Cross-cultural validity and reliability of the comprehensive assessment of acceptance and commitment therapy processes (CompACT) in people with multiple sclerosis.

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.

User appraisal of a booklet for advance care planning in multiple sclerosis: a multicenter, qualitative Italian study.

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.

Improvements in quality of life over 2 years with cladribine tablets in people with relapsing multiple sclerosis: The CLARIFY-MS study.

BACKGROUND: Multiple sclerosis (MS) negatively affects health-related quality of life (HRQoL). OBJECTIVE: To evaluate HRQoL in people with highly active relapsing MS treated with cladribine tablets (CladT; 3.5 mg/kg cumulative dose over 2 years) in CLARIFY-MS. METHODS: Changes in the MS quality of life (MSQoL)-54 scores were analysed using a repeated mixed-effects linear model. Subgroup analyses were performed for participants who were pretreatment-naïve and those pretreated with disease-modifying therapies (DMTs) before initiating CladT. Safety and tolerability of CladT were also assessed. RESULTS: MSQoL-54 physical (mean change = 4.86; 95% confidence interval (CI) = 3.18, 6.53) and mental health (4.80; 95% CI = 3.13, 6.46) composite scores (primary endpoints) showed significant improvement at Month 24 versus Baseline (p < 0.0001). Changes in the MSQoL-54 scores were consistent across the pretreatment-naïve and DMT-pretreated subgroups. No new severe or opportunistic infections occurred. Most post-baseline lymphopenia events were Grade 1-2 in severity. Transient Grade-3 lymphopenia was observed in 19.7% (95/482) of participants. Grade-4 lymphopenia was not observed. CONCLUSIONS: CladT treatment significantly improved the mean MSQoL-54 physical and mental health composite scores over 2 years. CladT efficacy in HRQoL, relapse rates and Expanded Disability Status Scale scores demonstrates its multidimensional effects in MS treatment.

Knowledge and worries on motherhood choice in multiple sclerosis - a cross-sectional study on patient-reported outcome measures.

BACKGROUND: Since multiple sclerosis (MS) is often diagnosed in young women, pregnancy is a common topic for women with MS (wwMS). The study aimed to assess the measurement properties of two patient-reported outcome measures on motherhood choice in MS, and to explore the information and support needs of wwMS concerning motherhood. METHODS: We conducted an anonymous web-based survey to validate the motherhood/pregnancy choice and worries questionnaire (MPWQ, 31 items plus up to 3 additional items) and the motherhood choice knowledge questionnaire (MCKQ, 16 items). We used mailing lists and social media for nationwide recruitment in Germany, and included women of childbearing age with relapsing-remitting MS, clinically isolated syndrome or suspected MS who were considering pregnancy or were pregnant. For the MPWQ, we assessed item difficulty, discriminatory power, and internal consistency (Cronbach's alpha; CA). We analysed construct validity using the Leipzig Questionnaire of Motives to have a Child, the Decisional Conflict Scale, the Hospital Anxiety and Depression Scale, and the Pregnancy-Related Anxiety Questionnaire-revised 2. We studied the structural validity using exploratory factor analysis (EFA). The MCKQ was evaluated descriptively. We explored the information and support needs of wwMS on motherhood descriptively. We examined correlations between MCKQ, MPWQ and clinical characteristics and performed exploratory group comparisons considering the following binary variables: having children and being pregnant. RESULTS: 325 wwMS started the survey; 232 wwMS met our inclusion criteria and were analysed. Their mean age was 30 years (SD 5). Most women had relapsing-remitting MS (n = 218; 94%), 186 (80%) had no children, and 38 (16%) were pregnant. Internal consistency was good for the worries subscale (CA>0.8), while it was unsatisfactory for the attitude and coping subscales (CA<0.7). The EFA did not support the three-scale structure (coping, attitude, and worries). Due to these findings, we decided to keep the worries scale without any subscale. The items from the coping scale and attitude scale could be assessed as additional descriptive items. Convergent and divergent construct validity of the MPWQ was satisfactory. 206 wwMS (89%) completed the MCKQ. On average, 9 of 16 (56%) items were answered correctly (range 2-15), and the questionnaire showed a good balance between easy and difficult items. Questions on immunotherapy, disease activity, and breastfeeding were the most challenging. WwMS were confident in getting pregnant and raising a child (n = 222; 96%). Most wwMS were worried about postpartum relapses (n = 200; 86%) and the long-term effects of pregnancy on disease evolution (n = 149; 64%). About half of the wwMS (n = 124; 54%) did not know where to find professional help and 127 (55%) had no strategies to cope with future impairments so that they could take care of a child. CONCLUSION: Our results support the suitability and acceptability of both questionnaires as potential patient-reported measures for assessment of knowledge and worries around motherhood/pregnancy in MS. The survey results highlight the need for evidence-based information on motherhood in MS to increase knowledge, reduce worries and support wwMS in making informed decisions.

