Vitamin D status and COVID-19 prevention in a worker subgroup in Italy.

BACKGROUND: Low levels of vitamin D are widespread in the world's population and associated with sun exposure, genetics, and lifestyles. Office workers in different occupational sectors seem more vulnerable than others. Scientific evidence reports a contribution of vitamin D in resistance to infections, opening to supplementation as a preventive action against pathogens, including SARS-CoV-2. OBJECTIVE: A pilot campaign in the workplace during the coronavirus 2019 (COVID-19) pandemic was conducted based on the preliminary measurement of vitamin D amount and its integration. METHODS: A preventive action to contrast the deficiency of vitamin D was offered to a population of 700 bank employees. Vitamin D supplementation was performed between April and June 2021, on workers (n = 139) and showed 25(OH)D serum levels ≤ 30 ng/ml. Demographic, anthropometric and lifestyle information were collected by survey and changes in the serum 25(OH)D amounts were monitored. RESULTS: The adherence of the target population to the prevention campaign was 21%. 75% of the enrolled workers had low levels of vitamin D. After the intervention, serum vitamin D levels increased (1.28-fold;p = 0.0001) and 80% of the subjects reported optimal values > 30 ng/ml. Only 2.9% reported slight flu-like symptoms, but only 0.7% was confirmed as COVID-19, with respect to a ten-fold higher incidence in the general population. CONCLUSIONS: Vitamin D supplementation can be achieved by simple and noninvasive approaches and can bring along further insights into health literacy on diet and lifestyles, representing an opportunity to protect the population by the widespread state of vitamin deficiency.

Ethical Decision Making in Iot Data Driven Research: A Case Study of a Large-Scale Pilot.

IoT technologies generate intelligence and connectivity and develop knowledge to be used in the decision-making process. However, research that uses big data through global interconnected infrastructures, such as the 'Internet of Things' (IoT) for Active and Healthy Ageing (AHA), is fraught with several ethical concerns. A large-scale application of IoT operating in diverse piloting contexts and case studies needs to be orchestrated by a robust framework to guide ethical and sustainable decision making in respect to data management of AHA and IoT based solutions. The main objective of the current article is to present the successful completion of a collaborative multiscale research work, which addressed the complicated exercise of ethical decision making in IoT smart ecosystems for older adults. Our results reveal that among the strong enablers of the proposed ethical decision support model were the participatory and deliberative procedures complemented by a set of regulatory and non-regulatory tools to operationalize core ethical values such as transparency, trust, and fairness in real care settings for older adults and their caregivers.

The role of vitamin D in prevention OF COVID-19 and its severity: an umbrella review.

BACKGROUND AND AIM: Vitamin D is known to modulate immune response and its deficiency was associated with respiratory distress in patients hospitalized for pneumonia. Nevertheless, numerous reviews on vitamin D in COVID-19 patients have shown conflicting results, as previously reported also for other respiratory diseases (e.g., influenza). METHODS: This umbrella review aims to assess whether low serum 25-OHD is associated with susceptibility to COVID 19, their severity, and mortality. A total of 1559 studies were excluded after the title, abstract and full-text articles screening and 9 papers were included in this review: 2 systematic reviews and 7 metanalysis. RESULTS: The findings of this review that summarized studies from 5 WHO regions (European Region, Region of the Americas, South-East Asia Region, Eastern Mediterranean Region, Western Pacific Region) to exclusion only African region, show that low serum 25-OHD levels are associated with higher infection risks for COVID-19. CONCLUSIONS: Although the umbrella findings indicate a potential role of vitamin D deficiency in COVID-19 severity in hospitalized patients and showing an association between Vitamin D supplementation and COVID-19 severity, however, more robust data from randomized controlled trials are further needed to confirm a possible association with the mortality rates.

IoT-Based Home Monitoring: Supporting Practitioners' Assessment by Behavioral Analysis.

