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Background: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease negatively impacting patients' physical, psychological and social well-being with a significant economic burden. Objectives: The study estimates MS burden and cost of illness in Italy from a societal perspective in 2019. Methods: Information on the impact of the disease on daily activities, symptoms, employment, resource utilization and the role of caregivers was collected through questionnaires completed by 944 patients and caregivers. Results were stratified according to both disease severity and payer. Mean costs and overall costs were extrapolated from the sample to the Italian MS population considering published distribution of severity. Results: The study showed a great impact of the disease on daily and work activities increasing with the disability. The overwhelming burden of fatigue emerged. Mean annual costs were estimated at €39,307/patient (€29,676, €43,464 and €53,454 in mild, moderate and severe cases, respectively). Direct healthcare costs were the major component (€21,069), followed by indirect costs (€15,004). The overall cost of the disease in Italy was €4.8 billion. The National Healthcare System (NHS) sustained most of the costs (80%), most notably direct healthcare costs, while patients paid almost all non-healthcare expenses. Conclusions: This study confirmed that MS carries a substantial burden to patients and society, highlighting the need for awareness of this disease. [ABSTRACT FROM AUTHOR]

Background: Regulatory agencies have been responsive to public demand for inclusion of the patient experience in evaluating and approving therapies. Over the years, patient-reported outcome measures (PROMs) have become increasingly prevalent in clinical trial protocols; however, their influence on regulators, payers, clinicians, and patients' decision-making is not always clear. We recently conducted a cross-sectional study aimed at investigating the use of PROMs in new regulatory approvals of drugs for neurological conditions between 2017 and 2022 in Europe. Methods: We reviewed European Public Assessment Reports (EPARs) and recorded on a predefined data extraction form whether they considered PROMs, their characteristics (e.g., primary/secondary endpoint, generic/specific instrument) and other relevant information (e.g., therapeutic area, generic/biosimilar, orphan status). Results were tabulated and summarized by means of descriptive statistics. Results: Of the 500 EPARs related to authorized medicines between January 2017 and December 2022, 42 (8%) concerned neurological indications. Among the EPARs of these products, 24 (57%) reported any use of PROMs, typically considered as secondary (38%) endpoints. In total, 100 PROMs were identified, of which the most common were the EQ-5D (9%), the SF-36 (6%), or its shorter adaptation SF-12, the PedsQL (4%). Conclusions: Compared to other disease areas, neurology is one where the use of patient-reported outcomes evidence is inherently part of the clinical evaluation and for which core outcome sets exist. Better harmonization of the instruments recommended for use would facilitate the consideration of PROMs at all stages in the drug development process. [ABSTRACT FROM AUTHOR]

Purpose. To determine the most commonly used manual wheelchair propulsion pattern by people with multiple sclerosis (MS) and to assess which factors influence the preference. Method. Sixty manual wheelchair users with MS from an MS outpatient rehabilitation centre in Northern Italy were assessed on upper limb range of motion and trunk stability to determine if these factors or demographic, disease or wheelchair use history, influenced the choice of wheelchair propulsion pattern. Results. Fifty-four (90%) subjects used the arcing propulsion pattern, the least efficient pattern as reported in the literature. Sixteen (26.7%) subjects had impaired trunk stability and 38 (63.3%) subjects demonstrated some deficit on either extremity for active range flexion–extension. Twenty (33%) subjects had no deficits on active range flexion–extension and had normal trunk control. Upper limb range of motion and trunk stability were not significant in determining the preference for propulsion pattern ( p = 1.05 and 0.38, respectively). Demographic and disease factors and wheelchair use history were also not significant in determining propulsion pattern. Conclusions. The person with MS uses the least efficient pattern overall, requiring frequent repetition, although a smaller range of movement. This may be an energy conservation technique that helps in managing fatigue. [ABSTRACT FROM AUTHOR]

Background: The mobile device diffusion has increasingly highlighted the opportunity to collect patient-reported outcomes (PROs) through electronic patient-reported outcomes measurements (ePROMs) during the clinical routine. Despite the ePROMs promises and advantages, the equivalence when a PRO measure is moved from the original paper-and-pencil to the electronic version is still little investigated. This study aims at evaluating equivalence between PROMs and ePROMs self-administration in people with multiple sclerosis (PwMS); in addition, preference of self-administration type was evaluated. Methods: The Manual Ability Measure-36 (MAM-36) and Fatigue Severity Scale (FSS) were selected for the equivalence test. The app ABOUTCOME was developed through a user-centered design approach to administer the questionnaires on tablet. Both paper-and-pencil and electronic versions were randomly self-administered. Intrarater reliability between both versions was evaluated through the intraclass correlation coefficient (ICC, excellent for values ≥ 0.75). Results: Fifty PwMS (35 females) participated to the study (mean age: 54.7±11.0 years, disease course: 27 relapsing-remitting and 23 progressive; mean EDSS: 4.7±1.9; mean disease duration: 13.3±9.5 years). No statistically significant differences were found for the means total scores of MAM-36 (p = 0.61) and FSS (p = 0.78). The ICC value for MAM-36 and FSS was excellent (0.98 and 0.94, respectively). Most of participants preferred the tablet version (84%). Conclusion: The results of the study provide evidence about the equivalence between the paper-and-pencil and electronic versions of PROs administration. In addition, PwMS prefer electronic methods rather than paper because the information can be provided more efficiently and accurately. The results could be easily extended to other MS PROs. [ABSTRACT FROM AUTHOR]

Introduction: Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked. This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register. Methods: The Register collects, through a standardized Web-based Application, unique patients. Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated. Results: The Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients. The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000–2015) to 60% (enrolment period 2016–2022). In the cohort of patients registered after 2016, there were ≥ 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2). Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months. Conclusions: Data from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications. [ABSTRACT FROM AUTHOR]

Background: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients. Objective: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis. Methods: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death). Results: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course. Conclusion: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy. [ABSTRACT FROM AUTHOR]

