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Biomedical subjects

Dafna D Gladman

Publications and source records attributed to Dafna D Gladman.

At least 19 recordsLinked to original sources
PubMed2006

Atherosclerotic vascular events in a single large lupus cohort: prevalence and risk factors.

OBJECTIVE: To determine prevalence and type of atherosclerotic vascular events (AVE) occurring after entry to the University of Toronto Lupus Clinic; and to compare risk factors in patients with systemic lupus erythematosus (SLE) with AVE to matched SLE controls without AVE. METHODS: Patients with SLE attending the University of Toronto Lupus Clinic who did not have AVE prior to clinic entry were included. Patients have been followed at 2-6 months since 1970 according to a standard protocol. Cases with AVE were matched for sex, era at first clinic visit (1970s, 1980s, 1990s +), inception status, age at first visit, and duration of followup. Chi-square, Fisher's exact, paired T test, and McNemar test were used. Comparison of risk factors for the development of AVE was done using a stepwise conditional logistic regression model for matched pairs. RESULTS: In a total cohort of 1087 SLE patients followed from 1970 until 2004, the prevalence of AVE was 10.9%, and in 561 inception patients it was 9.6%. In multivariate analyses, neuropsychiatric involvement was significantly associated with AVE in both the total and inception cohorts. Smoking was also associated with AVE in the inception cohort, whereas the number of coronary artery disease (CAD) risk factors and vasculitis were significant in the total cohort. CONCLUSION: AVE are major contributors to the clinical presentation of late-stage lupus. A combination of lupus related factors and classic CAD risk factors contributed to the development of AVE.

Adult↗
PubMed2006

The effect of menopause on disease activity in systemic lupus erythematosus.

OBJECTIVE: To determine the effect of menopause on disease activity and course of systemic lupus erythematosus (SLE). METHODS: Patients were identified from the University of Toronto lupus clinic database. Menopause was diagnosed on the basis of 12 months of amenorrhea. A 3 part study was carried out. Part 1 included an inception cohort of 190 women with SLE diagnosed in the premenopausal years (Group A) and an inception cohort of 55 women with SLE diagnosed in the postmenopausal years (Group B), both followed for a minimum of 3 years. Part 2 included 49 patients followed in the clinic for at least 3 years before and 3 years after their menopause (Group C). Part 3 included 193 patients followed for 6 years entirely in the premenopausal period (Group D) and 76 patients followed for 6 years entirely in the postmenopausal period (Group E). Disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the adjusted mean SLEDAI-2K (AMS). Damage was assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index. Comparisons were made using t-tests and chi-square and McNemar tests. A multivariate linear regression model was used to establish the impact of menopausal status on change in disease related features. RESULTS: In the first 3 years of disease, AMS was higher in Group A than Group B (6.6 +/- 3.8 vs 5.0 +/- 3.3, p = 0.003). Damage accrual was higher in Group B than in Group A both in the first year and at 3 years. For Group C, AMS and the number of flares per 3 year interval were lower in the postmenopausal period. SLICC/ACR damage index was greater during the 3 years in the postmenopausal period then in the premenopause (p = 0.006). SLEDAI-2K was higher among Group D than Group E at the start of the study (6.71 vs 4.86, p = 0.04). AMS for the 6 years was higher in the premenopausal than postmenopausal women (5.14 vs 3.54, p </= 0.0001), however, the magnitude of change in the first and second 3 year periods was not different between Group D and E. The 3 year AMS of patients in Groups C, D, and E was plotted by age and menopausal status. The slopes of AMS in the pre- and postmenopausal periods were identical, indicating that time and not menopausal status is associated with the decrease in disease activity. On the other hand, SLICC damage index showed a greater damage in postmenopausal women at any of the time points of the study. To further delineate the effect of menopausal status on changes in disease activity and damage, multiple linear regressions were performed including age at diagnosis, disease duration, and SLEDAI-2K at presentation as independent variables. No changes in AMS, number of flares, or SLICC/ACR damage index score were associated with the menopausal status. CONCLUSION: Although premenopausal women with SLE have more disease activity than postmenopausal women with SLE, we have shown that there is a constant rate of improvement over time, be it in the premenopause, across the menopause, or postmenopause. This improvement is not due to change in menopausal status. Thus clinicians should not be anticipating the postmenopausal era in a patient's course as a period of natural disease improvement.

