Relationship between physical activity and hip pain in persons with and without cam or pincer morphology: a population-based case-control study.

OBJECTIVES: The purpose of the study was to determine if physical activity (PA) is a risk factor for persistent or recurrent hip pain in young and middle-aged persons with and without radiographic findings of cam or pincer morphology (CPM). METHODS: A population sample of persons aged 20-49 with (cases) and without (controls) hip pain in Metro Vancouver, Canada, was selected through random digit dialing (RDD). Self-reported PA was expressed as average energy expenditure (MET-hours) per year, over lifetime. CPM was defined as alpha angle >55°, lateral centre edge angle (LCE) >40°, or positive cross-over sign. RESULTS: Data were obtained for 500 subjects, 269 cases and 231 controls. Prevalence of radiographic CPM was 49% in the cases and 44% in the controls. In a logistic regression model adjusted for age, gender and CPM, total lifetime PA, including occupational, domestic and recreational activities, was significantly associated with hip pain (Odds ratio (OR) 1.30 per 1000 MET-hours, 95% CI 1.15-1.38). The effect of total PA was observed in those with CPM (1.44, 1.17-1.78) and without CPM (1.23, 1.04-1.45). For domestic activities, the association was seen only in those with CPM (significant interaction). When PA was categorized into quartiles, higher levels of PA were associated with a greater risk of pain. CONCLUSIONS: PA, as measured by average energy expenditure over lifetime is a risk factor for hip pain in young and middle-aged persons. For some activities, the risk is likely increased in persons with radiographic evidence of CPM.

The validity of a non-radiologist reader in identifying cam and pincer femoroacetabular impingement (FAI) using plain radiography.

The purpose of this study was to evaluate the validity and reliability of a radiographic diagnosis of femoroacetabular impingement (FAI) by a non-radiologist. Symptomatic FAI is prevalent and thought to be a cause of hip osteoarthritis. However, the diagnosis is often delayed by 1-2 years, in large part because radiographic findings are often subtle and clinicians have been unaware of their significance. The purpose of this study was to evaluate the validity of a radiographic diagnosis of FAI by a non-radiologist. A population-based sample of 701 subjects was recruited in Vancouver, Canada. For the current study, 50 subjects were selected-40 randomly from the population sample and 10 from an orthopedic practice with confirmed FAI. An anterior-posterior pelvis and bilateral Dunn radiographs were acquired and read by a fellowship-trained musculoskeletal radiologist and a third-year medical student who received basic training in radiographic signs of FAI. Three radiographic signs were evaluated: the lateral center edge angle, alpha angle and crossover sign. Validity was assessed using sensitivity and specificity, Bland-Altman limits of agreement and kappa. The sample contained 65% women (n = 31), was 62% Caucasian and 38% Chinese and had a mean age of 38.3 years. For correctly diagnosing FAI, the non-radiologist reader had a sensitivity of 0.83 and specificity of 0.87. Intra-rater κ value was 0.72, and prevalence-adjusted bias-adjusted κ was 0.76. This study provides evidence that a non-radiologist can accurately and reliably identify FAI on plain films.

The relationship between subchondral sclerosis detected with MRI and cartilage loss in a cohort of subjects with knee pain: the knee osteoarthritis progression (KOAP) study.

PURPOSE: To assess the association between subchondral sclerosis detected at baseline with MRI and cartilage loss over time in the same region of the knee in a cohort of subjects with knee pain. METHODS: 163 subjects with knee pain participated in a longitudinal study to assess knee osteoarthritis progression (KOAP). Subjects received baseline knee radiographs as well as baseline and 3-year follow-up MRI examinations. Baseline subchondral sclerosis and bone marrow lesions (BMLs) were scored semiquantitatively on MRI in each region from 0 to 3. Cartilage morphology at baseline and follow-up was scored semiquantitatively from 0 to 4. The association between baseline subchondral sclerosis and cartilage loss in the same region of the knee was evaluated using logistic regression, adjusting the results for age, gender, body mass index, and the presence of concomitant BMLs. RESULTS: The prevalence of subchondral sclerosis detected by MRI in the regions of the knee varied between 1.6% (trochlea) and 17% (medial tibia). The occurrence of cartilage loss over time in regions varied between 6% (lateral tibia) and 13.1% (medial femur). The prevalence of radiographically-detected subchondral sclerosis in compartments varied from 2.9% (patellofemoral) to 14.2% (medial tibiofemoral). In logistic regression models, there were no significant associations between baseline subchondral sclerosis detected by MRI and cartilage loss in the same region of the knee. CONCLUSION: Baseline subchondral sclerosis as detected by MRI did not increase the risk of cartilage loss over time.