Background and purpose: Although two doses of COVID‐19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease‐modifying therapies (DMTs) showed less efficient responses. Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. Results: Four hundred seventy‐three pwMS were analyzed. Compared to untreated patients, there was a 50‐fold decrease (95% confidence interval [CI] = 14.3–100.0, p < 0.001) in serum SARS‐CoV‐2 antibody levels in those on rituximab, a 20‐fold decrease (95% CI = 8.3–50.0, p < 0.001) in those on ocrelizumab, and a 2.3‐fold decrease (95% CI = 1.2–4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti‐CD20 drugs rituximab and ocrelizumab showed a 2.3‐fold lower gain (95% CI = 1.4–3.8, p = 0.001), whereas those on fingolimod showed a 1.7‐fold higher gain (95% CI = 1.1–2.7, p = 0.012), compared to patients treated with other DMTs. Conclusions: All pwMS increased their serum SARS‐CoV‐2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff. [ABSTRACT FROM AUTHOR]

Italy is a high risk area for multiple sclerosis (MS) as confirmed by the numerous prevalence and incidence studies conducted in several regions/districts of the country. Nevertheless, there are no recent published epidemiological data, nor studies about the total prevalence of MS in Italy. Our aim was to update as of 2015 the prevalence rates of MS in different geographical areas using already published epidemiological studies, and to estimate the overall prevalence of the disease in Italy. We made a search in MEDLINE database of all published studies on epidemiology of MS in Italy. Then, we applied, to the already published prevalence data, the last published incidence and mortality rates to recalculate, as of 2015, the prevalence of MS. So, we calculated the mean prevalence rate from our extrapolations, and we applied it to the population in 2015 to estimate the number of MS patients in Italy. Our prevalence extrapolations ranged from 122 to 232 cases/100,000 in the mainland and Sicily, with an average of 176/100,000, and from 280 to 317 cases/100,000 in Sardinia with an average of 299/100,000. Applying these media to the Italian population in 2015, we obtained an estimate of more than 109,000 MS patients in Italy. Our estimates were higher than the latest published rates but consistent with the annual increase of prevalence due to incidence that exceeds mortality, with the increase of survival and, maybe, with the probable increase of incidence. [ABSTRACT FROM AUTHOR]

Objective: Chronic comorbidities are common in people with multiple sclerosis (PwMS), thus worsening their prognosis and quality of life, and increasing disease burden. The aim of the present study was to evaluate the prevalence of common comorbidities in PwMS in Tuscany (Central Italy) and to compare it with the general population. Methods: The prevalence of comorbidities, including diabetes, chronic obstructive pulmonary disease (COPD), hypertension, stroke, heart failure (HF), cardiac infarction and ischemic heart disease (IHD), was assessed in PwMS and in general population resident in Tuscany, aged > 20 years, using administrative data. Results: In total, we identified 8,274 PwMS. Among them, 34% had at least one comorbidity, with hypertension being the most common (28.5%). Comparing PwMS with the general population, PwMS had a higher frequency of hypertension and stroke when considering the whole group, and of diabetes, COPD, and IHD when considering sex and age subgroups. This increased risk was especially evident in the young and intermediate age groups, where multiple sclerosis may play an important role as risk factor for some comorbidities. In PwMS, as well as in the general population, prevalence of chronic diseases was higher in males and increased with age. Conclusions: Comorbidities frequently coexist with multiple sclerosis and they may have an impact on this complex disease, from the health, clinical, and socioeconomic points of view. Therefore, a routine screening of chronic comorbidities should be a crucial step in clinical practice, as well as the promotion of healthy lifestyles to prevent the onset and to reduce their burden. [ABSTRACT FROM AUTHOR]

Background: We aimed to summarise the prevalence of unemployment and early retirement among people with MS and analyze data according to a spatio-temporal perspective. Methods: We undertook a systematic search of PubMed/MEDLINE, Scopus, SciVerse ScienceDirect, and Web of Science. We included any peer-reviewed original article reporting the prevalence of unemployment and early retirement in the working-age population with MS. We excluded articles off-topic, with other study designs, whose study sample were unlikely to be representative of the MS population and in case of unavailability of the full text or essential information. A random-effects meta-analysis was used to measure overall prevalence estimates of unemployment and early retirement. We used meta-regression and subgroup analysis to evaluate potential moderators of prevalence estimates and the leave-one-out method for sensitivity analyses. Results: Our research identified 153 studies across 29 countries encompassing 188436 subjects with MS. The pooled overall effect size for unemployment and early retirement was 35.6% (95% CI 32.8–38.4; I2 = 99.31) and 17.2% (95% CI 14.6–20.2; I2 = 99.13), respectively. The prevalence of unemployment varied according to the year of publication (p < 0.001) and there was a statistically significant decrease in the prevalence of unemployment over time (p = 0.042). Regarding early retirement, only seven (31.8%) estimates obtained from studies that were published before 2010 were below the overall effect size in comparison to 27 (60.0%) estimates extracted from data published between 2010 and 2021 (p = 0.039). There was a significant difference in prevalence according to countries (p < 0.001). Psychiatric illness was an important clinical feature responsible for patients leaving the workforce in regions with a high MS prevalence. Conclusions: Unemployment and early retirement due to MS remain highly prevalent, despite a slight decline in the last decade. The prevalence of unemployment and early retirement varies globally. [ABSTRACT FROM AUTHOR]

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination. [ABSTRACT FROM AUTHOR]