Adult↗
PubMed2006

Predictors for radiological damage in psoriatic arthritis: results from a single centre.

BACKGROUND: The predictors for the development of clinical damage in psoriatic arthritis (PsA) have been reported previously. AIM: To identify predictors for radiological damage in PsA. METHODS: Patients followed-up prospectively according to a standard protocol at The University of Toronto between 1978 and 2004 were included. The principal outcome was the change in the number of damaged joints between visits, both clinically and radiologically. Explanatory variables considered included: sex, age, duration of arthritis at first visit, time in clinic, number of tender swollen joints, functional class, erythrocyte sedimentation rate (ESR), concentration of drugs and, to adjust for within-patient correlation, the number of clinically damaged joints at the first of the two visits over which change was observed. RESULTS: At the time of this analysis, 625 patients were recorded in the database. Multivariate analyses of predictors for both clinical and radiological damage show that age, time in clinic, initial ESR, number of tender and swollen joints at previous visit, and number of deformed joints at previous visit were related to both clinical and radiological damage. CONCLUSIONS: The number of actively inflamed joints, particularly the number of swollen joints, was associated with the progression of radiological damage. The higher the number of previously damaged joints, the higher the risk for progression of damage. Thus, patients with PsA need to be treated, even in the presence of damage as long as there is evidence of inflammation, to prevent the progression of damage.

Adolescent↗
PubMed2006

Ethnic variation in disease patterns and health outcomes in systemic lupus erythematosus.

OBJECTIVE: In a single-center multiethnic lupus cohort, to investigate the influence of ethnicity on the prevalence of cumulative renal and central nervous system (CNS) lupus disease and damage, overall end-organ damage, and mortality. METHODS: Clinical features, end-organ damage, and mortality were compared by ethnic origin among patients at a lupus clinic followed prospectively in a longitudinal design over a 32-year period. Statistical analysis to compare demographic features, cumulative disease manifestations, and damage included chi-square test as well as linear, logistic, and Poisson regressions adjusting for disease duration, age at diagnosis, and presence of dialysis and hypertension. Kaplan-Meier and proportional hazard analyses were performed to compare survival. RESULTS: There were a total of 1017 patients: 853 Caucasian, 88 African-Canadian, and 76 Chinese-Canadian. Age at diagnosis was younger and disease duration was shorter for Chinese-Canadians compared to Caucasians, but similar between African-Canadians and Caucasians. There was no significant difference in CNS disease, comparing Caucasians to Chinese-Canadians. However, CNS disease was greater in African-Canadians than Chinese-Canadians. There was no significant difference between ethnic groups in CNS damage. Renal disease was more common in African-Canadians than Caucasians, with no significant difference between Caucasian and Chinese-Canadian patients. Renal damage was more common in African-Canadians and Chinese-Canadians than Caucasians. There was no significant difference in mortality among the 3 ethnic groups. CONCLUSION: In this single referral center cohort study, there was no significant difference in CNS damage or mortality among the 3 ethnic groups. African-Canadians had a higher prevalence of renal disease and damage. Further investigation into other determinants such as genetic predisposition, treatment, and cultural perceptions is needed.

Adolescent↗
PubMed2006

Anti-dsDNA antibody testing by Farr and ELISA techniques is not equivalent.

OBJECTIVE: To determine the degree of correlation between Farr and ELISA methods of detecting anti-dsDNA antibodies in patients with systemic lupus erythematosus (SLE), and their association with measures of disease activity. METHODS: Anti-dsDNA antibodies were assayed using the Farr and ELISA methods in patients followed between January 1, 2000, and December 31, 2002. Statistical correlations between Farr and ELISA were determined. Relationships between the 2 assays and measures of disease activity [SLE Disease Activity Index 2000 (SLEDAI-2K-DNA), renal, central nervous system (CNS), and vasculitis] were determined for the same clinic visit. RESULTS: 550 patients with 2940 clinic visits met the inclusion criteria. Correlation between Farr and ELISA levels was 0.46 using the first visit for each patient. When the Farr was abnormal, the ELISA was equally likely to be normal or abnormal. Abnormal Farr results were associated with higher SLEDAI-2K scores than normal Farr results (6.2 vs 4.3, respectively; p < 0.0001). There was less of a distinction with ELISA results (5.9 vs 4.8; p = 0.04). Farr levels were significantly associated with the presence of renal disease and vasculitis, while ELISA levels were not. Neither Farr nor ELISA results correlated with the presence of active CNS involvement. CONCLUSION: Farr and ELISA techniques for the detection of anti-dsDNA antibodies in patients with SLE are poorly correlated. The Farr is superior to the ELISA in correlating with measures of global disease activity, as well as renal and vasculitis involvement. The Farr technique should continue to be used in clinical practice. The ELISA adds no additional information.

