Quality of Life and the Experience of Living with Early-Stage Alzheimer's Disease.

BACKGROUND: There is a need to better understand the experience of patients living with Alzheimer's disease (AD) in the early stages. OBJECTIVE: The aim of the study was to evaluate the perception of quality of life in patients with early-stage AD. METHODS: A multicenter, non-interventional study was conducted including patients of 50-90 years of age with prodromal or mild AD, a Mini-Mental State Examination (MMSE) score ≥22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5.-1.0. The Quality of Life in Alzheimer 's Disease (QoL-AD) questionnaire was used to assess health-related quality of life. A battery of self-report instruments was used to evaluate different psychological and behavioral domains. Associations between the QoL-AD and other outcome measures were analyzed using Spearman's rank correlations. RESULTS: A total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years and mean disease duration was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1). The mean QoL-AD score was 37.9 (4.5). Eighty-three percent (n = 124) of patients had moderate-to-severe hopelessness, 22.1% (n = 33) had depressive symptoms, and 36.9% (n = 55) felt stigmatized. The quality of life showed a significant positive correlation with self-efficacy and negative correlations with depression, emotional and practical consequences, stigma, and hopelessness. CONCLUSION: Stigma, depressive symptoms, and hopelessness are frequent scenarios in AD negatively impacting quality of life, even in a population with short disease duration and minimal cognitive impairment.

Impact of Neuromyelitis Optica Spectrum Disorder on Quality of Life from the Patients' Perspective: An Observational Cross-Sectional Study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is associated with a reduced health-related quality of life (HRQoL). The purpose of this study was to describe the impact of NMOSD on HRQoL from the patients' perspective and its relationship with other disease factors. METHODS: An observational, cross-sectional study was conducted at 13 neuroimmunology clinics in Spain. Patients with NMOSD diagnosis (2015 Wingerchuk criteria) were included. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was used to assess the HRQoL. Different questionnaires were used to measure symptom severity, stigma, mood disorders, pain, fatigue, and difficulties in the workplace. Factors that impact HRQoL were identified by Spearman's correlation and multivariate linear regression analysis. RESULTS: Seventy-one patients were included (mean age 47.4 ± 14.9 years, 80.3% female, mean time since disease onset 9.9 ± 8.1 years). The median Expanded Disability Status Scale score was 3.0 (1.5-4.5). The mean (± SD) physical and psychological MSIS-29 sub-scores were 41.9 ± 16.8 and 20.9 ± 8.3, respectively. Fatigue and body pain were the most prevalent symptoms. Depressive symptoms were found in 44.3% (n = 31) of patients. The physical MSIS-29 dimension showed the highest correlation with symptom severity (ρ = 0.85584, p < 0.0001), whereas the highest correlations for psychological MSIS-29 dimension were pain, MSIS-29 physical dimension, and depression (ρ = 0.76487, 0.72779, 0.71380; p < 0.0001, respectively). Pain was a predictor of both dimensions of MSIS-29. CONCLUSION: Fatigue, pain, and depressive symptoms are frequent problems among patients with NMOSD, impacting on their quality of life. Assessment of patient-oriented outcomes may be useful to achieve a holistic approach, allowing early specific interventions.

Quantifying the patient´s perspective in neuromyelitis optica spectrum disorder: Psychometric properties of the SymptoMScreen questionnaire.