The association of magnetic resonance imaging (MRI)-detected structural pathology of the knee with crepitus in a population-based cohort with knee pain: the MoDEKO study.

Osteoarthritis (OA) is the most common arthropathy of the knee joint(1). Symptoms reported by patients and signs noted during physical examination guide clinicians in identifying subjects with knee OA(2-4). Pain is one of the most important symptoms reported by subjects with knee OA(2,3). Although very common, pain is a non-specific symptom, related to pathology in several structures within the knee joint, and includes synovitis(5), subchondral bone marrow lesions(6), and joint effusion(7). Further, pain is a subjective symptom that cannot be directly measured or assessed during physical examination. Crepitus or crepitation in association with arthritis is defined as a crackling or grinding sound on joint movement with a sensation in the joint. Crepitus may occur with or without pain and is a common finding during physical examination in subjects with knee OA(2-4,8,9). It is not known whether crepitus is related to pathology in various structures within the knee. The aim of our study was to determine the cross-sectional associations of structural pathologies within the knee with crepitus in a population-based cohort with knee pain, using magnetic resonance imaging (MRI). Subjects with knee pain were recruited as a random population sample, with crepitus assessed in each compartment of the knee using a validated and standardized approach during physical examination(10). MRI of the knee was performed to assess cartilage morphology, meniscal morphology, osteophytes, cruciate ligaments, and collateral ligaments. For both compartment-specific and whole-knee analyses, a multiple logistic regression analysis was performed to assess the associations of MRI-detected structural pathology with crepitus, adjusting for potential confounders. Variables were selected by backwards elimination within each compartment and in the overall knee models, and only statistically significant variables remained in the "selected" models; remaining variables in these models are adjusted for each other. An increased risk for compartment-specific crepitus was associated with osteophytes at the patellofemoral (PF) and lateral tibiofemoral (LTF) joints. Crepitus was associated with osteophytes and medial collateral ligament (MCL) pathology at the medial tibiofemoral (MTF) compartment, but cartilage damage was negatively associated with crepitus at this compartment. In the selected whole-knee model, only meniscal tears were associated with an increased risk for general crepitus. Thus, it seems that crepitus may be associated with pathology in several internal structures.

Natural history of cartilage damage and osteoarthritis progression on magnetic resonance imaging in a population-based cohort with knee pain.

OBJECTIVES: To determine the natural history of cartilage damage and of osteoarthritis (OA) progression using magnetic resonance imaging (MRI); to evaluate whether OA progression varies by stage of disease. METHODS: A population-based cohort with knee pain was assessed clinically, with X-ray (Kellgren-Lawrence [KL] grading) and MRI. Cartilage was graded 0-3 on six joint surfaces. Frequency of cartilage damage change was determined for each joint site. Progression of OA was defined as a worsening of MRI cartilage damage by ≥1 grade in at least two joint sites or ≥2 grades in at least one joint site. The association of KL grade with OA progression was evaluated using parametric lifetime regression analysis. RESULTS: 163 subjects were assessed at baseline and follow-up (mean 3.2 years). KL grade ≥2 was present in 39.4% at baseline. An increase in cartilage damage by ≥1 grade was seen in 8.0-14.1% of subjects at different joint sites. OA progression on MRI was present in 15.5%. Baseline KL grade was a significant predictor of OA progression with hazard ratio (HR) of 6.5 (95% confidence interval [CI] 1.4-30.7), 6.1 (95% CI 1.3-28.9), and 9.2 (95% CI 1.9-44.9) for KL grades 1, 2 and ≥3, respectively. CONCLUSION: A low OA progression rate was seen over 3 years in this population-based symptomatic cohort. Radiographic severity, including KL grade 1, was a significant predictor of OA progression. Future interventions aimed at reducing progression will need to target not only radiographic OA, but also those with early abnormalities suggestive of pre-radiographic OA.

