Showing papers by "Janet E. Pope published in 2008"

Employment and work disability in systemic lupus erythematosus: a systematic review

Abstract: Objectives. Many studies have provided information on employment and work disability (WD) rates in patients with SLE, yet are often limited by small sample sizes, poor generalizability or fail to examine the risks and outcomes of WD. Our objective was to systematically review the literature on WD in SLE to identify a more generalizable point estimate and range of WD in SLE patients. Methods. A search was conducted using Medline, EMBase, PubMed and Cochrane databases to identify publications related to SLE and employment and/or WD. Characteristics of the study samples and employment/WD data were extracted. Descriptive statistics, a test for heterogeneity and random effects models were performed to obtain pooled estimates of employment and WD rates for all patients. Results. Twenty-six studies with a total of 9886 SLE patients were found; however, not all patients were reviewed for WD. Larger studies demonstrated the prevalence of WD at 20–40%, and pooled estimates found that 46% (95% CI 40%, 52%) were employed with SLE and 34% (95% CI 24%, 44%) had WD. WD was related to psychosocial and disease-related factors including age, race, socioeconomic status (SES), education, disease activity and duration, pain, fatigue, anxiety and neurocognitive involvement. Conclusions. This study provides strong evidence that costs of SLE may be very high due to job loss at a younger age in SLE patients, and identifies some risk factors associated with WD, which should be targeted by interventions aimed at preventing job loss.

The minimally important difference for the fatigue visual analog scale in patients with rheumatoid arthritis followed in an academic clinical practice.

Abstract: ### Objective To estimate the minimally important difference (MID) for a fatigue visual analog scale (VAS) using patient-reported anchors (fatigue, pain, and overall health). ### Methods Patients with rheumatoid arthritis (RA; n = 307) had 2 clinic visits at a median of 5.9 months apart. They completed a fatigue VAS (0–10 scale) and the retrospective anchor items, “How would you describe your overall fatigue/pain/overall health since the last visit?” with response options: Much worsened, Somewhat worsened, Same, Somewhat better, or Much better. The fatigue anchor was used for primary analysis and the pain/overall health anchors for sensitivity analyses. The minimally changed group was defined by those reporting they were somewhat better or somewhat worsened. ### Results The mean [standard deviation (SD)] age was 59.4 (13.2) years, disease duration was 14.1 (11.5) years, and 83% of patients were women. The baseline mean (SD) Health Assessment Questionnaire–Disability Index score was 0.84 (0.75). The baseline fatigue VAS score was 4.2 (2.9) and at followup was 4.3 (2.8) [mean change of −0.07 (2.5); p = not significant]. The fatigue change score (0–10 scale) for Somewhat better and Somewhat worsened for the fatigue anchor averaged −1.12 and 1.26, respectively. Using the pain anchor, the fatigue change score for Somewhat better and Somewhat worsened averaged −0.87 and 1.13; and using the global anchor, the fatigue change score for Somewhat better and Somewhat worsened averaged −0.82 and 1.17, respectively. Effect size estimates using 3 anchors were small for the Somewhat better (range 0.27–0.39) and Somewhat worsened (0.40–0.44) groups, but larger than for the no-change group (0.03–0.08). ### Conclusion The MID for fatigue VAS is between −0.82 for −1.12 for improvement and is 1.13 to 1.26 for worsening on a 0–10 scale in a large RA clinical practice, and is similar to that seen in RA clinical trials. This information can aid in interpreting fatigue VAS in day-to-day care in clinical practice

The cost of systemic sclerosis.

Abstract: Objective To assess costs related to systemic sclerosis (SSc) and their determinants. Methods The Canadian Scleroderma Research Group is comprised of 15 centers contributing to a registry of adult patients with SSc. Available cross-sectional data included clinical variables and standardized measures of health resource use and time loss. Annualized averages of direct medical costs were calculated by multiplying health service utilization levels by the appropriate unit prices, determined from government fee schedules, professional associations, and other sources. Indirect costs were calculated from the subjects' self-reported time loss related to illness and to seeking health care, as well as caregiver time losses. Costs were represented in 2007 Canadian dollars. Results In the sample of 457 patients with SSc, the average direct cost per patient was $5,038 per year (95% confidence interval [95% CI] $4,400, $5,676). Regarding indirect costs, the value of potential productivity loss related to paid labor was estimated at an average of $5,345 per patient per year (95% CI $4,598, $6,092), and the cost of lost productivity related to unpaid labor contributed another $8,070 per patient annually. The average total annual cost was estimated at $18,453 (95% CI $16,598, $20,308) per patient. Total annual costs were strongly associated with younger age, greater disease severity, and poorer health status. Conclusion Costs related to SSc are considerable, and there is a high impact of disease severity and health status on economic burden.