Adolescent↗
PubMed2006

Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis.

OBJECTIVE: Autoantibodies that bind citrullinated antigens are a sensitive and specific marker for rheumatoid arthritis (RA). While synthetic cyclic citrullinated peptides (CCP) are typically used to identify these antibodies, little is known about antibody reactivity to the predominant citrullinated protein found in the inflamed synovium, citrullinated fibrinogen (CitFib). We assessed the prevalence of anti-CitFib antibodies in patients with various rheumatic diseases. METHODS: In total, 65 patients with established RA and 63 patients with other rheumatic diseases were tested for serum IgM rheumatoid factor (RF), IgG anti-CCP2, and IgG anti-CitFib antibodies. This cohort was used to determine optimal positive cutoff values for antibody reactivity to CitFib through receiver operating characteristic curve analysis. The specificity of these assays was confirmed with sera from 49 patients with psoriatic arthritis. RESULTS: Antibodies to both citrullinated antigens were identified in the majority of RA patients tested. The overall sensitivity and specificity of the assays were: CCP 82%, 96%, CitFib 75%, 98%, and IgM RF 80%, 64%, respectively. All but one patient that was positive for CitFib was also positive for CCP2, and close to half the RF-negative RA patients were positive for CitFib and CCP2. CONCLUSION: These results suggest that autoimmunity to CitFib is common in patients with RA and may play a role in disease pathogenesis.

Adult↗
PubMed2006

Association of the IL1 gene cluster with susceptibility to ankylosing spondylitis: an analysis of three Canadian populations.

OBJECTIVE: To examine the association between the IL1 gene cluster and susceptibility to ankylosing spondylitis (AS) in 3 independent case-control cohorts. METHODS: We analyzed 394 patients and 446 controls from Alberta, Newfoundland, and Toronto, Canada. Samples were genotyped using a panel of 38 single-nucleotide polymorphism (SNP) markers within the IL1 gene cluster. Data from 20 informative and nonredundant SNP markers were analyzed using several association test strategies. First, we used the program WHAP to identify single-marker associations. Second, we used WHAP to analyze "sliding windows" of 3 contiguous markers along the entire extent of the IL1 gene cluster in order to identify haplotypic associations. Third, we used the linkage disequilibrium mapping program DMLE to estimate the posterior probability distribution of a disease locus. RESULTS: A total of 14 SNP markers showed significant single-locus disease associations, the most significant being rs3783526 (IL1A) (P = 0.0009 in the Alberta cohort, P = 0.04 in the Newfoundland cohort) and rs1143627 (IL1B) (P = 0.0005 in the Alberta cohort, P = 0.02 in the Newfoundland cohort). Analysis of 3-marker sliding windows revealed significant and consistent associations with all of the haplotypes in the IL1A and IL1B loci in the Alberta cohort and with IL1B in the Newfoundland cohort, especially haplotypes rs1143634/rs1143630/rs3917356 and rs1143630/rs3917356/rs3917354 (P = 0.006-0.0001). With DMLE, a strong peak in the probability distribution was estimated near IL1A in both the Alberta and the Newfoundland populations. CONCLUSION: These results indicate that the IL1 locus, or a locus close to IL1, is associated with susceptibility to AS.

