Dimethyl fumarate-induced lymphocyte count drop is related to clinical effectiveness in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Dimethyl fumarate (DMF) causes a mean lymphocyte count drop of approximately 30% in relapsing-remitting multiple sclerosis (RRMS) patients. The relationship between this reduction and DMF effectiveness is controversial. The objective was to investigate if the decrease in absolute lymphocyte count (ALC) from baseline during DMF treatment is associated with clinical and magnetic resonance imaging (MRI) disease activity. A secondary aim was to evaluate ALC variations over time in a real-life cohort of DMF-treated patients. METHODS: Demographic, laboratory, clinical and MRI data were collected in this observational multicentre study, conducted on RRMS patients treated with DMF for at least 6 months. Multivariate Cox models were performed to evaluate the impact of 6-month ALC drop on time to no evidence of disease activity (NEDA-3) status loss. NEDA-3 is defined as absence of clinical relapses, MRI disease activity and confirmed disability progression. RESULTS: In all, 476 patients (312 females, age at DMF start 38.4 ± 9.97 years) were analysed up to 5-year follow-up. A greater lymphocyte decrease was associated with a lower risk of NEDA-3 status loss (hazard ratio 0.87, P = 0.01). A worse outcome in patients with lower ALC drop (<11.5%), compared with higher tertiles (11.5%-40.5% and >40.5%), was observed (P = 0.008). The nadir of ALC drop (-33.6%) and 35% of grade III lymphopaenia cases occurred after 12 months of treatment. CONCLUSION: A higher lymphocyte count drop at 6 months is related to better outcomes in DMF-treated patients. A careful ALC monitoring should be pursued up to 24 months of treatment.

COVID-19 mortality and health-care resources: Organization / Mortalidad de COVID-19 y recursos sanitarios: organización

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Post-stroke rehabilitation in Italy: inconsistencies across regional strategies.

BACKGROUND: Remarkable differences among European countries have been found in stroke rehabilitation models, owing to the fact that stroke rehabilitation services are embedded in health care systems. Comprehensive data on service utilization by stroke survivors in Italy are lacking, but would be instrumental in improving efficiency and effectiveness of post-acute stroke care, and consequently, in containing costs and improving outcomes. AIM: The purpose of the present study was to survey the Italian regional legislations in order to examine the provision of rehabilitation services for stroke survivors in Italy. DESIGN: This is a cross-sectional, observational study. SETTING: Post-stroke intra- and extra-hospital rehabilitation. POPULATION: All decrees and resolutions as to post-acute stroke rehabilitation were collected from each Italian region. METHOD: All decrees and resolutions were examined by the means of a check list including quantitative and qualitative characteristics, selected in accordance with national official recommendations. Each completed check list was then sent to each regional reference person, who filled in the section on the implementation of the indications and compliance. RESULTS: The study was carried out from November 2009 to September 2010. The documents were collected from 19 out of the 20 Italian regions. The results of the study indicate that there are many, remarkable regional variations in health policies concerning post-stroke care. Instruments for evaluation and criteria for allocating stroke patients to proper rehabilitation setting vary across regions, but data on the potential impact of these variations on clinical outcomes are still lacking. CONCLUSION: The study highlights the issue that, in Italy, delivery of post-stroke rehabilitation services is not uniform nation-wide and varies substantially across regions. The lack of a comprehensive post-acute stroke strategy is a major obstacle to service availability. CLINICAL REHABILITATION IMPACT: The study results advocate the need for a consistent and comprehensive strategic planning of post-stroke rehabilitation in Italy.

Updating on Italian stroke units: the "CCM study".