Cognitive rehabilitation in multiple sclerosis (MS) aims at reducing patients' cognitive impairments, improving their awareness and ability to take cognitive difficulties into account in their daily living. However, at this moment, more high-quality randomized trials are needed to draw conclusion about the effectiveness of cognitive interventions in MS. Although existing studies provide clear descriptions of intervention key ingredients (e.g. targeted cognitive domain as well as treatment frequency and duration) and the practical details needed to manage these key elements (e.g. restorative approaches, compensatory strategies, or environmental modifications), other crucial aspects received less attention in rehabilitation research. The aim of this topical review is to try to elucidate some critical issues that were only partly addressed and analyzed by the scientific literature: setting (center-based vs home-based) and mode (individual vs group) of the cognitive rehabilitation treatment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate mortality for Parkinson's disease (PD) in Italy during a long time period (1980-2015) and to discuss the role of possible general and specific influencing factors.Methods: Based on mortality data provided by the Italian National Institute of Statistics, sex- and age-specific crude mortality rates were computed, for the whole country and for its main geographical sub-areas. Rates were standardized using both direct (annual mortality rates AMRs) and indirect (standardized mortality rates SMRs) methods. SMRs were used to evaluate geographical differences, whereas AMRs and joinpoint linear regression analysis to study mortality trends.Results: Considering the entire period, highest mortality rates were observed in males (AMR/100,000: 9.0 in males, 5.25 in females), in North-West and Central Italy (SMR > 100). Overall PD mortality decreased from mid-eighties onwards and then rapidly reversed the trend in the period 1998-2002, rising up to a maximum in 2015, with some differences according to sex and geographical areas.Conclusions: Several factors may have contributed to the rapid inversion of decreasing trend in mortality observed in the last part of XX century. Possible explanations of this rising trend are related to the increasing burden of PD (especially in males and in certain Italian regions), caused by different factors as population aging, physiological prevalence rise due to incidence exceeding mortality, and growing exposure to environmental or occupational risk factors. In addition, the accuracy of death certificate compilation could account for geographical differences and for the temporal trend. The role of levodopa and recently introduced dopaminergic drugs is also discussed. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has unmasked even more clearly the need for research and care to form a unique and interdependent ecosystem, a concept which has emerged in recent years. In fact, to address urgent and unexpected missions such as "fighting all together the COVID-19 pandemic", the importance of multi-stakeholder collaboration, mission-oriented governance and flexibility has been demonstrated with great efficacy. This calls for a policy integration strategy and implementation of responsible research and innovation principles in health, promoting an effective cooperation between science and society towards a shared mission. This article describes the MULTI-ACT framework and discusses how its innovative approach, encompassing governance criteria, patient engagement and multidisciplinary impact assessment, represents a holistic management model for structuring responsible research and innovation participatory governance in brain conditions research. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerability, and activity of autologous MSCs derived from bone marrow and infused intravenously in patients with active multiple sclerosis.Methods: MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18-50 years) with active relapsing-remitting or progressive multiple sclerosis were included if they had a disease duration of 2-15 years since onset of multiple sclerosis and an Expanded Disability Status Scale score of 2·5-6·5. Patients were randomly assigned (1:1), according to a crossover design, to receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at week 24, with a follow-up visit at week 48. Primary objectives were to test safety and activity of MSC treatment. The primary safety endpoint was to assess the number and severity of adverse events within each treatment arm. The primary efficacy endpoint was the number of gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after all participants completed the week 24 visit. Efficacy endpoints were evaluated using a predefined statistical testing procedure. Safety was monitored throughout the study by recording vital signs and adverse events at each visit.Findings: From July 16, 2012, until July 31, 2019, 144 patients were randomly assigned to first receive early intravenous infusion of autologous bone marrow-derived MSCs (n=69) or placebo (n=75). MSC treatment did not meet the primary endpoint of efficacy on the total number of GELs accumulated from baseline to week 24 (rate ratio [RR] 0·94, 95% CI 0·58-1·50; p=0·78). 213 adverse events were recorded, similarly distributed between groups (93 cases recorded in 35 [51%] of 69 patients treated first with MSCs vs 120 cases in 42 [56%] of 75 patients infused first with placebo). The most frequent adverse events reported were infection and infestations, with a total of 54 (25%) of 213 adverse events (18 [19%] of 93 in the early-MSC group and 36 [30%] of 120 in the delayed-MSC group). Nine serious adverse events were reported in seven patients treated with placebo versus none in the MSC group. All serious adverse events were considered to be unrelated to the treatment infusion. No deaths were reported during the study.Interpretation: Bone marrow-derived MSC treatment was safe and well tolerated but did not show an effect on GELs, an MRI surrogate marker of acute inflammation, in patients with active forms of multiple sclerosis, at week 24. Thus, this study does not support the use of bone marrow-derived MSCs to treat active multiple sclerosis. Further studies should address the effect of MSCs on parameters related to tissue repair.Funding: Fondazione Italiana Sclerosi Multipla (FISM), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and the Multiple Sclerosis International Federation (MSIF) for centralised activities. Individual trials participating in the MESEMS network are funded by the following agencies: FISM and Compagnia di San Paolo (Italy); The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors' Research Foundation (Denmark); the Spanish Health Research Institute Carlos 3 and the Andalusian Public Foundation Progreso y Salud (Spain); the Royan Institute for Stem Cell Biology and Technology (Iran); the Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, and Salzburg (Austria); the Fondation pour l'aide à la recherche sur la sclérose en plaques (ARSEP), French Muscular Dystrophy Association (AFM)-Telethon (France); the UK Multiple Sclerosis Society and the UK Stem Cell Foundation (UK); and the Multiple Sclerosis Society of Canada and The Multiple Sclerosis Scientific Research Foundation and Research Manitoba (Canada). [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) related disorders are considered to be uncommon. We hypothesize that urinary dysfunction may occur in ALS patients in the context of spasticity of pelvic floor musculature. We recorded data on 54 subjects with ALS. All subjects were evaluated with ALSFRS and M-Ashworth Scale for lower limbs. Bladder scan procedure was performed to asses post void residual (PVR) in all subjects. Forty-one percent of subjects were symptomatic for urinary disorders and 35% of subjects had a PVR > 50 ml. Linear correlation was found between PVR and ALSFRS with a R2 0.95 and p == 0.025; a linear correlation was also noted between PVR and lower limbs Ashworth Scale. We conclude that urinary retention is common in ALS. Urological evaluation is indicated in ALS patients with prominent spasticity. [ABSTRACT FROM AUTHOR]

