Identifying definite patterns of unmet needs in patients with multiple sclerosis using unsupervised machine learning.

INTRODUCTION: People with multiple sclerosis (PwMS) exhibit a spectrum of needs that extend beyond solely disease-related determinants. Investigating unmet needs from the patient perspective may address daily difficulties and optimize care. Our aim was to identify patterns of unmet needs among PwMS and their determinants. METHODS: We conducted a cross-sectional multicentre study. Data were collected through an anonymous, self-administered online form. To cluster PwMS according to their main unmet needs, we performed agglomerative hierarchical clustering algorithm. Principal component analysis (PCA) was applied to visualize cluster distribution. Pairwise comparisons were used to evaluate demographics and clinical distribution among clusters. RESULTS: Out of 1764 mailed questionnaires, we received 690 responses. Access to primary care was the main contributor to the overall unmet need burden. Four patterns were identified: cluster C1, 'information-seekers with few unmet needs'; cluster C2, 'high unmet needs'; cluster C3, 'socially and assistance-dependent'; cluster C4, 'self-sufficient with few unmet needs'. PCA identified two main components in determining the patterns: the 'public sphere' (access to information and care) and the 'private sphere' (need for assistance and social life). Older age, lower education, longer disease duration and higher disability characterized clusters with more unmet needs in the private sphere. However, demographic and clinical factors failed in explaining the four identified patterns. CONCLUSION: Our study identified four unmet need patterns among PwMS, emphasizing the importance of personalized care. While clinical and demographic factors provide some insight, additional variables warrant further investigation to fully understand unmet needs in PwMS.

Cost-Analysis of Telemedicine Interventions Compared with Traditional Care in the Management of Chronic Neurological Diseases: A Systematic Review.

Background: Telemedicine has proven successful in relieving the burden of chronic neurological disorders from the national health care systems by ensuring a highly customized and effective management plan. Although many studies focus on assessing telemedicine effectiveness, little is known about the economic implications of telemedicine applications in chronic neurological diseases (CNDs). This issue could account for a lack of widespread implementation. Objective: Our study attempted to fill this gap by systematically reviewing scientific literature on the economic evaluation of telemedicine compared with traditional care in the management of CNDs. Methods: We performed a literature search on PubMed, Google Scholar, Scopus, Embase, and Medline. The inclusion criteria were as follows: (1) studies with a full cost-analysis; (2) randomized controlled trials; (3) studies comparing telemedicine interventions with traditional care; (4) articles focusing only on CNDs. Conversely, the exclusion criteria were as follows: (1) studies focusing on acute neurological conditions or other diseases and (2) study protocols, case report, duplicate articles, abstract only, books, letters to editors, and review articles. Results: Ten articles met the inclusion criteria. Three different approaches of telemedicine intervention could be identified: digital cognitive-behavioral therapy (CBT), motor telerehabilitation, and home monitoring and assessment devices. Conclusion: Cost-analysis showed an overall benefit in terms of both cost and effectiveness from the application of telemedicine instead of in-presence management in CNDs. Among the identified interventions, digital CBT proved to be the most cost-saving. However, promising results were also found in monitoring and assessment devices and in telerehabilitation. Definitely, however, more thorough, comprehensive, and high-quality economic evaluation studies are needed.

Validation of an iPad version of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS).

BACKGROUND: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is the most widely used screening tool for cognitive impairment in Multiple Sclerosis (MS). However, the administration and scoring procedures of the paper version are time consuming and prone to errors. Aim of our study was to develop a tablet version of BICAMS (iBICAMS), and to assess its reliability compared to the paper version. METHODS: We administered both BICAMS and iBICAMS to 139 MS patients in two different sessions. We compared scores on both versions using a paired t-test. We used a repeated measures ANOVA to test the impact of rater, order of administration and test-retest time on test-retest performances. We used the Intraclass Correlation Coefficient (ICC) to assess the reliability between BICAMS and iBICAMS. RESULTS: All three sub-tests of the BICAMS (SDMT, CVLT-II and BVMT-R) were different between the paper and the tablet versions. Order of administration influenced test-retest performances at the SDMT (p<0.001), CVLT- II (p<0.001) and BVMT-R (p<0.001). Intraclass coefficient correlation (ICC) revealed a high level of agreement between the paper BICAMS and the iPad version for all three tests: SDMT (0.92), CVLT-II (0.83) and BVMT-R (0.82). CONCLUSIONS: We found a high reliability between BICAMS and iBICAMS. Considering the inherent advantages of automated scoring, digital storage of data, standardized timing, the iBICAMS could become a standard in clinical practice.