BACKGROUND: The assessment of self-reported outcomes in neuromyelitis optica spectrum disorder (NMOSD) is limited by the lack of validated disease-specific measures. The SymptoMScreen (SyMS) is a patient-reported questionnaire for measuring symptom severity in different domains affected by multiple sclerosis (MS), but has not been thoroughly evaluated in NMOSD. The aim of this study was to assess the psychometric properties of the SyMS in a sample of patients with NMOSD. METHODS: A non-interventional, cross-sectional study in adult subjects with NMOSD (Wingerchuk 2015 criteria) was conducted at 13 neuroimmunology clinics applying the SyMS. A non-parametric item response theory procedure, Mokken analysis, was performed to assess the underlying dimensional structure and scalability of items and overall questionnaire. All analyses were performed with R (v4.0.3) using the mokken library. RESULTS: A total of 70 patients were studied (mean age: 47.5 ± 15 years, 80% female, mean Expanded Disability Status Scale score: 3.0 [interquartile range 1.5, 4.5]). Symptom severity was low (median SyMS score: 19.0 [interquartile range 10.0, 32.0]). The SyMS showed a robust internal reliability (Cronbach's alpha: 0.90 [95% confidence interval 0.86, 0.93]) and behaved as a unidimensional scale with all items showing scalability coefficients > 0.30. The overall SyMS scalability was 0.45 conforming to a medium scale according to Mokken's criteria. Fatigue and body pain were the domains with the highest scalability coefficients. The SyMS was associated with disability (rho: 0.586), and physical and psychological quality of life (rho: 0.856 and 0.696, respectively). CONCLUSIONS: The SyMS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement option to measure symptom severity in patients with NMOSD.

Perception of Stigma in Patients with Neuromyelitis Optica Spectrum Disorder.

BACKGROUND: Perception of stigma was associated with low self-esteem, psychological problems, and decreased health-seeking behavior among patients with different neurological disorders. The purpose of this study was to assess stigmatization and its impact in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: A non-interventional study was conducted at thirteen neuroimmunology clinics in Spain. Patients with a diagnosis of NMOSD (2015 Wingerchuk criteria) were included. The 8-item Stigma Scale for Chronic Illness (SSCI-8), the Expanded Disability Status Scale (EDSS), the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the Beck Depression Inventory-Fast Screen (BDI-FS), the MOS Pain Effects Scale (MOS-PES) and the Fatigue Impact Scale for Daily Use (D-FIS) were used to assess the perception of stigma, disability, quality of life, mood, pain, and fatigue, respectively. Associations between outcome measures were analyzed using Spearman's rank correlation. RESULTS: Seventy-one patients were studied (mean age: 47.4 years ± 14.9, 81.7% female, mean time since disease onset: 9.9 years ± 8.1). The median EDSS score was 3.0 (interquartile range 1.5, 4.5). Stigma prevalence was 61.4% (n=43). Thirty-one patients (43.6%) had depression. The SSCI-8 score showed a significant correlation with both physical (rho=0.576, p<0.0001) and psychological (rho=0.608, p<0.0001) MSIS-29 scales scores, EDSS score (rho=0.349, p=0.0033), BDI-FS score (rho= 0.613, p<0.0001), MOS-PES score (rho= 0.457, p<0.0001), and D-FIS score (rho=0.556, p<0.0001). CONCLUSION: Stigma is a common phenomenon affecting over 6 out of 10 patients with NMOSD. Understanding stigma may be useful to develop educational strategies improving NMOSD knowledge.

Short-term data on disease activity, cognition, mood, stigma and employment outcomes in a cohort of patients with primary progressive multiple sclerosis (UPPMS study).

BACKGROUND: Primary progressive multiple sclerosis (PPMS) has long been defined by progressive disability accrual in the absence of initial relapses. However, its underlying neurodegenerative process seems to be accompanied by central nervous system inflammation. A new classification defined multiple sclerosis courses according to clinical/radiological activity and progression. We provide further insight into PPMS activity according to this classification and other daily living aspects. METHODS: This was a multicentre, prospective, cohort study including 55 adult patients with PPMS according to 2010 McDonald criteria, within ten years from neurologic symptom onset and not receiving disease-modifying therapies during the past six months, who were followed up for 12 months. The primary study endpoint was the percentage of patients with active disease based on clinical relapses and/or magnetic resonance activity. Disability progression, cognitive function, physical/psychological impact, depression symptoms, stigma and employment were secondary endpoints. RESULTS: Eleven (25.6%) patients exhibited multiple sclerosis activity throughout the 12-month study follow-up. Fourteen showed non-active multiple sclerosis without progression, 11 non-active multiple sclerosis with progression, 6 active multiple sclerosis without progression and 4 active multiple sclerosis with progression; one patient with disease activity was not assessable for progression. Cognitive function scores remained unchanged or increased, disease physical impact was maintained and disease psychological impact significantly decreased. The proportion of patients with depression symptoms or stigma remained without significant changes as well as employment outcomes. CONCLUSION: This study shows that one-fourth of PPMS patients may exhibit disease activity over one year, with disability progression in approximately one-third but without worsening of cognitive function, disease impact, depression, stigma or employment outcomes.

