Showing papers in "The Journal of Rheumatology in 1999"

How to read radiographs according to the Sharp/van der Heijde method.

Abstract: This article is a short overview of the development of the Sharp/van der Heijde methods for scoring radiographs of hands and feet in rheumatoid arthritis, in addition to a detailed description on how to use the scoring method.

Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures: an open prospective study.

Abstract: Objective. To assess the efficacy and safety of percutaneous vertebroplasty in osteoporotic vertebral compression fractures responsible for severe and persistent pain. Methods. Sixteen patients were included in this open prospective study. Inclusion criteria were: one or 2 vertebral fractures responsible for severe pain, i.e., higher than 50 mm on a visual analog scale (VAS: 0-100 mm), scores 3, 4 or 5 according to the McGill-Melzack scoring system, and evolving for more than 3 months. Assessment criteria were the changes over time (Days 3, 30, 90, 180) in VAS and McGill-Melzack scoring system. The changes over time in a generic health status instrument score [the Nottingham Health Profile (NHP)] were also assessed. Statistical comparisons were performed using the Wilcoxon T test. Results. There were 9 women and 7 men: postmenopausal osteoporosis (n = 7), corticosteroid induced osteoporosis (n = 2), and male osteoporosis (n = 7). Vertebroplasty was performed in 20 vertebrae. A statistically significant decrease of both VAS (-53%, p < 0.0005) and McGill-Melzack scoring system (p < 0.005) was observed at Day 3. The results were also significant at Days 30, 90, and 180 for both scales (p < 0.005 and p < 0.01, respectively). A significant decrease over time for 5/6 dimensions of the NHP score was also noted: pain (p < 0.01), physical mobility (p < 0.05), emotional reactions (p < 0.05), social isolation (p < 0.05), and energy (p < 0.05). We observed no adverse event, and no vertebral fracture has occurred after 6 months of followup. Conclusion. Percutaneous vertebroplasty is a useful and safe procedure for treating persistent painful osteoporotic fractures. Controlled studies with longterm followup are required.

Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis. A retrospective cohort study from disease onset.

Abstract: OBJECTIVE: To identify predictors for cardiovascular disease (CVD) and for overall survival in patients with rheumatoid arthritis (RA) followed from disease onset. METHODS: A retrospective cohort of patients with seropositive RA and disease onset between 1974 and 1978 (n = 211) was followed up at the end of 1995. Potential predictors for CVD, as measured by "the first cardiovascular event," and for overall survival were registered. The predictors were identified by extended Cox regression models. RESULTS: In simple Cox regression analysis, male sex, higher age at disease onset, HLA-B27, high disease activity, corticosteroid treatment early in disease, and hypertension significantly increased risk of cardiovascular event. Higher educational level, extensive disease modifying antirheumatic drug (DMARD) treatment, and corticosteroids > or =1 yr before event decreased the risk. In multiple Cox regression analysis, male sex, high age at disease onset, hypertension, higher haptoglobin level at disease onset, and corticosteroid treatment early in disease increased risk of CVD. In a multiple model comprising only patients with CVD, corticosteroids delayed the event. A high last registered erythrocyte sedimentation rate (ESR) value before event increased CVD risk, in particular when early in disease progression. Decreased life span was predicted by higher age at disease onset, male sex, low education level, high disease activity, hypertension, and CVD. HLA-B27 was associated with decreased life span, as was early, but not extensive corticosteroid treatment. DMARD treatment was associated with decreased mortality risk, as was the presence of joint prosthesis. In multiple regression, male sex, higher age at disease onset, atlantoaxial subluxation early in disease, hypertension, and cardiovascular event increased mortality. A high last registered ESR value before event or death added to that risk. CONCLUSION: The study emphasizes the importance of inflammation as an important risk indicator for CVD and mortality in RA. The positive impact of disease activity reducing treatment on CVD risk and survival is suggested.

A disease severity scale for systemic sclerosis: development and testing.

Abstract: Objective To develop and test a severity scale for individual organ involvements in systemic sclerosis (SSc, scleroderma). Methods An international study group completed the following tasks: (1) developed a glossary of terms including all pertinent variables for 9 potentially affected organ systems; (2) collected prospective data to determine the feasibility and practicality of each proposed variable; (3) revised the initial list of variables; (4) determined the association of each variable with mortality (a proxy for morbidity) using 579 patients in an existing comprehensive longitudinal scleroderma databank; (5) developed a severity grading scale for each organ system by discussion and consensus; and (6) externally validated the scale using an independent group of 680 patients from the same databank. Results Nine organ-specific severity scales were developed from 0 (no documented involvement) to 4 (endstage disease). The data required for scale completion are relatively easy and practical for all physicians to obtain. Conclusion This preliminary severity scale will be useful for assessing disease severity status in individual patients both at one point in time and longitudinally. The severity scale will assist in the design and conduct of clinical trials and the comparison of study populations with one another. The scale will serve as a framework for developing a scleroderma disease activity index.

The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario.

Abstract: Objective. To estimate the point prevalence of fibromyalgia syndrome (FM) among noninstitutionalized Canadian adults; and to assess the effect of demographic variables on the odds of having FM. Methods. A screening questionnaire was administered via telephone to a random community sample of 3395 noninstitutionalized adults residing in London, Ontario. Individuals screening positive were invited to be examined by a rheumatologist to confirm or exclude FM using the 1990 American College of Rheumatology classification criteria. Results. One hundred confirmed cases of FM were identified, of whom 86 were women. Mean age among FM cases was 49.2 years among women, 39.3 years among men (p < 0.02). FM affects an estimated 4.9% (95% CI 4.7%, 5.1%) of adult women and 1.6% (1.3%, 1.9%) of adult men in London, for a female to male ratio of roughly 3 to one. In women, prevalence rises steadily with age from < 1% in women aged 18-30 to almost 8% in women 55-64. Thereafter, it declines. The peak prevalence in men also appears to be in middle age (2.5%; 1.1%, 5.7%). FM affects 3.3% (3.2%, 3.4%) of noninstitutionalized adults in London. Female sex, middle age, less education, Idwer household income, being divorced, and being disabled are associated with increased odds of having FM. Conclusion. FM is a common musculoskeletal disorder among Canadian adults, especially among women and persons of lower socioeconomic status.

Effects of selective slow wave sleep disruption on musculoskeletal pain and fatigue in middle aged women.

Abstract: Objective. To determine whether disrupted slow wave sleep (SWS) would evoke musculoskeletal pain, fatigue, and an alpha electroencephalograph (EEG) sleep pattern. We selectively deprived 12 healthy, middle aged, sedentary women without muscle discomfort of SWS for 3 consecutive nights. Effects were assessed for the following measures: polysomnographic sleep, musculoskeletal tender point pain threshold, skinfold tenderness, reactive hyperemia (inflammatory flare response), somatic symptoms, and mood state. Methods. Sleep was recorded and scored using standard methods. On selective SWS deprivation (SWSD) nights, when delta waves (indicative of SWS) were detected on EEG, a computer generated tone (maximum 85 decibels) was delivered until delta waves disappeared. Musculoskeletal tender points were measured by dolorimetry; skinfold tenderness was assessed by skin roll procedure; and reactive hyperemia was assessed with a cotton swab test. Subjects completed questionnaires on bodily feelings, symptoms, and mood. Results. On each SWSD night, SWS was decreased significantly with minimal alterations in total sleep time, sleep efficiency, and other sleep stages. Subjects showed a 24% decrease in musculoskeletal pain threshold after the third SWSD night. They also reported increased discomfort, tiredness, fatigue, and reduced vigor. The flare response (area of vasodilatation) in skin was greater than baseline after the first, and again, after the third SWSD night. However, the automated program for SWSD did not evoke an alpha EEG sleep pattern. Conclusion. Disrupting SWS, without reducing total sleep or sleep efficiency, for several consecutive nights is associated with decreased pain threshold, increased discomfort, fatigue, and the inflammatory flare response in skin. These results suggest that disrupted sleep is probably an important factor in the pathophysiology of symptoms in fibromyalgia.

Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis.

Abstract: Our aim was to determine whether C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) is more appropriate in measuring disease activity in ankylosing spondylitis (AS). We studied 191 consecutive outpatients with AS in The Netherlands, France, and Belgium. Patients were attending secondary and tertiary referral centers. The external criterion for disease activity was: physician and patient assessment of disease activity on a visual analog scale (VAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). In each measure we defined 3 levels of disease activity: no activity, ambiguous activity, and definite disease activity. The patients with AS (modified New York criteria) were divided into 2 groups: those with spinal involvement only (n=149) and those who also had peripheral arthritis and/or inflammatory bowel disease (IBD) (n=42). For each criterion of disease activity, the patients with no activity and with definite activity were included in receiver operator curves and used to determine cutoff values with the highest sensitivity and specificity. We also calculated Spearman correlations. The median CRP and ESR were 16 mg/l and 13 mm/h, respectively, in the spinal group and 25 mg/l and 21 mm/h, respectively, in the peripheral/IBD group. In both groups the Spearman correlation coefficients between CRP and ESR were around 0.50. There was moderate to poor correlation between CRP, ESR, and the 3 disease activity variables (0.06-0.48). Sensitivity for both ESR and CRP was 100% for physician assessment and between 44 and 78% for patient assessment of disease activity and the BASDAI, while specificity was between 44 and 84% for all disease activity measures. The positive predictive values of CRP and ESR in our setting were low (0.15-0.69). We conclude that neither CRP nor ESR is superior to assess disease activity.

Selection of instruments in the core set for DC-ART, SMARD, physical therapy, and clinical record keeping in ankylosing spondylitis. Progress report of the ASAS Working Group. Assessments in Ankylosing Spondylitis.

Abstract: To select specific instruments for each domain of the core set for endpoints in ankylosing spondylitis (AS), we gathered all instruments described in the literature to assess the domains chosen as endpoints in AS and sent them to 43 members of the Assessments in Ankylosing Spondylitis (ASAS) Working Group The following domains were taken into account: function, pain, spinal mobility, patient global assessment, morning stiffness, peripheral joints and entheses, acute phase reactants, x-ray spine, x-ray hips, fatigue For each instrument the members were asked to judge if the instrument was feasible and relevant If an instrument was judged to be not feasible or not relevant by more than 50% of the respondents the instrument was deleted from the list These data were presented during an ASAS workshop and the final decisions were about which instruments to include in the core set This process was repeated separately for the settings disease controlling antirheumatic therapy (DC-ART), symptom modifying antirheumatic drugs (SMARD) and physical therapy, and clinical record keeping The response rate to the questionnaire was 72% For each domain one or more instruments were selected, except for Entheses and Fatigue The chosen instruments were similar for the 3 above settings Core sets of specific instruments were selected for the OMERACT filter test for relevance and feasibility For all these instruments the remaining aspects of the OMERACT filter (truth and discrimination) should be assessed by literature review and if needed by additional research It is recommended to use these instruments in all research projects in AS

Determinants of pain severity in knee osteoarthritis: effect of demographic and psychosocial variables using 3 pain measures.

