Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris.

BACKGROUND: The classic treatment for pemphigus vulgaris is prednisolone. Immunosuppressive drugs can be used in association. OBJECTIVE: To compare the efficacy of Azathioprine in reducing the Disease Activity Index (DAI). PATIENTS AND METHODS: A double blind randomized controlled study was conducted on 56 new patients, assigned to two therapeutic groups: (i) prednisolone plus placebo; (ii) prednisolone plus Azathioprine. Patients were checked regularly for 1 year. 'Complete remission' was defined as healing of all lesions after 12 months, and prednisolone <7.5 mg daily, (DAI ≤ 1). Analysis was done by 'Intention To Treat' (ITT) and 'Treatment Completed Analysis' (TCA). RESULTS: Both groups were similar in age, gender, disease duration, and DAI. Primary endpoint: By ITT and TCA, the mean DAI improved in both groups with no significant difference between them. The difference became significant for the last trimester (3 months; ITT: P = 0.033, TCA: P = 0.045). Secondary endpoint: The total steroid dose decreased significantly in both groups, with no significant difference between them, except for the last trimester (ITT: P = 0.011, TCA: P = 0.035). The mean daily steroid dose decreased gradually in both groups becoming statistically significant in favour of azathioprine, in the last trimester, especially at 12th months (ITT: P = 0.002, TCA: P = 0.005). Complete remission was significant at 12 months only for TCA (AZA/Control: 53.6%/39.9%, P = 0.043). LIMITATIONS: Sample size was rather small to demonstrate all differences. Other limitations include the choice of primary and secondary endpoints and the unavailability to measure thiopurine methyltransferase activity. CONCLUSION: Azathioprine helps to reduce prednisolone dose in long-run.

Multiple Imputation to Deal with Missing Clinical Data in Rheumatologic Surveys: an Application in the WHO-ILAR COPCORD Study in Iran.

BACKGROUND: The aim of the article is demonstrating an application of multiple imputation (MI) for handling missing clinical data in the setting of rheumatologic surveys using data derived from 10291 people participating in the first phase of the Community Oriented Program for Control of Rheumatic Disorders (COPCORD) in Iran. METHODS: Five data subsets were produced from the original data set. Certain demographics were selected as complete variables. In each subset, we created a univariate pattern of missingness for knee osteoarthritis status as the outcome variable (disease) using different mechanisms and percentages. The crude disease proportion and its standard error were estimated separately for each complete data set to be used as true (baseline) values for percent bias calculation. The parameters of interest were also estimated for each incomplete data subset using two approaches to deal with missing data including complete case analysis (CCA) and MI with various imputation numbers. The two approaches were compared using appropriate analysis of variance. RESULTS: With CCA, percent bias associated with missing data was 8.67 (95% CI: 7.81-9.53) for the proportion and 13.67 (95% CI: 12.60-14.74) for the standard error. However, they were 6.42 (95% CI: 5.56-7.29) and 10.04 (95% CI: 8.97-11.11), respectively using the MI method (M=15). Percent bias in estimating disease proportion and its standard error was significantly lower in missing data analysis using MI compared with CCA (P< 0.05). CONCLUSION: To estimate the prevalence of rheumatic disorders such as knee osteoarthritis, applying MI using available demographics is superior to CCA.

Squatting, sitting on the floor, or cycling: are life-long daily activities risk factors for clinical knee osteoarthritis? Stage III results of a community-based study.