Influence of lifetime hip joint force on the risk of self-reported hip osteoarthritis: a community-based cohort study.

OBJECTIVE: To investigate the influence of cumulative lifetime hip joint force on the risk of self-reported medically-diagnosed hip osteoarthritis (OA). DESIGN: Prospective cohort. SETTING: General population. PARTICIPANTS: Members of Canadian Association of Retired Persons, community-dwelling. MAIN OUTCOME: Health-professional diagnosed hip OA, self-reported. METHODS: Exposure data on lifetime physical activity type (occupational, household, sport) and dose (frequency, intensity, duration) was collected in 2005. Subjects were ranked in terms of a 'cumulative peak force index' (CFPI), a measure of lifetime mechanical hip joint force. Multivariable survival analyses were performed to obtain adjusted effects for mean lifetime exposure and during 5-year age periods. RESULTS: Of 2918 subjects aged 45-85, 176 (6.03%) developed hip OA during the 2-year follow up (43 men, 133 women). The highest quintile of mean lifetime hip CPFI (HR 2.32; 95% CI 1.31-4.12), and high hip force in three age periods (35-39, 40-44, 45-49) were independently associated with hip OA. Previous hip injury was an approximate five-fold risk for development of hip OA across all models. In analysis by activity domain (occupation, sport, household), there was a trend (non-significant) for the highest quintile of occupational force, but not sport or household, to be associated with hip OA. CONCLUSIONS: A newly proposed measure of lifetime mechanical hip force was used to estimate the risk of self-reported, medically-diagnosed hip OA. While there are important limitations, this prospective study suggests that lifelong physical activity is generally safe. Very high levels of lifetime force from all domains combined, and in particular from occupational forces, may be important in the etiology of hip OA.

Proposed response criteria for neurocognitive impairment in systemic lupus erythematosus clinical trials.

The objective of this study was to identify reliable and valid instruments to measure cognitive impairment in systemic lupus erythematosus (SLE), and to define minimally important change of cognitive impairment in SLE for clinical trials. Neurocognitive measures used in randomized clinical trials in SLE were reviewed, and response criteria were developed using consensus expert opinion. The definition of cognitive impairment in the ACR nomenclature for neuropsychiatric lupus syndrome was adopted. Cognitive impairment is a deficit of 2.0 or more standard deviations (SD) below the mean, compared to normative data, in the key domains of attention, memory and psychomotor speed. Cognitive decline is defined as a deficit of 1.5-1.9 SD below the mean. Focal decline is defined if impairment exists in one or more measures within one domain, and multifocal decline if impairment exists on measures spanning two or more domains. The combination of ACR neuropsychological battery and the Cognitive Symptoms Inventory (CSI) is recommended to quantitate cognitive function. A clinically important response is defined as an improvement of > or = 1.0 SD with an effect size of 1.0 in the key domains of the ACR neuropsychological testing, and an improvement of > or = 1.0 SD with an effect size of 1.0 in functional performance of the CSI.

Not all "quality-adjusted life years" are equal.