Abstract: Objectives Why some patients with knee osteoarthritis (OA) report greater pain severity than others is unclear. We examined the demographic variables, psychosocial variables, and physical findings that predict severity of pain in patients with symptomatic knee OA comparing 3 different pain scales. Methods Pain severity was measured in 68 outpatients with knee OA using the WOMAC OA Index, the McGill Pain Questionnaire (MPQ), and a 0-100 visual analog scale (VAS). Depression, anxiety, fatigue, helplessness, self-efficacy, and quality of life were measured using standard instruments. Pain threshold was measured by dolorimetry and a standard knee examination performed. Radiographs were viewed when available. Results Significant correlations (r = 0.39-0.61) were found between pain measures. In unadjusted analysis, BMI and helplessness correlated with all 3 scales; race, education, female sex, and osteophyte score also correlated with at least one instrument. Depression, anxiety, and fatigue correlated only with the MPQ. Age, duration, and quality of life were not related to pain severity. After adjusted analysis the following variables remained: education, helplessness, and osteophyte score (WOMAC); BMI and helplessness (MPQ); duration, education, helplessness, and osteophyte score (VAS). "Sitting pain" and "night pain" had different associations from pain on walking, standing, or using stairs. Conclusion Different pain scales measure different facets of the pain experience in knee OA and cannot be used interchangeably. The WOMAC pain scale has advantages over other instruments. Helplessness, education, and BMI appear to be important, potentially treatable, factors in determining self-reported pain severity in knee OA: other associations vary with both the pain scale used and the situation in which pain occurs, supporting the hypothesis that pain in knee OA is heterogeneous.

Early detection of sacroiliitis on magnetic resonance imaging and subsequent development of sacroiliitis on plain radiography. A prospective, longitudinal study.

Abstract: Objective. To investigate the diagnostic value of magnetic resonance imaging (MRI) in the detection of early sacroiliitis. Methods. Twenty-five consecutive HLA-B27 positive patients with inflammatory low back pain and ≤ grade 2 unilateral sacroiliitis on conventional radiography (modified New York criteria) were studied. Erythrocyte sedimentation rate, C-reactive protein, plain radiography (PR), and MRI of the sacroiliac (SI) joints were obtained at study entry and PR of the SI joints after 3 years. Each radiograph and MR image set was interpreted independently. SI joints were scored according to the modified New York Criteria for radiological sacroiliitis. MRI scans were also scored for the presence of subchondral marrow edema. The relationship between ≥ grade 2 sacroiliitis (by modified New York criteria for radiological sacroiliitis) shown on MRI and the subsequent development of ≥ grade 2 sacroiliitis on PR after 3 years was investigated. Results. At study entry ≥ grade 2 sacroiliitis was found on MRI in 36 of 50 SI joints. Edema was found in 20 of 50 SI joints. After 3 years ≥ grade 2 sacroiliitis was found on PR in 21 of 44 SI joints. The positive predictive value of ≥ grade 2 sacroiliitis on MRI for the development of ≥ grade 2 sacroiliitis on PR after 3 years was 60%; sensitivity was 85% and specificity 47%. Conclusion. Our data suggest that MRI of the SI joints can be used to identify sacroiliitis earlier than PR.

How to read radiographs according to the Sharp/van der Heijde method : Part 3: Rheumatoid Arthritis: Response

Abstract: This article is a short overview of the development of the Sharp/van der Heijde method for scoring radiographs of hands and feet in rheumatoid arthritis, in addition to a detailed description on how to use the scoring method.

Comorbidity in arthritis.

Abstract: Objective To describe the relative frequency of selected comorbidities in 2 population based prevalence cohorts of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) compared to age and sex matched community controls. Methods Using the population based data resources of the Rochester Epidemiology Project, we assembled 3 prevalence cohorts of all residents of Olmsted County, Minnesota, with RA (1987 American College of Rheumatology criteria) and age and sex matched controls without arthritis on January 1, 1965, January 1, 1975, and January 1, 1985. Cases and controls were followed longitudinally through their complete (inpatient and outpatient) medical records beginning 10 years prior to the prevalence (or index) date until death, migration from the county, or January 1, 1995. Comorbidity was assessed yearly using the Charlson Comorbidity Index and the Index of Co-existent Diseases (ICED). Descriptive statistics were used to illustrate the baseline characteristics of the study population and the frequency of individual comorbidities in each of the 3 groups over the followup period. Cox proportional hazards modeling was used to assess the risk for each individual comorbidity among patients with arthritis compared to controls and to identify significant predictors of an increase in comorbidity level over time. Results Our study population included 450 RA, 441 OA, and 891 control subjects. The age and sex distributions of cases and their controls were similar. Over the followup period, patients with RA had a higher likelihood of developing congestive heart failure, chronic pulmonary disease, dementia, and peptic ulcer disease, while cases with OA had a significantly higher risk of developing peptic ulcer disease and renal disease. Among patients with either RA or OA, age, male sex, and baseline comorbidity were significant predictors of a rise in comorbidity. The presence of RA was a highly significant predictor of a rise in comorbidity from one year to the next, even after controlling for the effects of age, sex, and baseline comorbidity (p = 0.0004 for the Charlson and p = 0.006 for the ICED). Conclusion These data indicate that the burden of illness among people with arthritis is higher than for nonarthritics and that this burden appears to be increasing over time, particularly in RA. These results suggest that specialized chronic disease care will be increasingly important for the future health care needs of people with RA.

