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Purpose: This study aims to evaluate the feasibility and effectiveness of a mindfulness-based group intervention (The COndiVIDere program) delivered online to people with MS (PwMS) in the time of COVID-19., Materials and Methods: This is a single-arm longitudinal study with a nested qualitative study. The COndiVIDere program is composed of five weekly sessions (1-h each) plus three booster monthly sessions. Data were collected immediately before the beginning of the program, after the five weekly sessions, and at 3- and 6-month follow-ups., Results: Fifty PwMS participated in the program. Participants improved in anxiety, stress, loneliness and mindfulness ("non-judgmental inner experience" component). Improvements on most outcomes occurred at post-intervention and reached the statistically significant threshold at 3-month follow-up. Mindfulness improvements keep increasing at each time point. Qualitative data confirmed the COndiVIDere program feasibility and the positive psychological impacts on participants. Mindfulness, compassion and the group setting were considered the most important active elements., Conclusions: Study findings support COndiVIDere feasibility and effectiveness with PwMS and its broad applicability in this population.

Purpose: The Comprehensive assessment of Acceptance and Commitment Therapy (CompACT) is a 23-item questionnaire measuring psychological flexibility, a quality of life protective factor. An 18-item version was recently produced. We assessed validity and reliability of CompACT, and equivalence of paper and electronic (eCompACT) versions in people with multiple sclerosis (PwMS) in Italy, Germany and Spain., Methods: We used confirmatory factor analysis and assessed CompACT-23 and CompACT-18 measurement invariance between the three language versions. We assessed construct validity (Spearman's correlations) and internal consistency (Cronbach's alpha). Test-retest reliability (intraclass correlation coefficient, ICC) and equivalence of paper and eCompACT (ICC and linear regression model for repeated measures) were assessed in subsamples of PwMS., Results: A total of 725 PwMS completed the study. The three-factor structure of the CompACT-23 showed poor fit (RMSEA 0.07; CFI 0.82; SRMR 0.08), while the fit of the CompACT-18 was good (RMSEA 0.05; CFI 0.93; SRMR 0.05). Configural and partial metric invariance were confirmed, as well as partial scalar invariance (reached when five items were allowed to vary freely). The CompACT-18 showed good internal consistency (all alpha ≥ 0.78); and test-retest reliability (all ICCs ≥ 0.86). Equivalence between paper and eCompACT was excellent (all ICCs ≥ 0.86), with no mode, order, or interaction effects., Conclusion: Results support using the refined CompACT-18 as a three-factor measure of psychological flexibility in PwMS. Paper and eCompACT-18 versions are equivalent. CompACT-18 can be used cross-culturally, but sub-optimal scalar invariance suggests that direct comparison between the three language versions should be interpreted with caution., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: Implementation of advance care planning (ACP) in people with progressive multiple sclerosis (PwPMS) is limited. We aimed to involve users (PwPMS, significant others, and healthcare professionals involved in PwPMS care) in the evaluation and refinement of a booklet to be used during the ACP conversations., Methods: This qualitative study consisted of cognitive interviews with PwPMS and significant others and a focus group with healthcare professionals from three Italian centers. We analyzed the interviews using the framework method and the focus group using thematic analysis., Results: We interviewed 10 PwPMS (3 women; median age 54 years; median Expanded Disability Status Scale score 6.0) and three significant others (2 women; 2 spouses and one daughter). The analysis yielded three themes: booklet comprehensibility and clarity, content acceptability and emotional impact, and suggestions for improvement. Twelve healthcare professionals (7 neurologists, 3 psychologists, one nurse, and one physiotherapist) participated in the focus group, whose analysis identified two themes: booklet's content importance and clarity and challenges to ACP implementation. Based on analysis results, we revised the booklet (text, layout, and pictures) and held a second-round interviews with two PwPMS and one significant other. The interviewees agreed on the revisions but reaffirmed their difficulty in dealing with the topic and the need for a physician when using the booklet., Conclusions: Appraisal of the booklet was instrumental in improving its acceptability and understandability before using it in the ConCure-SM feasibility trial. Furthermore, our data reveal a lack of familiarity with ACP practice in the Italian context., (© 2023. The Author(s).)

Background: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is one of the most commonly-used MS-specific health-related quality of life (HRQOL) measures. It is a multidimensional, MS-specific HRQOL inventory, which includes the generic SF-36 core items, supplemented with 18 MS-targeted items. Availability of an adaptive short version providing immediate item scoring may improve instrument usability and validity. However, multidimensional computerized adaptive testing (MCAT) has not been previously applied to MSQOL-54 items. We thus aimed to apply MCAT to the MSQOL-54 and assess its performance., Methods: Responses from a large international sample of 3669 MS patients were assessed. We calibrated 52 (of the 54) items using bifactor graded response model (10 group factors and one general HRQOL factor). Then, eight simulations were run with different termination criteria: standard errors (SE) for the general factor and group factors set to different values, and change in factor estimates from one item to the next set at < 0.01 for both the general and the group factors. Performance of the MCAT was assessed by the number of administered items, root mean square difference (RMSD), and correlation., Results: Eight items were removed due to local dependency. The simulation with SE set to 0.32 (general factor), and no SE thresholds (group factors) provided satisfactory performance: the median number of administered items was 24, RMSD was 0.32, and correlation was 0.94., Conclusions: Compared to the full-length MSQOL-54, the simulated MCAT required fewer items without losing precision for the general HRQOL factor. Further work is needed to add/integrate/revise MSQOL-54 items in order to make the calibration and MCAT performance efficient also on group factors, so that the MCAT version may be used in clinical practice and research., (© 2023. The Author(s).)

Purpose: This study aims to evaluate the effectiveness of an Acceptance and Commitment Therapy-based group resilience intervention (The REsilience and Activities for every DaY program, READY) delivered to people with MS (PwMS) via frontline Italian services., Materials and Methods: This is a single-arm longitudinal study (with a nested qualitative study). READY is composed of seven weekly in-person sessions (2.5-h each) plus a booster session five weeks later. Data were collected immediately before the program, after the booster session, and at 3-months follow-up., Results: Thirty-three READY groups (237 participants) were run by thirty-three trained psychologists. Participants improved in resilience (primary outcome), anxiety, depression, stress, health-related quality of life (HRQoL), and psychological flexibility and associated processes (acceptance, defusion, and values). Improvements on most outcomes occurred post-intervention and were maintained at a 3-month follow-up. No demographic or illness variables predicted these improvements. Psychological flexibility mediated improvements in resilience, anxiety, depression, stress, and HRQoL. Qualitative data confirmed READY feasibility and the positive psychological impacts on participants., Conclusions: Study findings support READY effectiveness with PwMS, its broad applicability in this population, and its delivery through frontline services.IMPLICATIONS FOR REHABILITATIONREADY for MS is a highly structured, brief manualized group intervention.It is effective in improving participants' psychological functioning (resilience, anxiety, depression, stress, HRQoL, psychological flexibility, and related ACT processes).Psychological flexibility mediated the improvements in resilience, anxiety, depression, stress, HRQoL.READY can be effectively delivered through frontline services for PwMS without limitation in terms of participants' demographic and illness characteristics.

Purpose: This single-arm longitudinal study evaluated the effectiveness of a program for training psychologists in delivering an acceptance and commitment therapy-based program (REsilience and Activities for every DaY; READY) for people with multiple sclerosis (PwMS)., Materials and Methods: The training encompassed three phases: (1) training workshop; (2) READY participation; (3) READY delivery to PwMS. Self-report data were collected immediately before the workshop, before and after participation in READY, and at 3- and 15-month follow-ups., Results: Forty psychologists successfully completed the training. The training was effective in fostering the acquisition of knowledge and skills for effective delivery of READY to PwMS. Participants improved over the course of training in resilience, positive affect, wellbeing, psychological flexibility, and associated processes. These improvements peaked during the participation in READY phase and continued to accrue at a slower rate three months later. Psychological flexibility mediated the improvements in resilience, positive affect, and wellbeing. Qualitative data confirmed the personal, professional, and multiple sclerosis (MS) psychologist community level positive training impacts., Conclusions: The training fostered positive professional and personal development in trainees and consolidated the integration of READY into a frontline service for PwMS. To date, more than 50 READY groups for PwMS have been conducted in Italy.Implications for rehabilitationTraining psychologists in delivering an acceptance and commitment therapy (ACT)-based resilience intervention for people with multiple sclerosis (MS) is associated with positive personal and professional impacts for the trainees.The training program strengthened the sense of community among members of the professional network who attended as trainees.In ACT training, psychological flexibility plays a key role in improving resilience, positive affect, and wellbeing in trainees, and is therefore an important intervention target.ACT training for practitioners fosters the integration of ACT-based interventions into frontline services.