Disability assessment using Google Maps.

OBJECTIVES: To evaluate the concordance between Google Maps® application (GM®) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). MATERIALS AND METHODS: This is a cross-sectional multicenter study. AS and EDSS were calculated using GM® and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. RESULTS: Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM® and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1-7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01-1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04-1.17, p = 0.002) were associated with discrepancies between GM® and routine clinical scoring. CONCLUSION: GM® could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM® should be considered for validation in further clinical studies.

Assessment of Multiple Sclerosis Disability Progression Using a Wearable Biosensor: A Pilot Study.

BACKGROUND: The evaluation of walking activity of people with multiple sclerosis (pwMS) is desirable. We evaluate the power of the correlation of motor parameters detected by the accelerometer in the Samsung Gear S2 smartwatch with multiple sclerosis (MS) disability measures and patient reported outcomes (PROs). METHODS: We enrolled 25 relapsing remitting MS patients. We assessed disability with the expanded disability status scale, two-minute walking test (2MWT), timed 25-foot walk test (T25FWT), and nine-hole peg test. We collected PROs measuring fatigue, ambulatory ability, depression, quality of life, and bladder/bowel function. Participants were asked to wear the accelerometer for a period of 30 days. RESULTS: The Spearman's rank correlation coefficient showed a moderate negative correlation between the patient-determined disease steps (PDDS) score with the mean steps/day, a strong negative correlation between the PDDS score with the maximum number of daily steps (MNDS) and a moderate negative correlation between the fatigue severity scale score and MNDS. A moderate negative correlation between MNDS and the 2MWT and a moderate negative correlation between MNDS and the T25FW was found. CONCLUSION: Our results suggest that motor parameters derived from the accelerometer could be a reliable measure of motor disability in pwMS.

Multidimensional assessment of the effects of erenumab in chronic migraine patients with previous unsuccessful preventive treatments: a comprehensive real-world experience.

BACKGROUND: erenumab was safe and effective in clinical trials for the prevention of migraine. However, real-life data are still lacking. Here we report the clinical experience from an Italian real-world setting using erenumab in patients with chronic migraine experiencing previous unsuccessful preventive treatments. METHODS: Seventy patients with chronic migraine and failure to ≥4 migraine preventive medication classes initially received monthly erenumab 70 mg s.c. Patients without a clinically meaningful improvement, considered as a > 30% reduction in headache days per month, after ≥3 months of therapy switched to monthly erenumab 140 mg. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity and migraine-related disability and impact, and validated questionnaires to explore depression/anxiety, sleep, and quality of life (QoL). Finally, the Pain Catastrophizing Scale, Allodynia Symptom Checklist-12 and MIGraine attacks-Subjective COGnitive impairments scale (MIG-SCOG) were administered. RESULTS: 70% of patients were "responders" after the third administration of erenumab 70 mg, whereas 30% switched to erenumab 140 mg; 29% (6 pts) responded after the sixth administration. The headache-day frequency was reduced from 21.1 ± 0.7 to 11.4 ± 0.9 days after the third administration (p < 0.001) and to 8.9 ± 0.7 days after the sixth administration (p < 0.001). 53% and 70% of patients, respectively, showed a reduction of ≥50% of headache days/month after the third and the sixth administrations. Also improved were headache pain severity, migraine-related disability, and impact on daily living, QoL, pain catastrophizing and allodynia (all p < 0.001), quality of sleep, symptoms of depression or anxiety (p < 0.05) but not MIG-SCOG. There were no new adverse event signals. CONCLUSION: These real-world data support monthly erenumab 70 or 140 mg s.c. as a safe and effective preventive treatment to reduce headache frequency and severity in chronic migraine patients experiencing previous unsuccessful preventive treatments.

Online Validation of a Battery of Questionnaires for the Assessment of Family Functioning and Related Factors.

