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BACKGROUND: The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment (BENEFIT) trial investigated the effect of treatment with interferon beta-1b after a clinically isolated syndrome. The 5-year active treatment extension compares the effects of early and delayed treatment with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after randomisation. Patients and study personnel remained unaware of initial treatment allocation throughout the study. Primary endpoints were time to CDMS, time to confirmed disability progression measured with the expanded disability status scale, and the functional assessment of multiple sclerosis trial outcomes index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211. FINDINGS: 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment reduced the risk of CDMS by 37% (hazard ratio [HR] 0.63, 95% CI 0.48-0.83; p=0.003) compared with delayed treatment. The risk for confirmed disability progression was not significantly lower in the early treatment group (0.76, 0.52-1.11; p=0.177). At 5 years, median FAMS-TOI scores were 125 in both groups. No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b. INTERPRETATION: Effects on the rate of conversion to CDMS and the favourable long-term safety and tolerability profile support early initiation of treatment with interferon beta-1b, although a delay in treatment by up to 2 years did not affect long-term disability outcomes. FUNDING: Bayer Schering Pharma. ispartof: The Lancet Neurology vol:8 issue:11 pages:987-997 ispartof: location:England status: published

The concentrations of sialic acid in the serum of patients with benign and malignant diseases were determined and the criteria of diagnostic validity (sensitivity, specificity, efficiency, likelihood ratio, predictive values) were calculated. The concentrations of sialic acid in sera of patients with benign diseases (median 0.826 g/l, 5. percentile 0.62 g/l, 95. percentile 1.27 g/l, p less than 0.001) and malignant diseases (median 0.90 g/l, 5. percentile 0.67 g/l, 95. percentile 1.48 g/l, p less than 0.001) were significantly higher than those in a population of healthy persons (median 0.62 g/l, 5. percentile 0.52 g/l, 95. percentile 0.78 g/l). In malignant diseases, the serum sialic acid concentrations are significantly higher (p less than 0.005) than those in benign diseases. In the group of benign diseases marked increases were seen in patients with rheumatoid arthritis and collagenoses (median 1.03 g/l) and infectious-inflammatory diseases (median 0.97 g/l). In the group of malignant diseases increases were seen in cases of gastrointestinal carcinomas (median 1.1 g/l), bladder tumours (n = 2, 1.12 g/l, 1.08 g/l) and carcinoma of the uterus (median 1.0 g/l). The sensitivity at a decision limit of 0.78 g/l for benign diseases is 0.68, for malignant diseases 0.83 and for both categories 0.71. The specificity for benign diseases is 0.94, for malignant diseases 0.32, for both categories 0.94. For benign diseases, the positive predictive values at a decision limit of 0.78 g/l are 0.55 and 0.72 (given prevalences 0.1 and 0.2, respectively); for malignant diseases, 0.11 and 0.23 (prevalences 0.1 and 0.2); for both categories 0.77 and 0.88 (prevalences of 0.1 and 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)