MxA mRNA quantification and disability progression in interferon beta-treated Multiple Sclerosis patients

Even though anti-interferon beta (IFNβ) antibodies are the main determinants of IFNβ bioactivity loss and Myxovirus-resistance protein A (MxA) is the most established marker of IFNβ biological activity in IFNβ-treated multiple sclerosis patients, their usefulness in the routine clinical practice is still debated. Therefore, 118 multiple sclerosis patients naïve for treatment were enrolled for a 3-year longitudinal observational study mimicking the conditions of a real-world setting. In order to evaluate the kinetics of bioactivity loss in blood samples obtained every 6 months after therapy initiation, MxA and interferon receptor isoform/subunit mRNA were quantified by real-time PCR, anti-IFNβ binding antibodies were detected by radioimmunoprecipitation, and neutralizing antibodies by cytopathic effect inhibition assay. Clinical measures of disease activity and disability progression were also obtained at all time points. We found that, at the individual-patient level, the response to IFNβ therapy was extremely heterogeneous, including patients with stable or transitory, early or late loss of IFNβ bioactivity, and patients with samples lacking MxA mRNA induction in spite of absence of antibodies. No interferon receptor isoform alterations that could explain these findings were found. At the group level, none of these biological features correlated with the measures of clinical disease activity or progression. However, when MxA mRNA was evaluated not at the single time point as a dichotomic marker (induced vs. non-induced), but as the mean of its values measured over the 6-to-24 month period, the increasing average MxA predicted a decreasing risk of short-term disability progression, independently from the presence of relapses. Therefore, a more bioactive treatment, even if unable to suppress relapses, reduces their severity by an amount that is proportional to MxA levels. Together with its feasibility in the routine laboratory setting, these data warrant the quantification of MxA mRNA as a primary tool for a routine monitoring of IFNβ therapy

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry

Abstract BACKGROUND: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM). METHODS: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster. RESULTS: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters. CONCLUSIONS: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs

MS-rehab 1.0

La sclerosi multipla: La Sclerosi Multipla \ue8 una malattia infiammatoria demielinizzante e degenerativa, cronica del Sistema Nervoso Centrale; \ue8 la patologia neurologica non traumatica pi\uf9 comune dell\u2019et\ue0 giovane-adulta. Nel 40-70% dei pazienti si riscontrano deficit a carico di: velocit\ue0 di elaborazione delle informazioni, attenzione, funzioni esecutive, capacit\ue0 di problem solving, concentrazione, memoria verbale e visuo-spaziale a breve e lungo termine, fluenza verbale semantica e fonemica. Il training cognitivo: La ricerca clinica ha documentato che il training cognitivo migliora significativamente i deficit neuropsicologici, specie la memoria e l\u2019attenzione. Inoltre, sono riportati dati positivi rispetto all\u2019efficacia di training di riabilitazione cognitiva computerizzata individuale. Per i pazienti con Sclerosi Multipla che riscontrano dei deficit cognitivi \ue8 possibile effettuare, presso le strutture ospedaliere, dei cicli di riabilitazione (individuali o di gruppo) con operatori specializzati. Le terapie riabilitative che vengono proposte sono personalizzate a seconda dei deficit dei pazienti. Una delle criticit\ue1 principali per la piena attuazione della riabilitazione \ue8 mantenere la continuit\ue0 dell'intervento. L'obiettivo del progetto: L'obiettivo del progetto \ue8 quello di realizzare un ambiente integrato computerizzato per implementare e monitorare il processo riabilitativo sia presso la struttura ospedaliera che a domicilio, al fine di migliorare l'efficacia della riabilitazione sui singoli pazienti e di ottimizzare gli interventi degli operatori specializzati. Il sistema in corso di realizzazione, MS-rehab, ha la possibilit\ue0 di standardizzare il training e monitorare l'attivit\ue0 del paziente registrando i parametri di esecuzione, l\u2019esito della prestazione e l\u2019andamento nel tempo del processo riabilitativo, riducendo il margine di errore dell'operatore sia nella proposta dell\u2019attivit\ue0 che nella registrazione dei dati in sede di riabilitazione, sia di gruppo che individuale

Enhancing Cognitive Rehabilitation in Multiple Sclerosis with a Disease-Specific Tool

