A slower rate of progression of disease characterized EOMS patients, suggesting more plasticity to recover in developing CNS, but the early clinical manifestation cannot be considered a positive prognostic factor.

Objective:To investigate the impact of interferon-beta (IFN␤) on disease progression in relapsing-remitting multiple sclerosis patients. Methods: A cohort of 1,504 relapsing-remitting multiple sclerosis (1,103 IFN␤-treated and 401 untreated) patients was followed for up to 7 years. Cox proportional hazards regression adjusted for propensity score inverse weighting was used to assess the differences between the two groups for three different clinical end points: secondary progression (SP) and irreversible Expanded Disability Status Scale (EDSS) scores 4 and 6. Times from first visit and from date of birth were used as survival time variables. Results: The IFN␤-treated group showed a highly significant reduction in the incidence of SP (hazard ratio [HR], 0.38, 95% confidence interval [CI], 0.24 -0.58 for time from 1st visit; HR, 0.36, 95% CI, 0.23-0.56 for time from date of birth; p Ͻ 0.0001), EDSS score of 4 (HR, 0.70, 95% CI, 0.53-0.94 for time from first visit; HR, 0.69, 95% CI, 0.52-0.93 for time from date of birth; p Ͻ 0.02), and EDSS score of 6 (HR, 0.60, 95% CI, 0.38 -0.95 for time from first visit; HR, 0.54, 95% CI, 0.34 -0.86 for time from date of birth; p Յ 0.03) when compared with untreated patients. SP and EDSS scores of 4 and 6 were reached with significant delays estimated by times from first visit (3.8, 1.7, and 2.2 years) and from date of birth (8.7, 4.6, and 11.7 years) in favor of treated patients. Sensitivity analysis confirmed findings. Interpretation: IFN-␤ slows progression in relapsing-remitting multiple sclerosis patients.Ann Neurol 2007;61: 300 -306 Few experienced in the long-term management of multiple sclerosis (MS) patients would disagree that the development of unremitting disability progression represents the major adverse event in the course of this illness, and as a consequence, it is the most important target for clinical trials to evaluate their real cost effectiveness. Whether long-term treatment with the current interferon-␤ (IFN␤) products in relapsingremitting MS (RRMS) can alter the development of long-term disability is not yet known, but it can be surmised from short-term randomized controlled trials (RCTs) 1-3 and their continuous extensions at no more than 4 years 4 and 5 years. 5 This is the stage at which immunomodulatory therapy is likely to be most effective, but then the long-term benefits on disability have to be projected from the results generated during a much earlier and briefer period in the natural disease course. Long-term RCTs would undoubtedly provide definitive evidence, but they are impractical and considered by many to be unethical. 6 More recently, further data have been collected in noncontinuous and/or retrospective, open-label extensions of the IFN␤ RCTs 7-10 ; but in these studies, the protection against bias afforded by randomization was largely lost.11 Moreover, patients enrolled in the placebo arms of RCTs do not represent the natural history of MS because they are selected for having frequent attacks during a set interval before the study....

Incidence of dementia in Italy paralleled that in most industrialized countries. About 150,000 new cases per year are expected. A significant gender effect was evidenced for major dementia subtypes. The burden of VaD, especially in men, offers opportunities for prevention.

ContextThe benefit of aspirin for the primary prevention of cardiovascular events is relatively small for individuals with and without diabetes. This benefit could easily be offset by the risk of hemorrhage.Objective To determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking aspirin. Design, Setting, and ParticipantsA population-based cohort study, using administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. Individuals with new prescriptions for low-dose aspirin (Յ300 mg) were identified during the index period from January 1, 2003, to December 31, 2008, and were propensitymatched on a 1-to-1 basis with individuals who did not take aspirin during this period.Main Outcome Measures Hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage occurring after the initiation of antiplatelet therapy.Results There were 186 425 individuals being treated with low-dose aspirin and 186 425 matched controls without aspirin use. During a median follow-up of 5.7 years, the overall incidence rate of hemorrhagic events was 5.58 (95% CI, 5.39-5.77) per 1000 person-years for aspirin users and 3.60 (95% CI, 3.48-3.72) per 1000 personyears for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48-1.63). The use of aspirin was associated with a greater risk of major bleeding in most of the subgroups investigated but not in individuals with diabetes (IRR, 1.09; 95% CI, 0.97-1.22). Irrespective of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28-1.44). ConclusionsIn a population-based cohort, aspirin use was significantly associated with an increased risk of major gastrointestinal or cerebral bleeding episodes. Patients with diabetes had a high rate of bleeding that was not independently associated with aspirin use.

Objectives-Little is known about the aetiology of idiopathic adult onset dystonia. The Italian Movement Disorders Study Group promoted a case-control study on some hypothetical risk factors including past medical events, life events, life habits, occupational hazards, and family hystory of dystonia, parkinsonism, and tremor. Methods-Cases aVected by idiopathic adult onset dystonia (age at symptom onset >20 years, duration of disease >one year and

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BackgroundA female/male (F/M) ratio increase over time in multiple sclerosis (MS) patients was demonstrated in many countries around the world. So far, a direct comparison of sex ratio time-trends among MS populations from different geographical areas was not carried out.ObjectiveIn this paper we assessed and compared sex ratio trends, over a 60-year span, in MS populations belonging to different latitudinal areas.MethodsData of a cohort of 15,996 (F = 11,290; M = 4,706) definite MS with birth years ranging from 1930 to 1989 were extracted from the international MSBase registry and the New Zealand MS database. Gender ratios were calculated by six decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the respective national registries of births.ResultsAdjusted sex ratios showed a significant increase from the first to the last decade in the whole MS sample (from 2.35 to 2.73; p = 0.03) and in the subgroups belonging to the areas between 83° N and 45° N (from 1.93 to 4.55; p<0.0001) and between 45° N to 35° N (from 1.46 to 2.30; p<0.05) latitude, while a sex ratio stability over time was found in the subgroup from areas between 12° S and 55° S latitude. The sex ratio increase mainly affected relapsing-remitting (RR) MS.ConclusionsOur results confirm a general sex ratio increase over time in RRMS and also demonstrate a latitudinal gradient of this increase. These findings add useful information for planning case-control studies aimed to explore sex-related factors responsible for MS development.

Our data from a population-based study support the hypothesis that estrogen-replacement therapy is associated with a reduced prevalence of Alzheimer's disease in postmenopausal women. Prospective clinical trials are required to enable women and their physicians to weigh risks and benefits of estrogen-replacement therapy for the prevention of dementia.