Applying multidimensional computerized adaptive testing to the MSQOL-54: a simulation study.

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.

Italian cross-cultural adaptation of the Quality of Communication questionnaire and the 4-item advance care planning engagement questionnaire.

BACKGROUND: Advance care planning (ACP) is influenced by several factors (e.g., patient's readiness to engage, clinician's skills, and the cultural environment). Availability of reliable and valid self-reported measures of the ACP domains is crucial, including cross-cultural equivalence. AIM: To culturally adapt into Italian the 19-item Quality of Communication (QOC) and the 4-item ACP Engagement (4-item ACP-E) questionnaires. METHODS: We translated and culturally adapted the two questionnaires and produced a significant other (SO) version of the QOC (QOC-SO). Each questionnaire was field tested via cognitive interviews with users: nine patients (QOC, 4-item ACP-E) and three SOs (QOC-SO) enrolled at three palliative care services. RESULTS: We made minor changes to 5/19 QOC items, to improve clarity and internal consistency; we changed the response option 'didn't do' into 'not applicable'. Finally, we slightly revised the QOC to adapt it to the paper/electronic format. QOC debriefing revealed that the section on end of life was emotionally challenging for both patients and SOs. We simplified the 4-item ACP-E layout, added a sentence in the introduction, and revised the wording of one item, to improve coherence with the Italian ACP legislation. ACP-E debriefing did not reveal any major issue. CONCLUSIONS: Results were satisfactory in terms of semantic, conceptual and normative equivalence of both questionnaires. Acceptability was satisfactory for the 4-item ACP-E, while findings of the QOC cognitive debriefing informed a major amendment of a pilot trial protocol on ACP in multiple sclerosis (ConCure-SM): use of the interviewer version only, in an adaptive form. Psychometric testing of both questionnaires on a large, independent sample will follow.

Italian cross-cultural adaptation of the patient-reported outcome measure of ataxia.

BACKGROUND: The patient-reported outcome measure of ataxia (PROM-Ataxia) is the first patient-reported questionnaire specifically developed for use in patients with cerebellar ataxia. The scale was recently designed and validated in English language, and it consists of 70 items encompassing all aspects associated with the patient experience, including physical and mental health and their consequences on activities of daily living. The aim of the study was to translate and culturally adapt into Italian the PROM-Ataxia questionnaire, before assessing its psychometric properties. METHODS: We translated and culturally adapted into Italian the PROM-Ataxia following the ISPOR TCA Task Force guidelines. The questionnaire was field tested via cognitive interviews with users. RESULTS: The Italian patients found that the questionnaire was complete, and no significant contents related to the physical, mental, and functional dimensions were missing. Some items were found redundant or ambiguous. Most of the identified issues pertained to semantic equivalence, and a few to conceptual and normative equivalence, while the questionnaire did not contain any idiomatic expression. CONCLUSIONS: The translation and cultural adaptation of the PROM-Ataxia questionnaire in the Italian patient population represent the pre-requisite for the subsequent psychometric validation of the scale. This instrument may be valuable for cross-country comparability that would allow the merging of the data in collaborative multinational research studies.

Postpartum relapse risk in multiple sclerosis: a systematic review and meta-analysis.

The influence of pregnancy on the course of multiple sclerosis (MS) has long been controversial. While historical evidence suggests a substantial decline in relapse rates during pregnancy followed by a rebound in the postpartum period, more recent work yielded equivocal results. We performed a systematic review and meta-analysis on data from cohort studies to determine whether women with MS experience increased relapse rates after delivery. A systematic literature search was conducted in the databases MEDLINE and Epistemonikos on the topic 'motherhood choice in MS' in March 2022. We included cohort studies assessing the association between pregnancy and MS relapse activity defined by the annualised relapse rate after 3, 6, 9 and 12 months post partum. Furthermore, information about disease-modifying therapies (DMT) and breast feeding was considered, if available. 5369 publications were identified. Of these, 93 full-text articles on MS relapse activity during the postpartum period were screened. 11 studies including 2739 pregnancies were eligible. Women with MS showed a significantly increased relapse rate in the first 6 months post partum, compared with preconception with the incidence rate ratio (IRR) almost doubled in the first 3 months post partum (1.87, 95% CI 1.40 to 2.50). However, at 10-12 months post partum, the IRR decreased significantly (0.81, 95% CI 0.67 to 0.98). Subanalysis on influencing parameters suggested that preconceptional DMTs (IRR for highly-effective DMTs 2.76, 95% CI 1.34 to 5.69) and exclusive breast feeding (risk ratio 0.39, 95% CI 0.18 to 0.86) significantly influenced postpartum relapse risk. Increased postpartum annualised relapse rate and possible modifiers should be considered in counselling women with MS who are considering pregnancy.