Introduction: REsilience and Activities for every DaY (READY) is an Acceptance and Commitment Therapy-based group resilience-training program that has preliminary empirical support in promoting quality of life and other psychosocial outcomes in people with multiple sclerosis (PwMS). Consistent with the Medical Research Council framework for developing and evaluating complex interventions, we conducted a pilot randomized controlled trial (RCT), followed by a phase III RCT. The present paper describes the phase III RCT protocol., Methods and Analysis: This is a multi-centre cluster RCT comparing READY with a group relaxation program (1:1 ratio) in 240 PwMS from eight centres in Italy (trial registration: isrctn.org Identifier: ISRCTN67194859). Both interventions are composed of 7 weekly sessions plus a booster session five weeks later. Resilience (primary outcome), mood, health-related quality of life, well-being and psychological flexibility will be assessed at baseline, after the booster session, and at three and six month follow-ups. If face-to-face group meetings are interrupted because of COVID-19 related-issues, participants will be invited to complete their intervention via teleconferencing. Relevant COVID-19 information will be collected and the COVID-19 Peritraumatic Distress scale will be administered (ancillary study) at baseline and 3-month follow-up. Analysis will be by intention-to-treat to show superiority of READY over relaxation. Longitudinal changes will be compared between the two arms using repeated-measures, hierarchical generalized linear mixed models., Conclusion: It is expected that his study will contribute to the body of evidence on the efficacy and effectiveness of READY by comparing it with an active group intervention in frontline MS rehabilitation and clinical settings. Results will be disseminated in peer-reviewed journals and at other relevant conferences., Competing Interests: AMG reports a grant from Rehabilitation in Multiple Sclersis (RIMS) during the conduct of the study. AS reports grants from Fondazione Italiana Sclerosi Multipla (FISM), during the conduct of the study; personal fees from Biogen Idec, Merck Serono, Novartis, Almirall, and Excemed. As a staff member of the University of Queensland and co-Author of the READY program, KP receives royalties from UniQuest for commercial (not research) licensing arrangements entered into by third parties who want to deliver the program. PC has received honoraria for speaking or consultation fees from Novartis and Biogen, has received funding for travel to attend scientific events or speaker honoraria from Merck Serono, Biogen Idec, Teva and Roche. He has also received institutional research support from Merk-Serono, Novartis and Roche. He is also principal investigator in clinical trials for Biogen, Merck Serono, and Roche. This does not alter our adherence to PLOS ONE policies on sharing data. All the other authors reports no competing interests.

Purpose: The Comprehensive assessment of Acceptance and Commitment Therapy (ACT) processes (CompACT) is a 23-item self-report questionnaire assessing psychological flexibility, which is the overarching construct underpinning the ACT framework. We conducted a two-phase project to develop validated versions of the CompACT in three languages: phase 1-cross-cultural adaptation; and phase 2-psychometric validation of the questionnaire for use in Italy, Germany and Spain. This article focuses on the first phase., Methods: We translated and culturally adapted the CompACT in the three target languages, following the ISPOR TCA Task Force guidelines. The process was overseen by a translation panel (three translators, at least two multiple sclerosis (MS) researchers and a lay person), ACT experts and clinicians from the research team of each country and the original CompACT developers. We debriefed the new questionnaire versions via face-to-face interviews with a minimum of four adults from the general population (GP) and four adults with MS in each country., Results: The translation-adaptation process went smoothly in the three countries, with some items (7 in Italy, 4 in Germany, 6 in Spain) revised after feedback from ACT experts. Cognitive debriefing showed that the CompACT was deemed easy to understand and score in each target country by both GP and MS adults., Conclusions: The Italian, German and Spanish versions of the CompACT have semantic, conceptual and normative equivalence to the original scale and good content validity. Our findings are informative for researchers adapting the CompACT and other self-reported outcome measures into multiple languages and cultures.

Background: MSQOL-54 is a multidimensional, widely-used, health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). Findings from the validation study suggested that the two MSQOL-54 composite scores are correlated. Given this correlation, it could be assumed that a unique total score of HRQOL may be calculated, with the advantage to provide key stakeholders with a single overall HRQOL score. We aimed to assess how well the bifactor model could account for the MSQOL-54 structure, in order to verify whether a total HRQOL score can be calculated., Methods: A large international database (3669 MS patients) was used. By means of confirmatory factor analysis, we estimated a bifactor model in which every item loads onto both a general factor and a group factor. Fit of the bifactor model was compared to that of single and two second-order factor models by means of Akaike information and Bayesian information criteria reduction. Reliability of the total and subscale scores was evaluated with Mc Donald's coefficients (omega, and omega hierarchical)., Results: The bifactor model outperformed the two second-order factor models in all the statistics. All items loaded satisfactorily (≥ 0.40) on the general HRQOL factor, except the sexual function items. Omega coefficients for total score were very satisfactory (0.98 and 0.87). Omega hierarchical for subscales ranged between 0.22 to 0.57, except for the sexual function (0.70)., Conclusions: The bifactor model is particularly useful when it is intended to acknowledge multidimensionality and at the same time take account of a single general construct, as the HRQOL related to MS. The total raw score can be used as an estimate of the general HRQOL latent score., (© 2021. The Author(s).)

Psychological distress imposed by the SARS-CoV-2 outbreak particularly affects patients with pre-existing medical conditions, and the progression of their diseases. Patients who fail to keep scheduled medical appointments experience a negative impact on care. The aim of this study is to investigate the psychosocial factors contributing to the cancellation of medical appointments during the pandemic by patients with pre-existing health conditions. Data were collected in eleven Italian hospitals during the last week of lockdown, and one month later. In order to assess the emotional impact of the SARS-CoV-2 outbreak and the subject's degree of psychological flexibility, we developed an ad hoc questionnaire (ImpACT), referring to the Acceptance and Commitment Therapy (ACT) model. The Impact of Event Scale-Revised (IES-R), the Depression, Anxiety and Stress Scale (DASS) and the Cognitive Fusion Questionnaire (CFQ) were also used. Pervasive dysfunctional use of experiential avoidance behaviours (used with the function to avoid thought, emotions, sensations), feelings of loneliness and high post-traumatic stress scores were found to correlate with the fear of COVID-19, increasing the likelihood of cancelling medical appointments. Responding promptly to the information and psychological needs of patients who cancel medical appointments can have positive effects in terms of psychological and physical health.

Background: ManTra is a mixed-methods, co-production research project for developing an intervention (resource) for people with newly diagnosed secondary progressive multiple sclerosis (pwSPMS) in Italy and Germany. In previous project actions, six resources were outlined, meeting the needs prioritized by pwSPMS. Aims: This study aims to achieve multiple-stakeholder consensus on the most suitable resource and to refine the consensus resource. Methods: Two nominal group technique (NGT) meetings were held, one in Milan and one in Hamburg. Participants were pwSPMS (five in Italy/six in Germany), pwSPMS significant others (SOs, four/five), healthcare professionals (HPs, seven/four), and health service researchers/patient and citizen organizations representatives (HPCORs, five/five). Two of the four resources discussed in each meeting were the same in Italy and Germany: "Promoting the engagement of pwSPMS: a program for the patients and the HPs" and "Enriched physiotherapy program for pwSPMS." The other two were "A personalized care plan for pwSPMS" and "Roadmap for social and economic benefits" in Italy and "Metacognitive and everyday life training for pwSPMS" and "Psychological support for pwSPMS" in Germany. Each meeting consisted of two plenary sessions and a parallel group session (four stakeholder groups: pwSPMS, SOs, HPs, and HPCORs) in between. Meetings' narratives were analyzed thematically. Results: The two meetings were rich in participation and discussion. In Italy, the consensus resource was "A personalized care plan for pwSPMS." Refinements included enrichment with pwSPMS engagement, inclusion of additional HPs, improved definition of the MS nurse's role within the interdisciplinary panel, and community care integration. In Germany, the consensus resource was "Psychological support for pwSPMS." Refinements included reshaping this resource into a more comprehensive and adaptive rehabilitation intervention and training the psychologist in recognizing client's rehabilitative needs and enhancing his/her autonomy. Conclusions: The NGT eased multiple-stakeholder deliberation and resource fine-tuning in both countries., (Copyright © 2020 Giovannetti, Barabasch, Giordano, Quintas, Barello, Graffigna, Alfieri, Schiffmann, Muche-Borowski, Borreani, Heesen, Solari and the ManTra project.)

