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.

Post-Cerebrovascular Stroke and Early Dysphagia Assessment: A Systematic Review.

PURPOSE: We performed a systematic review on the early assessment of swallowing function after cerebrovascular stroke. MATERIALS AND METHODS: A systematic review of the English language literature of the past 20 years was performed regarding swallowing function and cerebrovascular stroke. All articles reporting swallowing evaluation through clinical examination validated scores, and diagnostic tools were included in the summary. RESULTS: The systematic review of the literature identified 1,768 potentially relevant studies with 7 papers retrieved with a total of 589 stroke dysphagic patients. While at the clinical neurological assessment, The National Institutes of Health Stroke Scale was more frequently used as a clinical outcome predictor. The Bedside screening approach was carried out in 6 papers to assess patients with probable swallowing disorders. Among the diagnostic tools, seven studies performed the Flexible Fiberoptic Endoscopic evaluation assessing scoring validated system while two papers reported early swallowing outcomes Videofluoroscopic Swallow Study. CONCLUSIONS: Our systematic review revealed the findings significantly associated with dysphagia in post-cerebrovascular patients. Endoscopic evaluation of swallowing proved to be the most used method in the literature, effective in identifying early predictors of dysphagia. Given the presence of different assessing scores employed and reduced study samples enrolled, further studies with large courts are necessary for a greater significance.

Patients with multiple sclerosis: a burden and cost of illness study.

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

Living with severe multiple sclerosis: Cost-effectiveness of a palliative care intervention and cost of illness study.

BACKGROUND: Little is known about the economic consequences of living with severe multiple sclerosis (SMS). AIMS: To assess the cost-effectiveness of a home-based palliative approach (HPA) for people with SMS (pwSMS). To assess direct healthcare costs in this population. METHODS: PwSMS from three Italian centers received (2:1 ratio) HPA or usual care over six months. Direct healthcare costs were collected on a monthly basis. Incremental cost-effectiveness was gauged from a national healthcare system (NHS) and a personal perspective, considering the Palliative Outcome Scale-Symptoms-MS (POS-S-MS) and the EuroQol five-dimension descriptive system quality-adjusted life years (EQ-5D-3L QALYs), both completed at baseline, after three and six months. RESULTS: Of 78 randomized pwSMS, 76 (50 HPA, 26 usual care) were analyzed. Mean QALYs were close to zero, and the mean group difference was -0.006 (95% CI -0.057 to 0.044). The mean baseline-adjusted cost difference was € -394 (95% confidence interval, CI -3,532 to 2,743). POS-S-MS cost-effectiveness showed a slight mean reduction of symptom burden (-1.9; 95% CI -1.1 to 5.0) with unchanged costs. Mean direct costs due to MS were € 23,195/year, almost equally distributed between NHS (€ 13,108) and pwSMS (€ 10,087). Personal care, medications and home rehabilitation accounted for 80% of total expenditures. Most personal care costs were covered by pwSMS, and these costs were 3/4 of pwSMS out-of-pocket. CONCLUSIONS: The slight reduction of symptom burden produced by the HPA was not associated with an increase in costs. NHS and pwSMS almost equally sustained these costs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN73082124.

Integrated characterization and risk management of marine sediments: The case study of the industrialized Bagnoli area (Naples, Italy).

The aim of the present work is to demonstrate the practical importance of a multidisciplinary approach and weighted criteria to synthesize and integrate different typologies of data (or lines of evidence, LOEs), including chemical levels in marine sediments, their bioavailability to specific indicator species, ecotoxicological effects measured through subcellular biomarkers and batteries of bioassays, and potential impacts of pollution on local benthic communities. The area of Bagnoli (Gulf of Naples, Southern Italy) was selected as a model case-study, as it is a coastal area chronically impacted by massive industrial contamination (trace metals and hydrocarbons), and dismissed decades ago without any subsequent remediation or habitat restoration. The results of each LOE were elaborated to provide specific hazard indices before their overall integration in a weight of evidence (WOE) evaluation. Levels of some trace metals and PAHs revealed a severe contamination in the entire study area. Bioavailability of hydrocarbons was evident particularly for high molecular weight PAHs, which also caused significant variations of cellular biomarkers, such as cytochrome P450 metabolization in fish, lysosomal membrane destabilization in mussels, genotoxic effects both in fish and molluscs. The results of a battery of bioassays indicated less marked responses compared to those obtained from chemical and biomarkers analyses, with acute toxicity still present in sediments close to the source of contamination. The analysis of benthic assemblages showed limited evidence of impact in the whole area, indicating a good functioning of local ecosystems at chronic contamination. Overall, the results of this study confirm the need of combining chemical and biological data, the quantitative characterization of various typologies of hazard and the importance of assessing an integrated environmental WOE risk, to orientate specific and scientifically-supported management options in industrialized areas.

Cost-Effectiveness Analysis of Cannabinoid Oromucosal Spray Use for the Management of Spasticity in Subjects with Multiple Sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a highly symptomatic disease, with a wide range of disabilities affecting many bodily functions, even in younger persons with a short disease history. The availability of a cannabinoid oromucosal spray (Sativex) for the management of treatment-resistant MS spasticity has provided a new opportunity for many patients. OBJECTIVE: Our study aimed to assess the cost effectiveness of Sativex in Italian patients with treatment-resistant MS spasticity. The analysis was based on the real-world data of a large registry of Italian patients. METHODS: A cost-utility analysis was conducted using data collected prospectively from an electronic registry of all patients who began to use Sativex for MS-resistant spasticity between January 2014 and February 2015 in 30 specialized MS units across Italy and were followed up for ≤ 6 months. Data on drug consumption and spasticity/utility were used to estimate the incremental cost-effectiveness ratio (ICER) of Sativex, as compared with no intervention. No costs or spasticity/utility changes were assumed for no treatment intervention. The ICER was expressed as quality-adjusted life-years (QALYs) gained, using the Italian NHS perspective and a 6-month time horizon. RESULTS: Sativex effectiveness and consumption was estimated analyzing data of 1350 patients from the registry. These patients reported a mean (SD) utility increment of 0.087 (0.069) after 1 month of treatment, 0.118 (0.073) after 3 months' treatment and 0.127 (0.080) after 6 months' treatment. The 6-month cost of treating the entire population with Sativex was €1,361,266, with a €1008 cost and 0.0284 QALYs gained per patient. The estimated ICER was €35,516 per QALY gained, with little variability around the central estimate of cost-effectiveness, as shown by the cost-effectiveness acceptability curve. CONCLUSION: The use of Sativex could improve the quality of life of patients with a reasonable incremental cost resulting as a cost-effective option for patients with MS-resistant spasticity. These results could help clinicians and decision makers to develop improved management strategies for spasticity in patients with MS, optimizing the use of available resources.

Ecological assessment of anthropogenic impact in marine ecosystems: The case of Bagnoli Bay.

Pollutants alter marine systems, interfering with provisioning of ecosystem services; understanding their interaction with ecological communities is therefore critical to inform environmental management. Here we propose a joint compositional- and interaction-based analysis for ecological status assessment and apply it on the benthic communities of the Bagnoli Bay. We found that contamination differentially affects the communities' composition in the bay, with prokaryotes influenced only by depth, and benthos not following the environmental gradient at all. This result is confirmed by analyses of the community structure, whose network structure suggest fast carbon flow and cycling, especially promoted by nematodes and polychaetes; the benthic prey/predator biomass ratio, adjusted for competition, successfully synthesise the status of predator taxa. We found demersal fish communities to separate into a deep, pelagic-like community, and two shallow communities where a shift from exclusive predators to omnivores occurs, moving from the most polluted to the least polluted sampling units. Finally, our study indicate that indices based on interspecific interactions are better indicators of environmental gradients than those defined based on species composition exclusively.

Pharmacoeconomics of synthetic therapies for multiple sclerosis.