Patient and carer involvement in the formulation of research questions: findings from the Italian guideline on palliative care in adults with glioma.

BACKGROUND: In 2017, the European Association for Neuro-Oncology (EANO) published the guideline for palliative care (PC) in adults with glioma. The Italian Society of Neurology (SIN), the Italian Association for Neuro-Oncology (AINO), and the Italian Society for Palliative Care (SICP) joined forces to update and adapt this guideline to the Italian context and aimed to involve patients and carers in the formulation of the clinical questions. METHODS: During semi-structured interviews with glioma patients and focus group meetings (FGMs) with family carers of deceased patients, participants rated the importance of a set of pre-specified intervention topics, shared their experience, and suggested additional topics. Interviews and FGMs were audio-recorded, transcribed, coded, and analyzed (framework and content analysis). RESULTS: We held 20 interviews and five FGMs (28 carers). Both parties considered the pre-specified topics as important, chiefly information/communication, psychological support, symptoms management, and rehabilitation. Patients aired the impact of focal neurological and cognitive deficits. Carers reported difficulties in dealing with patient's behavior and personality changes and appreciated the preservation of patient's functioning via rehabilitation. Both affirmed the importance of a dedicated healthcare path and patient's involvement in the decision-making process. Carers expressed the need to be educated and supported in their caregiving role. CONCLUSIONS: Interviews and FGMs were well informative and emotionally challenging. Both parties confirmed the importance of the pre-specified topics, and carers suggested one additional topic: education/support to caregivers. Our findings strengthen the importance of a comprehensive care approach and of addressing the needs of both patients and their family carers.

Health professional involvement in the formulation of research questions: findings from the Italian guideline on palliative care in adults with glioma.

BACKGROUND: In 2017, the European Association of Neuro-Oncology (EANO) published the guideline for palliative care in adults with glioma. The Italian Society of Neurology (SIN), the Italian Society for Palliative Care (SICP), and the Italian Association for Neuro-Oncology (AINO) joined forces to update the guideline, and adapt it to the Italian context. AIM: We involved patients, caregivers, and (herein presented) healthcare professionals (HPs) in the formulation of the guideline clinical questions. DESIGN AND PARTICIPANTS: Online survey of Italian HPs experienced in the care of patients with glioma. Participants rated the importance of 14 pre-specified intervention topics on a 0/10 scale and gave their free comments. RESULTS: Of 244 participants, 149 (61%) were palliative medicine (PM) HPs and 95 Neuro HPs. Their mean age was 48.9 years, 63% were women, and 48% had over 12 years of experience in the care of glioma patients. Physicians were 68%, followed by nurses (28%), psychologists (7%), therapists (3%), and social workers (2%). Most HPs rated the pre-specified topics as important (score ≥ 7) or critical (score ≥ 9), with some differences between PM and Neuro HP groups. There were 58 free comments: 46 (78%) on nine pre-specified topics, and 13 on four new topics, three of which were guideline-pertinent ("caregiver's support and education"; "family physician's training in neuro-oncology"; and "PM HPs' training in neuro-oncology"). CONCLUSIONS: Participation in the survey was high and information-rich, between-group rating differences reflecting HP background. Participants endorsed the 14 intervention topics devised by the guideline panel and identified three additional topics.

Motherhood choice in multiple sclerosis (MoMS) development and piloting of patient-reported outcome measures.

BACKGROUND: Multiple sclerosis (MS) particularly affects women between the age of 20 and 40. Therefore, pregnancy is often an important issue for women with MS (wwMS), but misunderstandings, misinformation, and uncertainties about MS and pregnancy are common. We developed and pilot-tested two questionnaires, one on knowledge (MCKQ), and one on attitudes, coping strategies and worries (MPWQ) of wwMS regarding pregnancy. METHODS: This mixed-methods study followed the MRC framework for the development and evaluation of complex interventions. Two questionnaires were developed based on an earlier questionnaire and a qualitative study, cognitively debriefed and pilot tested in a web-based survey. Qualitative data were analysed using thematic analysis. The psychometric analysis included item difficulty and reliability (for both questionnaires), convergent validity assessment and exploratory factor analysis (EFA) (for MPWQ). RESULTS: The qualitative study (three focus groups and interviews with 15 wwMS overall and interviews with 4 experts) revealed several topics requiring evidence-based decision support. A multidisciplinary panel produced the 16-item MCKQ and the 39-item MPWQ. The cognitive debriefing of both questionnaires went smoothly. Of 128 wwMS who approached the survey, 95 (74%) completed the MCKQ and 89 (70%) the MPWQ. The mean age of wwMS was 36.7 years, 88% had a relapsing MS, and 32% had no children. Item difficulty, reliability and convergent validity were acceptable for both questionnaires. The EFA did not confirm the three-scale structure (attitude, worries and coping). CONCLUSION: The developed questionnaires fill a gap in self-reported measures of knowledge (MCKQ) and attitudes, worries, and coping strategies (MPWQ) of wwMS regarding motherhood. Further refinement of the MPWQ and validation in a larger sample is warranted before its large-scale use.