Purpose: Computerized rehabilitation programs can be used to address cognitive deficits typically caused by multiple sclerosis (MS). However, there are still doubts on their effectiveness, due to mixed results obtained in clinical trials. The objective of this paper is to improve cognitive rehabilitation (CR) practices in MS, by presenting and assessing a MS-specific cognitive rehabilitation software. Methods: We conducted a detailed analysis of how CR is carried out in practice in MS rehabilitation centers. From the analysis, we elicited a reference CR process, and identified the essential features a software supporting the process should have. We designed and implemented MS-rehab, a novel MS-specific computerized rehabil- itation systems having the identified features. We experimented MS-rehab in a pilot study involving eight MS patients. To highlight the improvement with respect to the state of the art, we compared MS-rehab with available professional tools selected using well defined criteria. Results: This paper has three main contributions: (1) the identification of a set of essential features a computerized tool for CR in MS should provide; (2) MS- rehab, a novel CR system designed for MS therapists and patients, which embodies innovative MS specific features; (3) the assessment of MS-rehab efficacy in a pilot study with MS patients. Conclusions: The availability of a MS-specific CR system like MS-rehab fosters the design of more rigorous clinical studies on the effectiveness of computerized rehabilitation in MS. MS-rehab demonstrated its potential and innovativeness as a tool for cognitive rehabilitation in MS

AEDSS (Automatic EDSS) Expert System

We have developed an expert system (AEDSS - Automatic EDSS) able to compute the EDSS (Expanded Sisability Status Scale) grade starting from the scores of functional systems, asking the user if the data on functional systems are not enough. EDSS rules have been encoded in AEDSS exploiting OCML rules (an Operational Knowledge Modelling Language based on LISP). AEDSS program implements a set of rules which is very similar to the original EDSS definition of Kurtzke (1983) and can be trusted and understood by neurologists

MS-rehab 2.0

MS-rehab is a novel MS-specific software system designed to support the phases of cognitive rehabilitation in multiple sclerosis MS-rehab supports the clinical operators in: the Multidimensional Assessment phase, to build the cognitive profile of the patient; the Definition of Rehabilitation Program phase, to set up rehabilitation exercise sessions; performing live and long term monitoring of the patients in the Cognitive Rehabilitation Cycle. MS-rehab also supports patients in their execution of the rehabilitation exercises . Finally, it allows therapists to insert new instances of the neuropsychological profile after follow-up tests, to measure the treatment effects, and to tune the next rehabilitation cycles. In the rest of this section, we present the cognitive profile nd the exercises provided by MS-rehab, the services it offers to clinical operators, and its monitoring functionalities. The new version of MS-rehab presented in this paper extends the first prototype (version 1.0) with many rehabilitative exercises (52, with respect to 23 of the first prototype), and new advanced functionalities and components. It was optimized and tuned for routine clinical use thanks to a formative usability study. A preliminary assessment of MS-rehab in a pilot study involving a few MS patients gave indications that our system is potentially effective for CR and does not have negative side effects. In addition, the patients who used the systems gave a positive feedback on it, both on system usability, and as an instrument that motivates the patients in their CR process. A assessment with elderly people has started in October 2020, collaborating with AUSER Bologna

An advanced system to support cognitive rehabilitation in multiple sclerosis

Recent studies demonstrate the benefits of cognitive rehabilitation (CR) showing that it reduces cognitive impairment in Multiple Sclerosis (MS) improving performance of patients in memory and attention. However, CR procedures are still in a germinal stage and have not been accepted worldwide as a standard therapy yet. In this scenario, the use of computerized training systems has several advantages with respect to pen-and-paper based exercises (such as flexibility and immediate feedback), but the use of information technology is currently limited to provide general purpose tools (i.e., not tailored for specific diseases) that support rehabilitation exercises for single patients only. On the contrary, CR for MS patients must be considered as a part of a comprehensive and complex care process that involves many aspects that must be deeply analyzed to build an effective therapy program. In this paper, we argue that a computerized system, able to integrate the various phases of cognitive rehabilitation processes, may have an essential role in improving CR procedures, optimizing them for routine clinical use in MS. To illustrate our claim, we present MS-rehab, an advanced system specific for MS, highlighting its main features and comparing it with other computerized tools for CR

Assessment of EDSS in Multiple Sclerosis

The Expanded Disability Status Scale (EDSS) has been the most widely used measure of disability in multiple sclerosis clinical trials. Although EDSS has the advantage of familiarity with respect to recent proposals, yet is difficult to use consistently between evaluators. AEDSS (Automatic EDSS) is a computerized system designed to overcome this problem. It constrains the neurologist to follow precise reasoning steps enhancing EDSS reliability. In this paper we show how an accurate analysis of the neurological knowledge involved, and the development of an application ontology in the EDSS domain, can improve the performance of AEDSS. We present the details of the AEDSS application ontology and we highlight the enhancements to AEDSS due to this ontology. A validation experiment in four MS centers in italy showed that AEDSS improves EDSS reliability and in many cases is able to correct errors of neurologists