Introduction: An Australian case series study demonstrated the effectiveness of the REsilience and Activities for every DaY for people with multiple sclerosis (READY for MS), a resilience group training program based on Acceptance and Commitment Therapy, in improving quality of life in people with MS. This study aimed to evaluate the feasibility and acceptability of the Italian READY for MS program, and to preliminary assess its efficacy when compared to an active control intervention (group relaxation)., Methods: Single-blind phase II randomized controlled trial (RCT) and nested qualitative study (ISRCTN registration number: 38971970). Health-related quality of life (primary study outcome), mood, resilience, psychological flexibility and its protective factors were measured at baseline, after seven, 12 and 24 weeks. READY participants completed the purpose-built satisfaction questionnaire after 12 weeks. After trial completion, the control group also received READY. One-to-one participant interviews were conducted within three months of finishing the READY groups., Results: Four intervention groups were conducted with 39 participants (20 READY, 19 relaxation). Two patients (READY) withdrew before beginning the intervention due to unexpected work commitments. Feasibility and acceptability of READY were good, with high participant engagement and satisfaction. No statistical effects of READY were detected vs relaxation. Thirty participants were interviewed (18 READY; 12 relaxation + READY). Content data analysis revealed seven overarching themes: "Attitudes towards participation"; "Perceptions of program composition"; "Program impacts on life domains"; "Program active elements"; "Program improvement trajectories"; "Program differences and similarities"; "Suggested READY improvements"., Conclusion: READY was well accepted by MS patients with varied socio-demographic and clinical characteristics. Qualitative (but not quantitative) data provided evidence in favour of READY. Our findings will inform methodological and intervention refinements for the multi-centre RCT that will follow., Competing Interests: AS reports grants from Fondazione Italiana Sclerosi Multipla (FISM), during the conduct of the study; personal fees from Biogen Idec, Merck Serono, Novartis, Almirall, and Excemed. As a staff member of the University of Queensland and co-Author of the READY program, KP receives royalties from UniQuest for commercial (not research) licensing arrangements entered into by third parties who want to deliver the program. PC acted as an Advisory Board member of Biogen and Novartis; received funding for traveling from Biogen, Merck, Teva, Novartis; received honoraria for speaking or writing from Biogen and Novartis. He received support for research project by Novartis and Merk and is involved as principal investigator or co-investigator in clinical trials for Teva, Novartis, Biogen and Merk. RQ received funding for conducting research and clinical projects from AIM Education (Novartis) and Fondazione Serono (Merck) in 2019. This does not alter our adherence to PLOS ONE policies on sharing data.

Purpose: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is a specific multiple sclerosis (MS) health-related quality of life inventory consisting of 52 items organized into 12 subscales plus two single items. No study was found in literature assessing its measurement invariance across language versions. We investigated whether MSQOL-54 items provide unbiased measurements of underlying constructs across Italian and English versions., Methods: Three constrained levels of measurement invariance were evaluated: configural invariance where equivalent numbers of factors/factor patterns were required; metric invariance where equivalent factor loadings were required; and scalar invariance where equivalent item intercepts between groups were required. Comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR) fit indices and their changes between nested models were used to assess tenability of invariance constraints., Results: Overall, the dataset included 3669 MS patients: 1605 (44%) Italian, mean age 41 years, 62% women, 69% with mild level of disability; 2064 (56%) English-speaking (840 [41%] from North America, 797 [39%] from Australasia, 427 [20%] from UK and Ireland), mean age 46 years, 83% women, 54% with mild level of disability. The configural invariance model showed acceptable fit (RMSEA = 0.052, CFI = 0.904, SRMR = 0.046); imposing loadings and intercepts equality constraints produced negligible worsening of fit (ΔRMSEA < 0.001, ΔCFI = - 0.002, ΔSRMR = 0.002 for metric invariance; ΔRMSEA = 0.003, ΔCFI = - 0.013, ΔSRMR = 0.003 for scalar invariance)., Conclusions: These findings support measurement invariance of the MSQOL-54 across the two language versions, suggesting that the questionnaire has the same meaning and the same measurement paramaters in the Italian and English versions.

Background: Conversion to secondary progressive multiple sclerosis (SPMS) is associated with a relatively poor prognosis, and SPMS is responsible for the majority of the social and economic costs associated with MS. Managing the Transition to SPMS (ManTra) is a mixed methods project conducted in Italy and Germany aimed to set up a user-led resource to empower and improve the quality of life of newly diagnosed SPMS patients., Aims: To assess the experiences and the needs of Italian people who recently converted to SPMS, patient significant others (SOs), neurologists and other health professionals (HPs)., Methods: We conducted 15 personal semistructured interviews (PSIs) with SPMS patients who transitioned up to five years, and three focus group meetings (FGMs), one of SPMS SOs, one of neurologists, and one of other HPs. Participants were purposely selected from the three geographic areas of Italy, and varied in terms of gender, education and (for patients) disease severity. PSIs and FGMs were audiorecorded, transcribed and analyzed by two researchers using the framework analysis., Results: One hundred sub-categories were identified, grouped into 13 categories and four themes: 'awareness of the transition', 'communication of the transition', 'dealing with symptoms worsening', and 'needs'. The major unmet needs were collected in four dimensions 'organization and management; 'empowerment training'; 'information'; and 'policies'., Conclusions: Two are the main findings: first, the widespread lack of awareness around the transition; second, the need to improve the quality of the care pathway in the Italian context. It was particularly stressed the need for a holistic and multidisciplinary approach (with patients and SOs as members of the team), the development of an ad hoc plan of follow up visits with easy access to MS specialists' consultation/treatment; specialized training for each stakeholders; more information on SPMS, daily management and changes at policy level., Competing Interests: AS is affilliated with Biogen Idec, Merck Serono, Novartis, Almirall, and Excemed. CH is affiliated with Biogen, Genzyme, Sanofi Aventis, Merck, Novartis, and Roche. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: This cross-sectional study aims to identify the predictors of work-related difficulties in a sample of employed persons with multiple sclerosis as addressed with the Multiple Sclerosis Questionnaire for Job Difficulties. Materials and methods: Hierarchical linear regression analysis was conducted to identify predictors of work difficulties: predictors included demographic variables (age, formal education), disease duration and severity, perceived disability and psychological variables (cognitive dysfunction, depression and anxiety). The targets were the questionnaire's overall score and its six subscales. Results: A total of 177 participants (108 females, aged 21-63) were recruited. Age, perceived disability and depression were direct and significant predictors of the questionnaire total score, and the final model explained 43.7% of its variation. The models built on the questionnaire's subscales show that perceived disability and depression were direct and significant predictors of most of its subscales. Conclusions: Our results show that, among patients with multiple sclerosis, those who were older, with higher perceived disability and higher depression symptoms have more and more severe work-related difficulties. The Multiple Sclerosis Questionnaire for Job Difficulties can be fruitfully exploited to plan tailored actions to limit the likelihood of near-future job loss in persons of working age with multiple sclerosis. Implications for rehabilitation Difficulties with work are common among people with multiple sclerosis and are usually addressed in terms of unemployment or job loss. The Multiple Sclerosis Questionnaire for Job Difficulties is a disease-specific questionnaire developed to address the amount and severity of work-related difficulties. We found that work-related difficulties were associated to older age, higher perceived disability and depressive symptoms. Mental health issues and perceived disability should be consistently included in future research targeting work-related difficulties.

Background: Few studies have investigated the experiences of patients around the conversion to secondary progressive multiple sclerosis (SPMS). ManTra is a mixed-method, co-production research project conducted in Italy and Germany to develop an intervention for newly-diagnosed SPMS patients. In previous project actions, we identified the needs and experiences of patients converting to SPMS via literature review and qualitative research which involved key stakeholders. Aims: The online patient survey aimed to assess, on a larger and independent sample of recently-diagnosed SPMS patients: (a) the characteristics associated to patient awareness of SPMS conversion; (b) the experience of conversion; (c) importance and prioritization of the needs previously identified. Methods: Participants were consenting adults with SPMS since ≤5 years. The survey consisted of three sections: on general and clinical characteristics; on experience of SPMS diagnosis disclosure (aware participants only); and on importance and prioritization of 33 pre-specified needs. Results: Of 215 participants, those aware of their SPMS diagnosis were 57% in Italy vs. 77% in Germany ( p = 0.004). In both countries, over 80% of aware participants received a SPMS diagnosis from the neurologist; satisfaction with SPMS disclosure was moderate to high. Nevertheless, 28-35% obtained second opinions, and 48-56% reported they did not receive any information on SPMS. Participants actively seeking further information were 63% in Germany vs. 31% in Italy ( p < 0.001). Variables independently associated to patient awareness were geographic area (odds ratio, OR 0.32, 95% CI 0.13-0.78 for Central Italy; OR 0.21, 95% CI 0.08-0.58 for Southern Italy [vs. Germany]) and activity limitations (OR 7.80, 95% CI 1.47-41.37 for dependent vs. autonomous patients). All pre-specified needs were scored a lot or extremely important, and two prioritized needs were shared by Italian and German patients: "physiotherapy" and "active patient care involvement." The other two differed across countries: "an individualized health care plan" and "information on social rights and policies" in Italy, and "psychological support" and "cognitive rehabilitation" in Germany. Conclusions: Around 40% of SPMS patients were not aware of their disease form indicating a need to improve patient-physician communication. Physiotherapy and active patient care involvement were prioritized in both countries.