Brain region volumes and their relationship with disability progression and cognitive function in primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Evidence on regional changes resulting from neurodegenerative processes underlying primary progressive multiple sclerosis (PPMS) is still limited. We assessed brain region volumes and their relationship with disability progression and cognitive function in PPMS patients. METHODS: This was an MRI analysis of 43 patients from the prospective Understanding Primary Progressive Multiple Sclerosis (UPPMS) cohort study. MRI scans were performed within 3 months before enrollment and at month 12. RESULTS: Gray matter volume of declive and white matter volumes adjacent to left straight gyrus, right calcarine sulcus, and right inferior occipital gyrus significantly decreased from baseline to month 12. Baseline white matter volumes adjacent to right amygdala and left cuneus significantly differed between patients with and without disability progression, as well as baseline gray matter volumes of left cuneus, right parahippocampal gyrus, right insula, left superior frontal gyrus, declive, right inferior temporal gyrus, right superior temporal gyrus (pole), and right calcarine sulcus. Baseline gray matter volumes of right cuneus and right superior temporal gyrus positively correlated with 12-month Selective Reminding Test and Word List Generation performance, respectively. Gray matter changes in right superior semilunar lobe and white matter adjacent to left declive and right cerebellar tonsil also positively correlated with Word List Generation scores, while white matter change in left inferior semilunar lobe positively correlated with Symbol Digit Modalities Test performance after 12 months. CONCLUSIONS: White and gray matter volumes of specific brain regions could predict disability progression and cognitive performance of PPMS patients after one year.

A Pilot Study to Explore Patient Satisfaction With a Virtual Rehabilitation Program in Multiple Sclerosis: The RehabVR Study Protocol.

Background: Virtual reality (VR) has emerged as a promising treatment approach in rehabilitation for patients with multiple sclerosis (MS) due to its potential to increase patient motivation and rehabilitation adherence. One of the key features for rehabilitation adherence is patient satisfaction with the VR rehabilitation (VRR) program, and information on user satisfaction and not only effectiveness is required to systematically include VRR in routine clinical practice. Given that information on patient satisfaction with VRR is scarce, the primary objective of this study is to assess long-term patient satisfaction with a novel VRR program. This program has been specifically designed for MS patients by a multidisciplinary team of specialists, based on an effective conventional rehabilitation (CR) program. Secondarily, discomfort with VRR will be evaluated, and therapy adherence and changes in a variety of domains typically affected by MS will be compared between patients receiving VRR and patients receiving CR. Methods: In this prospective single-center 6-months follow-up study, 32 and 16 MS patients will receive VRR or CR, respectively. Patients will attend twice weekly rehabilitation sessions on site during 4 weeks, and they will continue with rehabilitation at home for five additional months. Satisfaction, assessed by the User Satisfaction Evaluation Questionnaire (USEQ), at 6 months of the VRR program initiation will be the primary outcome. Secondary outcomes include adherence, disability, spasms and spasticity, balance, fatigue, activities of daily living (ADLs), depression, anxiety, work status, cognition, demographic, and clinical characteristics (in the VRR and CR groups), and discomfort (in the VRR group). Outcome measures will be assessed at baseline, and at 1 and 6 months of rehabilitation initiation. Discussion: The study is intended to provide a better understanding of long-term patient satisfaction with a VRR program specifically designed for MS patients. Additionally, the study will provide information on long-term adherence, changes in motor symptoms, cognitive functions and patient-reported outcomes after the rehabilitation program. The results from this study will help to gather valuable knowledge on the use of rehabilitation with a new VR tool in MS patients.

CSF chitinase 3-like-1 association with disability of primary progressive MS.