Motor imagery (MI) is the mental simulation of an action without any overt motor execution. Interestingly, a temporal coupling between durations of real and imagined movements, i.e., the so-called isochrony principle, has been demonstrated in healthy adults. On the contrary, anisochrony has frequently been reported in elderly subjects or those with neurological disease such as Parkinson disease or multiple sclerosis (MS). Here, we tested whether people with MS (PwMS) may have impaired MI when they imagined themselves walking on paths with different widths. When required to mentally simulate a walking movement along a constrained pathway, PwMS tended to overestimate mental movement duration with respect to actual movement duration. Interestingly, in line with previous evidence, cognitive fatigue was found to play a role in the MI of PwMS. These results suggest that investigating the relationship between cognitive fatigue and MI performances could be key to shedding new light on the motor representation of PwMS and providing critical insights into effective and tailored rehabilitative treatments. [ABSTRACT FROM AUTHOR]

Introduction: Arm and hand function deficits are commonly in people with multiple sclerosis (PwMS). The Arm Function in Multiple Sclerosis Questionnaire (AMSQ) is a novel self-administered instrument specifically developed to evaluate upper limb function in MS. The aim of this study was to translate and adapt the AMSQ into Italian and to assess its psychometric properties in PwMS. Validity (structural, construct, and known-groups) and reliability (internal consistency, test-retest, and measurement error) were assessed. Materials and methods: From June 2017 to February 2018, a prospective cohort of PwMS among those followed as outpatients at the Rehabilitation Services of the Italian Multiple Sclerosis Society (AISM) of Genoa, Padua, and Vicenza was involved in the study. Construct validity of AMSQ was determined by examining correlations with the Italian version of ABILHAND, Modified Fatigue Impact Scale (MFIS), and Functional Independence Measure (FIM). Results: A total of 234 PwMS were enrolled. The mean AMSQ total score was 67.3 (SD = 38.4). Factor analysis results suggested one factor. As expected, moderate to high correlation coefficients were found between AMSQ and ABILHAND (− 0.79), MFIS (0.50) and its subsets, and FIM (− 0.60) and its subsets involving upper limb functioning. PwMS with higher EDSS reported worse total score of AMSQ than patients with low disability. The internal consistency of the 31 items was high (Cronbach's α, 0.98). Test-retest reliability, as measured with ICC, was 0.96 (95% IC, 0.93–0.98), and measurement error was about 8.3 points showing good reliability. Discussion: AMSQ has been adapted and validated, it is a reliable questionnaire for Italian PwMS. [ABSTRACT FROM AUTHOR]

Machine learning (ML) applied to patient-reported (PROs) and clinical-assessed outcomes (CAOs) could favour a more predictive and personalized medicine. Our aim was to confirm the important role of applying ML to PROs and CAOs of people with relapsing-remitting (RR) and secondary progressive (SP) form of multiple sclerosis (MS), to promptly identifying information useful to predict disease progression. For our analysis, a dataset of 3398 evaluations from 810 persons with MS (PwMS) was adopted. Three steps were provided: course classification; extraction of the most relevant predictors at the next time point; prediction if the patient will experience the transition from RR to SP at the next time point. The Current Course Assignment (CCA) step correctly assigned the current MS course with an accuracy of about 86.0%. The MS course at the next time point can be predicted using the predictors selected in CCA. PROs/CAOs Evolution Prediction (PEP) followed by Future Course Assignment (FCA) was able to foresee the course at the next time point with an accuracy of 82.6%. Our results suggest that PROs and CAOs could help the clinician decision-making in their practice. [ABSTRACT FROM AUTHOR]

The aim of this work was to investigate changes in motor performance and in the brain activation pattern during finger movements, following upper limb motor training in multiple sclerosis. Thirty people with multiple sclerosis with mild upper limb sensorimotor deficits were randomly allocated to one of two groups: the experimental group (n = 15) received an upper limb treatment based on voluntary task-oriented movements; the control group (n = 15) underwent passive mobilization of shoulder, elbow, wrist and fingers. All participants completed three treatment sessions per week for eight weeks. Before and after the intervention, all participants were evaluated for motor performance by means of Action Research Arm Test, Nine Hole Peg Test, and grip strength by a dynamometer, and for brain activations by functional magnetic resonance imaging during right finger opposition movements. Similar effects on motor performance were found in the two groups. A significant improvement with time was found in both groups at NHPT and in GRIP strength; a similar trend was found at ARAT. However, only the experimental group showed increased lateralization towards more normal brain activation following treatment, with activation clusters mainly located in the left brain hemisphere and right cerebellum. In conclusion, both active and passive interventions were effective in improving motor performance. However, only the treatment based on voluntary task-oriented movements could induce changes in brain activity that may have reflected skill acquisition by the right hand, reducing the activation of compensatory areas and decreasing brain resource demand. • Motor performance improvements can be found after active or passive upper limb motor treatment in multiple sclerosis. • Only a task-oriented training can induce changes in the brain activation pattern during finger movements. • An active treatment could reduce the activation of compensatory areas, decreasing brain resource demand. [ABSTRACT FROM AUTHOR]

Background: Assessing the coverage by public or private resources in meeting health-related and social-related needs may be useful for service planning and guide optimization of care, important especially in view of an increase in the prevalence of multiple sclerosis (MS).Methods: An ad hoc questionnaire assessed satisfaction of health-related and social care-related needs in a cross-sectional study of 1014 people with MS identified through MS outpatient clinics and local branches and social media channels of the Italian MS Society.Results: 87.1% and 79.8% of the responders had experienced at least one health-related or social-related need, respectively. The study demonstrated significant gaps between perceived needs and service provision. Rehabilitation, residential care, and psychological support were most frequently unsatisfied health-related needs, while the more commonly unmet social-related needs were financial support, elimination of architectural barriers, workplace adaptations, and career guidance. The multivariate analysis highlighted that the satisfaction of health-related needs was primarily associated with geographic area of residence. Social-related needs correlated with both clinical and sociodemographic aspects.Conclusion: The results provide insight into the range of interventions, care, and support people with MS report to be important to them at different points in their disease trajectory. More emphasis should be put on the inequitable distribution of NHS services in different geographic areas of Italy as well as on particularly fragile subgroups of the MS population (older individuals, and those with higher levels of disability) because the care of these individuals continues to be assumed by the family. [ABSTRACT FROM AUTHOR]