Background: We recently devised a shortened version of the 54-item Multiple Sclerosis Quality of Life (MSQOL-54) in paper (MSQOL-29, consisting of 25 items forming 7 subscales and 4 single items, and one filter question for 3 'sexual function' items) and electronic format (eMSQOL-29)., Objectives: To prospectively assess eMSQOL-29 psychometric properties, acceptability/equivalence versus MSQOL-29., Methods: Multiple sclerosis (MS) patients ( n = 623; Expanded Disability Status Scale (EDSS) range 0.0-9.0) completed eMSQOL-29, Hospital Anxiety and Depression Scale, Functional Assessment of MS (FAMS), European Quality of life Five Dimensions-3L, and received EDSS and Symbol Digit Modalities Test (SDMT). Equivalence versus MSQOL-29 was assessed in 242 patients (randomized cross-over design)., Results: 'Sexual function' items were filtered out by 273 patients (47%). No multi-item scale had floor effect, while five had ceiling effect. Cronbach's alpha range was 0.88-0.90. Confirmatory factor analysis showed good overall fit and the two-factor solution for composite scores was confirmed. Criterion validity was sub-optimal for 'cognitive function' (vs SDMT, r = 0.25) and 'social function' (vs FAMS social function, r = 0.38). eMSQOL-29 equivalence was confirmed and its acceptability was good., Conclusion: eMSQOL-29 showed good internal consistency, factor structure and no floor effect, while most subscales had some ceiling effect. Criterion validity was sub-optimal for two subscales. Equivalence and acceptability were good.

Pain assessment in patients with disorders of consciousness (DoC) is a controversial issue for clinicians, who require tools and standardised procedures for testing nociception in non-communicative patients. The aims of the present study were, first, to analyse the psychometric properties of the Italian version of the Nociception Coma Scale and, second, to evaluate pressure pain thresholds in a group of patients with DoC. The authors conducted a multi-centre study on 40 healthy participants and 60 DoC patients enrolled from six hospitals in Italy. For each group an electronic algometer was used to apply all nociceptive pressure stimuli. Our results show that the Italian version of the NCS retains the good psychometric properties of the original version and is therefore suitable for standardised pain assessment in clinical practice. In our study, pressure pain thresholds measured in a group of patients in vegetative and minimally conscious state were relatively lower than pain threshold values found in a group of healthy participants. Such findings motivate additional investigation on possible pain sensitisation in patients with severe brain injury and multiple co-morbidities, and on application of tailored therapeutic approaches useful for pain management in patients unable verbally to communicate their feelings.

Objectives: Patients with chronic migraine (CM) display a considerable amount of comorbidities, particularly psychiatric and cardiovascular, and the presence of multiple comorbidities, that is, the so-called multimorbidity, is a risk factor for migraine chronification or maintenance of CM. Our aim was to address the rate and impact of multimorbidity in patients with CM and medication overuse headache (MOH)., Materials & Methods: In a sample of patients with CM attending a structured withdrawal for coexisting MOH, we defined multimorbidity as the presence of two or more conditions in addition to CM-MOH. We compared patients with and without multimorbidity for demographic and clinical variables, quality of life, and disability; we also tested whether patients with multimorbidity had higher likelihood to attend emergency room, relapse into CM, and require further withdrawal treatments by 12 months., Results: One hundred and ninety-four patients were enrolled as follows: 61% had at least one comorbidity, the most common being mental (34%), circulatory (18%), and endocrine conditions (13%); 32% were multimorbidity cases. Patients with multimorbidity had higher headaches frequency, older age, lower education and lower employment rates, higher disability and lower QoL. They were more frequently opioids/barbiturates overusers and were more likely to attend ER (OR: 2.36), relapse into CM (OR: 2.19), and undergo another withdrawal (OR: 2.75) by 12 months after discharge, after controlling for age, gender, years of education, and headache frequency., Conclusions: Recognizing multimorbidity in patients with CM-MOH is important to enhance the management of these complex patients, who are at risk of polypharmacy and increased health care utilization., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 ISRCTN73082124 (Registered 19/06/2014)., Competing Interests: FP has received speaking honoraria from, and has been a board member of: Alimirall, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi Genzyme, and Teva. VTC has been a board member of Merck, Novartis, Sanofi Genzyme. She has received travel expenses from Almirall, Biogen, Merck; speaking/writing honoraria from Almirall, Merck, and Teva; and support from Almirall for a research project. AS has been a board member of Biogen, Merck, and Novartis; she has received speaker honoraria from Almirall, Excemed, Merck, Sanofi Genzyme, and Teva. The authors confirm that this declaration does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

Objective: To explore the inflammatory processes in the pathogenesis of psychiatric symptoms and the prognostic value of psychiatric comorbidities in multiple sclerosis (MS)., Methods: Four hundred five patients with relapsing-remitting (RR) MS underwent psychiatric evaluation by means of Beck Depression Inventory II (BDI-II) and State/Trait Anxiety Inventory (STAI-Y). The inflammatory activity level was assessed by MRI. In a subset of 111 treatment-naive patients, CSF levels of proinflammatory cytokines were determined. Correlation and regression analyses were performed to determine associations between variables., Results: Relapsing patients demonstrated greater values of STAI-state and BDI-II compared with remitting patients but comparable trait-anxiety scores. There were no significant differences in psychometric parameters between relapsing and asymptomatic MRI-active patients, highlighting the effect of subclinical inflammation on mood disturbances. A significant reduction of STAI-state and BDI-II scores was recorded, along with the subsiding of neuroinflammation. Interleukin-2 CSF levels were found to correlate with STAI-state, while tumor necrosis factor-α and interleukin-1β correlated with BDI-II. Because emotional disorders were associated with subclinical inflammation, variations of the psychometric profile were able to detect subclinical reactivation earlier. In line with this, high STAI-state values considerably predicted the possibility of disease reactivation., Conclusions: Mood alterations are induced by intrathecal inflammation, even though not clinically apparent, and are able to predict inflammatory reactivations in RRMS. Inflammation is therefore a biological event, not less important than the traditional psychosocial factors, involved in mood disorders., (© 2017 American Academy of Neurology.)

Objective: The study compared the metric characteristics (discriminant capacity and factorial structure) of two different methods for scoring the items of the Coma Recovery Scale-Revised and it analysed scale scores collected using the standard assessment procedure and a new proposed method., Design: Cross sectional design/methodological study., Setting: Inpatient, neurological unit., Participants: A total of 153 patients with disorders of consciousness were consecutively enrolled between 2011 and 2013., Intervention: All patients were assessed with the Coma Recovery Scale-Revised using standard (rater 1) and inverted (rater 2) procedures., Main Outcome Measures: Coma Recovery Scale-Revised score, number of cognitive and reflex behaviours and diagnosis., Results: Regarding patient assessment, rater 1 using standard and rater 2 using inverted procedures obtained the same best scores for each subscale of the Coma Recovery Scale-Revised for all patients, so no clinical (and statistical) difference was found between the two procedures. In 11 patients (7.7%), rater 2 noted that some Coma Recovery Scale-Revised codified behavioural responses were not found during assessment, although higher response categories were present. A total of 51 (36%) patients presented the same Coma Recovery Scale-Revised scores of 7 or 8 using a standard score, whereas no overlap was found using the modified score. Unidimensionality was confirmed for both score systems., Conclusion: The Coma Recovery Scale Modified Score showed a higher discriminant capacity than the standard score and a monofactorial structure was also supported. The inverted assessment procedure could be a useful evaluation method for the assessment of patients with disorder of consciousness diagnosis.