BACKGROUND: There is evidence that utility elicitation methods used in the calculation of quality-adjusted life years (QALYs) yield different results. It is not clear how these differences impact economic evaluations. METHODS: Using a mathematical model incorporating data on efficacy, costs, and utility values, we simulated the experiences of 100,000 hypothetical rheumatoid arthritis patients over 10 years (50,000 exposed to infliximab plus methotrexate [MTX] and 50,000 exposed to MTX alone). QALYs, were derived from the Health Utilities Index 2 and 3 (HUI2 and HUI3), the Short Form 6-D (SF-6D), and the Euroqol 5-D (EQ-5D). Incremental cost-utility ratios were determined using each instrument to calculate QALYs and the results were compared using cost-effectiveness acceptability curves. RESULTS: Using the different utility measurement methods, the mean difference in QALYs between the infliximab plus MTX and MTX groups ranged from a high of 1.95 QALYs (95% CI=1.93-1.97) using the HUI3 to 0.89 QALYs (95% CI=0.88-0.91) using the SF-6D. Adopting the commonly cited value of society's willingness to pay for a QALY of $50,000, 91% of the simulations favored the cost utility of infliximab plus MTX when using the HUI3 to calculate QALYs. However, when using the EQ-5D, HUI2, or the SF-6D utility values to calculate QALYS, the proportion of simulations that favored the cost utility of infliximab were 63%, 45%, and 12%, respectively. CONCLUSION: Depending on the method for determining utility values used in the calculation of QALYs, very different incremental cost-utility ratios are generated.

Methotrexate in systemic lupus erythematosus.

The most appropriate treatment of moderate, nonorgan threatening disease activity in systemic lupus erythematosus (SLE) remains poorly defined, although methotrexate (MTX) is commonly used. The results of 20 uncontrolled case series and a single retrospective cohort study tend to support its use to treat active skin and joint disease. Unfortunately, three prospective randomized trials have reported conflicting results. Two reported improvement in overall disease activity and decreased corticosteroid requirement with MTX. The third trial showed no benefit from MTX for disease activity, but did report a reduction in corticosteroid requirements. Difficulties in conducting trials in moderately active SLE are discussed.

The systemic lupus erythematosus tri-nation study: longitudinal changes in physical and mental well-being.

OBJECTIVE: We have shown that SLE patients in Canada and the UK incurred 20% and 13% lower health costs than those in the US, respectively, but did not experience worse outcomes as expressed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. We now compare change in quality of life in these patients. PATIENTS AND METHODS: Seven hundred and fifteen SLE patients (Canada 231, US 269, UK 215) completed the SF-36 annually over four years. The annual change in the SF-36 Physical and Mental Component Summary (PCS and MCS) scores over the course of the study were summarized by estimating a linear trend for each individual patient using hierarchical modelling. Cross-country comparison of the slopes in the PCS and MCS scores was then performed using simultaneous regressions. RESULTS: The estimated mean annual changes (95% credible interval [CrI]) in the PCS scores in Canada, the US, and the UK were 0.18 (-0.07, 0.43), -0.05 (-0.27, 0.17), and 0.03 (-0.20, 0.27), respectively; the mean annual changes in the MCS scores were 0.15 (-0.04, 0.34), 0.23 (0.09, 0.37), and 0.08 (-0.10, 0.27), respectively. Regression results showed that the mean annual changes in PCS and MCS scores did not substantially differ across countries. CONCLUSION: Quality of life remained stable across countries. Despite Canadian and British patients incurring lower health costs, on average, patients experienced similar changes in physical and mental well-being.

The impact of low family income on self-reported health outcomes in patients with rheumatoid arthritis within a publicly funded health-care environment.

OBJECTIVE: Self-rated health (SRH) is an independent, strong predictor of morbidity and mortality. Socio-economic status (SES) is strongly associated with SRH. This study investigated the relationship between SES and SRH outcomes in a sample of patients with rheumatoid arthritis (RA) in Canada. METHODS: Both generic preference-based [Health Utilities Index Mark 3 (HUI3) and Short Form 6D (SF-6D)] and non-preference-based [disease-specific (Rheumatoid Arthritis Quality of Life, RAQoL) and a functional status (Health Assessment Questionnaire, HAQ)] SRH questionnaires were administered to 313 RA patients. Both proximate (education and annual household income) and contextual (neighbourhood income, education and unemployment) measures of SES were captured. Ordinary least squares (OLS) regression was used to adjust for RA severity while assessing the relationship between SRH and SES measures. Two-stage least-squares (TSLS) regression was used to determine if there was an inter-relationship between SES and SRH measures. RESULTS: The sample was well distributed across RA severity and SES measures. Contextual and proximate measures of SES were poorly correlated. Lower levels of proximate SES measures (but not contextual) were associated with poorer SRH outcomes. The OLS regressions showed significant associations between the HUI3 and the SF-6D overall scores and the HAQ for self-reported income. The RAQoL did not differ significantly across SES. TSLS regression confirmed the finding that self-reported income was similarly associated with the SRH measures. CONCLUSIONS: Even in a country with universal access to health-care, the impact of a chronic disease such as RA on SRH is associated with self-reported income. The finding that preference-based measures vary with income independently of RA severity could bias economic evaluation.