Shifting our thinking about uncommon disease trials: the case of methotrexate in scleroderma.

Abstract: Objective. Randomized trials for uncommon diseases suffer from methodological challenges: difficulty in recruiting sufficient numbers of patients and low power to detect important treatment effects. Using traditional (frequentist) analysis, p values > 0.05 mean investigators are unable to reject the null hypothesis (of no treatment effect). The medical community often labels trials with p values > 0.05 as “negative.” Our study demonstrates how Bayesian analysis conveys more relevant information to clinicians — using the example of methotrexate (MTX) in systemic sclerosis (SSc). Methods. Data from 71 patients with diffuse SSc (n = 35 MTX, n = 36 placebo) in the trial were reanalyzed using Bayesian models. We examined 3 primary outcomes: modified Rodnan skin score (MRSS), University of California Los Angeles (UCLA) skin score, and physician global assessment of overall disease activity. Using noninformative prior probability distributions, the probability of beneficial treatment effects for each outcome and the probability of simultaneous benefit in outcomes were computed. Results. The probability that treatment with MTX results in better mean outcomes than placebo was 94% for MRSS, 96% for UCLA skin score, and 88% for physician global assessment. There was 96% probability that at least 2 of 3 primary outcomes were better on treatment. Conclusion. Bayesian analysis of uncommon disease trials allows for more flexible and clinically relevant interpretations of the data. From the trial data, clinicians can infer that MTX has a high probability of beneficial effects on skin score and global assessment.

An update in pulmonary hypertension in systemic lupus erythematosus - do we need to know about it?

Abstract: Pulmonary hypertension (PH) is a serious form of pulmonary complication that occurs less frequently in lupus than in other connective tissue diseases like scleroderma; however, it is likely that it is under-recognized in lupus. The symptoms of PH in lupus are non-specific (dyspnea, fatigue, impaired exercise tolerance) and can also be caused by other factors such as pleural or pericardial effusions, interstitial lung disease and many more, making it possible to miss the diagnosis. There are several potential causes of PH in lupus including thromboembolic disease, pulmonary vasculitis, and hypoxia and fibrosis from interstitial lung disease. Endothelin-1 is elevated in lupus and may be associated with PAH. In some studies, pulmonary arterial hypertension (PAH) has been found to be a major cause of mortality in lupus patients. Echocardiograms are a screening tool, but may yield false positives, and a right heart catheterization must be performed to confirm PAH. Early identification is important and can alter the natural history of this dangerous complication of lupus. Treatment of PAH associated with lupus includes standard PAH treatment as well as immunosuppression.

Patients with scleroderma may have increased risk of osteoporosis. A comparison to rheumatoid arthritis and noninflammatory musculoskeletal conditions.

Abstract: Objective To investigate if subjects with scleroderma (systemic sclerosis, SSc) have increased risk for developing osteoporosis (OP). Methods A survey assessing demographics, diagnosis/investigations for OP, and risk factors for OP was mailed to 129 patients with SSc, 158 controls with noninflammatory musculoskeletal (MSK) disease, and 230 positive controls with rheumatoid arthritis (RA). All available charts were reviewed and results were included in analyses of demographics, OP status, past bone mineral density (BMD), and past steroid use. In addition, we recorded BMD results (T score) of SSc patients with their matched RA controls. Analyses adjusted for age were done for SSc versus MSK and SSc versus RA. Results The response rate was 61% for patients with SSc (n = 28 diffuse, 51 limited disease), RA 67%, and MSK 59%; however, through chart review, 159 SSc, 140 MSK, and 235 RA patients were included in the analyses. Mean age and proportion of women did not differ between groups. Disease duration was longer in RA versus SSc group (16.5 vs 11.5 yrs; p Conclusion The prevalence of OP in patients with SSc was comparable to those with RA, but higher than in the MSK group. Age was found to be an important factor, as expected. Also, our results indicated that BMD (T score) in SSc was similar to or even lower than in patients with RA. Increasing the awareness to order BMD measurements in patients with SSc may be warranted based on our results, especially for older patients.