OBJECTIVE: To assess the role of CSF chitinase 3-like-1 (CHI3L1), chitinase 3-like-2 (CHI3L2), and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS). METHODS: We analyzed CSF CHI3L1, CHI3L2, and NfL levels in 25 patients with PPMS with disease duration ≤10 years and no disease-modifying therapy for ≥6 months from the prospective Understanding Primary Progressive Multiple Sclerosis cohort study. CSF samples taken at disease diagnosis were analyzed using commercial ELISAs and following the manufacturer's instructions. Data on Expanded Disability Status Scale (EDSS) scores, disability progression, and cognitive function according to the Brief Repeatable Neuropsychological Battery were also assessed throughout the 1-year study follow-up. RESULTS: Increasing CHI3L1 levels correlated with higher EDSS scores at baseline (ρ = 0.490, 95% CI 0.118-0.742, p = 0.013) and month 12 (ρ = 0.455, 95% CI 0.063-0.725, p = 0.026) and tended to be associated with a higher risk of disability progression according to EDSS scores (OR = 1.008, 95% CI 0.999-1.017, p = 0.089). Increasing CHI3L2 levels also tended to correlate with lower baseline EDSS scores (ρ = -0.366, 95% CI -0.676-0.054, p = 0.086). There was no correlation with regard to NfL levels. CONCLUSIONS: This analysis supports the association between CSF CHI3L1 levels and neurologic disability according to EDSS scores in patients with PPMS. Other chitinase-like proteins such as CHI3L2 may also be involved. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CSF CHI3L1 is associated with neurologic disability in patients with PPMS.

Assessing Stigma in Multiple Sclerosis: Psychometric Properties of the Eight-Item Stigma Scale for Chronic Illness (SSCI-8).

BACKGROUND: The stigma associated with neurologic disorders plays a part in poor health-related quality of life. The eight-item Stigma Scale for Chronic Illness (SSCI-8) is a brief self-assessment tool for measuring perceived level of stigma. The psychometric performance of the SSCI-8 in people with multiple sclerosis (MS) was assessed. METHODS: A multicenter, cross-sectional study in adults with relapsing-remitting or primary progressive MS was performed. A nonparametric item response theory procedure, Mokken analysis, was done to preliminarily study the dimensional structure of the SSCI-8. A confirmatory factor analysis (CFA) model was then fit, and the behavior and information covered by the eight items were assessed by parametric item response theory analysis. RESULTS: A total of 201 patients (mean ± SD age, 43.9 ± 10.5 years; 60.2% female; 86.1% with relapsing-remitting MS) were studied. The Mokken analysis found that the SSCI-8 is a unidimensional strong scale (scalability index H = 0.56) with high reliability (Cronbach α = 0.88). The CFA model confirmed the unidimensionality (comparative fit index = 0.975, root mean square error of approximation = 0.077). The information covered by the SSCI-8 items ranges from 3.79 to 13.52, for a total of 66.56. More than half (66%) of the SSCI-8 overall information is conveyed by four items: 1 ("Some people avoided me"), 2 ("I felt left out of things"), 3 ("People avoided looking at me"), and 7 ("People were unkind to me"). CONCLUSIONS: The SSCI-8 shows appropriate psychometric characteristics and is, therefore, a useful instrument for assessing stigma in people with MS.

Perception of stigma in patients with primary progressive multiple sclerosis.

Stigma associated with neurological disorders may contribute to a poor health-related quality of life. However, limited information is available in primary progressive multiple sclerosis. We investigated the presence and impact of stigma in patients with primary progressive multiple sclerosis. A non-interventional, cross-sectional study was conducted. A total of 55 primary progressive multiple sclerosis patients were studied (mean age 55.8±9.5 years, 56.4% male). The median Expanded Disability Status Scale score was 5.5 (4.0-6.5). Stigma prevalence was 78.2% (n=43). Twenty-four patients (43.6%) were classified as depressed. Scores on the eight-item Stigma Scale for Chronic Illness correlated with physical (rho=0.464, p<0.001) and psychological (rho=0.358, p=0.007) 29-item Multiple Sclerosis Impact Scale subscores. Stigma predicted concurrent depression (odds ratio=1.13; p=0.046). Stigma was highly prevalent with a detrimental effect on quality of life and mood in primary progressive multiple sclerosis.