Introduction: 15 years after clinical onset, about 50% of patients with relapsing-remitting multiple sclerosis convert to secondary progressive multiple sclerosis (SPMS). Notwithstanding the importance of this transition, knowledge of the experiences and needs of patients and carers is fragmentary, and targeted interventions are not available. Managing the Transition to SPMS (ManTra) is a mixed methodology project to develop and test a user-led resource for newly diagnosed patients with SPMS. Here, we describe the developmental phase, consisting of a literature review and a new research study involving key stakeholders, in which we construct the resource., Methods and Analysis: Round 1: The literature review and study will be conducted in parallel. The latter will identify patient needs using a qualitative approach consisting of: personal semistructured interviews with >15 recently diagnosed patients with SPMS; three focus group meetings (one with significant others of patients, one with neurologists and one with other health professionals caring for patients with SPMS). An online survey (>200 recently diagnosed Italian patients with SPMS) will follow to verify needs in a larger independent sample. An expert panel will outline a set of candidate resources/interventions that aim to satisfy the needs thus identified. Round 2: Consensus on the final resource will be obtained in a 1-day meeting of recently diagnosed patients with SPMS, significant others, health professionals and other stakeholders, using the nominal group technique. The expert panel will refine the resource, identify the outcome measures to assess its efficacy and ascertain the most suitable comparator (ManTra Phase 2, not part of this protocol)., Ethics and Dissemination: The study protocol was approved by the ethics committees of each of the involved centres: Foundation IRCCS Neurological Institute C Besta, Milan ; G D'Annunzio University of Chieti-Pescara and the Aldo Moro University of Bari. The results will be published in peer-reviewed journals, presented at conferences and a lay summary sent to participants., Competing Interests: Competing interests: AS has been a board member of Biogen Idec, Merck Serono and Novartis; she has received speaker honoraria from Almirall, Excemed, Merck Serono, Sanofi Genzyme and Teva. CT has received speaker honoraria from Biogen, Merck Serono, Novartis, Genzyme, Teva, Almirall, Schering and Excemed., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The aim of this study was to report the most frequent psychosocial difficulties (PSDs) in patients with Parkinson disease (PD), to explore the relationship between PSDs, disability and quality of life (QoL), and to address the predictors of PSDs. Patients with PD were interviewed using a protocol composed of a questionnaire investigating PSDs (PARADISE 24), QoL, disability, comorbidity, and social support questionnaires, scales on resilience, personality traits, and empathy in physician. Most frequent PSDs were reported. Spearman's correlation was used to address the relationship between PARADISE 24 and QoL and disability measures. Multiple linear regression was performed to investigate predictors of PARADISE 24. Eighty patients were enrolled: 40% women, mean age 61.2 years. The most frequent PSDs were related to cognitive and motor slowness, tiredness, sleeping, facing all things to do, depressive mood, and anxiety. PARADISE 24 were correlated with disability (ρ=0.831) and QoL (ρ=-0.685). Lower QoL, higher disability, early age at onset, and shorter disease duration were significant predictors of PSDs (adjusted R=0.762). PARADISE 24 is an easy to use questionnaire that could contribute toward describing the impact of PD on patients' life more extensively, thus helping to define more tailored interventions.

Purpose: Multiple Sclerosis (MS) is a progressive neurological disease characterized by an unpredictable risk to develop relevant disability over time. Few studies focused on the core psychological features of difficulties in adjustment to MS. This qualitative study aims to explore the illness experience of people with difficulties in adjustment to MS, paying more attention to both illness representation and shifting perspective., Method: Nineteen persons with difficulties in adjustment to MS participated in the study and their interviews were analyzed using thematic analysis., Results: Considering the Shifting Perspective Model, illness is rigidly placed in the foreground, and wellness decisively pushed in the background, with a lack of flexibility in shifting between the two perspectives. The thematic analysis delineated three main topics: illness representation; coping strategies; relationships with others. The illness representation is characterized by invalidating symptoms; unclear cause; sudden onset; unpredictable course and uncertain prognosis; severe impact on person's functioning; and low sense of internal control. Participants reported to mainly use emotion-focused coping strategies., Conclusions: Adjustment can be supported activating psychological intervention addressed to patients' illness representations and more flexibility in the shifting between illness and wellness in the foreground. Implications for Rehabilitation Adjustment to MS is influenced by illness perception. It is important to pay more attention to contents about vulnerability and unpredictability associated to MS. With regards to the Shifting Perspectives Model, difficulties in adjustment are related to the rigidity that prevents an adequate shift between the two perspectives (illness and wellness), with the predominance of the illness perspective in the foreground. Hence, it is important to assess the shifting perspectives preference and flexibility, and the contents of illness representation of a person with MS. Clinicians can support process of adjustment, activating psychological intervention addressed to patients' illness representations and promotion of a more flexibility in the shifting between illness and wellness in the foreground. The Illness Representation Model should be enriched by a social component, able to take into consideration the impact of the disease on interactions with others.

Background: Studies addressing relapse rates conflate relapse into chronic migraine (CM) and medication overuse (MO), and the consequent need to repeat withdrawal. We aim to identify 12-months predictors of relapse into CM (based on headaches frequency) separately from occurrence of another structured withdrawal., Methods: Hospitalized patients with CM-MO under withdrawal were enrolled. Candidate predictors included demographic, disability, quality of life, depression scores, general self-efficacy, social support, headaches frequency and intensity, class of overused medications, history of withdrawal treatment in the three years prior to enrollment, attendance to emergency room (ER) between enrollment and follow-up, nonattendance to outpatient neurological examinations. Logistic regressions was used to address the significant predictors for the two outcomes., Results: Complete data were available for 177 patients: 60 (33.9%) relapsed into CM, 38 (21.5%) underwent another withdrawal treatment. Recent history of withdrawal treatments, ER admission after discharge and high baseline BDI-II scores were significant predictors in both models. In addition to this, high baseline headache frequency predicted relapse into another withdrawal treatment., Conclusions: Predictors or relapse into CM and of occurrence of another withdrawal by 12-months are somehow similar. It is important to assess presence of recent previous withdrawal treatments and to plan regular follow-up afterwards, in particular for patients with high headache frequency and relevant mood disturbances: in this way, it will be more likely that situations requiring further structured withdrawal treatments can be identified before patients have to refer to ER., (© 2016 American Headache Society.)

The aim of this study is to identify the most relevant psychosocial difficulties (PSDs) experienced by persons with multiple sclerosis (PwMS); to evaluate the relation between an overall level of PSDs measured with the PARADISE-24 and other variables; to assess which factors may predict PARADISE-24 overall score. Adults PwMS were consecutively enrolled and completed a battery of eight self-reported instruments (i.e. SCQ, EUROHIS-QOL 8, BRS, BFI-10, JSPE, OSS-3, WHODAS-12, PARADISE-24). A clinical evaluation was performed for each patient and the Expanded Disability Status Scale (EDSS) score was determined by neurologists. A total of 80 PwMS, mean age 41.0, 65% women, 62% married, and 76.3% working, 86.3% relapsing-remitting MS, with an EDSS median score of 1.5, took part in the study. The mean disease duration was 7.7 years. The most frequently reported PSDs involved motor and emotional functioning. Free of charge access to medicines; health treatments and family, friends and health professionals' assistance represented the most important facilitators. WHODAS-12 and EUROHIS-QOL 8 were excluded from regression because of their strong correlation with PARADISE-24. EDSS, BRS, OSS-3, and neuroticism were the main predictors of the PARADISE-24 score. Despite MS heterogeneity, a common pattern of PSDs can be observed among PwMS. The level of physical impairment and personal resilience were the main predictors of the overall level of PSDs in PwMS, with a lower but significant additional role played by social support and personality traits. Attention to PSDs and their predictors, using PARADISE-24, can help clinicians to plan tailored and personalized rehabilitation programs.

To explore the relationships between psychosocial difficulties (PSDs), quality of life (QoL), and disability and to explore the degree to which PSDs can be predicted by demographic variables, clinical variables, and risk and protective factors. Patients with episodic migraine completed a protocol inclusive of PARADISE 24 questionnaire (the 24-item Psychosocial Difficulties Relevant to Brain Disorders questionnaire), a new questionnaire that captures PSDs relevant to brain disorders, and assessments of disability, QoL, disease severity, presence of comorbidities, social support, and clinical and risk factors (i.e., smoking and body mass index). Spearman's correlation was used to address the relationship between PARADISE 24, and the assessments of disability and QoL; multivariable linear regression analysis was carried out to address PARADISE 24 predictors. Eighty patients were enrolled (86.3 % females, mean age 44.5). PARADISE 24 was well correlated with disability (ρ = 0.787) and moderately with QoL (ρ = -0.526). The regression analysis shows that younger age, higher migraine frequency, higher comorbidities index and being a smoker were predictors of PARADISE 24 (R 2 : 0.470). Addressing the burden associated with PSDs in migraineurs is important as these might be the reason why patients look for specialists in headache disorders. PARADISE 24 represents a viable way to address patients' difficulties in daily practice.

This paper aims to describe the longitudinal changes in disability, defined by the International Classification of Functioning, Disability, and Health - Children and Youth version (ICF-CY) biopsychosocial model, and developmental outcomes in a cohort of 56 very low birth weight children over 14-20 months. We used a neurofunctional assessment, the Griffiths Mental Development Scales-Revised: 2-8 years (Griffiths 2-8) to evaluate psychomotor development and the ICF-CY questionnaire for ages 0-3 and 3-6 to address children's disability. Extension indexes on the basis of ICF-CY categories were computed, and longitudinal change was tested. Complete follow-up was available for 55 children (mean age 36.7 months, SD 6.7). Considering the sample as a whole, neurofunctional assessment, Griffiths score and disability were basically stable. When the subsample of children with the higher baseline functioning was taken into account, some degree of worsening, in terms of an increase in the number of impairments and limitations, was found. Our results show that disability profiles, neurofunctional assessment and global development were basically stable, except for the subgroup of children who were in the intermediate/high-functioning cluster at baseline. The increased disability among these children might be because of the possibility to observe a wider set of age-specific problems, such as emotional, regulation and social abilities that are not detectable at an early stage of development and that might lead to reduced participation in social activities.