Adult↗
PubMed2006

Alefacept in combination with methotrexate for the treatment of psoriatic arthritis: results of a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of alefacept in combination with methotrexate (MTX) for the treatment of psoriatic arthritis (PsA). METHODS: Patients were eligible for this randomized, double-blind, placebo-controlled trial if they were ages 18-70 years and had active PsA (> or = 3 swollen joints and > or = 3 tender joints) despite treatment with MTX for > or = 3 months (a stable dosage for > or = 4 weeks prior to enrollment). Patients were stratified according to psoriasis body surface area (BSA) involvement (> or = 3% or < 3%). Alefacept (15 mg) or placebo was administered intramuscularly once weekly for 12 weeks in combination with MTX, followed by 12 weeks of observation during which only MTX treatment was continued. The primary efficacy end point was the proportion of patients achieving a 20% improvement in disease activity according to the American College of Rheumatology criteria (an ACR20 response) at week 24. RESULTS: One hundred eighty-five patients were randomly assigned to receive alefacept plus MTX (n = 123) or placebo plus MTX (n = 62). At week 24, 54% of patients in the alefacept plus MTX group achieved an ACR20 response, compared with 23% of patients in the placebo plus MTX group (P < 0.001). Mean reductions in tender and swollen joint counts in patients receiving alefacept plus MTX were -8.0 and -6.3, respectively. In patients with psoriasis involving > or = 3% BSA (n = 87), a 50% reduction from the baseline Psoriasis Area Severity Index at week 14 was achieved by 53% of patients receiving alefacept plus MTX compared with 17% of those receiving placebo plus MTX (P < 0.001). Most adverse events were mild to moderate in severity. In the alefacept plus MTX group, the incidence of serious adverse events was low (1.6%), and no opportunistic infections or malignancies were reported. CONCLUSION: Alefacept in combination with MTX may be an effective and safe treatment for PsA.

Adult↗
PubMed2006

Fatigue in systemic lupus erythematosus: contributions of disordered sleep, sleepiness, and depression.

OBJECTIVE: To clarify the role of sleep disorders, sleepiness, and depression in patients with systemic lupus erythematosus (SLE) who complain of disabling tiredness. METHODS: Patients with SLE (31 women, 4 men) with disabling tiredness were evaluated with the Epworth Sleepiness Scale (ESS) and overnight polysomnography, followed by daytime multiple sleep latency tests (MSLT) and the Beck Depression Inventory (BDI). Their polysomnography was compared with 17 healthy, asymptomatic controls. RESULTS: Polysomnography of the patients in comparison with healthy controls showed impaired sleep efficiency (p < 0.02), high arousal frequencies (p < 0.01), increased stage 1 sleep (p < 0.02), decreased stage 3/4 slow-wave sleep (p < 0.02), and a high percentage (77% of patients) with increased alpha-EEG non-REM sleep. In 23% of patients periodic limb movement (PLM) disorder was observed (mean PLM index 31.1 +/- 15); 26% of patients had obstructive sleep apnea (mean apnea/hypopnea index 19.3 +/- 10), and one patient had narcolepsy-cataplexy. Remarkably, 51% of patients were excessively sleepy on both the ESS and MSLT (mean sleep latency < 10 min). This excessive daytime sleepiness was not related to sleep restriction. There was no association between sleepiness and SLE disease features such as neuropsychiatric SLE, medications, fibromyalgia, or disease activity. As a whole, the study group reported mild to moderate depression (mean BDI = 15.8 +/- 9.9). Within the group, the sleepy patients had lower BDI scores than the non-sleepy patients (p < 0.02), and fewer of the sleepy patients were depressed (p < 0.04). CONCLUSION: Primary sleep disorders, sleepiness, and depression are common in tired SLE patients. Tiredness in SLE that is the result of excessive daytime sleepiness can be distinguished from tiredness of depression. Such distinctions will help identify appropriate treatment for tired patients with SLE.

Adult↗
PubMed2005

Description and prediction of physical functional disability in psoriatic arthritis: a longitudinal analysis using a Markov model approach.

OBJECTIVE: To describe the longitudinal course of physical functioning in patients with psoriatic arthritis. METHODS: Between June 1993 and June 2003, 341 patients attending the University of Toronto Psoriatic Arthritis Clinic completed 2 or more Health Assessment Questionnaires (HAQs). At the time of administration of each HAQ, patients were assigned to 1 of 3 physical functional disability states, based on their HAQ score. A Markov model that allowed for transitions to and from these 3 disability states was used to characterize the longitudinal course of physical functioning, as well as to identify factors for both progression and regression of disability. RESULTS: Despite patient variability in the course of physical functioning, the following 3 longitudinal patterns were observed: 1) a stable state of disability throughout the entire study period, with 28%, 12%, and 6% of patients experiencing no, moderate, or severe disability, respectively; 2) a steady improvement or deterioration in disability over time (this pattern was observed in 27% of patients); and 3) a fluctuating state of disability, occurring in 27% of the patients. Sex, age, disease duration, number of actively inflamed joints, and number of deformed joints predicted transitions between disability states. CONCLUSION: Although 28% of patients appeared resistant to becoming disabled over the duration of this study, the remaining patients were observed either to experience enduring disability or to move between disability states.