This paper introduces technical solutions devised to support the Deployment Site - Regione Emilia Romagna (DS-RER) of the ACTIVAGE project. The ACTIVAGE project aims at promoting IoT (Internet of Things)-based solutions for Active and Healthy ageing. DS-RER focuses on improving continuity of care for older adults (65+) suffering from aftereffects of a stroke event. A Wireless Sensor Kit based on Wi-Fi connectivity was suitably engineered and realized to monitor behavioral aspects, possibly relevant to health and wellbeing assessment. This includes bed/rests patterns, toilet usage, room presence and many others. Besides hardware design and validation, cloud-based analytics services are introduced, suitable for automatic extraction of relevant information (trends and anomalies) from raw sensor data streams. The approach is general and applicable to a wider range of use cases; however, for readability's sake, two simple cases are analyzed, related to bed and toilet usage patterns. In particular, a regression framework is introduced, suitable for detecting trends (long and short-term) and labeling anomalies. A methodology for assessing multi-modal daily behavioral profiles is introduced, based on unsupervised clustering techniques. The proposed framework has been successfully deployed at several real-users' homes, allowing for its functional validation. Clinical effectiveness will be assessed instead through a Randomized Control Trial study, currently being carried out.

First-line disease-modifying drugs in relapsing-remitting multiple sclerosis: an Italian real-life multicenter study on persistence.

OBJECTIVE: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing-remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation. METHODS: In this prospective, multi-center, real-life observational study, patients commencing any first-line DMD between 1 January 2015 and 31 July 2016 were enrolled and followed up for at least 12 months or until the drug was discontinued. RESULTS: Of the 520 included patients, 262 (49.6%) started an injectable and 258 (50.4%) an oral DMD. There was no difference in the proportion of patients on oral (n = 62, 24%) or on injectable (n = 60, 23%) DMDs discontinuing treatment, the most frequent reason being adverse events/side-effects. Higher baseline Expanded Disability Status Scale (EDSS) scores and younger age increased the odds of treatment withdrawal. Time to treatment discontinuation was not different between the two groups and was not influenced by the initiated DMD (oral versus injectable), even after adjustment for baseline differences. CONCLUSION: The route of administration alone (i.e. oral versus injectable) was not a significant predictor of persistence with first-line DMDs in RRMS.

Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial).

BACKGROUND AND PURPOSE: Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay. METHODS: According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends. RESULTS: We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60-1.08; P=0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (P=0.07). CONCLUSIONS: Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01881152.

Long-term disability progression in primary progressive multiple sclerosis: a 15-year study.

Prognostic markers of primary progressive multiple sclerosis evolution are needed. We investigated the added value of magnetic resonance imaging measures of brain and cervical cord damage in predicting long-term clinical worsening of primary progressive multiple sclerosis compared to simple clinical assessment. In 54 patients, conventional and diffusion tensor brain scans and cervical cord T1-weighted scans were acquired at baseline and after 15 months. Clinical evaluation was performed after 5 and 15 years in 49 patients. Lesion load, brain and cord atrophy, mean diffusivity and fractional anisotropy values from the brain normal-appearing white matter and grey matter were obtained. Using linear regression models, we screened the clinical and imaging variables as independent predictors of 15-year disability change (measured on the expanded disability status scale). At 15 years, 90% of the patients had disability progression. Integrating clinical and imaging variables at 15 months predicted disability changes at 15 years better than clinical factors at 5 years (R2 = 61% versus R2 = 57%). The model predicted long-term disability change with a precision within one point in 38 of 49 patients (77.6%). Integration of clinical and imaging measures allows identification of primary progressive multiple sclerosis patients at risk of long-term disease progression 4 years earlier than when using clinical assessment alone.