BACKGROUND: Family functioning relies on different factors that are related to the individual characteristics of each member, the social context in which the family nucleus is integrated, and the internal and interpersonal family factors. The Short Version of the Family Assessment Measure-III, Dyadic Adjustment Scale, Inventory of Parent and Peer Attachment, Twenty-item Toronto Alexithymia Scale, Hospital Anxiety and Depression Scale, and Multidimensional Scale of Perceived Social Support are among the most commonly employed self-report measures for the assessment of family functioning and related factors. Traditionally, these scales have been administered using paper-and-pencil versions. However, with increased access to the Internet, online administration of questionnaires has become more common. The present study aimed to validate an online version of each of the above-mentioned questionnaires in a heterogeneous sample of Italian healthy individuals. METHODS: One-hundred participants were recruited for each questionnaire. A crossover design was used in each validation. The minimum important difference (MID) was applied to evaluate the differences in the variances of the paper-and-pencil and online format scores. A MID >0.5 is a reasonable first approximation of a threshold of important change. Taking into account the cross over design, mean difference between pencil-and-paper and online versions, and Intraclass Correlation Coefficient were also estimated by mixed models. RESULTS: The MID was <0.5 for all the instruments used. Therefore, no significant difference was observed between the score variances of the paper-and-pencil and online formats of all the questionnaires. Moreover, for each questionnaire the difference between the means of online and paper-and-pencil administrations scores (mean O-P) was calculated. We reported 95% confidence intervals that did not include the 0; therefore, mean (O-P) was not statistically significant. CONCLUSIONS: The current findings indicate that the online versions of all the questionnaires we administered can be considered reliable tools for the assessment of family functioning and related factors.

Sativex in resistant multiple sclerosis spasticity: Discontinuation study in a large population of Italian patients (SA.FE. study).

BACKGROUND: The approval of Sativex for the management of multiple sclerosis (MS) spasticity opened a new opportunity to many patients. In Italy, the healthcare payer can be fully reimbursed by the involved pharma company with the cost of treatment for patients not responding after a 4 week (28 days) trial period (Payment by Results, PbR), and 50% reimbursed with the cost of 6 weeks (42 days) treatment for other patients discontinuing (Cost Sharing, CS). The aim of our study was to describe the Sativex discontinuation profile from a large population of spasticity treated Italian MS patients. METHODS: We collected data of patients from 30 MS centres across the country starting Sativex between January 2014 and February 2015. Data were collected from the mandatory Italian Medicines Agency (AIFA) web-registry. Predictors of treatment discontinuation were assessed using a multivariate Cox proportional regression analysis. RESULTS: During the observation period 631 out of 1597 (39.5%) patients discontinued Sativex. The Kaplan-Meier estimates curve showed that 333 patients (20.8%) discontinued treatment at 4 weeks while 422 patients (26.4%) discontinued at 6 weeks. We found after adjusted modeling that a higher NRS score at T1 (adjHR 2.23, 95% 2.07-2.41, p<0.001) and a lower baseline NRS score (adjHR 0.51 95% CI 0.46-0.56, p<0.001) were predictive of treatment discontinuation. CONCLUSION: These data show that the first 6 weeks are useful in identifying those patients in which Sativex could be effective, thus avoiding the cost of longer term evaluation.

Health-care disparities stemming from sexual orientation of Italian patients with Multiple Sclerosis: A cross-sectional web-based study.

Lesbian, gay, bisexual and transgender (LGBT) patients might experience unique difficulties and barriers to treatment of chronic diseases related to their sexual orientation. Thus, we investigated concerns experienced by LGBT patients with multiple sclerosis (MS). We conducted a web-based survey using a multi-choice questionnaire published in an Italian social-network (www.smsocialnetwork.com) for MS patients. The survey investigated: socio-demographic factors, lifestyle habits, MS-related health status and LGBT specific issues (e.g. friendliness to their sexual orientation and eventual homophobic behaviors in the MS Center). Among MS patients willing to use psychological services, LGBT patients were associated with a smaller number of psychological consultations, compared to heterosexuals (Coeff.=-0.449; p<0.001; 95%CI=-0.682 to -0.217). LGBT patients were more likely to change MS Center, compared to heterosexuals (OR=2.064; p=0.046; 95%CI=1.011-4.212). The number of MS Center changes was associated with MS Center friendliness (p=0.037; rho=-0.229) and with the occurrence of homophobic behaviors (p=0.036; rho=0.234). LGBT MS patients more frequently changed MS Center and had a reduced use of psychological services, compared to heterosexuals. The attitude towards LGBT MS patients might affect resource utilizations and LGBTs health status.