The systemic lupus erythematosus Tri-nation Study: absence of a link between health resource use and health outcome.

OBJECTIVE: Health consumption and health status in SLE in three countries with different health funding structures were compared. METHODS: Seven hundred and fifteen SLE patients (Canada 231, USA 269, UK 215) were surveyed semi-annually over 4 yr for health resource utilization and health status. Cross-country comparisons of (i) cumulative health expenditure (calculated by applying 2002 Canadian prices to resources in all countries) and (ii) disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, SLICC/ACR DI) at study conclusion were performed after adjustment. Missing expenditure and damage data were managed through multiple imputation using best predictive regressions with all available data from all patients as potential covariates. RESULTS: Four hundred and eighty-five patients provided data at study entry and conclusion and at least four resource questionnaires (Canada 162, USA 157, UK 166); 41 died (Canada 13, USA 18, UK 10); 189 withdrew, were lost to follow-up or provided data at entry and conclusion but fewer than four resource questionnaires (Canada 56, USA 94, UK 39). At conclusion, after imputation, in Canada, the USA and the UK respectively, mean cumulative costs per patient over 4 yr [95% confidence interval (CI)] were $15,845 (13,509, 18,182), $20,244 (17,764, 22,724) and $17,647 (15,557, 19,737) and mean changes in SLICC/ACR DI were 0.49 (0.39, 0.60), 0.63 (0.52, 0.74) and 0.48 (0.39, 0.57). After adjustment for baseline differences, on average (95% CI), Canadian and British patients utilized 20% (8%, 32%) and 13% (1%, 24%) less resources than patients in the USA respectively, but experienced similar health outcomes. CONCLUSION: Despite patients in the USA incurring higher health expenditures, they did not experience superior health outcomes.

Agreement among Ayurvedic practitioners in the identification and treatment of three cases of inflammatory arthritis.

OBJECTIVE: To conduct a preliminary investigation into the consistency of approach between three Ayurvedic medicine experts on treatments for inflammatory polyarthritis. METHODS: A convenience sample of three experienced Ayurvedic practitioners was recruited. These practitioners independently assessed three subjects with inflammatory polyarthritis for health status, treatment history, and lifestyle, conducted a physical examination, and then independently determined the treatment plan. The treatment plan was recorded on standardized collection forms. The subject examination order was randomized for each practitioner. Following completion of the assessments, a facilitated discussion among the practitioners permitted each to discuss all aspects of the recommended therapies. Proceedings were audio-taped and the content analyzed. RESULTS: All three practitioners agreed upon a unified concept of Ayurvedic disease origin, disease diagnosis, and treatment approach for each patient. Seven specific treatment groupings (i.e. modalities) emerged: diet, exercise, relaxation, analgesic, anti-inflammatory, immune-enhancing, and detoxification/cleansing. Based on the single visit, the practitioners agreed upon 17 of 21 treatment groups for the three patients. CONCLUSION: Despite Ayurvedic medicine's individualized approach, considerable agreement existed among the practitioners studied. The identified Ayurvedic treatment approaches require investigation in a controlled clinical setting.

A case-control analysis of nonsteroidal anti-inflammatory drugs and Alzheimer's disease: are they protective?