Introduction: Several multiple sclerosis studies matching self- and physician assessment of disease course and disability show moderate and high agreement respectively. However, the role played by socio-demographic, clinical, and quality of life (QoL) factors was not much investigated. The study aims at exploring how self-/physician agreement could depend on these variables.Materials and Methods: Participants were asked to report own disease course and disability according to preset categories. Kappa-value and confidence interval (CI) for disease course and two-way random interclass correlation coefficient (ICC) and CI for disability were calculated to evaluate self-/physician agreement. Χ2 was applied to examine whether other factors (gender, age, education, civil status, disease duration, fatigue, quality of life) had systematic effects.Results: Data analysis on 203 participants indicated fair agreement (Kappa-value = 0.30; 95% CI 0.23-0.38) and no dependency on the categories of each variable for disease course. Satisfactory correlation was found for disability (ICC = 0.74; 95% IC 0.67-0.80), good agreement was found for almost all variable categories, and significant differences were observed for education (better agreement for higher levels), disease duration, fatigue and QoL (better agreement for worse conditions).Discussion: Results seem to suggest that higher education and worse clinical and QoL conditions could engage the patient in developing more disease awareness and realistic self-perception and self-evaluation. [ABSTRACT FROM AUTHOR]

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups. [ABSTRACT FROM AUTHOR]

Background: We performed a qualitative study to investigate the experiences of participants in a multicentre randomized controlled trial on a home-based palliative approach (HPA) for adults with severe multiple sclerosis (MS) and their caregivers. Our aim was to explore the strengths and challenges of the intervention, and circumstances that may have influenced its efficacy. Methods: Participants to the qualitative study were the patients, their caregivers, patient referring physicians, and the teams who delivered the HPA intervention. We performed semi-structured one-on-one interviews with 12 patients and 15 informal caregivers chosen using a maximum variation strategy, two focus group meetings with patient referring physicians (4 participants each), and one with the HPA teams (9 participants). Results: From data analysis (framework method) 38 sub-categories emerged, which were grouped into 10 categories and 3 themes: 'expectations,' 'met and unmet needs', and 'barriers’. Intervention benefits were improved control of symptoms and reduced sense of isolation of the patient-caregiver dyads. Limitations were: factors related to experimental design (difficulty of dyads in identifying examiner and team roles, additional burden for caregivers); team issues (insufficient team building /supervision, competing priorities); limitations of the intervention itself (insufficient length, lack of rehabilitation input); and external factors (resource limitations, under-responsive services/professionals). The referring physician focus groups provided little experiential data. Conclusions: The HPA reduced patient symptoms and sense of isolation in patients and caregivers. The indirect role of the HPA teams, and insufficient length of the intervention were key limitations. The experimental design imposed additional burdens on the dyads. Key barriers were the paucity of available services, the demanding administrative procedures, and lack of networking facilities. These findings suggest that two major requirements are necessary for home palliative care to be effective in this patient population: HPA teams well-connected with MS rehabilitation services, and care delivered over the long-term, with variable intensity. Trial registration: Current Controlled Trials (Registered 19/06/2014). [ABSTRACT FROM AUTHOR]

Background: Evidence on the efficacy of palliative care in persons with severe multiple sclerosis (MS) is scarce. Objective: To assess the efficacy of a home-based palliative approach (HPA) for adults with severe MS and their carers. Methods: Adults with severe MS-carer dyads were assigned (2:1 ratio) to either HPA or usual care (UC). At each center, a multi-professional team delivered the 6-month intervention. A blind examiner assessed dyads at baseline, 3 months, and 6 months. Primary outcome measures were Palliative care Outcome Scale-Symptoms-MS (POS-S-MS) and Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW, not assessed in severely cognitively compromised patients). Results: Of 78 dyads randomized, 76 (50 HPA, 26 UC) were analyzed. Symptom burden (POS-S-MS) significantly reduced in HPA group compared to UC (p = 0.047). Effect size was 0.20 at 3 months and 0.32 at 6 months, and statistical significance was borderline in per-protocol analysis (p = 0.062). Changes in SEIQoL-DW index did not differ in the two groups, as changes in secondary patient and carer outcomes. Conclusion: HPA slightly reduced symptoms burden. We found no evidence of HPA efficacy on patient quality of life and on secondary outcomes. [ABSTRACT FROM AUTHOR]