Longitudinal assessment of immuno-metabolic parameters in multiple sclerosis patients during treatment with glatiramer acetate.

OBJECTIVE: We investigated the effect of glatiramer acetate (GA) on the modulation of immune cell subpopulations and serum levels of multiple immune/metabolic markers in patients with relapsing-remitting multiple sclerosis (RRMS) to understand whether the treatment with GA could induce a specific change in the immunometabolic asset of patients with RRMS. MATERIAL AND METHODS: We performed an extensive peripheral blood immunophenotyping and measured serum levels of several parameters involved in the pathogenesis of RRMS and also relevant in the pathogenesis of metabolic syndrome and obesity such as leptin, soluble leptin-receptor (sLep-R), myeloperoxidase (MPO), soluble CD40 ligand (sCD40-L), soluble tumor necrosis factor-receptor (sTNF-R), monocyte chemoattractant protein 1 (MCP-1), soluble Inter-Cellular Adhesion Molecule-1 (sICAM-1) and osteoprotegerin (OPG), in 20 naïve-to-treatment RRMS patients and 20 healthy controls. We repeated these analyses over time at 6 and 12 months after starting GA treatment. RESULTS: Our analysis showed that naïve-to-treatment RRMS patients had a lower number of CD16(+)CD56(+) NK cells, CD19(+) B cells, CD4(+) T cells co-expressing the MHC class II activation marker HLA-DR (CD4(+)DR(+)) and naïve CD4(+)CD45RA(+) T cells in basal conditions. GA treatment induced a specific and significant decrease of circulating CD19(+) B cells. Naïve-to-treatment RRMS patients also showed a significantly higher number of CD4(+) T cells with a memory phenotype (CD4(+)CD45RO(+)) whose peripheral frequency was not affected by GA treatment. These changes over time associated with a higher serum concentration of leptin and lower levels of MPO. GA treatment also reduced significantly the circulating levels of sCD40-L and sTNF-R overtime. CONCLUSIONS: Our data suggest that the clinical outcome of GA treatment is associated with changes in immune cell subpopulations and modulation of specific immunometabolic markers. These data add substantial evidence of the immune modulating effect of GA during RRMS and could be of relevance in understanding the pathogenesis of disease and its follow-up.

Multiparametric 3T MR approach to the assessment of cerebral gliomas: tumor extent and malignancy.

INTRODUCTION: Contrast-enhanced MR imaging is the method of choice for routine assessment of brain tumors, but it has limited sensitivity and specificity. We verified if the addition of metabolic, diffusion and hemodynamic information improved the definition of glioma extent and grade. METHODS: Thirty-one patients with cerebral gliomas (21 high- and 10 low-grade) underwent conventional MR imaging, proton MR spectroscopic imaging ((1)H-MRSI), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) at 3 Tesla, before undergoing surgery and histological confirmation. Normalized metabolite signals, including choline (Cho), N-acetylaspartate (NAA), creatine and lactate/lipids, were obtained by (1)H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. RESULTS: Perienhancing areas with abnormal MR signal showed 3 multiparametric patterns: "tumor", with abnormal Cho/NAA ratio, lower ADC and higher rCBV; "edema", with normal Cho/NAA ratio, higher ADC and lower rCBV; and "tumor/edema", with abnormal Cho/NAA ratio and intermediate ADC and rCBV. Perienhancing areas with normal MR signal showed 2 multiparametric patterns: "infiltrated", with high Cho and/or abnormal Cho/NAA ratio; and "normal", with normal spectra. Stepwise discriminant analysis showed that the better classification accuracy of perienhancing areas was achieved when regarding all MR variables, while (1)H-MRSI variables and rCBV better differentiated high- from low-grade gliomas. CONCLUSION: Multiparametric MR assessment of gliomas, based on (1)H-MRSI, PWI and DWI, discriminates infiltrating tumor from surrounding vasogenic edema or normal tissues, and high- from low-grade gliomas. This approach may provide useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.