Introduction: Recently, the economic impact of multiple sclerosis (MS), which includes both direct and indirect costs, has been increasing. While direct costs comprise health-care costs, such as the cost of pharmaceuticals, additional treatments such as physiotherapy, and medical aids, indirect costs are triggered by the productivity loss of patients and caregivers. Although new drugs for MS have changed the therapeutic scenario, they have increased the direct costs of health-care services. Areas covered: This review describes the pharmacoeconomic aspects of synthetic therapies for MS. Additionally, it discusses the economic impact of the various classes of licensed disease-modifying treatments (DMTs) for relapsing forms of MS. Expert opinion: The emerging and more expensive DMTs for MS represent a considerable challenge for health-care systems and resource consumption. Future research should focus on the long-term efficacy of DMTs and the cost of treating MS in a real-life setting. Future biological and radiological biomarkers could help stratify patients at early stages of MS, helping physicians design a personalized therapeutic approach that could have a positive impact in economic terms.

Correction to: Cognitive assessment in multiple sclerosis-an Italian consensus.

In the original article, Maria Pia Amato's second affiliation was not included. The second affiliation is IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy. The correct affiliation is presented here.

Cognitive assessment in multiple sclerosis-an Italian consensus.

The aim of this consensus paper was to define the state of the art on cognitive assessment of persons with multiple sclerosis (PwMS), with the purpose of providing recommendations for the Italian centers involved in MS management. While there are no formal guidelines published regarding the assessment of cognitive function in MS, on the basis of an expert opinion meeting, held in Milan (Italy) on July 4, 2016, we report the recommendations of a panel of Italian experts including MS neurologists and neuropsychologists for the assessment and follow-up of cognitive function in adult MS subjects.

The clinical value of Coop/Wonca charts in assessment of HRQoL in a large cohort of relapsing-remitting multiple sclerosis patients: Results of a multicenter study.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurological disease impacting patients' health-related quality of life (HRQoL). Since MS specific HRQoL questionnaire are often time consuming; thus, simple, feasible and ease administering instruments are needed to assess MS HRQoL in clinical practice and clinical trials. Hence, aim of our study was to investigated the HRQoL in a large cohort of MS patients using the Coop/Wonca charts. METHODS: This was multicenter, independent, non-sponsored, observational study, including patients from 40 Italian MS centers. Inclusion criteria were Expanded Disability Status Scale score between 1.0 and 5.5; stable disease at enrolment. HRQoL was assessed, using six Coop/Wonca charts for physical fitness, feelings, daily activities, social activities, changes in health, health condition, and the Composites Scores of Multiple Sclerosis Quality of Life-54 (MSQoL-54), physical health composite summary (PHCS) and the mental health composite summary (MHCS). RESULTS: Out of 648, 593 relapsing-remitting MS patients, 415 (70%) women, mean age years, 417 (70%) were finally enrolled. We found a inter-rater agreement of 0.8, ranging from 0.64 to 0.91, as expressed by the alpha coefficient. Intra-rater agreement was 0.82, ranging from 0.78 to 0.96. Coop/Wonca charts were scored with a Likert method from one to five (corresponding to best and worst HRQoL respectively). According to this scoring, study population was stratified into three categories (score 1-2 corresponding to better HRQoL; score 3 corresponding to neutral profile; score 4-5 corresponding to worse HRQoL). Coop/Wonca charts resulted significantly correlated with PHCS and with MHCS.

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.

Measuring the cost of cognitive-motor dual tasking during walking in multiple sclerosis.

Purposeful, safe locomotion requires higher-level cortical processes, to meet the real-life demands of walking while performing concurrent cognitive tasks (e.g. recalling a shopping list or attending to a conversation). The assessment of walking and a secondary cognitive task under these 'dual tasking' conditions may represent a more valid outcome measure in multiple sclerosis (MS), by examining the occurrence and magnitude of the cognitive-motor interference of walking. This topical review provides a state-of-the-art overview of research into dual-tasking during walking in persons with MS, based on 14 recent papers. Studies consistently demonstrate a slowing of ambulation under dual tasking, regardless of the cognitive task demand, the stage of the disease and the disability level. The reciprocal effect of walking on the cognitive tasks was rarely assessed. We present our main findings, highlight the different factors contributing to dual-task deficits, identify methodological shortcomings and offer recommendations for constructing dual-tasking paradigms useful in clinical practice and research.

Clinical case reviews and poster sessions in multiple sclerosis spasticity: main outcomes and highlights.