In many studies of nonsteroidal anti-inflammatory drugs (NSAIDs) and Alzheimer's disease (AD), the exposure to NSAIDs was concurrent with AD or based on self (or surrogate) report. We conducted a case-control analysis of the Québec participants in the Canadian Study of Health and Aging who received a diagnosis of AD (cases) or were found to be cognitively unimpaired on screening (controls). Information on drug use was obtained from the Québec Provincial Pharmaceutical Services Database. There was no significant difference in the proportion of cases and controls who had received any NSAID prescriptions in the 3 years prior to the onset of symptoms of dementia; amongst NSAID users, there was no difference in mean dose or duration. Our findings, using a measure of drug use prior to symptom onset and not subject to recall bias, do not support a protective effect for NSAIDs.

Living with lupus: a prospective pan-Canadian study.

OBJECTIVE: To portray life with lupus for women affected by this disease and to identify predictors of fatigue, a common symptom that compromises patients' quality of life. METHODS: A sample of 120 female patients (mean age 42.5 yrs) with systemic lupus erythematosus (SLE) from 9 rheumatology clinics across Canada were followed prospectively for 15 months. Assessments of psychosocial functioning took place at baseline, and at 3, 9, and 15 months. Physician examinations were conducted at baseline and 15 months. RESULTS: Significant time effects were found for: global psychological distress (p < 0.001), stress (p < 0.01), emotion-oriented coping (p < 0.001), physical health status (p < 0.001), and fatigue (p < 0.001), indicating that patients improved from baseline to 15 months. Disease activity worsened for 40.3%, improved for 50.8%, and remained the same for 8.8% of the patients from baseline to 15 months. Controlling for baseline disease activity and fatigue, and considering sleep problems, decreases in stress and depression predicted less fatigue at 15 months (p < 0.001; adjusted R2 = 0.43). CONCLUSION: Despite fluctuations in disease activity, patients with SLE, as a group, cope adequately with their disease over time. There is, nonetheless, a subset of patients (about 40%) who remain distressed and who may benefit from psychosocial interventions.

Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus.

OBJECTIVE: The frequency of coronary heart disease (CHD) and stroke are increased in systemic lupus erythematosus (SLE), but the extent of the increase is uncertain. We sought to determine to what extent the increase could not be explained by common risk factors. METHODS: The participants at two SLE registries were assessed retrospectively for the baseline level of the Framingham study risk factors and for the presence of vascular outcomes: nonfatal myocardial infarction (MI), death due to CHD, overall CHD (nonfatal MI, death due to CHD, angina pectoris, and congestive heart failure due to CHD), and stroke. For each patient, the probability of the given outcome was estimated based on the individual's risk profile and the Framingham multiple logistic regression model, corrected for observed followup. Ninety-five percent confidence intervals (95% CIs) were estimated by bootstrap techniques. RESULTS: Of 296 SLE patients, 33 with a vascular event prior to baseline were excluded. Of the 263 remaining patients, 34 had CHD events (17 nonfatal MIs, 12 CHD deaths) and 16 had strokes over a mean followup period of 8.6 years. After controlling for common risk factors at baseline, the increase in relative risk for these outcomes was 10.1 for nonfatal MI (95% CI 5.8-15.6), 17.0 for death due to CHD (95% CI 8.1-29.7), 7.5 for overall CHD (95% CI 5.1-10.4), and 7.9 for stroke (95% CI 4.0-13.6). CONCLUSION: There is a substantial and statistically significant increase in CHD and stroke in SLE that cannot be fully explained by traditional Framingham risk factors alone.

The effectiveness and toxicity of cyclosporin A in rheumatoid arthritis: longitudinal analysis of a population-based registry.

