The clinical data of 309 patients with definite multiple sclerosis were recorded in the European data base for multiple sclerosis (EDMUS) to determine the prognostic significance of several demographic and clinical variables. An interview with closed questions structured according to standardised criteria of disease phases and courses was used to assess the clinical course. The reliability was evaluated by four trained neurologists in a sample of 33 patients with multiple sclerosis. Both the within and between rater agreement on data collection was fair to high for the historical variables (K = 0.33-1). Between rater agreement was more variable for the evaluation of 12 different EDMUS event categories (K = 0-3-0.95). The predictive model for the time to reach a secondary progression showed that an age at onset older than 25 (p = 0 006) and an event at onset followed by disability >i3 on the Kurtzke expanded disability status scale (EDSS; p = 0-004) were the most unfavourable clinical variables in 249 patients with relapsing remitting (180) or relapsing progressive (69) courses. In the 69 patients with relapsing progressive disease, the time to reach severe disability (EDSS > 6) was negatively influenced by a first interval between attacks shorter than one year, a number of bouts with EDSS >2 in the first two years of the dis-

There is evidence that the clinical course of multiple sclerosis is age related. The present study evaluated the relationship between age and rate of disability progression in a large hospital-based cohort of definite cases of multiple sclerosis (n= 1,463). Patients were followed every 6 to 12 months for a total period of observation of 11,387.8 person-years. Expanded Disability Status Scale scores increased significantly with increasing current age and longer duration of disease (p=0.007). Median times to reach Expanded Disability Status Scale scores of 4.0 and 6.0, assessed using an extended Kaplan-Meier method with age as a categorical time-varying covariate, were significantly longer among patients aged 20 to 35 years compared with patients aged 36 to 50 and 51 to 65 years (p < 0.0001). Significant associations were observed between mean Expanded Disability Status Scale scores and age at disease onset, current age, and the interaction of age at disease onset and current age (p < 0.001). Current age had a greater effect (59% of variability in the model) on disease severity than did age at disease onset. Furthermore, a multiplicative effect on Expanded Disability Status Scale score was observed for age at disease onset and current age combined, indicating a faster rate of disease progression in older patients. In conclusion, the results of the current study demonstrate the impact of age on rate of disability progression in multiple sclerosis and suggest that an age-adjusted progression index may be a more relevant criterion for defining differences between multiple sclerosis groups.

This independent, population-based surveillance study monitored the efficacy and safety of interferon beta (IFNbeta) products in 1033 patients with relapsing-remitting multiple sclerosis (RRMS) from 15 centres in Italy. Relapses, Expanded Disability Status Scale (EDSS) scores, and adverse events were evaluated for up to 24 months. Data of patients with a baseline EDSS score < or = 3.5 are reported. The proportions of relapse-free patients were similar among the groups at 12 and 24 months (P = 0.10). IFNbeta products produced significant reductions from baseline in relapse rates at 12 and 24 months (P < 0.001), with no differences among treatments (P = 0.2). There were no significant differences in mean EDSS change among groups at 12 or 24 months. The IFNbeta-1b group showed a higher incidence of adverse events during the first year of treatment (P < 0.05) than IFNbeta-1a groups, and more withdrawals (10%) compared with Avonex (5%) at 24 months. IFNbeta products are equally effective in low disability RRMS, but IFNbeta-1a may have a more favorable efficacy/tolerability ratio.

Lung disease and Pseudomonas aeruginosa (P. aeruginosa) airway colonization represent a major cause of morbidity and mortality in cystic fibrosis (CF). Human b-defensin (hBD)-1 is believed to play an important role in mucosal innate immunity in the lung. This study aimed to investigate whether three single-nucleotide polymorphisms (SNPs) in the 5 0 -untranslated region of DEFB1, G-52A, C-44G and G-20A were associated with P. aeruginosa airway colonization in CF. A total of 224 CF patients and 196 control subjects were studied. DEFB1 SNPs were characterized by restriction fragment length polymorphisms. Patients' sputum samples were collected and analyzed by standard methods. Single SNP analysis suggested that CF patients carrying the À52AA and the À20GG genotypes had a higher rate of P. aeruginosa airway colonization than patients homozygous and heterozygous for the À52G and À20A alleles (P ¼ 0.01 and P ¼ 0.007, respectively). A significant association between the ACG haplotype and chronic P. aeruginosa infection was also identified (odds ratio (95% confidence interval): 3.00 (1.42-6.36), P ¼ 0.004). These results indicate that variant alleles in DEFB1 might contribute to the colonization of P. aeruginosa in CF.

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