The clinical value of Coop/Wonca charts in assessment of HRQoL in a large cohort of relapsing-remitting multiple sclerosis patients: Results of a multicenter study.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurological disease impacting patients' health-related quality of life (HRQoL). Since MS specific HRQoL questionnaire are often time consuming; thus, simple, feasible and ease administering instruments are needed to assess MS HRQoL in clinical practice and clinical trials. Hence, aim of our study was to investigated the HRQoL in a large cohort of MS patients using the Coop/Wonca charts. METHODS: This was multicenter, independent, non-sponsored, observational study, including patients from 40 Italian MS centers. Inclusion criteria were Expanded Disability Status Scale score between 1.0 and 5.5; stable disease at enrolment. HRQoL was assessed, using six Coop/Wonca charts for physical fitness, feelings, daily activities, social activities, changes in health, health condition, and the Composites Scores of Multiple Sclerosis Quality of Life-54 (MSQoL-54), physical health composite summary (PHCS) and the mental health composite summary (MHCS). RESULTS: Out of 648, 593 relapsing-remitting MS patients, 415 (70%) women, mean age years, 417 (70%) were finally enrolled. We found a inter-rater agreement of 0.8, ranging from 0.64 to 0.91, as expressed by the alpha coefficient. Intra-rater agreement was 0.82, ranging from 0.78 to 0.96. Coop/Wonca charts were scored with a Likert method from one to five (corresponding to best and worst HRQoL respectively). According to this scoring, study population was stratified into three categories (score 1-2 corresponding to better HRQoL; score 3 corresponding to neutral profile; score 4-5 corresponding to worse HRQoL). Coop/Wonca charts resulted significantly correlated with PHCS and with MHCS.

A Comprehensive Review on Copemyl®.

Economic sustainability is of paramount importance in the rapidly evolving therapeutic scenario of multiple sclerosis (MS). Glatiramoids are a class of drugs whose forefather, glatiramer acetate, has been used as a disease modifying drug (DMD) in patients with MS for over 20 years. Its patent expired in 2015; new versions of such drug are nowadays available on the market, potentially contributing to lowering prices and enhancing a better allocation of economic resources. In this review, we analyze the recommendations underlying the approval of both generic drugs and biosimilars by regulatory authorities, and we provide methodological tools to contextualize the design of studies on these new classes of drugs. We examine in more detail the preclinical and clinical data of Copemyl®, a new member of the glatiramoid class, focusing on its biological and immunological properties and illustrating randomized controlled trials that led to its authorization.

In silico pharmacogenetic approach: The natalizumab case study.

Natalizumab is a humanized monoclonal antibody to α4ß1 integrin and is approved for the treatment of Multiple Sclerosis. In patients there is a great variation in drug response and there is much evidence that genetic contributors play an important role in defining an individual's susceptibility. Natalizumab binds to α4-residues Gln-152, Lys-201, Lys256, and these seem to be essential for its activity. Studies on a range of species in disease model have showed a loss of reactivity when any one of those three residues were different to human. Based on these animal studies, we thought that the single nucleotide polymorphism in the ITGA4 human gene causing a lysine to arginine transversion at amino acid position 256 require further investigations in the context of individual drug susceptibility. So, the aim of our study was to investigate the association between this genetic polymorphism and the resistance to natalizumab. We had applied molecular dynamics simulation to study the possible conformational changes induced by Lys256Arg transversion on the overall structure of integrin and we have analyzed the binding affinities of natalizumab in the non-mutated and mutated structures through HINT score. We found that this SNP does not affect the VLA4-natalizumab interaction. Instead, the binding affinities are slightly higher in the mutated complex than in the wild-type. We reported one of the first work in which MD simulation was applied in the pharmacogenetic context, and this approach is rapid and cost effective, since a population survey is carried out only after the positive prediction of simulation.

Development of an education campaign to reduce delays in pre-hospital response to stroke.