Lipid profiles in untreated patients with rheumatoid arthritis.

Abstract: OBJECTIVE: To investigate lipid profiles in patients with untreated active rheumatoid arthritis (RA) and to assess the relationship of the inflammatory condition of RA with lipid profiles. METHODS: Forty-two patients with RA and 42 age and sex matched healthy controls were studied. Patients with RA had not been treated with corticosteroid or disease modifying antirheumatic drugs prior to the study. Total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apolipoprotein A1 (apo A1), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and C-reactive protein (CRP) were measured in both groups. RESULTS: The levels of apo A1 and HDL-cholesterol were significantly lower in patients than in controls (128.5 vs. 151.8 mg/dl, 41.2 vs. 54.9 mg/dl, respectively). The level of Lp(a) was significantly higher in patients than in controls (27.1 vs. 18.0 mg/dl). The ratios of apo B/apo A1, total cholesterol/HDL-cholesterol, and LDL-cholesterol/HDL-cholesterol were significantly higher in patients than in controls (0.82 vs. 0.67, 4.4 vs. 3.4, 2.8 vs. 1.9, respectively). CRP showed a significant correlation with apo A1 (r = -0.44, p<0.01) and HDL-cholesterol (r = -0.35, p<0.05). CONCLUSION: Our study suggests that patients with untreated active RA have altered lipoprotein and apolipoprotein patterns that may possibly expose them to higher risk of atherosclerosis. The inflammatory condition of RA may affect the metabolism of HDL-cholesterol and apo A1.

Substantial superiority of semiflexed (MTP) views in knee osteoarthritis: a comparative radiographic study, without fluoroscopy, of standing extended, semiflexed (MTP), and schuss views.

Abstract: Objective. To improve the radiographic assessment of cartilage loss, as measured by joint space width (JSW) in patients with osteoarthritis (OA) of the knees required to detect the effect of structure modifying drugs in OA trials. This was achieved by determining which of 3 nonfluoroscopic radiographic views - standing extended, semiflexed, and schuss - produced the most accurate radioanatomic positioning of the joint and greater reproducibility in joint repositioning and JSW measurement. Methods. Knees from 74 patients with OA of the knees who had medial tibiofemoral compartment JSW ≥2 mm in all views were studied. For all 3 radiographic views, accuracy in the radioanatomic positioning of the knee was determined for both joint rotation and flexion. Reproducibility in joint repositioning and JSW measurement were determined from the difference between repeat examinations taken within 2 h. Results. About 86% of knees in the 3 views had accurate rotational position of the joint at each visit. Radioanatomically, knees in the semiflexed view were significantly more accurately positioned in regard to knee flexion (p < 0.0005) than in the schuss view, which in turn was better (p < 0.014) than in the extended knee view. Joint repositioning was significantly more reproducible in the semiflexed (p <0.0001) than in the extended knee, which was better (p <0.013) than in the schuss position. JSW measurement was significantly more reproducible in the semiflexed (p < 0.014) than both schuss and extended knee positions, which were not significantly different from each other. Conclusion. Protocols defining the nonfluoroscopic radiographic procedures for the semiflexed view provide the most accurate radioanatomic joint positioning, and the most reproducible joint repositioning and JSW measurement. Using this method significantly fewer knees would be required to detect significant JSW changes in a structure modifying drug trial compared to the schuss and the extended knee positions.

Pathogenesis of joint damage in rheumatoid arthritis.

Abstract: Rheumatoid arthritis (RA) is characterized by the appearance of progressive joint damage that may be identified only months after the onset of symptoms. Early cartilage and bone erosion is associated with the accumulation of several cell populations in the synovial membrane (SM) and the formation of a proliferating pannus. The synovial sublining layer contains several cell populations including macrophages, T and B lymphocytes, dendritic cells, and polymorphonuclear leukocytes. The lining layer contains large numbers of macrophages and fibroblast-like synoviocytes. The interface between pannus and cartilage is occupied predominantly by activated macrophage populations and synoviocytes capable of secreting destructive proteases in abundance. We have observed that macrophages aggregate preferentially adjacent to the cartilage-pannus junction (CPJ) and express differentiation phenotypes that are absent from the lining layer macrophages of more remote SM. Moreover, in a prospective study, the number of SM macrophages correlated with the degree ofjoint damage occurring over one year. Similar results were obtained when SM biopsy samples were analyzed and correlated with clinical and radiological changes occurring over 6 years. Macrophages and synoviocytes at the CPJ express matrix metalloproteinase and cathepsin mRNA from the earliest stage of RA. The mechanisms involved in the secretion of tissue degrading enzymes by macrophages and synoviocytes are undergoing further investigation and preliminary results suggest that different regulation pathways may exist.

ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials. American College of Rheumatology European League of Associations for Rheumatology

Abstract: We compared the validity of the American College of Rheumatology (ACR) and the European League of Associations for Rheumatology (EULAR) definitions of response in rheumatoid arthritis (RA) clinical trials. US: ACR and EULAR improvement criteria were calculated in 7 large randomized RA clinical trials. The discriminant validity of the response criteria between treatment groups was studied using the Mantel-Haenszel chi-squared value. To compare both sets of criteria the chi-squared ratio was determined for each trial. Europe: In 2 large randomized RA clinical trials, ACR and EULAR criteria were calculated, once with extensive and once with 28 joint counts. The classification of patients with these 4 criteria were compared with each other using cross tables. We further studied the difference in response between treatment groups per trial, the association of response with patient and investigator assessment of improvement, and the association of response with radiological progression. US: The chi-squared ratio for most trials was close to 1. There was no clear pattern suggesting that the discriminant validity of the ACR criteria was stronger than the discriminant validity of the EULAR definition of response or vice versa. Europe: Conflicting results between ACR and EULAR were present in only 3% of patients in both trials. The discriminant validity of all 4 criteria (ACR and EULAR with reduced and extensive joint counts) was comparable. All criteria were related with the overall assessment of improvement by both investigator and patient. The association with radiographic progression was comparable for EULAR and ACR improvement criteria. There is a high level of agreement between ACR and EULAR improvement classification, and their validity is equivalent. The discriminating potential of the criteria between treatment groups is comparable, as is the association with patient's and investigator's overall assessment and with radiographic progression.

Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: a double blind, randomized, multicenter, placebo controlled trial.

Abstract: Objective. To compare the efficacy and safety of controlled release oxycodone given every 12 h around the clock with immediate release oxycodone-acetaminophen (APAP) given 4 times daily for osteoarthritis (OA) pain. Methods. Adults (n = 167) with moderate to severe OA pain despite regular use of nonsteroidal antiinflammatory drugs (NSAID) entered open label titration for 30 days with immediate release oxycodone qid; 107 qualified for randomization to double blind, parallel group treatment for 30 days with placebo, controlled release oxycodone, or immediate release oxycodone-APAP. Results. Following titration with immediate release oxycodone, mean (SE) pain intensity (0, none to 3, severe) decreased from 2.44 (0.04) to 1.38 (0.05) (p = 0.0001), and quality of sleep (1, very poor; 5, excellent) improved from 2.58 (0.08) to 3.57 (0.07) (p = 0.0001). Mean dose was about 40 mg/day. Pain intensity and quality of sleep were significantly improved in both active groups compared with the placebo group (p < 0.05) during the double blind trial. Pain intensity and sleep scores were comparable in both active groups during double blind treatment. Nausea (p = 0.03) and dry mouth (p = 0.09) were less common with controlled release oxycodone than immediate release oxycodone-APAP. Conclusion. Controlled release oxycodone q12h and immediate release oxycodone-APAP qid, added to NSAID, were superior to placebo for reducing OA pain and improving quality of sleep. The active treatments provided comparable pain control and sleep quality. Controlled release oxycodone was associated with a lower incidence of some side effects.

Work disability in rheumatoid arthritis 10 years after the diagnosis.

Abstract: OBJECTIVE: To describe employment status of patients with early rheumatoid arthritis (RA) 10 years after diagnosis; and to identify predictive and associative factors related to permanent work disability. METHODS: The study population consisted of 82 patients with early RA who were gainfully employed at onset of RA. Patients were prospectively followed for an average of 10 years and were treated according to the "sawtooth" strategy. RESULTS: After a time since diagnosis of 2 and an average of 9.9 years, respectively, 19/82 (19%) and 36/82 (44%) cases have been retired merely or partly due to RA. Further, at the latest checkup 42/82 (51%) patients were still gainfully employed, while the prevalence of patients working full time under the common retirement age of 65 yrs was 58% (42/72). Cox regression analysis revealed that physically heavy work at baseline was the strongest independent predictive factor for permanent work disability. Ten years after disease onset, however, work disabled patients had more severe disease than those who continued in work. CONCLUSION: Our study confirms that the working capacity of patients with RA is in danger from the very start. Despite early and active therapy with disease modifying antirheumatic drugs, at 10 years the cumulative work disability prevalence was 44%.

Current tobacco smoking, formal education, and the risk of rheumatoid arthritis.

Abstract: Objective. To identify if tobacco smoking or sociodemographic characteristics are risk factors of rheumatoid arthritis (RA). Methods. From a county RA register 361 patients in the age range 20-79 years were recruited from incidence cohorts with recent disease onset (mean 3.4 years) and compared with 5851 randomly selected individuals from the same population area. Data on selected risk factors were collected by questionnaires (response rate 75 and 59%, respectively) and associations with smoking and risk factors were expressed as odds ratios (OR) with 95% confidence intervals (CI) in a multiple regression analysis. Results, Age and female sex were, as expected, identified as risk factors of RA. In addition, current smoking was an overall risk factor (OR 1.46, 95% CI 1.10-1.94), in men (OR 2.38, 95% CI 1.45-3.92), especially in men with seropositive RA (OR 4.77, 95% CI 2.09-10.90). Separate analyses revealed no statistically significant risk in women (OR 1.14, 95% CI 0.80-1.62). Low level of formal education, body mass index, marital or employment status were not significantly associated with risk of RA. Conclusion, Current smoking in men was identified as an independent risk factor for RA. whereas surrogate markers of socioeconomic status were unrelated to the onset of RA.

Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee.