Measuring burden in caregivers of people with multiple sclerosis: psychometric properties of the CSI questionnaire.

BACKGROUND: Understanding caregiver strain may be crucial to determine which interventions are most needed to mitigate the negative impact of caring for people with multiple sclerosis (MS). The Caregiver Strain Index (CSI) is a brief self-assessment tool for measuring the caregivers' perceived level of burden. Limited information is available on the psychometric performance of the CSI in MS. OBJECTIVE: The objective of this study was to assess the factor structure and construct validity of the CSI in MS. METHODS: A multicenter, cross-sectional study in adults with relapsing-remitting and primary-progressive MS (McDonald 2010 criteria) was conducted. A non-parametric item response theory (IRT) procedure, Mokken analysis, was conducted to assess the dimensional structure of the CSI. A parametric IRT model for dichotomous responses, Rasch model, was conducted to assess item characteristics. Discriminative validity was assessed comparing the distribution of its overall score between people with mild and moderate-severe disability according to the Expanded Disability Status Scale. RESULTS: A total of 72 MS caregivers were studied. The prevalence of a high level of strain was 23.6% (n=17). Internal reliability was high (Cronbach's alpha =0.91). According to Mokken analysis, CSI represented a unidimensional construct of caregiver burden although two of the total 13 items (#1 and #13) could not be assigned to any factor by an automatic item selection procedure. Without these items, the scalability moved from a weak (Hi =0.37) to a medium scale (Hi =0.44). However, the item characteristic curve of the Rasch model showed a range of appropriate difficulty and the item and person parameters showed good fit (Andersen likelihood ratio test =18.40, df =11; P-value =0.07; all item values for the infit). The CSI score showed a good discriminative validity between the levels of disability of the care recipient. CONCLUSION: The CSI questionnaire shows appropriate psychometric characteristics being a useful instrument to assess different aspects of burden in MS caregivers in clinical practice.

Spanish validation of a specific measure to assess work-related problems in people with multiple sclerosis: The Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23).

INTRODUCTION: Unemployment is a significant problem for people with multiple sclerosis (MS). The MS Work Difficulties Questionnaire (MSWDQ-23) is a self-report tool to assess work-related problems in people with MS across three domains: physical, psychological/cognitive, and external barriers. The aim of this study was to assess the psychometric properties of the Spanish version of the MSWDQ-23. METHODS: A multicentre, non-interventional, cross-sectional study in adult patients with relapsing-remitting multiple sclerosis (RRMS) or primary progressive (PPMS) multiple sclerosis (McDonald 2010 criteria) was conducted. Socio-demographic and clinical characteristics as well as health-related quality of life using the 29-item Multiple Sclerosis Impact Scale (MSIS-29) were collected. RESULTS: A total of 201 subjects were studied (mean age: 43.9 years, 60% female, 86% with RRMS). Median Expanded Disability Status Scale (EDSS) (score: 2.0 [IQR: 1.0-3.5]). The employment rate was 47.3% (n = 95). The MSWDQ-23 was feasible (90% response rate), with high internal consistency and test-retest reliability (Cronbach's alpha = 0.94 and intraclass correlation coefficient-ICC > 0.87). MSWDQ-23 scores significantly and positively correlated with EDSS and both MSIS-29 physical and psychological subscales scores, showing an adequate convergent validity. Regarding construct validity, scores of patients with PPMS were higher than those of patients with RRMS, reaching statistically significance in MSWDQ-23 physical barriers domain and total scores. CONCLUSION: The Spanish version of the MSWDQ-23 shows appropriate feasibility, reliability, and discriminative performance as a patient-reported outcome. MSWDQ-23 may be a valuable addition to measure the impact of a comprehensive spectrum of difficulties experienced by people with MS in the workplace.

Psychometric properties of the SDM-Q-9 questionnaire for shared decision-making in multiple sclerosis: item response theory modelling and confirmatory factor analysis.