BACKGROUND: Systematic reviews call for well-designed trials with clearly described intervention components to support the effectiveness of educational campaigns to reduce patient delay in stroke presentation. We herein describe the systematic development process of a campaign aimed to increase stroke awareness and preparedness. METHODS: Campaign development followed Intervention Mapping (IM), a theory- and evidence-based tool, and was articulated in two phases: needs assessment and intervention development. In phase 1, two cross-sectional surveys were performed, one aiming to measure stroke awareness in the target population and the other to analyze the behavioral determinants of prehospital delay. In phase 2, a matrix of proximal program objectives was developed, theory-based intervention methods and practical strategies were selected and program components and materials produced. RESULTS: In phase 1, the survey on 202 citizens highlighted underestimation of symptom severity, as in only 44% of stroke situations respondents would choose to call the emergency service (EMS). In the survey on 393 consecutive patients, 55% presented over 2 hours after symptom onset; major determinants were deciding to call the general practitioner first and the reaction of the first person the patient called. In phase 2, adult individuals were identified as the target of the intervention, both as potential "patients" and witnesses of stroke. The low educational level found in the patient survey called for a narrative approach in cartoon form. The family setting was chosen for the message because 42% of patients who presented within 2 hours had been advised by a family member to call EMS. To act on people's tendency to view stroke as an untreatable disease, it was decided to avoid fear-arousal appeals and use a positive message providing instructions and hope. Focus groups were used to test educational products and identify the most suitable sites for message dissemination. CONCLUSIONS: The IM approach allowed to develop a stroke campaign integrating theories, scientific evidence and information collected from the target population, and enabled to provide clear explanations for the reasons behind key decisions during the intervention development process. TRIAL REGISTRATION: NCT01881152 . Retrospectively registered June 7 2013.

Definitive childlessness in women with multiple sclerosis: a multicenter study.

The frequency of definitive childlessness in women with multiple sclerosis (MS) may be higher than in the general population. MS may also affect decisions on the delivery procedure and on breast-feeding issues. Aim of the study was to assess the frequency of childlessness and its possible causes, the proportion of cesarean deliveries (CD), and the frequency of breast-feeding in patients and controls who have reached the end of their reproductive period. Female MS patients (>43 years) and controls (>45 years) filled out a questionnaire. We enrolled 303 patients and 500 controls. MS was associated with a higher frequency of childlessness (22 vs 13%) and less patients were in a stable relationship (83 vs 89%). There was no difference in the reported rates of infertility and miscarriages, while elective abortions were more frequent in patients (20 vs 12%). MS did not significantly affect the frequency of CD or of breast-feeding. MS-related reasons for childlessness, reported by 16% of childless patients, included disability/fear of future disability, fear of genetically transmitting MS, fear of not starting/discontinuing treatments, and discouragement by physician. Definitive childlessness is more frequent in women with MS compared to controls. A portion of voluntary childlessness may be avoided through correct/tailored information to patients.

A 12-month prospective, observational study evaluating the impact of disease-modifying treatment on emotional burden in recently-diagnosed multiple sclerosis patients: The POSIDONIA study.

INTRODUCTION: Depression and anxiety are common among patients with multiple sclerosis (MS) and are frequently present at the time of MS diagnosis. METHODS: POSIDONIA was a 12-month, observational, prospective study conducted in Italy to evaluate the impact of disease-modifying treatment (DMT) on emotional burden in patients with recently-diagnosed MS. The Hospital Anxiety and Depression Scale (HADS), specifically HADS anxiety (HADS-A) and depression (HADS-D) subscale scores, the Short-Form 36 Health Survey (SF-36) and the Impact of Event Scale - Revised (IES-R) were used to measure patient-reported outcomes. The Hamilton Depression Rating Scale (HDRS), HDRS-17, was used as a measure of healthcare provider-reported outcomes. The primary study outcome was change from baseline in feelings of anxiety and depression over 12months (via HADS). RESULTS: Of 250 enrolled patients, 222 (88.8%) completed the study. At baseline, mean HADS total, HADS-A and HADS-D subscale scores were within the normal range. There were no significant changes over time in mean HADS total and HADS-A and HADS-D subscale scores, although the subgroup of patients with baseline scores indicative of anxiety or depression tended to improve over time. Both the HDRS and IES-R total scores improved over time, but there were no statistically significant changes in SF-36. CONCLUSION: In the patient population of the POSIDONIA study depression and anxiety were present in a minority of patients thus not allowing to detect the impact of starting DMT. However DMT appears to have a positive effect in patients with measurable anxiety or depression at baseline.

Illness Perception and Well-Being Among Persons with Multiple Sclerosis and Their Caregivers.

This study jointly examined illness beliefs held by persons with multiple sclerosis (PwMS) and caregivers in relation to well-being. A group of 68 PwMS and their caregivers completed the Revised Illness Perception Questionnaire, Psychological Well-being Scales, Satisfaction with Life Scale and Positive Affect and Negative Affect Schedule. Findings revealed that PwMS' well-being was primarily predicted by their own illness beliefs, and that also caregivers' well-being was primarily predicted by their own beliefs. Across the two groups, well-being was positively associated with their belief that they understood the disease, and inversely associated with their representations of negative emotions. In addition, among PwMS, well-being was inversely associated with the number of symptoms they specifically attributed to their illness, while among caregivers, well-being was positively associated with beliefs that treatment could control the disease. Based on the study findings, psychoeducational and cognitive-behavioral strategies are suggested to promote well-being among PwMS and caregivers.

Previous treatment influences fingolimod efficacy in relapsing-remitting multiple sclerosis: results from an observational study.

OBJECTIVE: Fingolimod (FTY) is licensed as a disease-modifying treatment in highly active relapsing-remitting multiple sclerosis. The aim of the study was to evaluate the efficacy and safety of FTY in a real-life setting and to explore the possible role of clinical and MRI parameters, including previous treatment type, in predicting its efficacy. METHODS: Clinical and MRI data was collected on 127 patients assigned to treatment with FTY in six multiple sclerosis centers in Emilia-Romagna, Italy, between August 2011 and June 2013. RESULTS: During a mean follow-up period of 10 months (range 1-22), we observed a total of 47 relapses in 39 patients (30.7%); new T2 lesions or gadolinium-enhancing (Gd+) lesions were present at follow-up MRI in 32/71 patients (45%). Expanded disability status scale (EDSS) at the end of the follow-up period was not different when compared to the baseline EDSS. Serious adverse events occurred in three patients (2.4%). A higher proportion of patients previously treated with natalizumab showed clinical (41%) or MRI activity (54%). Previous treatment with natalizumab increased the risk of a relapse within 30 days (versus immunomodulatory drugs; OR: 4.3; p = 0.011) and at survival analysis (versus remaining patients; HR: 1.9; p = 0.046). Study limitations include a small population sample, a short observation period with variable timing of follow-up MRI and different baseline characteristics of patients previously treated with natalizumab compared to those treated with immunomodulatory drugs. CONCLUSIONS: This study confirms the efficacy of FTY in reducing relapse rate in patients previously treated with immunomodulatory drugs, while it seems to be less effective in patients discontinuing natalizumab. Due to the short duration of follow-up it is not possible to evaluate disability progression; however, no difference was observed between the groups.

Interferon-beta-1a treatment has a positive effect on quality of life of relapsing-remitting multiple sclerosis: results from a longitudinal study.

PURPOSE: The impact of interferon beta (IFNß) therapy on a patient's quality of life (QoL) has not been completely clarified. This multicenter, independent, observational and longitudinal study was aimed to evaluate the impact of different pharmaceutical formulations of IFNß-1a on QoL in patients affected by relapsing-remitting multiple sclerosis (RRMS). METHODS: The multiple sclerosis quality of life-54 questionnaire was used to assess patients' QoL. RESULTS: 394 (66%) patients completed the two-year study; 152 were treated with IFNß-1a i.m. weekly injected (group a), 152 with IFNß-1a 44 µg s.c. injected three times a week (group b) and 90 were untreated (group c). After two years, a significant increase was found in the physical health composite score (Δ = +3.1 in group a, Δ = +3 in group b, p < 0.05 in both), mental health composite score (Δ = +4.7 in group a, Δ = +5.5 in group b, p < 0.001 in both), in eight MSQoL sub-items of group a and in seven sub-items in group b. Conversely, the untreated group showed a slight decrease in seven domains. The variable "therapy with DMDs" was associated with improved QoL. CONCLUSION: QoL of RRMS could be improved by IFNß-1a treatment, despite natural history data which seem to demonstrate that QoL could get worse over the time.