Work Disability in Scleroderma is Greater than in Rheumatoid Arthritis and is Predicted by High HAQ Scores

Abstract: Objectives: To estimate the frequency of work disability (WD) in a cohort of patients with Systemic Sclerosis (SSc) vs an internal control group of patients with rheumatoid arthritis (RA) with a known high frequency of WD; and to investigate the association between WD and other factors including Health Assessment Questionnaire Disability Index (HAQ-DI) scores, HAQ pain, age, sex, disease duration and education level. Methods: Cross-sectional data on WD status were obtained from a questionnaire sent to all SSc (n = 35 limited (lcSSc), 26 diffuse (dcSSc)) and a subset of RA patients (n=104) from a rheumatology practice. WD data, HAQ-DI scores, and demographic/clinical features (age, sex, high school education, disease duration and SSc disease subtype (dcSSc vs lcSSc)) were recorded. Results: The proportion with WD was 0.56 in SSc (95% CI: 0.43-0.68) vs 0.35 in RA (95% CI: 0.25-0.44), p= 0.009. HAQ-DI scores were significantly higher in work-disabled SSc and RA patients vs those who were employed (p=0.0001, and p < 0.0001). Multivariate logistic regression analysis demonstrated that higher HAQ-DI scores (�=1.78, p < 0.001), disease type (dcSSc, lcSSc, RA) (� =1.32 for dcSSc, p=0.032), and self-reported disease duration (� =0.04, p=0.042) were significantly associated with WD (R 2 =0.311). Adding a work-related factor (self-reported physically demanding work) improved the regression model (R 2 =0.346) and strengthened the HAQ-DI (�=1.86, p < 0.001) and lcSSc (� =1.24, p=0.024) coefficients. Conclusion: The frequency of WD in SSc was high and was greater than in RA. SSc (and dcSSc) had significantly more WD than RA. The HAQ-DI was strongly associated with WD in SSc.

Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity.

Abstract: Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives. Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry. We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait. The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity.

Learning from past mistakes: assessing trial quality, power and eligibility in non-renal systemic lupus erythematosus randomized controlled trials

Abstract: Objectives. To evaluate the post hoc study power of randomized controlled trials (RCTs) in the treatment of non-renal SLE and to determine the generalizability of these RCTs using an SLE database. Methods. RCTs in non-renal SLE were identified using PubMed (1975–2007). Inclusion/exclusion criteria, trial quality (5-point scale) and results of each study were recorded. The inclusion/exclusion criteria were compared with an SLE database to determine the proportion of patients from the database who would theoretically be eligible for these trials. For each negative study, we calculated the post hoc study power. We also looked for temporal improvements of trials in the literature and examined if pharmaceutical involvement influenced trial quality. Results. Sixty-four articles were included; the mean power of 30 negative studies was 24.6 � S.E.M. 3.9% (range 2.5–81.1%). Only one study had a power > 80%. Overall, potential eligibility of SLE patients in the database was 45.1 � S.E.M. 3.6%. Only 14 studies (21.9%) were of good quality. Fortunately, RCT quality is improving over time (trials 2003; P < 0.001). Trials with pharmaceutical involvement had a significantly higher number of enrollees and better study quality. Conclusions. Negative RCTs in SLE were mostly underpowered but the generalizability of these trials was high. Determination of study power and the impact of eligibility criteria on generalizability of study results are crucial in the design of clinical trials to ensure applicabilit yt o clinical practice.

Reports of abnormal cervical cancer screening tests in systemic sclerosis

Abstract: Objective To assess the prevalence of abnormal cervical cancer screening (Pap tests) reported by women with SSc onset before the age of 50 yrs. Methods Female members of a Canadian multi-centre SSc cohort completed standardized assessments and were questioned regarding a history of an abnormal Pap test. Potential correlates examined included demographics, reproductive history, smoking, diffuse vs limited SSc type, immunosuppressant exposure and SSc duration. Results In the 320 women with SSc onset before the age of 50 yrs, the life-time prevalence of an abnormal Pap test (according to self-report) was 25.4% (95% CI CI 20.9, 30.4%). By comparison, self-reported prevalence of abnormal Pap tests among general population Canadian females was recently reported at 13.8% (95% CI 11.6, 16.4%). Women with diffuse SSc (n = 142), tended to have a higher prevalence of self-reported cervical dysplasia (31.7%) compared with those with limited disease (20.7%), but the CIs overlapped. A multivariate logistic regression found a significant positive association between self-reported abnormal Pap test and diffuse disease [odds ratio (OR) 1.87; 95% CI 1.01, 3.47]. An independent association of an abnormal Pap test with smoking (OR 2.43; 95% CI 1.23, 4.78) and with younger age at disease onset was also noted. Conclusions We noted a high prevalence of abnormal Pap tests self-reported in our sample. Increased risk was seen among those with diffuse SSc, and also among smokers and those with a younger age at disease onset. Thus, it seems prudent to ensure that adequate attention is paid to cervical cancer screening for women with SSc.