A group resilience training program for people with multiple sclerosis: Study protocol of a multi-centre cluster-randomized controlled trial (multi-READY for MS).

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.

Cross-Country Adaptation of a Psychological Flexibility Measure: The Comprehensive Assessment of Acceptance and Commitment Therapy Processes.

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.

Evaluation of a program for training psychologists in an acceptance and commitment therapy resilience intervention for people with multiple sclerosis: a single-arm longitudinal design with a nested qualitative study.

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.

Treatment satisfaction, safety, and tolerability of cladribine tablets in patients with highly active relapsing multiple sclerosis: CLARIFY-MS study 6-month interim analysis.

Background Multiple sclerosis (MS) is a chronic disabling disease that is associated with negative effects on health-related quality of life (HRQoL) due to reduced physical and psychosocial functioning. Cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years) have been approved for the treatment of adult patients with highly active relapsing multiple sclerosis (RMS). The ongoing CLARIFY-MS study (NCT03369665; EudraCT number: 2017-002632-17) aims to assess the effect of cladribine tablets 3.5 mg/kg on HRQoL of patients with highly active RMS. Objective To report on the design of the CLARIFY-MS study, baseline patient characteristics, and results of a pre-planned interim analysis focusing on treatment satisfaction, safety, and tolerability that includes all data reported till 6 months after start of treatment. Methods The CLARIFY-MS study is a 2-year, open-label, single-arm, prospective, multicenter, phase IV study. Eligible patients with highly active RMS were assigned to receive cladribine tablets 3.5 mg/kg over 2 years. Treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM, v1.4; scale range from 0 to 100, higher values indicating higher satisfaction). Safety assessments, including occurrence of treatment-emergent adverse events (TEAEs; any adverse event reported after drug administration), serious adverse events (SAEs), and lymphocyte counts, were summarized descriptively. Results A total of 482 patients from 85 sites in Europe were treated with cladribine tablets. Mean patient age was 37.4 years, 338 (70.1%) were women, median EDSS was 2.5, and 345 (71.6%) were prior users of disease-modifying therapy (DMT). During the first 6 months after the start of treatment, and before reaching the full dose of cladribine tablets, mean TSQM global satisfaction score for the overall population was 70.4 (standard deviation, ± 18.48). The side effects score was 91.9 (± 17.68), convenience scored 86.6 (± 13.57), and effectiveness was 65.8 (± 21.14). A total of 275 patients (57.1%) reported at least one TEAE and 9 patients (1.9%) had a SAE. The majority of observed lymphopenia cases were of grade 1 or 2; 33 (6.8%) of the total study cohort had grade 3 lymphopenia, and no grade 4 lymphopenia was reported. Conclusion Patients reported high treatment satisfaction (TSQM) with cladribine tablets in this pre-planned interim analysis at 6 months. Few serious, and no unexpected, adverse events were reported, and there were no instances of grade 4 lymphopenia over the first 6 months. These preliminary data indicate good tolerability and convenience of administration of cladribine tablets in patients with highly active RMS.

Advance Care Planning in Neurodegenerative Disorders: A Scoping Review.

Advance care planning (ACP) is increasingly acknowledged as a key step to enable patients to define their goals/preferences for future medical care, together with their carers and health professionals. We aimed to map the evidence on ACP in neurodegenerative disorders. We conducted a scoping review by searching PubMed (inception-December 28, 2020) in addition to trial, review, and dissertation registers. From 9367 records, we included 53 studies, mostly conducted in Europe (45%) and US-Canada (41%), within the last five years. Twenty-six percent of studies were qualitative, followed by observational (21%), reviews (19%), randomized controlled trials (RCTs, 19%), quasi-experimental (11%), and mixed-methods (4%). Two-thirds of studies addressed dementia, followed by amyotrophic lateral sclerosis (13%), and brain tumors (9%). The RCT interventions (all in dementia) consisted of educational programs, facilitated discussions, or videos for patients and/or carers. In conclusion, more research is needed to investigate barriers and facilitators of ACP uptake, as well as to develop/test interventions in almost all the neurodegenerative disorders. A common set of outcome measures targeting each discrete ACP behavior, and validated across the different diseases and cultures is also needed.

Effectiveness of a group resilience intervention for people with multiple sclerosis delivered via frontline services.

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.

Diagnosis and treatment of Chiari malformation and syringomyelia in adults: international consensus document.

BACKGROUND: Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing. AIM OF THE STUDY: to reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults. METHODS: A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019). RESULTS: Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved. CONCLUSIONS: The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia.