The Italian multiple sclerosis register

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups

The Italian multiple sclerosis register

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups

Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Introduction Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked.This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register.MethodsThe Register collects, through a standardized Web-based Application, unique patients.Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated.ResultsThe Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients.The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000-2015) to 60% (enrolment period 2016-2022). In the cohort of patients registered after 2016, there were >= 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2).Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months.ConclusionsData from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian Consensus Conference on Pain in Neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Musical and psychomotor interventions for cognitive, sensorimotor, and cerebral decline in patients with Mild Cognitive Impairment (COPE): a study protocol for a multicentric randomized controlled study

Background: Regular cognitive training can boost or maintain cognitive and brain functions known to decline with age. Most studies administered such cognitive training on a computer and in a lab setting. However, everyday life activities, like musical practice or physical exercise that are complex and variable, might be more successful at inducing transfer effects to different cognitive domains and maintaining motivation. "Body-mind exercises", like Tai Chi or psychomotor exercise, may also positively affect cognitive functioning in the elderly. We will compare the influence of active music practice and psychomotor training over 6 months in Mild Cognitive Impairment patients from university hospital memory clinics on cognitive and sensorimotor performance and brain plasticity. The acronym of the study is COPE (Countervail cOgnitive imPairmEnt), illustrating the aim of the study: learning to better "cope" with cognitive decline. Methods: We aim to conduct a randomized controlled multicenter intervention study on 32 Mild Cognitive Impairment (MCI) patients (60–80 years), divided over 2 experimental groups: 1) Music practice; 2) Psychomotor treatment. Controls will consist of a passive test–retest group of 16 age, gender and education level matched healthy volunteers. The training regimens take place twice a week for 45 min over 6 months in small groups, provided by professionals, and patients should exercise daily at home. Data collection takes place at baseline (before the interventions), 3, and 6 months after training onset, on cognitive and sensorimotor capacities, subjective well-being, daily living activities, and via functional and structural neuroimaging. Considering the current constraints of the COVID-19 pandemic, recruitment and data collection takes place in 3 waves. Discussion: We will investigate whether musical practice contrasted to psychomotor exercise in small groups can improve cognitive, sensorimotor and brain functioning in MCI patients, and therefore provoke specific benefits for their daily life functioning and well-being. Trial registration: The full protocol was approved by the Commission cantonale d’éthique de la recherche sur l'être humain de Genève (CCER, no. 2020–00510) on 04.05.2020, and an amendment by the CCER and the Commission cantonale d'éthique de la recherche sur l'être humain de Vaud (CER-VD) on 03.08.2021. The protocol was registered at clinicaltrials.gov (20.09.2020, no. NCT04546451).</p

Synthesis and Preliminary Evaluation in Tumor Bearing Mice of New 18F‑Labeled Arylsulfone Matrix Metalloproteinase Inhibitors as Tracers for Positron Emission Tomography

New fluorinated, arylsulfone-based matrix metalloproteinase (MMP) inhibitors containing carboxylate as the zinc binding group were synthesized as radiotracers for positron emission tomography. Inhibitors were characterized by Ki for MMP-2 in the nanomolar range and by a fair selectivity for MMP- 2/9/12/13 over MMP-1/3/14. Two of these compounds were obtained in the 18F-radiolabeled form, with radiochemical purity and yield suitable for preliminary studies in mice xenografted with a human U-87 MG glioblastoma. Target density in xenografts was assessed by Western blot, yielding Bmax/Kd = 14. The biodistribution of the tracer was dominated by liver uptake and hepatobiliary clearance. Tumor uptake of 18F-labeled MMP inhibitors was about 30% that of [18F]fluorodeoxyglucose. Accumulation of radioactivity within the tumor periphery colocalized with MMP-2 activity (evaluated by in situ zimography). However, specific tumor uptake accounted for only 18% of total uptake. The aspecific uptake was ascribed to the high binding affinity between the radiotracer and serum albumin