arthritis referral study -- phase 2: analysis of the comprehensive arthritis referral tool.

OBJECTIVE: Rheumatologists triage referrals to assess those patients who may benefit from early intervention. We describe a referral tool and formally evaluate its sensitivity for urgent and early inflammatory arthritis (EIA) referrals. METHODS: All referrals received on a standardized referral tool were reviewed by a rheumatologist and, based on the information conferred, assigned a triage grade using a previously described triage system. Each referral was also dichotomized as suspected EIA or not. After the initial rheumatologic assessment, the diagnosis was recorded and a consultation grade, blinded to referral grade, was assigned to each case. Agreement between referral and consultation grades was assessed. A regression analysis was performed to determine factors that predicted truly urgent referrals including EIA. RESULTS: We evaluated 696 referrals. A total of 210 (30.2%) were categorized as urgent at the time of consultation. The referral tool was able to successfully detect 169 of these referrals (sensitivity 80.5%, specificity 79.4%). EIA occurred in 95 (13.6%); of those referrals, 86 were correctly classified as urgent at the time of triage (sensitivity 90.5%, specificity 69.6%). Items that helped correctly discriminate urgent or EIA referrals included patient age < 60, duration of disease, morning stiffness, patient-reported joint swelling, a personal or family history of psoriasis, urgency as rated by referring physician, prior assessment by a rheumatologist, elevated C-reactive protein, and a positive rheumatoid factor. CONCLUSION: A 1-page referral tool that includes parts completed by the referring physician and patient has good sensitivity to detect urgent referrals including EIA.

A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis.

BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.

A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis.

BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.

Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients with early rheumatoid arthritis: a meta-analysis of randomized controlled trials.

OBJECTIVE: To conduct a meta-analysis of the rates of serious infection and malignancy in patients with early rheumatoid arthritis (RA) who have started anti-tumor necrosis factor (anti-TNF) therapy and had not received treatment with disease-modifying antirheumatic drugs (DMARDs) or methotrexate (MTX). METHODS: A systematic literature search was conducted through the summer of 2009. All studies included were randomized, double-blind, placebo-controlled trials involving patients with early RA who were started on anti-TNF therapy without prior DMARD/MTX use. Six trials met the inclusion criteria for the meta-analysis, comprising a total of 2,183 patients receiving biologic therapy and 1,236 patients receiving MTX. The data extracted were from published trials. RESULTS: A pooled odds ratio (OR) (determined using Mantel-Haenszel methods, with a continuity correction designed for sparse data) was calculated for serious infections (requiring hospitalization) and malignancies, comparing anti-TNF therapy to MTX control. The pooled OR for serious infections was 1.28 (95% confidence interval [95% CI] 0.82-2.00) and that for malignancies was 1.08 (95% CI 0.50-2.32). There was no significant difference in either the rate of serious infections or the rate of malignancies between the anti-TNF therapy group and the control group. CONCLUSION: Whereas other meta-analyses have shown an increased risk of serious infection and malignancy in patients receiving anti-TNF therapy, the results of the present meta-analysis show that there is not an increased risk when the patients have early disease and have not previously been treated with DMARDs and/or MTX.

A randomized trial of pictorial versus prose-based medication information pamphlets.

OBJECTIVE: The goal of this study was to compare prose and pictorial-based information pamphlets about the medication methotrexate in the domains of free recall, cued recall, comprehension and utility. METHODS: A single blind, randomized trial of picture versus prose-based information pamphlets including 100 participants aged 18-65 years of age, who had not completed high school, could read English, and had no prior knowledge about methotrexate. Superiority of pamphlet type was assessed using immediate free recall, cued recall and comprehension. RESULTS: There were no differences between picture and prose pamphlets in free recall, cued recall, and comprehension either immediately or after a 1-week interval. Immediate free recall of important information was 17-26%; free recall fell even lower to 7-16% after 1 week. The pictorial pamphlet was preferred over the prose-based pamphlet. CONCLUSION: This study found no benefit in free recall, cued recall, or comprehension through the addition of pictograms to a simple prose-based medication pamphlet. PRACTICE IMPLICATIONS: In order for them to be effective in clinical practice, even simple medication information pamphlets that have been assessed for patients' ability to comprehend them cannot be used as the sole means for conveying important medication-related information to patients.

Patient-oriented methotrexate information sites on the Internet: a review of completeness, accuracy, format, reliability, credibility, and readability.

