Contributions of Observational Cohort Studies in Systemic Lupus Erythematosus: The University of Toronto Lupus Clinic Experience
Section snippets
Setting
The University of Toronto Lupus clinic is located at the Centre for Prognosis Studies in The Rheumatic Diseases at the Toronto Western Hospital, Toronto, Ontario. The Lupus Clinic was established in 1970 to provide care for patients who have SLE, to study clinical laboratory correlations in this disease, and to better understand long-term outcomes of the disease [3].
Assessments
To produce valid observations, it was important to standardize means of assessment of patients and the disease, and of recording
Results
Using the Lupus Clinic database, the authors have been able to make several observations with respect to clinical manifestations, clinical–laboratory correlation studies, prognosis and outcome studies, organ-specific outcome studies, risk factor studies, and therapeutic studies that have contributed new information to understanding of this disease.
Clinical observations
Based on the observations of skin manifestations of patients who have SLE in the authors' clinic, several different nail changes associated with the disease were identified [15]. The authors' description of neuropsychiatric lupus highlighted the importance of lupus headache, a severe headache unresponsive to narcotic analgesics as a manifestation of central nervous system (CNS) lupus [16] and showed that single photon emission computerized tomography scanning of the brain could identify
Prognosis/Outcome studies
In 1974, the authors first described the bimodal mortality pattern in SLE [21], showing that early mortality in SLE is associated with lupus disease activity and infection, whereas late mortality is associated with atherosclerotic complications [22]. Subsequent studies from the authors' cohort confirmed this pattern in the clinic, in postmortem studies and compared with the Ontario population [23], [24], [25].
The authors recently described a prevalence of 13.2% of arterial and venous events
Osteonecrosis (avascular necrosis)
In a study of the 744 patients recorded in the Lupus Clinic database, 95 (12.8%) were documented to have osteonecrosis [31]. The joints most commonly affected were the hips and knees, often in a bilateral distribution. Most of the patients (70.5%) had two or more joints affected, while less than a third of the patients had osteonecrosis in only one joint. Independent risk factors for the development of osteonecrosis included glucocorticosteroid use, the presence of arthritis, and the use of
Renal disease
In a study of 148 renal biopsies in patients who had SLE, the authors documented that there was frequently discordance between clinical features of renal disease and biopsy results [34]. This study showed that there were patients who had proliferative lupus nephritis who had had no evidence of clinical renal disease and that patients who had minimal renal lesion could have important clinical evidence of renal disease. These findings confirmed the necessity for renal biopsy in patients who have
Neuropsychiatric lupus
Patients who have SLE often complain of cognitive impairment, even in the absence of active disease. The authors performed neurocognitive studies in patients who had inactive SLE compared with healthy controls. Neurocognitive dysfunction was documented in 43% of SLE patients compared with 19% of healthy controls. SLEDAI greater than 10 at first presentation to the Lupus Clinic and previous vasculitis were associated with neurocognitive dysfunction, but previous CNS disease, renal disease, renal
Clinical laboratory correlation studies
A major initiative in the establishment of the University of Toronto Lupus Clinic was to evaluate the relationship between clinical and laboratory features. Prevailing dogma suggested that the presence of anti-DNA antibodies predicted subsequent lupus disease activity. In 1979, the authors demonstrated that 12% of their SLE clinic cohort had serologically active but clinically quiescent disease [41]. This was confirmed by a larger study [42].
The authors further identified another group of SLE
Therapeutic trials where randomized controlled trials are difficult or unethical
The authors sought to identify the effect of hormone replacement therapy in SLE. In a nested case control study, they were able to demonstrate that hormone replacement therapy was not associated with increased risk of flares in patients who had SLE [44].
To investigate the clinical observation that smoking cessation led to improvement in refractory cutaneous lupus, the authors performed a retrospective cohort study from the University of Toronto Lupus Clinic. Patients who had either acute
Discussion
In the past, observational cohort studies typically used historical controls or administrative databases. Recent longitudinal observational cohort studies use appropriate Clinimetrics as defined by Feinstein through consistent, reproducible processes of observation and expression [2]. Based on rigorous definition of case ascertainment, clinical observation, and recording, the data included in these observational cohorts are valid. The analytic approach to this data uses modern principles of
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