BACKGROUND: Shared decision-making is a cornerstone of patient-centred care. The 9-item Shared Decision-Making Questionnaire (SDM-Q-9) is a brief self-assessment tool for measuring patients' perceived level of involvement in decision-making related to their own treatment and care. Information related to the psychometric properties of the SDM-Q-9 for multiple sclerosis (MS) patients is limited. The objective of this study was to assess the performance of the items composing the SDM-Q-9 and its dimensional structure in patients with relapsing-remitting MS. METHODS: A non-interventional, cross-sectional study in adult patients with relapsing-remitting MS was conducted in 17 MS units throughout Spain. A nonparametric item response theory (IRT) analysis was used to assess the latent construct and dimensional structure underlying the observed responses. A parametric IRT model, General Partial Credit Model, was fitted to obtain estimates of the relationship between the latent construct and item characteristics. The unidimensionality of the SDM-Q-9 instrument was assessed by confirmatory factor analysis. RESULTS: A total of 221 patients were studied (mean age = 42.1 ± 9.9 years, 68.3% female). Median Expanded Disability Status Scale score was 2.5 ± 1.5. Most patients reported taking part in each step of the decision-making process. Internal reliability of the instrument was high (Cronbach's α = 0.91) and the overall scale scalability score was 0.57, indicative of a strong scale. All items, except for the item 1, showed scalability indices higher than 0.30. Four items (items 6 through to 9) conveyed more than half of the SDM-Q-9 overall information (67.3%). The SDM-Q-9 was a good fit for a unidimensional latent structure (comparative fit index = 0.98, root-mean-square error of approximation = 0.07). All freely estimated parameters were statistically significant (P < 0.001). All items presented standardized parameter estimates with salient loadings (>0.40) with the exception of item 1 which presented the lowest loading (0.26). Items 6 through to 8 were the most relevant items for shared decision-making. CONCLUSIONS: The SDM-Q-9 presents appropriate psychometric properties and is therefore useful for assessing different aspects of shared decision-making in patients with multiple sclerosis.

Conjoint analysis to understand preferences of patients with multiple sclerosis for disease-modifying therapy attributes in Spain: a cross-sectional observational study.

OBJECTIVE: To assess patients' preferences for a range of disease-modifying therapy (DMT) attributes in multiple sclerosis (MS). DESIGN: A cross-sectional observational study. SETTING: The data reported were from 17 MS units throughout Spain. PARTICIPANTS: Adult patients with relapsing-remitting MS. MAIN OUTCOME: A conjoint analysis was applied to assess preferences. A total of 221 patients completed a survey with 10 hypothetical DMT profiles developed using an orthogonal design and rating preferences from 1 (most acceptable) to 10 (least acceptable). Medication attributes included preventing relapse, preventing disease progression, side effect risk, route and frequency of administration. RESULTS: Patients placed the greatest relative importance on the side effect risk domain (32.9%), followed by route of administration (26.1%), frequency of administration (22.7%), prevention of disease progression (10.0%) and prevention of relapse (8.3%). These results were independent of the Expanded Disability Status Scale score. The importance assigned to side effect risk was highest for patients with a recent diagnosis. Patients who had previously received more than one DMT gave a higher importance to relapse rate reduction than patients receiving their first DMT. CONCLUSIONS: Patient DMT preferences were mainly driven by risk minimisation, route of administration and treatment schedule. The risk-benefit spectrum of available DMT for MS is becoming increasingly complicated. Understanding which treatment characteristics are meaningful to patients may help to tailor information for them and facilitate shared decision-making in clinical practice.

Decision-making in Multiple Sclerosis: The Role of Aversion to Ambiguity for Therapeutic Inertia among Neurologists (DIScUTIR MS).