Arthritis, Psoriatic↗
PubMed2005

Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody, was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis (PsA). METHODS: Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks. Study visits were at baseline, weeks 2 and 4, and every 4 weeks thereafter. The primary efficacy end points were the American College of Rheumatology 20% improvement (ACR20) response at week 12 and the change in the modified total Sharp score of structural damage at week 24. Secondary end points were measures of joint disease, disability, and quality of life in all patients, as well as the severity of skin disease in those patients with psoriasis involving at least 3% of body surface area. RESULTS: At week 12, 58% of the adalimumab-treated patients (87 of 151) achieved an ACR20 response, compared with 14% of the placebo-treated patients (23 of 162) (P < 0.001). At week 24, similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo (P < 0.001). Among the 69 adalimumab-treated patients evaluated with the Psoriasis Area and Severity Index (PASI), 59% achieved a 75% PASI improvement response at 24 weeks, compared with 1% of the 69 placebo-treated patients evaluated (P < 0.001). Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo. Adalimumab was generally safe and well-tolerated. CONCLUSION: Adalimumab significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active PsA.

Adalimumab↗
PubMed2005

Epidemiology of psoriatic arthritis in the population of the United States.

BACKGROUND: Estimates of the prevalence of psoriatic arthritis vary widely and are usually not determined by population-based studies. OBJECTIVES: We sought to determine the prevalence of psoriatic arthritis and the impact of the disease on quality of life in the US population. METHODS: Patients were selected randomly from the US population and were interviewed by telephone. Cases were defined as patients who reported a physician diagnosis of psoriasis and psoriatic arthritis. RESULTS: Interviews of 27,220 persons were conducted; 601 of the interviewees had psoriasis and 71 had psoriasis and psoriatic arthritis. The prevalence of psoriatic arthritis was 0.25% (95% confidence interval [CI]: 0.18%, 0.31%). The prevalence of psoriatic arthritis among patients with psoriasis was 11% (95% CI: 9%, 14%) and varied substantially based on self-reporting of the extent of skin involvement with psoriasis. Thirty-nine percent of patients with psoriatic arthritis indicated that it was a large problem in everyday life. LIMITATIONS: Psoriatic arthritis was classified on the basis of the patient's self-report. CONCLUSION: Psoriatic arthritis affects an estimated 520,000 patients in the US population, and many rate it as a large problem in everyday life. The prevalence varies widely based on the extent of skin involvement, which demonstrates the importance of performing broadly representative studies to measure the prevalence of psoriatic arthritis.

Adult↗
PubMed2005

Premature atherosclerosis in systemic lupus erythematosus.

Significant advances have been made in defining the spectrum of clinical manifestations and the prognosis of systemic lupus erythematosus (SLE). With the use of corticosteroids and other immunosuppressive agents as well as better management of complications such as infection, there has been a dramatic improvement in the short-term prognosis of patients who have SLE from less than 50% survival at 5 years to 93% at 5 years and 85% and 10 years. However, many patients who survive early complications of organ failure and sepsis later develop premature coronary artery disease (CAD). In this evidence-based review, the magnitude of the problem of premature atherosclerosis in SLE is defined and evaluation of the strength of association of risk factors determined to date. The authors focus on the emerging role of new modalities for noninvasive assessment of vascular health in patients who have SLE and offer a strategy for screening and management of those at risk of CAD. The article concludes with a discussion on the important questions that remain to be answered and future directions for research.

Arteriosclerosis↗
PubMed2005

Traditional and newer therapeutic options for psoriatic arthritis: an evidence-based review.

Psoriatic arthritis (PsA) is a destructive form of inflammatory arthritis that occurs in about one-third of patients with psoriasis. The pathogenesis of PsA includes genetic and immunological factors. A review of the currently available therapies reveals that traditional disease-modifying medications have provided only marginal relief from joint inflammation in patients with PsA, and have not been successful in controlling the disease and preventing joint damage. On the basis of current understanding of the pathogenesis of joint destruction in PsA, several new medications have been introduced, including anti-tumour necrosis factor (TNF) agents and agents that interfere with T-cell function. Most of these medications have been found to be effective in both psoriasis and PsA. Recent randomised controlled trials suggest that at least anti-TNF agents may help prevent progression of joint destruction.

Antirheumatic Agents↗