To date, a lack of accurate information about how the different rehabilitation settings are actually delivered to people with multiple sclerosis (PwMS) is still present. Here, we described how PwMS use the different rehabilitation settings in Italy. An observational retrospective study was designed and data collected through an anonymous questionnaire distributed attending MS clinical centers, rehabilitation units, or among PwMS affiliated to the Italian MS Society. We considered as settings: out-patient ambulatory therapy (OUT), hospitalized therapy (HOSP, in-patient and out-patient hospitalized therapy), and home-based therapy (HOME). One thousand six hundred eighty-six subjects at all disability levels were included in the analysis. A high number (53%, n = 890) did not receive rehabilitation care in the last 3 months before the interview. Main causes were probably due to organizational aspects and poor transports and road networks especially in Center and the Islands. The rehabilitation setting profile of the 796 subjects obtaining rehabilitation care consisted in 58.3% (n = 464) receiving only OUT setting, 9.4% (n = 75) only HOSP setting, and 21.7% (n = 173) only HOME setting. We observed a percentage of overlap among different rehabilitation settings: 3.9% (n = 31) OUT-HOME, 3.6% (n = 29) OUT-HOSP, 2.6% (n = 21) HOSP-HOME, and 0.4% (n = 3) OUT-HOME-HOSP. The physiotherapy was the treatment more common among different rehabilitation settings. Only in the in-patient hospitalized therapy setting, the patient received more frequently diversified treatment. Considering the results, the admission to rehabilitation care in Italy is still far from the standards outlined by the recent guidelines that hypothesize a multidisciplinary evaluation and a more individualized rehabilitation plan. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is common in multiple sclerosis (MS), but the definition of the best cognitive rehabilitation tools and features is still an open issue among researchers. The aims of the present study were to evaluate the effectiveness of COGNI-TRAcK (a customized application software delivering personalized working memory-based exercises) on cognitively impaired people with MS and to investigate the effects of an adaptive vs. a non-adaptive cognitive training administered by means of COGNI-TRAcK. Methods: Twenty eight patients (20 women, age 47.5 ± 9.3 years, Expanded Disability Status Scale score 3.8 ± 1.9) were randomized in two homogeneous groups, both performing a 8-week home-based cognitive rehabilitation treatment by means of COGNI-TRAcK. The study group (ADAPT-gr) underwent an adaptive training given by the automatic adjustment of tasks difficulty to the subjects' performance, whilst the control group (CONST-gr) was trained at constant difficulty levels. Before and after the treatment, patients' cognitive status was assessed using a gold standard neuropsychological evaluation. Moreover, the mostly affected cognitive domains in MS (i.e., attention, concentration and information processing speed) were also assessed 6 months after the end of the treatment. Results: The analysis of variance showed a significant Group*Time interaction in six out of ten tests of the cognitive evaluation. Post-hoc analysis revealed a significant improvement between the performances before and after the intervention only in the ADAPT-gr in tests evaluating verbal memory acquisition (p <0.05) and delayed recall (p = 0.001), verbal fluency (p = 0.01), sustained attention, concentration and information processing speed (p < 0.01). This last effect was maintained also after 6 months (p < 0.05). Conclusions: We concluded that COGNI-TRAcK represents a suitable tool to administer a personalized training to cognitively impaired subjects and that an adaptive working load is a crucial feature determining the effectiveness of cognitive treatment, allowing transfer effects to several cognitive domains and long-term maintenance of results. [ABSTRACT FROM AUTHOR]

This cross-sectional study has investigated the diagnostic and therapeutic management of patients suffering from multiple sclerosis (MS) in the Campania Region (Italy). A survey involving all the reference centers for MS in Campania Region was conducted from March to August 2011. Centers responded to a web-administered questionnaire on management and clinical characteristics of MS patients. In the study period, 3263 patients (mean age 37 years, 66 % females) accessed the centers. Patients received a first diagnosis of MS in 161 cases (4.9 %). About 37 % of the subjects without a previous diagnosis came to the centers on their own initiative. All patients underwent a complete neurological examination and expanded disability status scale. The other most common investigations were magnetic resonance imaging (44.0 %) and evoked potentials (22.1 %). The number of treated patients was 2797 (87.1 %). The most used drugs were interferon β and glatiramer acetate. The time between diagnosis and initiation of therapy exceeded 6 months in 32 % of cases. Second-line drugs were under-used: 16 % of patients who might benefit from them show high clinical and radiological disease activity despite treatment with immunomodulant drugs. The MS care management of the surveyed centers showed consistent margins for improvement in 2011. Even though these data do not represent the current situation, they can be used to monitor improvements in MS care. [ABSTRACT FROM AUTHOR]

The impact of the multiple sclerosis (MS) on the individual's ability to work is important especially because the onset of the disease occurs mainly between 20 and 30 years of age. This study evaluated different factors associated with job maintenance using a questionnaire that defined what factors are considered obstacle or help in work management. A cross-sectional study of people with MS was carried out in Italy. A total of 1016 individuals with MS were enrolled in the study. Our results showed that negative item related to job maintenance as 'attitudes of other in the workplace' was associated with a lower likelihood of being employed (OR 0.65, 95% CI 0.57-0.76), while 'your attitudes toward work' (OR 1.37, 95% CI 1.19-1.59), 'attitudes of other in the workplace' (OR 1.41, 95% CI 1.17-1.69) and 'personal considerations' (OR 1.54, 95% CI 1.23-1.93), positive items related to job maintenance, were associated with a higher likelihood of being employed. In addition, a poor quality of life and severity disease as well same demographic characteristics (i.e. to be resident in South Italy or in the Islands, living in own original family, have lower educational level) inhibited significantly the job maintenance together with a heavy job and a fixed-term contract. In conclusion, a complex set of variables contribute to the barriers faced by PwMS who are employed suggesting that different stakeholders may play an important role in difficult management of the work for people with MS. [ABSTRACT FROM AUTHOR]

Background: Altered integration of signals from visual (VIS), somatosensory (PROP) and vestibular system (VEST) lead to balance control impairments affecting the daily living activities of patients with multiple sclerosis (PwMS). As a consequence, tailored interventions could be crucial in improving efficacy of balance rehabilitation treatments. Objective: The objective of this paper is to assess the efficacy of tailored rehabilitation treatments for balance disorders based on visual, somatosensory and vestibular deficits versus traditional rehabilitation exercises. Methods: Thirty-two PwMS were assessed with the Berg Balance Scale (BBS), the composite score (CS) obtained by computerized dynamic posturography (CDP) test and the Modified Fatigue Impact Scale (MFIS). Based on CDP analysis, prevalent VIS, PROP or VEST deficits were identified and patients randomly allocated to a personalized (PRG) or traditional (TRG) rehabilitation group. Results: BBS score showed a significant difference between pre- and post-treatment scores of 6.3 and 2.0 points respectively for PRG and TRG. CS showed a significant difference between pre- and posttreatment scores of 16.6 and 7.6 points respectively for PRG and TRG. No interaction effect was found for MFIS score. Conclusions: BBS and CS showed changes in the PRG group that met clinical relevant difference, underlining that tailored rehabilitation interventions based on patient-specific sensory system impairment could improve balance and postural control in PwMS. [ABSTRACT FROM AUTHOR]