Abstract: Objective Glucosamine products have been used extensively for the management of pain in osteoarthritis (OA). We investigated the efficacy of the hydrochloride salt of glucosamine on pain and disability in knee OA. Methods At Week -2, subjects were examined, randomized, and instructed to take only prescribed acetaminophen for pain. At Week 0 patients were examined, prescribed acetaminophen, and either placebo or glucosamine hydrochloride (glucosamine). At Week 4 the prescriptions for acetaminophen and placebo or glucosamine were renewed. At Weeks 4 and 8, patients returned diaries and unused medications, and were examined. The WOMAC questionnaire was administered at Weeks -2, 0, and 8. After completing the randomized 8 week trial, subjects were offered known glucosamine hydrochloride capsules in an 8 week open label trial, with followup telephone survey after the 8 week open label trial. Results The primary endpoint (statistically significant difference in WOMAC pain score between Week 0 and Week 8) was not met. However, positive trends were noted for the glucosamine group in 23 of 24 WOMAC questions. A significant difference was noted from Week 5 through Week 8 in the knee examination (p = 0.026) and in the response to a daily diary pain question (p = 0.018). However, responding to the question, "Are you better than at the start of the trial?", 40% of placebo and only 49% of glucosamine subjects answered in the affirmative (p = 0.58). At the end of the randomized trial, 34% of placebo and 47% of glucosamine subjects believed that they had been given glucosamine. After the end of the 8 week open label trial, 77% of the subjects were still taking glucosamine, although now obliged to pay for commercially available products. Conclusion There was no significant difference in pain reduction between the glucosamine hydrochloride and placebo groups as measured by WOMAC. However, the secondary endpoints of cumulative pain reduction as measured by daily diary and knee examination were favorable, suggesting that glucosamine hydrochloride benefits some patients with knee OA.

High resolution imaging of normal and osteoarthritic cartilage with optical coherence tomography.

Abstract: Objective. We describe optical coherence tomography (OCT), a high resolution micron scale imaging technology, for assessment of osteoarthritic articular cartilage microstructure. OCT is analogous to ultrasound, measuring the intensity of backreflected infrared light rather than acoustical waves. Methods. OCT imaging was performed on over 100 sites on 20 normal and osteoarthritic cartilage specimens in vitro. Results. Microstructures that were identified included fibrillations, fibrosis, cartilage thickness, and new bone growth at resolutions between 5 and 15 μm. In addition, the polarization sensitivity of imaging suggested a diagnostic role of polarization spectroscopy. Conclusion. OCT represents an attractive new technology for intraarticular imaging due to its high resolution (greater than any available clinical technology), ability to be integrated into small arthroscopes, compact portable design, and relatively low cost.

Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia.

Abstract: Objective. To determine whether there is a difference in the concentration of nerve growth factor (NGF) in the cerebrospinal fluid (CSF) from patients diagnosed with primary fibromyalgia syndrome (FM), fibromyalgia associated with other secondary conditions (SFM), patients with other painful conditions but lacking fibromyalgia (OTHER), and healthy controls. Methods. The clinical measures of pain threshold included the tender point index, a measure of pain threshold intensity measured by digital pressure, and the average pain threshold measured by dolorimetry. Concentrations of NGF in the CSF were measured using a 2 site enzyme immunoassay. Results. The mean (± SEM) concentration of NGF measured in patients with FM was significantly increased (41.8 ± 12.7 pg/ml) compared to controls (9.1 ± 4.1 pg/ml), but with large variability. Concentrations of NGF in SFM (8.9 ± 4.4 pg/ml) and OTHER (16.2 ± 8.4 pg/ml) were not elevated compared to controls. Conclusion. The findings of increased concentrations of NGF in patients with FM suggest a central mechanism, involving abnormalities in neuropeptides such as NGF, may be a factor in the pathogenesis of FM.

The cholesterol lowering effect of antimalarial drugs is enhanced in patients with lupus taking corticosteroid drugs

Abstract: Objective. To examine the relationship between antimalarial therapy and total cholesterol in patients with systemic lupus erythematosus (SLE) with or without steroid therapy. Methods. Retrospective study for the University of Toronto Lupus Clinic database between 1976 and 1997. The effects of antimalarials on random total cholesterol levels were assessed in the following situations: patients not receiving steroids (part I) that either initiated or discontinued antimalarials: patients receiving steroids (part II) that were either on a stable dose or initiating antimalarials; and patients initiating steroids with or without antimalarials (part III). Paired t test. Fisher's exact test, and 2 way analysis of variance were used when appropriate. Results. Initiation of antimalarials reduced the baseline total cholesterol by 4.1% at 3 months in 53 patients (p = 0.020) and by 0.6% at 6 months in 30 patients (p = NS), while the cessation of antimalarials increased the total cholesterol by 3.6% at 3 months in 38 patients (p = NS) and 5.4% at 6 months in 22 patients (p = NS ). In 181 patients taking steroids and antimalarials, the mean total cholesterol was 11% less than for 201 patients receiving a comparable dose of steroids alone (p = 0.0023). Initiation of antimalarials on a stable dose of steroids reduced the total cholesterol by 11.3% at 3 months in 29 patients (p = 0.0002) and 9.4% at 6 months in 20 patients (p = 0.004). For patients initiating steroids, the percentage increase in cholesterol was lower in those taking antimalarials compared to patients without antimalarial therapy (p = 0.0149). Conclusion. Antimalarials lower total cholesterol in patients receiving steroids and may minimize steroid induced hypercholesterolemia.

Prevalence of rheumatoid arthritis and spondyloarthropathy in Brittany, France. Société de Rhumatologie de l'Ouest.

Abstract: Objective To document the prevalence of rheumatoid arthritis (RA) and spondyloarthropathy (SpA) in Brittany, France. Methods (1) Members of rheumatism self-help groups screened cases using questionnaires. (2) Rheumatologists in our unit contacted persons who had possible inflammatory rheumatic diseases and persons who refused the first interview. (3) When diagnosis remained unknown or discordant with the questionnaire, the general practitioner or the rheumatologist of these patients was interviewed. (4) Patients without diagnosis and who had not had a rheumatological examination were examined without charge by a rheumatologist. Results An overall prevalence rate of 0.62% (0.33-0.91) and 0.47% (0.22-0.72) was found for RA and for SpA, respectively. The prevalence of RA and SpA was 0.86 (0.39-1.33) and 0.53 (0.16-0.9) in women and 0.32 (0.01-0.63) and 0.41 (0.05-0.77) in men. The minimum prevalence of RA and SpA calculated on the estimated initial group (3189 persons) was 0.53 (0.28-0.78) and 0.41 (0.18-0.63), respectively. Conclusion Our telephone survey revealed that the prevalences of RA and SpA are nearly similar among our population and that SpA is as common in women as in men.