OBJECTIVES: Limited information is available on physician-related factors influencing therapeutic inertia (TI) in multiple sclerosis (MS). Our aim was to evaluate whether physicians' risk preferences are associated with TI in MS care, by applying concepts from behavioral economics. DESIGN: In this cross-sectional study, participants answered questions regarding the management of 20 MS case scenarios, completed 3 surveys, and 4 experimental paradigms based on behavioral economics. Surveys and experiments included standardized measures of aversion ambiguity in financial and health domains, physicians' reactions to uncertainty in patient care, and questions related to risk preferences in different domains. The primary outcome was TI when physicians faced a need for escalating therapy based on clinical (new relapse) and magnetic resonance imaging activity while patients were on a disease-modifying agent. RESULTS: Of 161 neurologists who were invited to participate in the project, 136 cooperated with the study (cooperation rate 84.5%) and 96 completed the survey (response rate: 60%). TI was present in 68.8% of participants. Similar results were observed for definitions of TI based on modified Rio or clinical progression. Aversion to ambiguity was associated with higher prevalence of TI (86.4% with high aversion to ambiguity vs. 63.5% with lower or no aversion to ambiguity; p = 0.042). In multivariate analyses, high aversion to ambiguity was the strongest predictor of TI (OR 7.39; 95%CI 1.40-38.9), followed by low tolerance to uncertainty (OR 3.47; 95%CI 1.18-10.2). CONCLUSION: TI is a common phenomenon affecting nearly 7 out of 10 physicians caring for MS patients. Higher prevalence of TI was associated with physician's strong aversion to ambiguity and low tolerance of uncertainty.

Decision making under uncertainty, therapeutic inertia, and physicians' risk preferences in the management of multiple sclerosis (DIScUTIR MS).

BACKGROUND: The management of multiple sclerosis (MS) is rapidly changing by the introduction of new and more effective disease-modifying agents. The importance of risk stratification was confirmed by results on disease progression predicted by different risk score systems. Despite these advances, we know very little about medical decisions under uncertainty in the management of MS. The goal of this study is to i) identify whether overconfidence, tolerance to risk/uncertainty, herding influence medical decisions, and ii) to evaluate the frequency of therapeutic inertia (defined as lack of treatment initiation or intensification in patients not at goals of care) and its predisposing factors in the management of MS. METHODS/DESIGN: This is a prospective study comprising a combination of case-vignettes and surveys and experiments from Neuroeconomics/behavioral economics to identify cognitive distortions associated with medical decisions and therapeutic inertia. Participants include MS fellows and MS experts from across Spain. Each participant will receive an individual link using Qualtrics platform(©) that includes 20 case-vignettes, 3 surveys, and 4 behavioral experiments. The total time for completing the study is approximately 30-35 min. Case vignettes were selected to be representative of common clinical encounters in MS practice. Surveys and experiments include standardized test to measure overconfidence, aversion to risk and ambiguity, herding (following colleague's suggestions even when not supported by the evidence), physicians' reactions to uncertainty, and questions from the Socio-Economic Panel Study (SOEP) related to risk preferences in different domains. By applying three different MS score criteria (modified Rio, EMA, Prosperini's scheme) we take into account physicians' differences in escalating therapy when evaluating medical decisions across case-vignettes. CONCLUSIONS: The present study applies an innovative approach by combining tools to assess medical decisions with experiments from Neuroeconomics that applies to common scenarios in MS care. Our results will help advance the field by providing a better understanding on the influence of cognitive factors (e.g., overconfidence, aversion to risk and uncertainty, herding) on medical decisions and therapeutic inertia in the management of MS which could lead to better outcomes.

Severity and outcomes according to stroke etiology in patients under 50 years of age with ischemic stroke.

UNLABELLED: To analyze the association of stroke etiological subtypes with severity and outcomes at 3 and 12 months in patients ≤50 years. Observational study of patients admitted to a stroke unit (2007-2013). VARIABLES: demographic data, vascular risk factors, comorbidities, severity on admission (NIHSS), and good functional outcome (mRS ≤ 1) at 3 and 12 months. We used multivariate analyses to evaluate the influence of stroke etiology on severity and outcomes. We included 214 patients, 58.3 % men, mean age 41.4 years. General linear models showed all etiologies were more severe than lacunar strokes (P < 0.05). Atherothrombotic strokes showed greater severity than those of undetermined and uncommon etiology, whereas cardioembolic strokes were more severe than cryptogenic. Taking into account specific etiologies, atherothrombotic strokes (B = 5.860; 95 % CI 2.979-8.751), cervical artery dissection (CAD) [B = 7.485; 95 % confidence interval (CI) 4.734-10.237], and atrial fibrillation (AF) strokes (B = 5.773; 95 % CI 2.704-8.132) were more severe than other etiologies. Logistic regression models showed that strokes of uncommon etiology, especially those not related to CAD, had a lower probability of good outcome at 3 months [odds ratio (OR) = 0.197; CI 95 % 0.044-0.873], whereas atherothrombotic strokes were associated with this probability at 12 months (OR = 0.187; 95 % CI 0.037-0.951; P = 0.007). In patients ≤50 years of age, strokes of atherothrombotic, cardioembolic (particularly those due to AF), and uncommon etiology had a greater severity than the rest. Furthermore, strokes of uncommon etiology, especially those different from CAD, decreased the probability of a good outcome at 3 months, as did atherothrombotic strokes at 1 year.