OBJECTIVE: With continuing use of the Internet, rheumatologists are referring patients to various websites to gain information about medications and diseases. Our goal was to develop and evaluate a Medication Website Assessment Tool (MWAT) for use by health professionals, and to explore the overall quality of methotrexate information presented on common English-language websites. METHODS: Identification of websites was performed using a search strategy on the search engine Google. The first 250 hits were screened. Inclusion criteria included those English-language websites from authoritative sources, trusted medical, physicians', and common health-related websites. Websites from pharmaceutical companies, online pharmacies, and where the purpose seemed to be primarily advertisements were also included. Product monographs or technical-based web pages and web pages where the information was clearly directed at patients with cancer were excluded. Two reviewers independently scored each included web page for completeness and accuracy, format, readability, reliability, and credibility. An overall ranking was provided for each methotrexate information page. RESULTS: Twenty-eight web pages were included in the analysis. The average score for completeness and accuracy was 15.48+/-3.70 (maximum 24) with 10 out of 28 pages scoring 18 (75%) or higher. The average format score was 6.00+/-1.46 (maximum 8). The Flesch-Kincaid Grade Level revealed an average grade level of 10.07+/-1.84, with 5 out of 28 websites written at a reading level less than grade 8; however, no web page scored at a grade 5 to 6 level. An overall ranking was calculated identifying 8 web pages as appropriate sources of accurate and reliable methotrexate information. CONCLUSION: With the enormous amount of information available on the Internet, it is important to direct patients to web pages that are complete, accurate, readable, and credible sources of information. We identified web pages that may serve the interests of both rheumatologists and patients.

Triage of referrals to an outpatient rheumatology clinic: analysis of referral information and triage.

OBJECTIVE: Rheumatologists triage referrals in order to assess those patients who may benefit from early intervention. Success of triage strategies requires accurate transfer of clinical information between the primary caregiver and rheumatologist. We describe a prototype triage system and formally evaluate the quality of referral content to a rheumatologist's practice. METHODS: All new referrals were reviewed by a rheumatologist and, based on the information conferred, assigned a grade using a prototype triage system. This grade reflected each case's suspected urgency and guided the timing of consultation. After the initial rheumatologic consultation a post hoc grade was assigned to each case based on the clinical information gathered. Agreement between referral and consultation grades was assessed. All cases graded as urgent at the time of consultation, and thus felt to be truly urgent, were examined for the quality of content of their referral letters. RESULTS: Two hundred six referrals were evaluated. Ninety-six cases (47%) experienced a grade change between referral and consultation. Thirty-five cases (17%) were upgraded to urgent status after consultation, reflecting inappropriately triaged truly urgent patients. Analysis of referral letters for truly urgent cases revealed the absence of a presumptive diagnosis, symptom duration, and documentation of involved joints in over 30% of referrals. CONCLUSION: The absence of basic historical, examination, and laboratory markers accounted for inappropriate triage of urgent cases. Our study recognizes dysfunction within the current model of care and questions the development of standardized referral tools as a solution. Other models of care should be investigated for this patient population.

Increased prevalence of scleroderma in southwestern Ontario: a cluster analysis.

OBJECTIVE: To estimate the prevalence of scleroderma (systemic sclerosis, SSc) in 3 cities, Windsor, Sarnia, and Woodstock, Ontario, within our referral area, which has a referral base population of 1 million. METHODS: To compare the addresses and exposures of referrals with SSc, we performed a case control study using our patients with scleroderma and 2 age and sex matched controls from the same rheumatologist's practice. RESULTS: Sixty-seven of 91 patients with SSc and 87 of 154 controls responded. The mean age of patients with SSc was 53.2 years versus 52.8 years in controls. There was no statistically significant increase in the number of SSc patients from Windsor (population 197,694): 14 patients (15.4%) with SSc versus 18 controls (11.6%) (p < 0.41); or Sarnia (population 72,738): 7 patients (7.7%) with SSc versus 7 controls (4.5%) (p < 0.31). However, there were 9 cases (9.9%) from Woodstock (population 32,086) versus one control (0.64%) (p < 0.0004). The point prevalence of scleroderma was at least 0.71/10,000 in Windsor, 0.96/10,000 in Sarnia, and 2.8/10,000 in Woodstock. There were no significant between-group differences in exposure to industrial toxins or chemicals including vinyl chloride, silica, and benzene, but exposure rates in both groups were low. Occupations and proportion of those who were work disabled were not different. Patients with SSc were not more likely to have smoked cigarettes (p < 0.43); however, they were more likely to drink at least 6 drinks of alcohol per week (p < 0.04) and had more dental fillings (p < 0.05). Patients with SSc knew on average 3.2 others with this disease, and controls knew only 0.25 others with scleroderma (p < 0.00001). Two patients with SSc knew someone with SSc in their workplace versus none of the controls. CONCLUSION: Our a priori expected higher prevalence of scleroderma in Windsor and Sarnia did not reach significance, but the cluster in Woodstock seems statistically validated, and the exact reason for this cluster remains unclear. It is unlikely that all patients with SSc in Woodstock were seen by us, so the prevalence of scleroderma is at least 2.8/10,000, which is a medium to high prevalence compared to other studies. Associations with alcohol and dental fillings require further study.