Background: Preliminary evidence suggests that palliative care may be useful for people with severe multiple sclerosis (MS). The aim of this study is to determine the effectiveness of a home-based palliative approach (HPA) for people with severe MS and their carers. Methods/design: This is a single-blind randomized controlled trial with a nested qualitative study. Seventy-five severe MS-carer dyads are being randomized (at three centers, one in each area of Italy) to HPA or usual care (UC) in a 2:1 ratio. Each center has a specially trained team consisting of four professionals (physician, nurse, psychologist, social worker). The team makes a comprehensive assessment of the needs of the dyads. HPA content is then agreed on, discussed with the patient's caring physician, and delivered over six months. The intervention is not intended to replace existing services. At later visits, the team checks the HPA delivery and reviews/modifies it as necessary. HPA and UC dyads are assessed at home by a blind examiner at baseline, and three and six months later; they also receive monthly telephone interviews. Dyads assigned to UC receive the examiner's visits and telephone interviews, but not the team visits. Primary outcome measures are changes in symptoms (Palliative care Outcome Scale-Symptoms-MS, POS-S-MS), and quality of life (the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), not assessed in patients with severe cognitive compromise) at three and six months. Other outcomes are changes in patient functional status and mood; changes in carer quality of life, mood and caregiving burden; costs; incorporation with standard care; unplanned hospital admissions; referrals to hospice; and deaths. The experience of participants will be evaluated qualitatively by individual semi-structured interviews (HPA patients and carers) and focus group meetings (HPA patients' caring physicians). Discussion: The results of our study will show whether the HPA is feasible and beneficial to people with severe MS and their carers living in the three Italian geographic areas. The nested qualitative study will add to the understanding of the strengths and limitations of the intervention. [ABSTRACT FROM AUTHOR]

Background: Few data on services for people with severe multiple sclerosis (MS) are available. The Palliative Network for Severely Affected Adults with MS in Italy (PeNSAMI) developed a home palliative care program for MS patients and carers, preceded by a literature review and qualitative study (here reported). Objective: To identify unmet needs of people with severe MS living at home by qualitative research involving key stakeholders, and theorize broad areas of intervention to meet those needs. Method: Data were collected from: at least 10 personal interviews with adults with severe MS (primary/secondary progressive, EDSS≥8.0); three focus group meetings (FGs) of carers of people with severe MS; and two FGs of health professionals (HPs). Grounded theory guided the analysis of interview and FG transcripts, from which the areas of intervention were theorized. Results: Between October 2012 and May 2013, 22 MS patients, 30 carers and 18 HPs participated. Forty-eight needs themes were identified, grouped into 14 categories and four domains. Seven, highly interdependent intervention areas were theorized. Patients had difficulties expressing needs; experiences of burden and loneliness were prominent, chiefly in dysfunctional, less affluent families, and among parent carers. Needs differed across Italy with requirements for information and access to services highest in the South. All participants voiced a strong need for qualified personnel and care coordination in day-to-day home care. Personal hygiene emerged as crucial, as did the need for a supportive network and preservation of patient/carer roles within family and community. Conclusions: Unmet needs transcended medical issues and embraced organizational and psychosocial themes, as well as health policies. The high interdependence of the seven intervention areas theorized is in line with the multifaceted approach of palliative care. At variance with typical palliative contexts, coping with disability rather than end-of-life was a major concern of patients and carers. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Evaluate the efficacy of outcome measures routinely used in a physical therapy service for Multiple Sclerosis (MS). DESIGN: We performed a retrospective review of 500 medical records of MS patients from the outpatients service of AISM Rehabilitation Centre, Genova, Italy. PATIENTS: All records of outpatients followed by AISM Rehabilitation Centre who underwent physical therapy from 2006 to 2008 were evaluated. METHODS: Modified Fatigue Impact Scale (MFIS) and Ambulation Index (AI) were reviewed for all records at the begin and at the end of the rehabilitation treatment. RESULTS: The number of assessments recorded was 295 in 209 patients. Out of the 209 patients, 133 were female and 76 were male. The mean age was 51.6 ± 11.68 years, the mean Expanded Disability Status Scale (EDSS) score was 4.98 ± 1.79, and 185 patients were ambulatory. In nonambulatory patients neither scale showed a significant increase. In ambulatory patients (275 assessments) significant changes were observed in AI, MFIS total score and subscores. CONCLUSION: Physical therapy has a positive impact on fatigue, and the MFIS seems to be a good outcome measure in ambulatory patients. The AI and MFIS seem to be not indicated for use in non-ambulatory patients. [ABSTRACT FROM AUTHOR]

Background: Fatigue is one of the most common disabling symptoms in multiple sclerosis (MS). There is growing evidence in the literature for beneficial effects of magnetic fields on different MS symptoms and this has been reported to be beneficial in patients with MS, especially those with fatigue.Objectives: The aim of the study was to assess the effects on primary fatigue with a pulsed systemic low frequency magnetic field by means of clinical scales in a population of MS subjects.Methods: Randomized double-blind cross-over trial with 50 MS subjects with primary fatigue who were recruited among those followed as outpatients at the AISM Rehabilitation Centre, Genova, Italy. Subjects were randomized into two groups: magnetic field group and sham therapy group and evaluated with the Modified Fatigue Impact Scale (MFIS), the Fatigue Severity Scale (FSS), VAS and Time Walking Test 10 meter (TWT10m.) at the time points of the study. Each group received both sham therapy and magnetic field therapy with a wash-out period of 5 months. Subjects were treated for 24 min per session, three times per week, for 8 weeks. Statistical analysis was performed using multivariate analysis.Results: Results showed a statistically significant improvement in MFIS Physical Score for T0 − T1 (p < 0.05) for TIME but not for TREATMENT and TIME*TREATMENT factors. No statistically significant differences were found for all other parameters considered in the study.Conclusions: Exposure to a low frequency magnetic field, within the parameters of this treatment protocol, has no advantage over sham exposure in reducing the impact of fatigue. [ABSTRACT FROM AUTHOR]