Lack of correlation of the health assessment questionnaire disability index with lung parameters in systemic sclerosis associated pulmonary arterial hypertension.

Abstract: Objective Pulmonary arterial hypertension (PAH) affects the quality of life (QoL) and the ability to perform the activities of daily living (ADLs) in patients with systemic sclerosis (SSc). We determined whether the Health Assessment Questionnaire -Disability Index (HAQ-DI), a self-assessment measure of function, correlates with a patient's PAH status in a population of SSc patients with PAH. Methods Forty-one patients from one centre with systemic scleroderma, dyspnea and PAH were included. All patients filled in a HAQ-DI, and underwent evaluation with pulmonary function tests (PFTs), 6-minute walk distance (6MWD), degree of dyspnea (Borg dyspnea index), NYHA functional class, and expert PAH physician global assessment every 6 months. Change in HAQ DI was studied to determine relationship to changes in PAH. Results The HAQ-DI scores had no significant correlation with PAH, including NYHA functional class (r=0.38, p=0.39), Borg dyspnea index (r=0.60, p=0.37), 6MWD (r=-0.04, p=0.86), % predicted DLCO (r=0.31, p=0.25), % predicted FVC (r=0.02, p=0.93), and expert PAH physician global assessment (r=0.06, p=0.97). Conclusion HAQ-DI is not an adequate measure of PAH status in SSc patients with PAH. Although PAH causes severe morbidity and death, changes in PAH severity were not reflected in an overall functional status change as assessed by the HAQ-DI. Thus, HAQ-DI changes do not reflect PAH status in SSc.

Assessment of unmet needs and the lack of generalizability in the design of randomized controlled trials for scleroderma treatment

Abstract: Objective To determine the generalizability of randomized controlled trials (RCTs) in the treatment of systemic sclerosis (SSc) using the Canadian Scleroderma Research Group (CSRG) database Methods We identified articles related to SSc published from 1958 to 2006 Key points on trial design were recorded The inclusion/exclusion criteria were used in conjunction with the CSRG database to determine the proportion of patients with SSc who would theoretically be eligible for these trials Articles were classified into subcategories according to the target system The CSRG database contains 438 patients with SSc from 14 Canadian centers Results were in median (%) and mean (%) with 95% confidence intervals (95% CIs) Results In total, 210 articles were evaluated and 73 were selected for inclusion in this study The mean percentage of eligible patients with SSc associated with other conditions was 35% (95% CI 17–53) for Raynaud's phenomenon, 24% (95% CI 1–47) for digital ulcers, 48% (95% CI 27–68) for gastrointestinal (GI) involvement, 32% (95% CI 20–43) for overall disease modification, 6% (95% CI 4–8) for pulmonary arterial hypertension, 2% (95% CI 0–4) for interstitial lung disease, and 38% (95% CI 12–64) for other categories Conclusion Except for GI trials, <38% of the identified patients with SSc would have been suitable to enter the RCTs Although some patients would be ineligible because they lack certain organ involvement, RCTs designed to include appropriate patients with SSc are needed; there are few proven treatments and trials typically do not include the majority of those who could potentially benefit from the intervention

The temporal relationship of Raynaud's phenomenon and features of connective tissue disease in rheumatoid arthritis.

Abstract: Objective In a prospective cohort study we examined the relationship between Raynaud’s phenomenon (RP) onset and other connective tissue disease (CTD) characteristics in rheumatoid arthritis (RA) to determine if RP is predictive of RA severity and associated with other CTD signs, and if late onset RP in RA has an effect on prognosis compared to other patients with RA. Methods Using a standardized assessment, data were collected on 328 subjects with RA [mean age 60.3 ± 0.7; 77% women; 76% erosions, 75% positive rheumatoid factor (RF)] seen at one London, Ontario, rheumatology clinic. The data included RA disease duration; presence and duration of RP; presence of nodules, joint damage, telangiectasia, and sclerodactyly; and RF status (+/−), RF value, antinuclear antibodies, and E-nuclear antibodies. Results The mean RA disease duration was 12 ± 0.6 years. Seventy-one (22%) had RP and the mean RP duration was 9.2 ± 1.5 years. Patients presented with RP a mean of 3.8 ± 1.4 years after the diagnosis of RA. RP status was positively associated with the presence of sclerodactyly (p Conclusion Idiopathic RP may have a different clinical effect on RA than secondary RP; the latter is correlated with more severe RA. Sclerodactyly is associated with erosive arthritis and RP in RA. Higher RF values were indicative of increased RA and RP duration.