Can we improve the early detection of atrial fibrillation in a stroke unit? Detection rate of a monitor with integrated detection software.

INTRODUCTION: It is unknown whether monitors that include atrial fibrillation recognition software (AF-RS) increase the rate of early atrial fibrillation (AF) detection in acute stroke. We aimed to evaluate the AF detection rate of an AF-RS monitor and compare it with standard monitoring. METHODS: This was a retrospective, single-centre observational study conducted on consecutive patients with acute transient ischaemic attack or brain infarction attended in a stroke unit (SU) with six beds. Five beds had a standard monitor with a three-lead electrocardiogram (ECG)-tracing monitor that did not automatically detect AF, and one bed had a 12-lead ECG monitor with integrated AF-RS. All patients were monitored for at least 24 h and underwent a daily ECG during their stay in the SU. In case of unknown stroke aetiology, the patients underwent 24 h Holter monitoring. RESULTS: A total of 76 patients were included: 59 patients in the standard monitor group and 17 patients in the AF-RS monitor group. The mean age was 72.11 (±13.09) years, and 59.2% were men. A total of 20 new cases of AF were identified. The AF-RS monitor showed a higher rate of AF detection than the standard devices (57.1% vs 7.7%, p=0.031). The AF-RS monitor showed sensitivity, specificity, positive predictive value, and negative predictive values of 57.1%, 100%, 100% and 76.9%, respectively. For the standard monitors, these values were 7.7%, 100%, 100% and 79.3%, respectively. CONCLUSION: The monitor with AF-RS demonstrated a higher detection rate for AF than standard ECG monitoring in acute stroke patients in a SU.

Antiphospholipid antibodies correlate with stroke severity and outcome in patients with antiphospholipid syndrome.

BACKGROUND: Our goal was to analyze the association of the level of antiphospholipid antibodies (aPLs) with stroke severity and outcome in patients with antiphospholipid syndrome (APS). METHODS: Observational study included consecutive patients with ischemic stroke younger than 55 years (2007-2012). We analyzed serum levels of aPLs, including anticardiolipin (aCL) antibodies, anti-ß2-glycoprotein I antibodies (anti-ß2GPI) and antiprothrombin antibodies (aPS/PT) within the first 48 h after admission, and again, in the case of a positive result, at least 12 weeks after the first measurement. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS), and the three-month stroke outcome by the modified Rankin Scale (mRS). Multiple linear regression models were used to analyze the correlation between the aPLs and stroke severity and outcome. RESULTS: Overall 255 stroke patients were included, 22 (8.6%) with APS. Among them, a positive correlation was found between immunoglobulin M (IgM) aCL levels within 48 h and NIHSS (rho = 0.471; p = 0.027), as well as a tendency toward a positive correlation between immunoglobulin G (IgG) anti-ß2GPI levels within 48 h and three-month mRS (rho = 0.364; p = 0.096). Multiple linear regression analyses showed a positive correlation between levels of IgM aCL < 48 h and the NIHSS (ß-coefficient [standard error; SE] = 0.127 [0.044]), as well as the levels of IgG anti-ß2GPIwithin 48 h and the three-month mRS (ß-coefficient [SE] = 0.034 [0.011]). CONCLUSIONS: In young stroke patients with APS, serum levels of IgM aCL within 48 h are correlated with stroke severity and levels of IgG anti-ß2GPI within 48 h are correlated with three-month outcomes.