The stroke units (SUs) have been demonstrated to be efficient and cost effective for acute stroke care. Nevertheless, the level of stroke unit implementation in Italy does not correspond to expectations yet. This study is a survey, which aims at assessing the current status of in-hospital stroke care in the Italian regions and at updating SUs. The survey was conducted by means of a semi-structured questionnaire, based on 18 stroke care "quality indicators", submitted to all the Italian centres that had taken part in the SITS-MOST study, and to other centres advised by the coordinator of SITS studies and by regional opinion leaders of stroke. SUs were defined as acute wards, with stroke-dedicated beds and dedicated teams that had been formally authorised to administer rt-PA. A statistical analysis was performed by a descriptive statistics and logistic regression model. The study was carried out from November 2009 to September 2010. A total of 168 forms were sent out and 153 replies received. Seven centres, which had not performed any thrombolytic treatment, and 16 which did not fulfil the criteria for the definition of SU were excluded from the study. Most of the centres reported more than 100 stroke patient admissions per year, i.e., 122 (84%) from 100 to 500, 18 (12%) more than 500. The 19% of the centres admitted more than 30% of patients within 3 h from the symptom onset and only 30% admitted more than 30% of patients within 4.5 h. The mean number of thrombolyses performed in the last 6 months was 10 for centres with a doctor on duty 24 h a day, 6 for those that have a doctor on duty from 8 a.m. to 8 p.m. and a doctor on call for night, and 5 for centres with a doctor on call 24 h a day. The territorial distribution of the SUs is remarkably heterogeneous: 87 SUs (67%) are located in the North of Italy, 28 (22%) in the central part of Italy and only 15 (11%) in the South. The last few years have witnessed a rise in both the diffusion of SUs and access to thrombolytic therapy in Italy. Despite this, there are a few large areas, mostly in the south, where the requirements of healthcare legislation are not met, and access to a dedicated SU and thrombolytic treatment is still limited and poor.

Immunomodulatory effects of IFN-beta1a treatment alone or associated with pentoxifylline in patients with relapsing-remitting multiple sclerosis (RRMS).

Interferon-beta1a (IFN-beta1a) and pentoxifylline (PTX) are reported to be active in relapsing-remitting multiple sclerosis (RRMS), but the mechanisms are not completely understood. In two groups of RRMS patients, we studied the phenotype of peripheral lymphocytes and the level of several cytokines both in sera and in supernatants of activated peripheral blood mononuclear cells (PBMC) before and after 8 months of therapy with IFN-beta1a alone or associated with PTX. Our data indicate that patients with RRMS, treated with IFN-beta1a, exhibited a significant increase in CD4(+)CD25(++) T suppressor cells, accompanied by a significant decrease in cytotoxic lymphocytes (CD8(+)CD28(-) and natural killer [NK] cells) and IFN-gamma production, which could both contribute to an explanation of the previously described beneficial effects of IFN-beta treatment in MS. The addition of PTX to IFN-beta1a treatment did not modify the immunomodulatory effects obtained with IFN-beta1a alone. Future studies are needed to demonstrate which immunologic parameters correlate with the clinical benefit of IFN-beta1a treatment.

History of migraine and the risk of spontaneous cervical artery dissection.

The pathophysiology of spontaneous cervical artery dissection (sCAD) is largely unknown. An association with migraine has been suggested, but not definitively proven. In the setting of a hospital-based prospective case-control study we assessed personal and family history of migraine in 72 patients with sCAD, 72 patients with cerebral infarct unrelated to a CAD (non-CAD) and 72 control subjects. Personal history of migraine was significantly associated to sCAD compared to non-CAD (59.7% vs. 30.6%; OR 3.14; 95% CI 1.41-7.01) and controls (18.1%; OR 7.41; 95% CI 3.11-17.64). As opposed to migraine with aura, migraine without aura was significantly more frequent among sCAD than among non-CAD (56.9% vs. 25.0%; OR 3.91; 95% CI 1.71-8.90) and controls (12.5%; OR 9.84; 95% CI 3.85-25.16). Similar results were observed when the frequencies of family history of migraine were compared. These findings are consistent with the hypothesis that migraine may represent a predisposing condition for sCAD.