Aim: The aim of this observational study was to test the effectiveness of the PARADISE 24 instrument in describing the psychosocial difficulties (PSDs) reported by people with epilepsy, their relation with disability, and quality-of-life (QoL) levels and, overall, to explore a horizontal epidemiology methodology applied to a sample of patients with epilepsy., Methods: A convenience sample of 80 adult patients with epilepsy was included in this cross-sectional study. Patients were interviewed using a structured protocol composed of demographic, clinical, and patient-reported outcome measures to collect PSDs associated with epilepsy., Results: There were 80 patients, 40 females; mean age was 41.2years; mean disease duration was 18.7years; and mean number of AED was 2.09. Moderate severity rating according to clinicians' rating scale, low impact of comorbidities (mean: 2.36, SD: 2.97), high levels of QoL (mean: 30.00, SD: 4.4), medium levels of resilience (mean: 13.56, SD: 2.66), high levels of perceived empathy (mean: 15.05, SD: 4.74), poor or moderate perceived social support, and low levels of disability (mean: 10.85, SD: 10.05) were observed. The most frequently reported PSDs were related to tiredness (80%), emotional problems (73.75%), anxiety (68.75%), depressive mood (66.25%), and driving problems (61.25%). The EUROHIS-QOL (p=.003) had a negative significant relationship with PARADISE 24 while WHODAS-12 (p=.000) and CRS (p=.027) had a positive significant relationship with PARADISE 24., Conclusions: The PARADISE 24 permits data comparison and the creation of a complete description of a person's functioning and of all of his/her PSDs and allows better and more tailored interventions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Individualized quality of life (QoL) measures differ from traditional inventories in that QoL domains/weights are not predetermined, but identified by the individual. We assessed practicability of the Schedule for the Evaluation of Individual QoL-Direct Weighting (SEIQoL-DW) interview in severely affected multiple sclerosis (MS) patients; the key QoL dimensions identified; and the correlation of the SEIQoL-DW index score with standard patient-reported outcome measures (PROMs)., Methods: Participants were people with severe MS who performed the baseline visit of the PeNSAMI trial (ISRCTN73082124). The SEIQoL-DW was administered at the patient's home by a trained examiner. Patients then received the following PROMs: the Core-Palliative care Outcome Scale (Core-POS), the Palliative care Outcome Scale-Symptoms-MS (POS-S-MS), the European Quality of Life Five Dimensions-3L (EQ-5D-3L), and the Hospital Anxiety and Depression Scale (HADS)., Results: Of 59 enrolled patients, 11 (19 %) did not receive the SEIQoL-DW (and the other PROMs) because of severe cognitive compromise or inability to communicate. SEIQoL-DW administration was completed and deemed valid in all 48 cases (mean age 60 years, 58 % women, median Expanded Disability Status Scale score 8.5). Mean SEIQoL-DW index score was 59.1 (SD 25.5). The most commonly nominated SEIQoL-DW areas were family (94 % of the patients), relationships, and leisure activities (both 65 %). Core-POS and POS-S-MS contained 70 % of the SEIQoL-DW-nominated areas. Nevertheless, correlations between SEIQoL-DW index, Core-POS, and POS-S-MS (and the other PROMs) were negligible., Conclusions: Individualized QoL can be assessed in severely affected MS patients, providing information that is not tracked by the standard inventories Core-POS, POS-S-MS, EQ-5D-3L, and HADS.

Introduction: The aim of this study was to assess the perceived effect of salbutamol in adult patients with spinal muscular atrophy and to evaluate the usefulness of the World Health Organization Disability Assessment Schedule II (WHODAS II) and Fatigue Severity Scale (FSS) for its measurement., Methods: A longitudinal mixed methods study was performed. Ten patients were interviewed and completed WHODAS II and FSS questionnaires to assess disability and fatigue at 2 time-points. Inductive thematic analysis was used for qualitative data. The non-parametric Wilcoxon test was performed for quantitative analysis., Results: All participants reported an improvement in their condition after salbutamol consumption. WHODAS II and FSS reliably captured changes in patients' disability and fatigue., Conclusions: The mixed methods design allowed us to identify the functional domains in which participants experienced effects of salbutamol. Patients were satisfied with the treatment as shown by decreased fatigue, improved functioning, and infrequent side effects. Muscle Nerve, 2016 Muscle Nerve 54: 843-849, 2016., (© 2016 Wiley Periodicals, Inc.)

Objectives: To study the changes in the burden of informal caregivers of patients with disorders of consciousness (DOC) over time., Materials and Methods: Short Form-12, Family Strain Questionnaire, Beck Depression Inventory and Coping Orientations to Problem Experiences were administered., Results: Data collected on 216 informal caregivers of patients with DOC (59.6% females, mean age 53.4 ± 12.7 years old) were analysed at two time-points (mean distance is 2.7 years). Results of the national study revealed that caregivers' mental health improved (T0: M = 41.1, SD = 11.8; T1: M = 45.8, SD = 11.7), whereas the emotional burden (T0: M = 7.4, SD = 3.6; T1: M = 6.6, SD = 3.9) and the presence of depressive symptoms (T0: M = 14.3, SD = 9.3; T1: M = 11.7, SD = 10.2) as well as the need for information about the disease (T0: M = 2.7, SD = 1.2; T1: M = 2.2, SD = 1.4), thoughts of death (T0: M = 3.6, SD = 1.5; T1: M = 3.1, SD = 1.6) and the use of avoiding coping strategy (T0: M = 7.8, SD = 1.0; T1: M = 6.0, SD = 1.3) decreased at T1. Furthermore, depressive symptoms positively correlated with the emotional burden (0.580) and negatively with the mental health component of caregivers' self-perceived health condition (-0.473). Physical (-0.308) and mental health (-0.444) negatively correlated with emotional burden. Finally, the acute event and patients' health condition still have a deep impact on the economic situation of the family., Conclusion: Although high level of burden was observed, it tends to decrease over time, except for financial burden. Hence, this study suggests the importance to plan strategies or targeted interventions in order to reduce the psychosocial and financial burden associated with caregiving., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: 4-aminopyridine (4-AP) is a potassium-channel blocker able to enhance walking speed in MS improving the action potentials of demyelinated axons on which internodal potassium channels are exposed., Objective: to study early 4-AP effect with clinical, subjective, neurophysiological and neuroradiological tools., Methods: Clinical (Timed 25-Foot Walk - T25FW, Timed Up-And-Go - TUG), subjective (MS Walking Scale-12 - MSWS-12), neurophysiological (Motor Evoked Potentials - MEPs) and imaging (Diffusion Tensor Imaging - DTI) evaluations were performed before (T0) and after (T1) 14days of 4-AP treatment. MEPs were recorded from Abductor Hallucis of both legs. A Tract-Based-Spatial-Statistics (TBSS) was performed on DTI., Results: We found a significant difference between T0 and T1 for T25FW, TUG, MSWS-12 (p≤0.001) in the whole patients' sample (23 subjects, median EDSS 6.0) and decrease of Central Motor Conduction Time and increase of mean Amplitude (Amp) at T1 (p=0.008 and p=0.006). We also recorded a significant difference of T25FW, TUG, MSWS-12 and Amp in clinical responder (CR) patients (CR: amelioration >20% at T25FW). TBSS showed a significant Mean and Radial Diffusivity reduction in the corticospinal tracts (p<0.05) of the whole group of patients; this reduction was also found in the CR subgroup., Conclusion: Neurophysiological and neuroradiological parameters were modified in MS patients treated with 4-AP, and most of them reported a subjective improvement of their motor performances after treatment. The use of clinical, subjective, neurophysiological and neuroradiological tools could help to better explore MS patients responsiveness to 4-AP., (Copyright © 2016. Published by Elsevier B.V.)

