Management of hepatitis B virus prophylaxis in patients treated with disease-modifying therapies for multiple sclerosis: a multicentric Italian retrospective study

Background: Patients with multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) that can expose them to reactivation of potential occult hepatitis B virus (HBV) infection (pOBI). We aimed to evaluate the MS Centers behavior regarding HBV screening and prophylaxis in a large cohort of MS patients receiving anti-CD20 or cladribine. Methods: Retrospective, multicentric study recruiting Italian MS patients treated with rituximab, ocrelizumab and cladribine. Results: We included 931 MS patients from 15 centers. All but 38 patients performed a complete HBV screening. Patients' age > 50 years was significantly associated with no history of vaccination and HBsAb titres < 100 mIU at baseline (p < 0.001). No significant correlation was found between post-vaccination HBsAb titres and type of treatment (p = 0.5), pre-or post-therapy vaccination (p = 0.2) and number of previous DMTs (p = 0.2). Among pOBI patients (n = 53), 21 received antiviral prophylaxis, while only 13 had HBV DNA monitoring and 19 patients neither monitored HBV DNA nor received prophylaxis. Conclusions: Baseline HBV screening in patients receiving anti-CD20 and cladribine is a consolidated practice. Nonetheless, HBV vaccination coverage is still lacking in such population and age is a significant factor associated with low HBV protection. Rituximab, ocrelizumab and cladribine did not impair HBV vaccine response. Almost 35% of pOBI patients fail to receive HBVr prevention. Management of HBV prophylaxis could be improved in MS patients and further prospective studies are needed to assess the effectiveness of prophylactic strategies in such patients

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

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

Automatic planning in cognitive training: application to multiple sclerosis

Multiple sclerosis (MS) is the second-most common cause of neurological disability among young adults. Cognitive impairment, which typically worsens over time, is a major symptom of MS. Signs of cognitive impairment can be observed in many cognitive domains, often including executive-function disorders. Planning is one of the main skills related to executive functions and is fundamental for many cognitive and motor tasks. Brain games, initially available in paper-and-pen format, have been designed to improve planning abilities. Current computerized cognitive training tools also include this kind of exercises; however, they have several limitations, which can be addressed exploiting automated planning. This solution enables advanced forms of human-computer interaction, but poses several design challenges. We tested the usability of two cognitive training exercises for executive functions based on automated planning, which include various features and interaction mechanisms. We present the results of a multidomain cognitive training addressed to individuals affected by MS, including the exercise that performed better in the test. The aim of this study is to clarify design issues concerning executive-function exercises based on automated planning, showing that they can be used in a multidomain cognitive training by participants affected by MS

The Mediterranean Sea Overturning Circulation

The time-mean zonal and meridional overturning circulations of the entire Mediterranean Sea are studied in both the Eulerian and residual frameworks. The overturning is characterized by cells in the vertical and either zonal or meridional planes with clockwise circulations in the upper water column and counterclockwise circulations in the deep and abyssal regions. The zonal overturning is composed of an upper clockwise cell in the top 600 m of the water column related to the classical Wust cell and two additional deep clockwise cells, one corresponding to the outflow of the dense Aegean water during the Eastern Mediterranean Transient (EMT) and the other associated with dense water formation in the Rhodes Gyre. The variability of the zonal overturning before, during, and after the EMT is discussed. The meridional basinwide overturning is composed of clockwise, multicentered cells connected with the four northern deep ocean formation areas, located in the Eastern and Western Mediterranean basins. The connection between the Wust cell and the meridional overturning is visualized through the horizontal velocities vertically integrated across two layers above 600 m. The component of the horizontal velocity associated with the overturning is isolated by computing the divergent components of the vertically integrated velocities forced by the inflow/outflow at the Strait of Gibraltar

How to Predict the Efficacy of Free-Product DNAPL Pool Extraction Using 3D High-Precision Numerical Simulations: An Interdisciplinary Test Study in South-Western Sicily (Italy)

Dense nonaqueous phase liquids (DNAPLs) are known to be denser than water and immiscible with other fluids. Once released into the environment, they migrate downward through the variably saturated zone, causing severe damage. For this reason, it is essential to properly develop a rapid response strategy, including predictions of contaminant migration trajectories from numerical simulations modeling. This paper presents a series of simulations of free-product DNAPL extraction by means of a purpose-designed pumping well. The objective is to minimize the environmental impact caused by DNAPL release in the subsurface, estimating the recoverable free-product DNAPL, depending on the hydraulic properties of the aquifer medium, and estimating the leaving residual DNAPL that could act as a long-term pollution source. Coupling the numerical simulations to the bacterial community characterization (through biomolecular analyses), it was verified that (i) the DNAPL recovery (mainly PCE at the study site) through a pumping well would be almost complete and (ii) the application of other remediation techniques (such as bioremediation) would not be necessary to remove the pollution source because (iii) a natural attenuation process is provided by the autochthonous bacterial community, which is characterized by genera (such as Dechloromonas, Rhodoferax, and Desulfurivibrio) that have metabolic pathways capable of favoring the degradation of chlorinated compounds