Objective. The objective of this study was to assess the relationship between active smoking as well as environmental tobacco smoke (ETS) exposure and severe small for gestational age (SGA) at term in a sample of pregnant Italian women. Methods. A case-control study was conducted in nine cities in Italy between October 1999 and September 2000. Cases of severe SGA were singleton, live born, at term children with a birth weight ≤ 5th percentile for gestational age. Controls (10:1 to cases) were enrolled from among singleton at term births that occurred in the same hospitals one or two days after delivery of the case, with a birth weight > 10th percentile for gestational age. A total of 84 cases of severe SGA and 858 controls were analyzed. A self-administered questionnaire was used to assess active smoking and ETS exposure, as well as potential confounders. Results. Multivariate logistic regression analysis showed a relationship between active smoking during pregnancy and severe SGA (adjusted odds ratio (OR) 2.10, 95% confidence interval (CI) 1.13-3.68). ETS exposure was associated with severe SGA (adjusted OR 2.51, 95% CI 1.59-3.95) with a dose-response relationship to the number of smokers in the home. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the relationship between preterm/early preterm delivery and active smoking as well as environmental tobacco smoke (ETS) exposure in a sample of pregnant Italian women. A case–control study was conducted in nine cities in Italy between October 1999 and September 2000. Cases of preterm birth were singleton babies born before the 37th gestational week; babies born before the 35th gestational week were considered early preterm births. Controls were babies with gestational ages ≥ 37th week. A total of 299 preterm cases (including 105 early preterm) and 855 controls were analysed. A self-administered questionnaire was used to assess active smoking and ETS exposure, as well as potential confounders. Multivariable logistic regression analysis showed a relationship between active smoking during pregnancy and preterm/early preterm delivery [adjusted ORs: 1.53; 95% CI 1.05, 2.21 and 2.00; 95% CI 1.16, 3.45, respectively]. A dose–response relationship was found for the number of cigarettes smoked daily. The adjusted ORs were 1.54 and 1.69 for preterm babies and 1.90 and 2.46 for early preterm babies for 1–10 and >10 cigarettes/day respectively. ETS exposure was associated with early preterm delivery [adjusted OR 1.56; 95% CI 0.99, 2.46] with a dose–response relationship with the number of smokers in the home. Smoking during pregnancy was strongly associated with preterm delivery with a dose–response effect. ETS exposure in non-smoking women was associated only with early preterm delivery. [ABSTRACT FROM AUTHOR]

Unfortunately in the original publication, the affiliation of the author Maria Pia Amato was incorrect. The author inadvertently missed out to include her second affiliation. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is common in multiple sclerosis (MS), but the definition of the best cognitive rehabilitation tools and features is still an open issue among researchers. The aims of the present study were to evaluate the effectiveness of COGNI-TRAcK (a customized application software delivering personalized working memory-based exercises) on cognitively impaired people with MS and to investigate the effects of an adaptive vs. a non-adaptive cognitive training administered by means of COGNI-TRAcK.Methods: Twenty eight patients (20 women, age 47.5 ± 9.3 years, Expanded Disability Status Scale score 3.8 ± 1.9) were randomized in two homogeneous groups, both performing a 8-week home-based cognitive rehabilitation treatment by means of COGNI-TRAcK. The study group (ADAPT-gr) underwent an adaptive training given by the automatic adjustment of tasks difficulty to the subjects' performance, whilst the control group (CONST-gr) was trained at constant difficulty levels. Before and after the treatment, patients' cognitive status was assessed using a gold standard neuropsychological evaluation. Moreover, the mostly affected cognitive domains in MS (i.e., attention, concentration and information processing speed) were also assessed 6 months after the end of the treatment.Results: The analysis of variance showed a significant Group*Time interaction in six out of ten tests of the cognitive evaluation. Post-hoc analysis revealed a significant improvement between the performances before and after the intervention only in the ADAPT-gr in tests evaluating verbal memory acquisition (p <0.05) and delayed recall (p = 0.001), verbal fluency (p = 0.01), sustained attention, concentration and information processing speed (p < 0.01). This last effect was maintained also after 6 months (p < 0.05).Conclusions: We concluded that COGNI-TRAcK represents a suitable tool to administer a personalized training to cognitively impaired subjects and that an adaptive working load is a crucial feature determining the effectiveness of cognitive treatment, allowing transfer effects to several cognitive domains and long-term maintenance of results. [ABSTRACT FROM AUTHOR]

Background: Preliminary evidence suggests that palliative care may be useful for people with severe multiple sclerosis (MS). The aim of this study is to determine the effectiveness of a home-based palliative approach (HPA) for people with severe MS and their carers.Methods/design: This is a single-blind randomized controlled trial with a nested qualitative study. Seventy-five severe MS-carer dyads are being randomized (at three centers, one in each area of Italy) to HPA or usual care (UC) in a 2:1 ratio. Each center has a specially trained team consisting of four professionals (physician, nurse, psychologist, social worker). The team makes a comprehensive assessment of the needs of the dyads. HPA content is then agreed on, discussed with the patient's caring physician, and delivered over six months. The intervention is not intended to replace existing services. At later visits, the team checks the HPA delivery and reviews/modifies it as necessary. HPA and UC dyads are assessed at home by a blind examiner at baseline, and three and six months later; they also receive monthly telephone interviews. Dyads assigned to UC receive the examiner's visits and telephone interviews, but not the team visits. Primary outcome measures are changes in symptoms (Palliative care Outcome Scale-Symptoms-MS, POS-S-MS), and quality of life (the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), not assessed in patients with severe cognitive compromise) at three and six months. Other outcomes are changes in patient functional status and mood; changes in carer quality of life, mood and caregiving burden; costs; incorporation with standard care; unplanned hospital admissions; referrals to hospice; and deaths. The experience of participants will be evaluated qualitatively by individual semi-structured interviews (HPA patients and carers) and focus group meetings (HPA patients' caring physicians).Discussion: The results of our study will show whether the HPA is feasible and beneficial to people with severe MS and their carers living in the three Italian geographic areas. The nested qualitative study will add to the understanding of the strengths and limitations of the intervention.Trial Registration: The trial was registered with Current Controlled Trials (identifier: ISRCTN73082124) on 19 June 2014. [ABSTRACT FROM AUTHOR]