Multiple Sclerosis (MS) mainly affects people of working age. The Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job) was designed to measure difficulties in work-related tasks. Our aim is to define cut-off score of MSQ-Job to identify potential critical situations that might require specific attention. A sample of patients with MS completed the MSQ-Job, WHODAS 2.0 and MSQOL-54 respectively for work difficulties, disability and health-related quality of life (HRQoL) evaluation. K-means Cluster Analysis was used to divide the sample in three groups on the basis of HRQoL and disability. ANOVA test was performed to compare the response pattern between these groups. The cut-off score was defined using the receiver operating characteristic (ROC) curve analyses for MSQ-Job total and count of MSQ-Job items scores ≥3: a score value corresponding to the maximum of the sensitivity-to-specificity ratio was chosen as the cut-off. Out of 180 patients enrolled, twenty were clustered in the higher severity group. The area under the ROC curve was 0.845 for the MSQ-Job total and 0.859 for the count of MSQ-Job items scores ≥3 while the cut-off score was 15.8 for MSQ-Job total and 8 for count of items scored ≥3. We recommend the use of MSQ-Job with this calculation as cut-off for identifying critical situations, e.g. in vocational rehabilitation services, where work-related difficulties have a significant impact in terms of lower quality of life and higher disability.

Objective: Depression, anxiety, disease severity, and cognitive functions impact on the quality of life of people with MS. However, the majority of studies were not based on multivariate models and did not target employed patients. The aim of this study was to investigate predictors of HRQoL in persons with MS in the workforce considering cognitive, psychological, disease severity, and disability-related variables., Methods: Cross-sectional study. Hierarchical block regression analyses were conducted to identify predictors of physical and mental components of HRQoL, measured with the MSQOL-54. Candidate predictors included cognitive functioning (a selection of Rao's BRB-NT), sample features (age, education, MS duration), depressive symptoms (BDI-II), anxiety (STAI-Y), disability (WHODAS 2.0), and MS severity (EDSS): those that correlated with PCS and MCS with p < .250 and those that correlated with other predictors with coefficients >.800 were excluded from regression analyses., Results: In total, 181 patients (60.8% females, mean age 39.6, median EDSS 1.5) were included. In both models, cognitive variables had a poor explicative power. The models improved significantly when psychological, as well as, disease severity and disability variables were added. R(2) of complete models was 0.732 for the physical component, 0.697 for the mental one: BDI-II, STAI-State and, some WHODAS 2.0 scales were significant predictors of HRQoL., Conclusions: Monitoring anxiety, depressive symptoms, and level of disability through self-reported questionnaires may provide useful suggestions to improve the HRQoL of persons with MS in the workforce, permitting to address possible problems in the work context and plan corrective actions.

The differential diagnosis between vegetative state and minimally conscious state is still complex and the development of an evaluation systems is one of the challenging tasks for researchers and professionals. The Coma Recovery Scale-revised is considered the gold standard for clinical/behavioral assessment and for the differential diagnosis of patients with disorder of consciousness. However, the scale presents some limitations in that (i) scores may partially overlap between different diagnoses and (ii) there is an underlying assumption that if a patient is able to show higher-level behaviors, he/she is also able to show lower-level responses. In the present study, a procedure to calculate a modified Coma Recovery Scale-revised score is presented that attempts to avoid these problems. To exemplify this new scoring approach, 60 patients with disorder of consciousness were studied and the results showed the usefulness of the Modified Score.

Objective: Multiple sclerosis (MS) affects young adults of working age. Difficulties in work-related activities are usually ascribed to MS symptoms, while the impact of workplace features is underestimated. This article presents the Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job), designed to assess working difficulties due to MS symptoms and workplace features., Methods: A sample of employed MS patients completed the MSQ-Job, the WHO-Disability Assessment Schedule (WHODAS 2.0) and the 54-items MS Quality of Life Questionnaires (MSQOL-54); the expanded disability status scale (EDSS) was used to define MS severity. Factor structure was evaluated using principal component extraction and Oblimin rotation; internal consistency was assessed with Cronbach's alpha; construct and discriminant validity using t-test (EDSS 0-2 vs >2; patients self-reporting need for support vs patients reporting no needs; full-time vs part-time employees); and Pearson's correlation with WHODAS 2.0 and MSQOL-54., Results: The MSQ-Job is a 42-item questionnaire with six scales and an overall factor. Scores range on a 0-100 scale (higher scores indicate more and more severe difficulties); patients with EDSS>2 and self-reporting support needs had worse scores than those with EDSS 0-2 and without needs. Correlations with WHODAS 2.0 and MSQOL-54 were generally significant (P < 0.0007) and below 0.70., Conclusions: The MSQ-Job jointly measures the impact of respondents' symptoms and workplace features on work activities and enables to assess the effects of clinical and occupational interventions and better describe the impact of MS indirect costs., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate quality of life (QoL) and its predictors, psychological burden and level of perceived social support in caregivers of patients with disorder of consciousness., Materials & Methods: World Health Organization Quality of Life-Bref (WHOQOL-BREF), State Trait Anxiety Inventory-Y (STAI-Y), Beck Depression Inventory (BDI-II), Prolonged Grief Disorder Questionnaire, Coping Orientations to Problem Experiences, State-Trait Anger Expression Inventory-2 (STAXI-2), and the Medical Outcome Study Social Support Survey (MOS-SSS) were administered. One-sample t-tests were performed to compare WHOQOL-BREF, STAI-Y and STAXI-2 mean scores to the respective normative sample (NS). Pearson correlation was calculated between time dedicated to patient's care, WHOQOL-BREF, BDI-II, STAI-Y and MOS-SSS scores. Hierarchical multiple regression analyses were performed to evaluate which variables have predictive power on QoL., Results: A total of 129 caregivers, 68.2% female, mean age 52.8 years, were enrolled. Three WHOQOL-BREF domains were significantly lower. Anxiety and anger were in line with NS. 28.7% of the sample reported high level of depressive symptoms; 20.9% satisfied the prolonged grief disorder criteria. No differences emerged between caregivers and chronic ill patients' scores at MOS-SSS. STAI-Y, BDI-II and WHOQOL-BREF scores positively correlated. MOS-SSS domains inversely correlate with BDI-II scores. BDI-II results the most relevant predictor of QoL., Conclusions: Study results provided innovative information about caregivers' poor QoL, difficulties in social support and high levels of burden. Time dedicated to care is not strictly related to burden, while social support perceived is highly associated with caregivers' depressive symptoms that are strong predictor of poor QoL. Supportive intervention able to integrate psychological, social and environmental levels is needed., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chronic migraine with medication overuse (CM-MO) impairs quality of life (QoL) and causes disability. Psychosocial variables such as depressive symptomatology, self-efficacy, and social support have been sparingly investigated, and their impact on disability and QoL is unknown., Methods: Patients with CM-MO under withdrawal were consecutively enrolled. Standardized measures of disability and QoL were used as outcomes; psychosocial (ie, mood state, self-efficacy, social support) and clinical (ie, headache frequency and intensity) variables were considered as associated variables. Associations between these variables, disability, and QoL were tested with Pearson's correlations. Hierarchical multiple regression was used to assess the cumulative contribution of psychosocial variables on disability and QoL variation when added to clinical variables., Results: One hundred ninety-four patients were enrolled; 82.5% were females and mean age was 43.9. Disability and QoL were moderately or little correlated to clinical and psychosocial variables. Models based on clinical variables explained 7.5-14.3% of disability and QoL variation, with pain intensity being the only significant predictor; when psychosocial variables were added, the explained variation increased to 21.5-35.2%, with depressive symptomatology always having independent predictive power and perceived social support having independent predictive power in the regression model over role-prevention component of QoL., Conclusions: Adding information on psychosocial variables to headache features improved our ability to understand disability and QoL of CM-MO patients. We deem that the inclusion of psychosocial variables in standard evaluation protocols may contribute to the global assessment of CM-MO patients, and eventually to their success in reducing the personal and social impact of this condition. Future longitudinal studies are needed to confirm this hypothesis., (© 2015 American Headache Society.)

Patients with chronic migraine with medication overuse (CM-MO) have decreased quality of life (QoL) and increased disability: the degree to which these outcomes are connected to disease severity and the pattern of MO towards disease severity are unclear. Patients under withdrawal were administered the Migraine Disability Assessment (MIDAS), the WHO Disability Assessment Schedule (WHODAS), and the Migraine-Specific Quality of Life Questionnaire (MSQ). They overused NSAIDs, triptans, NSAIDs and triptans, and other drugs (ergotamine, caffeine, opioids/barbiturates). We calculated the correlations between MIDAS, WHODAS, and MSQ; compared WHODAS to normative scores; compared MIDAS, WHODAS, and MSQ in patients with different CM-MO severity; and run a logistic regression to predict CM-MO severity based on overused drugs. One hundred ninety-four patients were enrolled: correlations between WHODAS, MSQ, and MIDAS were moderate; wide differences on WHODAS against normative were found; and no trend was found across severity groups. Compared to triptans overusers, patients overusing NSAID and other drugs had higher odds of severe CM-MO. Coupling different disability measures with QoL assessment offered different insights on the lived experience of CM-MO. Future studies are needed to clarify the relationship between overused drugs and CM-MO severity: we added evidence that NSAIDs do not have protective effect in high-frequency CM-MO., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Primary Objective: This study aimed at better understanding of the complex psychological process underlying the demanding situation of taking care of a relative with disorder of consciousness (DOCs)., Research Design: This is a qualitative study based on the grounded theory constant comparative method., Methods and Procedures: Narratives of informal caregivers were collected through in-depth interviews with a psychologist. A three-step coding scheme was applied: coding of narratives to label the specific contents; organization of codes into sub-categories and categories; and theoretical coding to describe the relation between categories., Main Outcomes and Results: Twenty informal caregivers participated in one in-depth interview between December 2011 and May 2012. Four major themes emerged: Another person with past in common; Losing and finding myself; Old and new ways of being in relationship; and Dealing with concerns. These themes represent caregivers' efforts to deal with the situation in which their relative is at the same time present and absent. The core salient feature emerging from all these themes is the experience of ambiguous loss., Conclusions: Features of ambiguous loss that emerged in this study could guide clinicians' interventions to support adjustment of caregivers of patients with DOCs.