OBJECTIVE: To evaluate the association between occupations, sports, life-long daily activities, and knee osteoarthritis. METHODS: In this case-control study, we randomly recruited 480 subjects with knee osteoarthritis, who had participated in the first stage of a community-based study in Tehran, and compared them with 490 controls. A questionnaire was used to record all occupations, sports, and the details of 10 daily activities. The mean +/- SD hours/day spent on these activities were calculated and compared using the lightest activity as reference. Generalized estimation equation was used with each knee as the unit of analysis. RESULTS: The mean +/- SD age and percentage of female distribution was 57 +/- 12 years, 69.8% women for cases, and 46.8 +/- 15 years, 64.1% women for controls. After adjusting for age, sex, and body mass index, 2 activities were risk factors for knee osteoarthritis: prolonged squatting (odds ratio [OR] 1.51, 95% confidence interval [95% CI] 1.12-2.04) and cycling (OR 2.06, 95% CI 1.23-3.45). Knee-bending had borderline significance (OR 1.98, 95% CI 0.98-3.99). Carrying loads (OR 1.24, 95% CI 0.87-1.76) or climbing stairs (OR 0.99, 95% CI 0.69-1.42) showed no extra risk for knee osteoarthritis. Prolonged standing, sitting on the floor, and walking up/downhill were not risks for knee osteoarthritis. Housewives were at greater risk (borderline-significant) of developing knee osteoarthritis (OR 1.68, 95% CI 0.93-3.03) than women whose main occupation was outside the home. Other types of jobs and sports did not show an extra risk of knee osteoarthritis. CONCLUSION: Our findings support the role of lifestyle in the pathogenesis of knee osteoarthritis for squatting and cycling. Education on preventable risk factors should be considered in order to ensure people use knee joints appropriately and avoid overuse.

Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet's disease.

Behçet's disease (BD) is a chronic inflammatory disease characterized by oral aphthous ulcers, genital ulcers, uveitis and skin lesions. Etiology and pathogenesis of BD are not fully elucidated, but the association with human leukocyte antigen (HLA)-B51 or B*5101 has been repeatedly reported. Previous studies have shown that there are few sequence variations in the protein-coding region of B51, while there is a report on many variations in the 5'-flanking region and intron. In this study, HLA-B*5101 gene from 37 individuals including Japanese, Turkish, Jordanian and Iranian patients and healthy controls were fully sequenced to further clarify the B*5101 gene in association with BD. We found that all the patients and healthy controls carried B*510101 with no variation in the 5'-flanking region, exon and intron. However, seven polymorphisms were found in the 3'-flanking region. These polymorphisms composed of six haplotypes that were shared and stretched over the ethnic groups, suggesting that the susceptibility to BD was conferred by the B*510101 itself and not by any genes in linkage disequilibrium with B*510101. In addition, phylogenetic analyses of B*510101 showed that the 3'-flanking sequences followed an evolutional divergence differently from that of the other regions, implying that a unifying selection might operate to conserve B*510101.

Evaluation of the effect of acetazolamide on cystoid macular oedema in patients with Behcet's disease.

AIM: To study the effect of acetazolamide on cystoid macular oedema (CMO) in patients with Behcet's disease. PATIENTS AND METHODS: A total of 67 eyes of 35 Behcet's patients with chronic, but well-controlled uveitis, and CMO were randomised into a double-masked, crossover trial comparing the effect of acetazolamide vs placebo. The patients received an initial 4-week course of either 250 mg acetazolamide twice daily (b.i.d.) or placebo, followed by a 4-week washout period. They then received a 4-week course of the reverse study medication. An improvement in visual acuity and fundus fluorescein angiographic findings was assessed. RESULTS: In total, 29 patients (55 eyes) completed the trial and were available for analysis. Of the 29, 16 men and 13 were women. The age range was 13-50 years (mean 33.6 years). Patients on acetazolamide showed a slightly better improvement of angiographic signs (at least by one grade improvement) over that of placebo (12 vs five eyes). They also had less deterioration of angiographic signs over that of placebo (three vs seven eyes). However, these findings were not statistically significant (P=0.99). Acetazolamide had no statistically significant effect (P=0.53) on the improvement of visual acuity of patients over that of placebo (13 vs eight eyes), nor on the deterioration of visual acuity (three vs 11 eyes). CONCLUSION: Despite seemingly favourable results, the 4-week course of acetazolamide (250 mg b.i.d.) has no statistically significant effect on the improvement of the visual acuity and the fluorescein angiographic findings in Behcet's patients with CMO.