Guidelines on the clinical use for the detection of neutralizing antibodies (NAbs) to IFN beta in multiple sclerosis therapy: report from the Italian Multiple Sclerosis Study group.

Interferon beta (IFNß) was the first specific disease-modifying treatment licensed for relapsing-remitting multiple sclerosis, and is still one of the most commonly prescribed treatments. A strong body of evidence supports the effectiveness of IFNß preparations in reducing the annual relapse rate, magnetic resonance (MRI) disease activity and disease progression. However, the development of binding/neutralizing antibodies (BAbs/NAbs) during treatment negatively affects clinical and MRI outcomes. Therefore, guidelines for the clinical use for the detection of NAbs in MS may result in better treatment of these patients. In October 2012, a panel of Italian neurologists from 17 MS clinics convened in Milan to review and discuss data on NAbs and their clinical relevance in the treatment of MS. In this paper, we report the panel's recommendations for the use of IFNß Nabs detection in the early identification of IFNß non-responsiveness and the management of patients on IFNß treatment in Italy, according to a model of therapeutically appropriate care.

The coexistence of well- and ill-being in persons with multiple sclerosis, their caregivers and health professionals.

BACKGROUND: Studies on emotional distress and health-related quality of life (HRQOL) broadened the traditional bio-medical focus in MS research, but little attention was paid to general well-being indicators. OBJECTIVE: To investigate for the first time both ill-being and well-being dimensions in persons with MS (PwMSs), caregivers and health professionals, in relation to both health and life in general. METHODS: A multi-center study assessed participants' depression (Beck Depression Inventory-II), HRQOL (Short Form-36), psychological well-being (Psychological Well-Being Scales), optimal experience (Flow Questionnaire), life satisfaction (Satisfaction with Life Scale), hedonic balance (Positive Affect and Negative Affect Schedule). Demographic and clinical information was also gathered. RESULTS: Overall, 71 PwMSs, 71 caregivers and 26 professionals were enrolled (N=168). Compared to healthy populations, PwMSs reported higher depression, lower HRQOL and lower general well-being; caregivers presented higher depression and lower general well-being; professionals reported the best ill- and well-being profiles. However, after controlling for demographic differences in age and education, hierarchical regressions highlighted that, though PwMSs reported higher depression and lower HRQOL than caregivers and professionals, their general well-being substantially leveled off. CONCLUSIONS: Well-being coexists with ill-being. It can counterbalance the negative effects of disease or caregiving, and its measurement could complement and support medical intervention.

Risk of multiple sclerosis following clinically isolated syndrome: a 4-year prospective study.

The aim of the study was to estimate the rate of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and to investigate variables predicting conversion in a cohort of patients presenting with symptoms suggestive of MS. Patients with a first symptom suggestive of MS in the preceding 6 months and exclusion of other diseases were enrolled in an observational prospective study from December 2004 through June 2007. Conversion from CIS to MS according to both McDonald and Clinically Defined Multiple Sclerosis (CDMS) criteria was prospectively recorded until March 2010. The multivariate Cox proportional hazard model was used to assess the best predictive factors of conversion from CIS to MS. Among 168 patients included in the analysis, 122 converted to MS according to McDonald criteria whereas 81 converted to MS according to CDMS criteria. The 2-year probability of conversion was 57% for McDonald Criteria and 36% for CDMS criteria. Variables at enrolment significantly associated with conversion according to McDonald criteria were age and positivity for Barkhof criteria, and according to Poser's CDMS criteria, age, positivity for Barkhof criteria and no disease modifying therapy. In this large prospective cohort study the conversion rate from CIS to MS in patients presenting with recent symptoms suggestive of MS was within the range of previous observational studies and lower than that reported in the placebo arm of randomized trials. We confirm the prognostic value of MRI in addition to the previous experimental data on the protective role of disease-modifying therapies.