Differential diagnosis between Vegetative State and Minimally Conscious State is a challenging task that requires specific assessment scales, involvement of expert neuropsychologists or physicians and use of tailored stimuli for eliciting behavioural responses. Although misdiagnosis rate as high as 40% has been reported, no clear guidelines are available in literature on the optimal setting for assessment. The present study aims to analyse score differences in behavioural assessments of persons with disorders of consciousness (DOC) with or without family members and to determine whether the presence of caregivers could improve clinical accuracy in diagnostic evaluation. The research was conducted on 92 adults with DOC among 153 consecutive patients enrolled in the Coma Research Centre of the Neurological Institute C. Besta of Milan between January 2011 and May 2013. The results indicate that in almost half of the sample the scoring, thus the performance, observed with caregivers was better than without them. Furthermore, in 16% of the sample, when assessment was performed with caregivers there was a change in diagnosis, from Vegetative to Minimally Conscious State or from that to Severe Disability. Finally, statistical differences were found in relation to diagnosis between mean scores in the "visual function" Coma Recovery Scale revised's subscale obtained by raters plus caregiver and rates only assessment. This study demonstrates how the presence of caregivers can positively affect behavioural assessments of persons with DOC, thus contributing to the definition of the optimal setting for behavioural evaluation of patients, to decrease misdiagnosis rates.

Caregivers of patients in vegetative state and minimally conscious state play a crucial role in the process of taking care and, as previous studies reported, they can suffer of high burden and negative health outcomes. The aim of this national cross-sectional study was to assess whether physical and mental health of caregivers, considering gender differences, is related to the presence of depressive symptoms, anxiety, age and patient's disease duration. Four-hundred and eighteen caregivers, 294 women and 124 men, completed the State Trait Anxiety Inventory-Y, Beck Depression Inventory, second version and Short Form-12. Hierarchical multiple regression analyses were performed to evaluate to which extent depressive and anxiety symptoms predict physical and mental health. Men reported higher levels of mental health state, whereas physical health was not different across gender. High levels of anxiety symptoms were associated to negative mental health outcomes in both genders, whereas depressive symptoms were found to impact on female's mental and physical health only. A comprehensive and cost-effective screening of anxiety and depressive symptoms may help to identify determinants of health worsening in order to plan, when necessary, caregivers' support., Key Practitioner Messages: Female caregivers of patients in vegetative state and minimally conscious state have poorer levels of mental health, whereas physical health is similar to men's. Anxiety symptoms are related to negative mental health outcomes in both male and female caregivers, whereas depressive symptoms are found to impact on female mental and physical health only. It is essential to consider and assess depressive and anxiety symptoms as they may contribute to caregivers' health worsening. This knowledge can lead to plan more comprehensive and tailored caregivers' supports and a better care for patients., (Copyright © 2013 John Wiley & Sons, Ltd.)

Involvement of family members is crucial to provide daily informal caring to patients in vegetative state and minimally conscious state. Previous studies showed that perceived burden is a risk factor for informal caregivers as it increases psychophysical distress. This research further investigated the relationship between these factors and aimed at providing a model that thoroughly describes this mechanism of functioning. In the frame of a national survey on people with disorders of consciousness, 487 informal caregivers of children and adult patients in vegetative and minimally conscious state were administered measures of depression, anxiety, caregiver needs, and family strain. Regression models proposed by Baron and Kenny and the Sobel test were adopted to investigate the relationship between depressive and anxiety symptoms, perceived burden and needs expressed. Our study shows that the relation between those symptoms and needs is mediated by burden, where higher burden accentuates and lower burden mitigates the needs expressed by caregivers. Our findings demonstrate that psychosocial components of the burden perceived by caregivers of patients with disorders of consciousness play a key role in shaping those caregivers' needs, especially their needs for information and communication. We recommend implementation of comprehensive steps to meet the needs of these caregivers, steps that incorporate improved economic and public health programs, social support, and use of psychological interventions to ameliorate caregivers' psychological distress and decrease their burden.

Clinicians need a comprehensive description of patients' functioning state to capture the complex interaction between symptoms and environmental factors, and to determine the actual level of functioning in patients in a vegetative state or a minimally conscious state. The aim of this study is to develop an International Classification of Functioning, Disability, and Health (ICF) checklist for patients with disorders of consciousness (DOC) so as to capture and describe, with a tailored list of categories, the most common health, disability, and functioning issues of adult patients with DOC. The WHO ICF checklist was used as a basis for collecting data. This was an observational, cross-sectional, multicenter study conducted in 69 Italian centers. Specific methodological procedures were used to identify the most appropriate categories for DOC patients to be added to or deleted from the ICF checklist so as to develop the ICF-DOC checklist. A total of 566 adult patients were enrolled: 398 in a vegetative state and 168 in a minimally conscious state. A total of 127 ICF categories reached the threshold of 20% concerning the presence of a problem: 37 categories from the body functions chapter, 13 from the body structures chapter, 46 from the activities and participations chapter, and 31 from the environmental factors chapter. ICF categories identified in this study can be useful guidelines for clinicians and researchers to collect data on functioning and disability of adult patients with DOC. The new ICF-DOC checklist allows monitoring of the effects of interventions on functional areas and possible changes in each patient in follow-up studies.

A significant proportion of patients who survive traumatic or nontraumatic severe acquired brain injuries experiences disorders of consciousness. The vegetative state and the minimally conscious state may have different prognoses, and while some patients regain awareness, others have negative outcomes and die. The aim of this work is to identify age-related, medical and behavioural risk factors for mortality in those patients. Participants were enrolled from June 2009 to March 2012 in 107 Italian health care institutions. Univariate and multivariate Cox proportional hazard models were adopted to screen and test candidate risk factors. The study enrolled 600 subjects in vegetative and minimally conscious states for an overall mortality rate of 180.1 per 1,000 person-years. The following traits were associated with a significantly lower chance of survival: age at the acute event higher than 51 years, disease duration less than 1 year, post-anoxic aetiology, absence of visual fixation, and the presence of endocrine, nutritional, and metabolic diseases, and immunity disorders. Clinical history, behavioural assessment, and age-related factors provide important prognostic information on negative outcomes that helps clinicians and researchers to predict patients who are at higher risk of mortality. This knowledge has important clinical, managerial, and ethical implications.

Background: Patients in vegetative (VS) and minimally conscious state (MCS) have different degrees of consciousness recovery but both display severe levels of disability., Aim: To describe and compare VS and MCS patients' functioning and disability according to ICF model (International Classification of Functioning, Disability and Health)., Design: Observational cross-sectional multi-center study involving sixty-nine Italian centers., Setting: Patients recruited in post-acute, long-term care facilities and at home in Italy., Population: Adult patients in VS and MCS., Methods: ICF Functioning profiles were completed and, for each ICF chapter and domain, extension and severity indexes were developed. Indexes have been compared between VS and MCS patients with Mann Whitney U test. Descriptive statistics have been applied to describe the most relevant categories that had a percentage of missing below 25% and that were reported as a problem by at least 50% of patients., Results: A total of 564 patients were enrolled: 396 in VS (mean age 56.8), 168 in MCS (mean age 54.2). Fifty-eight ICF categories were selected: of them, 24 were from Activity and Participation (A&P). Few differences between patients in VS and MCS were reported in Body Functions (BF), mostly referred to mental, sensory and digestive functions; among A&P, differences were found only in learning chapter. For VS patients less environmental barriers were reported than MCS patients., Conclusion: Patients in VS and MCS have similar functioning and disability profiles and similar needs thus levels of care and assistance should not be different across the two conditions., Clinical Rehabilitation Impact: An ICF-based methodology of data collection enables to describe VS and MCS patients' functioning and disability: this is helpful when rehabilitation programs based on the features of single patients with DOC need to be planned.