BACKGROUND: Individuals with multiple sclerosis (MS) spasticity present with a range of symptoms and disability levels that are frequently challenging to manage. Summary : Clinical case reviews in treatment-resistant MS spasticity were presented in five country-specific sessions conducted in parallel at the MS Experts Summit. Attendees at the Norwegian session discussed early response to new treatments for severe spasticity and highlighted the importance of titrating THC:CBD oromucosal spray (Sativex®) when adding it to baclofen. The French group focussed on MS symptoms and patient characteristics that interact with spasticity and agreed on a list of minimum ratings for diagnosis of MS spasticity symptoms. Attendees at the Spanish session concurred that THC:CBD oromucosal spray is effective and well tolerated as add-on therapy in treatment-resistant MS spasticity, particularly for pain, spasms and gait disturbances. The Italian group discussed the use of add-on THC:CBD oromucosal spray and other possible combination therapies for treatment-resistant MS spasticity. Attendees at the German session highlighted the need to address trigger factors for MS spasticity to reduce the potential for impact on activities of daily living (ADL) and quality of life (QoL). Three innovative studies of MS spasticity from the poster session were selected for closer review. The MOVE 1 EU epidemiological study indicated that, across western Europe, patients with MS spasticity continue to have unmet management needs. A literature review demonstrated that symptomatic relief of MS spasticity in patients who respond to THC:CBD oromucosal spray translates into sustainable improvements in ADL and QoL. Enriched-design studies of medications targeting the endocannabinoid system require careful interpretation due to possible pharmacodynamic 'priming', i.e. carry-over effects of successful active treatment during the enrichment phase. Key Messages: Sharing experiences of clinical practice, including experience with the use of THC:CBD oromucosal spray, may be useful to overcome some of the challenges in the overall management of patients with moderate to severe treatment-resistant MS spasticity.

Guidelines on the clinical use for the detection of neutralizing antibodies (NAbs) to IFN beta in multiple sclerosis therapy: report from the Italian Multiple Sclerosis Study group.

Interferon beta (IFNß) was the first specific disease-modifying treatment licensed for relapsing-remitting multiple sclerosis, and is still one of the most commonly prescribed treatments. A strong body of evidence supports the effectiveness of IFNß preparations in reducing the annual relapse rate, magnetic resonance (MRI) disease activity and disease progression. However, the development of binding/neutralizing antibodies (BAbs/NAbs) during treatment negatively affects clinical and MRI outcomes. Therefore, guidelines for the clinical use for the detection of NAbs in MS may result in better treatment of these patients. In October 2012, a panel of Italian neurologists from 17 MS clinics convened in Milan to review and discuss data on NAbs and their clinical relevance in the treatment of MS. In this paper, we report the panel's recommendations for the use of IFNß Nabs detection in the early identification of IFNß non-responsiveness and the management of patients on IFNß treatment in Italy, according to a model of therapeutically appropriate care.

Impact of sociodemographic characteristics on cognitive performance in an elderly Sicilian population.

OBJECTIVE: To assess cognitive levels in an elderly Sicilian population and to evaluate the role of education and other sociodemographic characteristics in cognitive performance. BACKGROUND: The pattern of cognitive performance in the elderly has not been investigated extensively in well-defined Italian populations. This study was conducted as part of a door-to-door survey of common neurologic disorders (the Sicilian Neuro-Epidemiologic Study project). METHODS: Thirteen physicians administered an Italian version of the Short Portable Mental Status Questionnaire (SPMSQ) to all subjects aged 50 years or older who, on November 1, 1987, resided in either of two Sicilian municipalities (Terrasini, Palermo province, and Riposto, Catania province; n = 3,999). Performance was scored as the number of errors on the SMPSQ. To define cognitive impairment we corrected the score for education as suggested by Pfeiffer [J Am Geriatr Soc 1975;23:433-441]. RESULTS: The median SPMSQ score was equal to 2, and cognitive impairment was present in 4.6% of the subjects. In a bivariate analysis, age, sex, education, employment status at interview and principal lifetime occupation were all significantly associated with cognitive impairment. In a multivariate analysis, the same pattern was seen, except that principal lifetime occupation lost its significance. CONCLUSION: Our findings suggest that age, sex, education and employment status are the sociodemographic characteristics associated with cognitive impairment in the elderly as measured by the SPMSQ.