Immunohistological analysis of cytokine expression in human osteoarthritic and healthy cartilage.

Abstract: Objective To investigate osteoarthritic cartilage in comparison to normal cartilage in humans for the presence of the most relevant cytokines/growth factors known to be important for degradation and formation of new cartilage Methods Cartilage from knee or hip joints was obtained from 10 patients with osteoarthritis (OA) and from 7 age matched control patients with intact cartilage Additionally, normal cartilage from 2 young patients (12 and 17 years old) was obtained after knee traumas Immunohistological staining of cartilage sections was performed using antibodies for the following cytokines/growth factors: tumor necrosis factor α (TNF-α), interleukin 1α (IL-1α), IL-1β, interferon-γ, IL-6, IL-4, IL-10, transforming growth factor β 1 (TGF-β 1 ), insulin-like growth factor I (IGF-I), IGF-II, platelet derived growth factor AA (PDGF-AA), and PDGF-BB Results Immunohistochemical stainings were positive for all cytokines in OA cartilage, while only a faint or no staining was found in healthy cartilage Activated chondrocytes expressing most of the cytokines were located in the middle and partly in the lower layer of cartilage, with the exception of IGF-I, which was expressed exclusively in the upper cartilage layer close to the surface More chondrocytes stained positive for TNF-α than for IL-1, and expression of the degrading cytokine TNF-α was inversely correlated to the expression of the regulatory cytokines IL-4, IL-10, and TGF-β Conclusion The most relevant cytokines known to be involved in cartilage metabolism are produced by chondrocytes themselves They are upregulated in OA cartilage, suggesting that they serve some regulatory function and could be a target for future treatment

The distribution, determinants, and clinical correlates of vertebral osteophytosis: a population based survey.

Abstract: OBJECTIVE: Vertebral osteophytes are a characteristic feature of intervertebral disc degeneration. There are, however, few population data concerning the occurrence of and clinico-biological correlates of vertebral osteophytes in both the dorsal and lumbar spine. Our purpose was to determine the frequency and distribution of anterior osteophytes in the thoracic and lumbar spine, and their relationship with both various putative risk factors, including physical activity and obesity, and self-reported back pain. METHODS: Men and women aged 50 years and over were recruited from primary care based registers in 5 UK centers. They were invited to attend for an interviewer administered lifestyle questionnaire, assessment of height and weight, and lateral spinal radiographs. Lateral spinal radiographs were evaluated by a single observer for the presence of osteophytes from T4 to L5 using a semiquantitative score (grade): 0 = none, 1 = doubtful, 2 = mild, 3 = moderate, 4 = severe. Based on these data 2 summary statistics were derived: the maximum osteophyte grade at any vertebral level (MAX), and the sum of the osteophyte grades at the individual vertebral levels (TOT). RESULTS: In total, 681 women, mean age 63.3 years, and 499 men, mean age 63.7 years, were studied; 84% of men and 74% of women had at least one vertebral level with a grade 1 or higher osteophyte. Both the sum of the individual grades (TOT) and the proportion of subjects with MAX > or =2 were greater in men than in women in both the dorsal and lumbar spine, and both increased with age. The pattern of spinal involvement was similar in the sexes, with osteophytes occurring most frequently at T9-10 and L3. Increasing body mass index was associated with more frequent osteophytes at both dorsal and lumbar spine, although the relationship was stronger at the dorsal spine. Heavy physical activity, particularly in young adult life, was associated with osteophytosis in men. Self-reported back pain, both ever and in the past year, was linked with lumbar osteophytes in men. CONCLUSION: The distribution within the spine in our study and the relationship with heavy physical activity points to mechanical factors being important in pathogenesis of vertebral osteophytosis. Prospective studies are needed to explore the types of physical activity that increase susceptibility to vertebral osteophytosis. In men, osteophytes affecting the lumbar spine are associated with back pain.

Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers.

Abstract: Objective. To investigate whether plasma levels of matrix metalloproteinases 3 (MMP-3, stromelysin), MMP-1 (collagenase), tissue inhibitor of metalloproteinases I (TIMP-1), and MMP-1/TIMP-1 complex (MT complex) are specifically elevated in erosive joint diseases compared to nonerosive rheumatic diseases, and to assess how these markers reflect the clinical activity of rheumatoid arthritis (RA) compared to circulating cytokines and markers of connective tissue turnover as well as established variables [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor titer]. Methods. Plasma levels of MMP-3, MMP- 1, TIMP-1, and MT complex were determined by ELISA. One hundred fifteen patients with RA, 20 with osteoarthritis (OA), 28 with psoriasis arthritis (PsA), 24 with ankylosing spondylitis (AS), 3 groups with systemic autoimmune diseases, and 30 healthy controls were analyzed. In patients with RA routine laboratory variables, circulating inflammatory cytokines [interleukin I (IL-1), tumor necrosis factor-α (TNF-α), and IL-6], collagen degradation products, and markers of bone formation were determined in parallel and were correlated to 4 variables of clinical activity. Results. MMP-3 levels were markedly elevated in RA compared to controls and OA, but also in all other groups, including 26 patients with systemic lupus erythematosus (SLE). MMP-I levels were significantly elevated in RA, but also in OA, PsA, SLE, and mixed connective tissue disease. In contrast, MT complex was elevated in RA only. TIMP- I was not different from controls. CRP levels, MMP-3, and ESR correlated best with clinical activity of RA. In contrast, there was no correlation of IL- 1 and TNF-α and only a weak correlation of IL-6 with clinical measures. Among variables of connective tissue turnover, only pyridinoline and deoxypyridinoline crosslinks were weakly correlated with disease activity. Conclusion. Elevated MMP-3 and MMP- I levels are not specific for RA or for erosive joint diseases in general. In contrast, elevated MT complex levels were observed in patients with RA. However, the correlation of MT- 1 with clinical data was weaker than that of MMP-3. Elevated MMP-3 levels reflected disease activity of RA better than cytokine levels or markers of connective tissue turnover. However, MMP-3 levels do not exceed the association of CRP with clinical activity.