OBJECTIVE: To determine factors associated with response or toxicity to cyclosporin A (CSA) in a population-based inception cohort with rheumatoid arthritis (RA). METHODS: Prospectively collected longitudinal measures including tender joint count (JC), duration of morning stiffness (MS), systolic and diastolic blood pressure (SBP, DBP), and serum creatinine (SCr) were modeled using generalized estimating equations. Survival methods were used to estimate CSA continuation time and its determinants. RESULTS: Of 133 patients (75% female, median RA duration 13 years), 37 discontinued CSA because of ineffectiveness (19) or because of toxicity (18) including increased SCr in 10, hypertension in 4, infections in 3, and gingival hyperplasia in 1. Patients remained on CSA a median of 75 months (95% confidence interval [CI] 38-112). Those receiving concomitant methotrexate (MTX) were more than 4 times as likely to continue on CSA therapy (hazard ratio 0.22, 95% CI 0.10-0.94). A lower final JC was predicted by a longer CSA treatment duration (relative risk [RR] 0.99 per month, 95% CI 0.98-0.99) and concomitant MTX therapy (RR 0.79, 95% CI 0.63-0.99); decreased MS was predicted only by longer CSA treatment duration (reduction of 2.0 minutes per month, 95% CI 1.1-3.0). Each previous disease-modifying antirheumatic drug (DMARD) exposure predicted a rise in SCr (35 micromole/liter, 95% CI 22-48), SBP (7.2 mm Hg, 95% CI 2.7-11.7), and DBP (3.8 mm Hg, 95% CI 3.0-6.4). CONCLUSIONS: Combination CSA/MTX prolongs therapy and reduces JC. Long-term CSA treatment was fairly well tolerated. Previous DMARD use appears to be a determinant for the development of toxicity.

Cyclosporin A in the treatment of refractory adult polymyositis/dermatomyositis: population based experience in 6 patients and literature review.

OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporin A (CSA) in the treatment of refractory adult polymyositis/dermatomyositis (PM/DM). METHODS: The province-wide British Columbia database for CSA use for persons with rheumatic diseases at Mary Pack Arthritis Centre was reviewed to identify all patients with PM/DM for the period January 1991 through June 1998. Also, a Medline search of English language literature was conducted for this topic from 1976 until January 1999, using the terms dermatomyositis, polymyositis, inflammatory myopathy, and cyclosporin A, and the reference lists of all papers were screened to include articles not identified by the Medline search. RESULTS: In British Columbia, 172 CSA users of whom 6 had PM/DM were identified (4 PM, 2 DM). Previous therapy included high dose prednisone (N = 6), methotrexate (N = 4), azathioprine (N = 4), intravenous immunoglobulin (N = 3), and cyclophosphamide (N = 3). The mean CSA dose was 3.5 mg/kg/day. All patients improved. Creatinine kinase (CK) levels declined 52% from baseline. All 6 patients continued CSA a median of 6 months (range 3-44 mo) after initiation of therapy. Toxicity included an increase in serum creatinine > 30% of baseline in 3 patients and hypertension in one patient. The literature review identified an additional 59 cases. Forty-eight (81%) had a reduction in CK levels and improved clinically, 9/59 (15%) developed nephrotoxicity, 5/59 (8%) hypertension responsive to dose reduction, and 9/59 (15%) had hypertrichosis, gingival hyperplasia, or tremor. CONCLUSION: Our population based experience with 6 patients and the 59 published cases suggests CSA is an effective therapy for resistant PM/DM, and toxicity is possibly more than expected in other rheumatic diseases.

Underestimating the value of women: assessing the indirect costs of women with systemic lupus erythematosus. Tri-Nation Study Group.

OBJECTIVE: Indirect costs result from diminished productivity and are incorporated in cost-benefit analysis to guide health resource allocation. Valuing the productivity impairment of those not involved in labor market activities is controversial but important for diseases affecting predominantly women if allocation decisions are to be economically efficient and equitable. We compared indirect costs incurred by women with systemic lupus erythematosus (SLE), a prototypical women's disease, calculated under varying assumptions for the value of diminished labor market and non-labor market activity. METHODS: Six hundred forty-eight female patients with SLE reported on employment status and time lost by themselves and their caregivers from labor market and non-labor market activities over a 6 month period. RESULTS: Average annual indirect costs ranged from $1,424 to $22,604 (1997 Canadian dollars) dependent on the value assigned to labor market and non-labor market activity. CONCLUSION: Indirect cost estimates that fail to consider longterm labor market absenteeism and diminished non-labor market productivity and do not use gender neutral wages to value labor market activity may lead to decisions that jeopardize resources for women's diseases.