Assessment of reproductive history in systemic sclerosis.

Abstract: Objective To assess the number of live births in women whose systemic sclerosis (SSc) onset occurred during their reproductive years, and to compare this with general population rates. Methods Within the Canadian Scleroderma Research Group cohort, we identified 320 women whose SSc symptoms began prior to age 50 years. We determined the number of children born in the years following first onset of symptoms. We summed the years of followup from the time of first symptoms in subjects up to age 50 years (or oldest age attained, if the subject was age <49 years). We applied age-specific birth rates for Canadian women to these years of followup in order to determine the expected number of live births for the period. We then calculated the standardized incidence ratio (SIR) of observed to expected live births. Results In the 320 women studied, the number of live births over the interval since symptom onset was below the expected number (111 live births observed versus 140 expected; SIR 0.79, 95% confidence interval [95% CI] 0.65–0.95). This finding was more prominent in women with diffuse cutaneous disease versus limited cutaneous disease. The mean and median numbers of live births were similar across SSc subgroups based on organ involvement or cyclophosphamide exposure. In repeat analyses, including the reproductive period before SSc symptom onset, the ratio of observed to expected births was 1.23 (95% CI 1.13–1.33). Conclusion Compared with the general population, fewer live births were noted in women with SSc, but this phenomenon was only apparent in the period after symptom onset.

Demographic and Clinical Factors Associated with Physician Service Use in Systemic Sclerosis

Abstract: Objective. To assess physician service use in a large sample of patients with systemic sclerosis (SSc), and to determine factors associated with physician use. Methods. Our sample was a national SSc registry maintaining data on demographics (age, sex, race/ethnicity, education, income) and clinical factors (disease onset, organ involvement, etc.). Registry cohort members completed detailed questionnaires, and rheumatologists provided clinical assessments. We examined cross-sectional data from 397 patients who provided information on physician visits in the past 12 months. Patients were classified as high physician-users if they reported more than the median number (6) of physician visits in the past year. In multivariate logistic regressions, we assessed the independent effects of race/ethnicity, education, degree of skin involvement, comorbidity, and SF-36 scores on physician use. Results. On average, subjects reported 3.8 visits per year to specialty physicians (SD 4.2) and 3.5 visits per year to family physicians (SD 4.3). Regression models suggested the following factors as independently associated with number of physician visits: high skin scores, greater comorbidity, and low physical component summary scores on the SF-36. Conclusion. There is evidence of independent relationships between clinical characteristics and physician use by patients with SSc.

The relationship between NSAID use and osteoarthritis (OA) severity in patients with hip and knee OA: results of a case control study of NSAID use comparing those requiring hip and knee replacements to those in whom surgery was not recommended.

Abstract: BACKGROUND: NSAIDs are not considered disease modifying in osteoarthritis (OA), though there has been debate that some may be chondroprotective and others chondrodestructive. We performed a case control study comparing NSAID use in subjects with hip or knee OA who had been treated surgically vs. medically. The purpose was to determine the relationship between NSAIDs and OA severity and if NSAIDs had a chondroprotective or chondrodestructive effect in our cohort. MATERIAL/METHODS: The study population was subjects who were referred to orthopedic surgeons or rheumatologists and had no inflammatory arthritis or secondary OA. A questionnaire was mailed asking about current/ever use of specific NSAIDs. Between groups analyses were conducted for surgically treated cases vs. medically treated controls with mild, moderate and severe OA. RESULTS: Of 618 subjects, 73 had radiographic mild, 133 moderate and 412 severe OA. Surgically treated cases were less likely to have taken any NSAID (OR 0.44, 95% CI [0.23, 0.81], p or = 3 NSAIDs being taken in those with mild vs severe OA (OR 3.7), mild vs moderate OA (OR 2.5), and moderate vs severe OA (OR 1.5), all with p or = 2 NSAIDs, p<0.0002. CONCLUSIONS: NSAID use and number of NSAIDs taken was greater in mild radiographic OA. We cannot support that some NSAIDs have negative cartilage effects from this study, and in fact, most NSAIDs were used in patients with less severe radiographic OA of the hip or knee.