Deborah Danoff

A Long-Term Study of Hydroxychloroquine Withdrawal on Exacerbations in Systemic Lupus Erythematosus

The ability of antimalarials to moderate severe disease activity in systemic lupus erythematosus (SLE) is plausible but undemonstrated. We evaluated the long-term effectiveness of maintaining treatment with hydroxychloroquine sulphate (HCQ) to prevent major flares in quiescent SLE. Forty-seven patients with quiescent SLE who had been randomized to take HCQ (n = 25) or placebo (n = 22) as part of a 24-week withdrawal trial were evaluated for an additional 3 years. The primary outcome was time to a major flare of SLE which resulted in either the institution of or an increase in the current dosage of prednisone of 10 mg/day or more, or institution of therapy with immunosuppressive agents. Secondary outcomes included the specific subtype of these major flares (glomerulonephritis, vasculitis or other) and hospitalization for an exacerbation of SLE. An intent-to-treat analysis was conducted. Over the 42 months of study, 11 of 22 (50%) patients randomized initially to placebo, and seven of 25 (28%) patients randomized to continue treatment experienced a major flare. The relative risk of major flare for those randomized to continue HCQ compared with controls was 0.43 (95% CI: 0.17, 1.12). The relative risks for subtypes of flares were 0.26 (95% CI: 0.03, 2.54) for nephritis, 0.51 (95% CI: 0.09, 3.08) for vasculitis and 0.65 (95% CI: 0.17, 2.41) for flares characterized by other symptoms. The relative risk of hospitalization for major flare for patients randomized to continue hydroxychloroquine was 0.58 (95% CI: 0.13, 2.60). While the results are not statistically significant, they are compatible with the clinical belief that HCQ has a long-term protective effect against major disease flares in SLE and suggest that on average, HCQ use reduces major flares by 57% (95% CI: 83% reduction to 12% increase).

The role of stress in functional disability among women with systemic lupus erythematosus: a prospective study.

OBJECTIVE In the last decade, the biopsychosocial approach has been applied to systemic lupus erythematosus (SLE) to understand the multiple factors involved in the disease course. This study examined the link between stress and changes in functional disability as assessed by the Stanford Health Assessment Questionnaire (HAQ) in women with SLE. METHODS Forty-two women with SLE were assessed at baseline and 8 months later. Major stress (Life Events), minor stressors (Hassles), depression (Beck Depression Inventory), disease activity (Systemic Lupus Activity Measure), and functional disability were collected at both time points, while demographic and disease damage variables (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were collected once at baseline. RESULTS Mean HAQ scores at baseline (0.52) and followup (0.46) indicated mild disability and remained fairly stable, although individual variation was observed (mean change -0.07; range -1.25-0.5). Demographic (age, education) and disease (duration, activity, damage) variables were not related to 8-month changes on the HAQ. Of the baseline stress measures, greater negative life events in the preceding 6 months was correlated with reduced functional ability (r = 0.42) 8 months later. Individual changes in depressed mood over the 8-month period were correlated (r = 0.33) with changes in functional ability. Hierarchical multiple regression revealed that after controlling for baseline HAQ scores and changes in depressed mood, baseline negative life events remained a significant predictor of changes in functional ability. CONCLUSION We found that the major short-term determinants of functional disability were not demographic- or disease-related factors, but rather stress caused by negative life events. Comprehensive treatment of SLE requires management of life stress.

Wegener's Granulomatosis: Clinical Features and Outcome in 13 Patients

Thirteen patients with Wegeners granulomatosis were seen over 10.5 years. The clinical features resembled those in previously reported series, except for the increased frequency of inflammatory arthritis, which was a prominent early feature in ten patients (77%). Four (31%) of the 13 had fulminant vasculitis and died before receiving an adequate course of cytotoxic drug therapy. Two of these four had a pulmonary-renal syndrome that mimicked Goodpastures syndrome. All of the remaining nine patients (69%) achieved an initial remission with cytotoxic agents (azathioprine or cyclophosphamide), but four died in less than one year with no evidence of vasculitis at autopsy. The 56% survival rate to one year in these nine patients contrasts with an 86% to 100% survival in other series. Chronic renal failure was a prominent sequela in those who survived one year.

Content specificity and oral certification examinations

This study reports on the generalizability of different skills assessed in the oral certification examinations in Internal Medicine of the Royal College of Physicians and Surgeons of Canada. Assessments from the 1992 examination were examined prospectively to determine (i) inter‐rater reliability, (ii) correlation from morning to afternoon sessions, and (iii) overall test reliability. While inter‐rater reliability was acceptable and in the range reported from previous studies, the generalizability across sessions was very low, ranging from 0.30 to 0.47, presumably reflecting content specificity. As a consequence, the overall test reliability was low, ranging from 0.57 to 0.69. Collapsing the overall scores into three decision categories (pass, borderline, fail) lowered the test reliability still further. Strategies to resolve this problem are suggested.