Outcome measures to be used in clinical trials in systemic lupus erythematosus

Abstract: The optimal outcome measures to be employed in clinical trials of systemic lupus erythematosus (SLE) have yet to be determined. Useful instruments should assess disease outcome in terms of all organ system involvement, as well as measures important to the patient. This article reviews those outcome measures that have been utilized in cohort studies in SLE, as well as their limited use in randomized clinical trials (RCT). Six disease activity measures have been developed: British Isles Lupus Assessment Group Scale (BILAG), European Consensus Lupus Activity Measure (ECLAM), Lupus Activity Index (LAI), National Institutes of Health SLE Index Score (SIS), Systemic Lupus Activity Measure (SLAM), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). They have been validated in cohort studies as reflecting change in disease activity, and against each other. RCT utilizing SLAM, SLEDAI, BILAG, ECLAM, SIS, SLAM, SLEDAI are ongoing. It is recommended that the disease activity index of choice be selected; but simultaneous computer generation of multiple indices will facilitate comparisons across therapeutic interventions. A damage index has been developed and validated as the Systemic Lupus International Cooperating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index or SDI. In several cohort studies it has been shown sensitive to change over time, and to reflect cumulative disease activity. There is no health status or disability instrument specific to SLE. The Medical Outcomes Survey (SF-20) captures health status/health related quality of life (HRQOL) better than the Health Assessment Questionnaire (HAQ) in patients with SLE, but does not adequately reflect fatigue. The SF-36 does assess fatigue, and correlates closely with the SF-20. These data indicate that any individual measure of clinical response to a therapeutic intervention in SLE may reflect only a portion of what might be termed the "true outcome." Based on this work, the way is now paved to attempt to develop consensus on the important domains to be measured in clinical trials in SLE, the most appropriate instruments to use and the minimal clinically important differences in their results.

Mortality in rheumatoid arthritis: Have we made an impact in 4 decades?

Abstract: Objective. To evaluate trends in survival among patients with rheumatoid arthritis (RA) over the past 4 decades. Methods. Three population based prevalence cohorts of all Rochester, Minnesota, residents age ≥ 35 years with RA (1987 American College of Rheumatology criteria) on January 1, 1965, January 1, 1975, and January 1, 1985; and an incidence cohort of all new cases of RA occurring in the same population between January 1, 1955 and January 1, 1985, were followed longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Mortality was described using the Kaplan-Meier method and the influence of age, sex, rheumatoid factor (RF) positivity, and comorbidity (using the Charlson Comorbidity Index) on mortality was analyzed using Cox proportional hazards models. Results. Mortality was statistically significantly worse than expected for each of the cohorts (overall p < 0.0001). A trend toward increased mortality in the 1975 and 1985 prevalence cohorts compared to the 1965 prevalence cohort was present, even after adjusting for significant predictors of mortality (age, RF positivity, and comorbidity). Survival for the general population of Rochester residents of similar age and sex improved in 1975 compared to 1965, and in 1985 compared to 1975. Conclusion. The excess mortality associated with RA has not changed in 4 decades. Moreover, people with RA have not enjoyed the same improvements in survival experienced by their non-RA peers. More attention should be paid to mortality as an outcome measure in RA.

Validity aspects of erythrocyte sedimentation rate and C-reactive protein in ankylosing spondylitis: a literature review.

Abstract: The preliminary core set for endpoints in disease controlling antirheumatic therapy includes acute phase reactants. The objective of this clinically oriented literature review was to examine and compare the validity of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in ankylosing spondylitis (AS) clinical trials. A MEDLINE search was performed covering the years 1967 through April 1998. AS studies were identified and selected if they included ESR and/or CRP and either presented data about their relation with disease activity or were designed as longitudinal clinical trials. Additional studies were identified by scrutinizing references cited in the retrieved studies. The selected studies were examined for truth (association with disease activity), discriminative power (sensitivity to change and discrimination between active and inactive treatment in longitudinal clinical trials), and feasibility (e.g., applicability and costs) of ESR and CRP in AS. We identified 12 articles on the association of ESR and/or CRP with disease activity and 13 longitudinal clinical trials reporting ESR and/or CRP data. Although the applied definitions or disease activity proved very inhomogenous, there was some evidence that both acute phase reactants are correlated with disease activity. In terms of discriminative capacity the available data are inconclusive. Relevant feasibility aspects are general availability, technically simple measurement, and an advantage in the cost of ESR and central laboratory facilities for CRP. Acute phase reactants do not comprehensively represent the disease process in AS. Their worth in AS clinical trials is limited. Based on the currently existing data neither measure is clearly superior in terms of validity. When selecting an acute phase reactant, feasibility aspects may be most relevant in choice of measure.