Inflammation and physical activity in multiple sclerosis patients. A systematic review and meta-analysis.

OBJECTIVES: Due to the inflammatory nature of multiple sclerosis (MS), the most widely used therapeutic approach targets the immune response but can comprise side effects (e.g. secondary immunosuppression). For these reasons, among non-pharmaceutical interventions without known side effects, physical activity (PA) gained importance because it is feasible, safe and a supportive complementary treatment strategy to alleviate symptoms in MS subjects. Consequently, the main aim of this systematic review is to analyze the effect of PA protocols, as a complementary therapy, on inflammatory status in MS patients. METHODS: Four electronic databases (PubMed, Embase, CINAHL, and Cochrane CENTRAL) were systematically searched up to 01 June 2023 (Prospero Protocol ID=CRD42021244418). The refined search strategy was based on three concepts: "MULTIPLE SCLEROSIS" AND "PHYSICAL ACTIVITY" AND "INFLAMMATION". RESULTS: three main findings emerged: 1) untrained subjects showed a negative modulation of inflammatory biomarkers concentrations when compared to trained people (-0.74, 95 %C.I.-1.16, -0.32); 2) training modulated positively inflammatory biomarkers (+0.47, 95 %C.I. 0.24,0.71); 3) Aerobic PA protocol enhance higher positive influence on inflammation. CONCLUSIONS: Persistent, low-grade inflammation in MS could be upregulated by non-pharmacological complementary therapies, in particular by regular aerobic PA that could reduce and positively modulate inflammation.

Quantitative and qualitative features of acute phase-adverse events following SARS-CoV-2 vaccination in a large sample of people with multiple sclerosis.

INTRODUCTION: Few data are available on adverse events (AE) associated to vaccines in persons with multiple sclerosis (pwMS). AIMS: to study the incidence of acute phase AE (AP-AE) related to SARS-CoV-2 mRNA vaccines in pwMS compared to a control group, and to analyze the association between AP-AE and disease modifying treatments (DMT). METHODS: This was a cross-sectional study on 438 PwMS and 481 age- and sex-matched subjects not affected by dysimmune diseases that underwent two doses of SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer/BioNtech). RESULTS: Two hundred and twenty five (51.4%) pwMS complained of ≥1 AP-AE after the first dose, 269 (61.4%) after the second dose. A logistic regression analysis revealed that only pwMS on Fingolimod and Ocrelizumab did not show a higher risk of developing AP-AE. The likelihood to present with ≥1 AP-AE, after correcting for age and sex, was significantly higher in pwMS than controls. CONCLUSIONS: This study reports qualitative and quantitative features of AP-AE associated with the first and second doses of SARS-CoV-2 vaccine in a large sample of pwMS. The only risk factor identified for developing AP-AE is female gender. AntiCD-20 monoclonal antibodies and S1P inhibitors are associated with a lower risk of AP-AE occurrence.

Daily music listening to reduce work-related stress: a randomized controlled pilot trial.

BACKGROUND: Literature shows that music can reduce stress conditions. This pilot study investigated the effects of music listening on work-related stress and well-being in healthcare professionals. METHOD: A total of 45 subjects were randomly assigned to three treatment groups: No Music, Individualized Music and Melomics-Health Listening. Music groups experienced a daily 30-min-playlist listening for 3 weeks at home. The Maugeri Stress Index-Revised (MASI-R) and the Psychological General Well-Being Index (PGWBI) were administered at baseline, after 3 weeks and after 7 weeks (follow-up). Longitudinal data were analyzed by means of a nested ANOVA model, testing the main effects of time and treatment and the interaction between them. RESULTS: MASI-R scores showed a positive trend in music groups and a worsening in the control group. Only the interaction time/treatment emerged as supporting a trend toward statistical significance (P = 0.07). PGWBI showed a stability in music groups and a clear decline in controls, without significant effects. CONCLUSIONS: Results from the study support the need for a larger clinical trial: it is suggested that daily music listening could be implemented to reduce work-related stress and that the effects may be related, not only to individual musical preferences and familiarity, but also to specific music structures and parameters.

Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study.

BACKGROUND: Dimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (MS) in randomized clinical trials. OBJECTIVES: To track and evaluate post-market DMF profile in real-world setting. MATERIALS AND METHODS: Patients receiving DMF referred to Italian MS centres were enrolled and prospectively followed, collecting demographic clinical and radiological data. RESULTS: Among the 735 included patients, 45.4% were naïve to disease-modifying therapies, 17.8% switched to DMF because of tolerance, 27.4% switched to DMF because of lack of efficacy, and 9.4% switched to DMF because of safety concerns. Median DMF exposure was 17 months (0-33). DMF reduced the annual relapse rate (ARR) by 63.2%. At 12 and 24 months, 85 and 76% of patients were relapse-free. NEDA-3 status after 12 months of DMF treatment was maintained by 47.5% of patients. 89 and 70% of patients at 12 and 24 months regularly continued DMF. Most frequent adverse events (AEs) were flushing (37.2%) and gastro-enteric AEs (31.1%). CONCLUSION: Our post-market study corroborated that DMF is a safe and effective drug. Additionally, the study suggested that naïve patients strongly benefit from DMF and that DMF improved ARR also in patients who were horizontally switched from injectable therapies due to tolerability and efficacy issues.

Heat shock protein 70-hom gene polymorphism and protein expression in multiple sclerosis.

Immune-mediated and neurodegenerative mechanisms are involved in multiple sclerosis (MS). Growing evidences highlight the role of HSP70 genes in the susceptibility of some neurological diseases. In this explorative study we analyzed a polymorphism (i.e. HSP70-hom rs2227956) of the gene HSPA1L, which encodes for the protein hsp70-hom. We sequenced the polymorphism by polymerase chain reaction (PCR), in 191 MS patients and 365 healthy controls. The hsp70-hom protein expression was quantified by western blotting. We reported a strong association between rs2227956 polymorphism and MS risk, which is independent from the association with HSP70-2 rs1061581, and a significant link between hsp70-hom protein expression and MS severity.

BREMSO: a simple score to predict early the natural course of multiple sclerosis.

BACKGROUND AND PURPOSE: Early prediction of long-term disease evolution is a major challenge in the management of multiple sclerosis (MS). Our aim was to predict the natural course of MS using the Bayesian Risk Estimate for MS at Onset (BREMSO), which gives an individual risk score calculated from demographic and clinical variables collected at disease onset. METHODS: An observational study was carried out collecting data from MS patients included in MSBase, an international registry. Disease impact was studied using the Multiple Sclerosis Severity Score (MSSS) and time to secondary progression (SP). To evaluate the natural history of the disease, patients were analysed only if they did not receive immune therapies or only up to the time of starting these therapies. RESULTS: Data from 14 211 patients were analysed. The median BREMSO score was significantly higher in the subgroups of patients whose disease had a major clinical impact (MSSS≥ third quartile vs. ≤ first quartile, P < 0.00001) and who reached SP (P < 0.00001). The BREMSO showed good specificity (79%) as a tool for predicting the clinical impact of MS. CONCLUSIONS: BREMSO is a simple tool which can be used in the early stages of MS to predict its evolution, supporting therapeutic decisions in an observational setting.

The students' reasons to choose a nursing degree program: an Italian exploratory study.

BACKGROUND: From the international literature very interesting cues emerge about students' motivations to choose a Nursing Degree Program. Unfortunately, this phenomenon is largely unexplored in Italy. An observational study was conducted at the University of Pavia, with the aim to investigate the reasons underpinning the students' choice to enter a Nursing Degree Program. METHODS: A semi-structured, self-administrated questionnaire was used for this single-center cross-sectional study. The questionnaire was aimed to investigate the reasons underpinning the students' choice to enter a Nursing Degree Program, using both open-ended and close-ended multiple choice questions. Descriptive statistics have been used to describe collected data. Open-ended response analysis was conducted through an exploratory and qualitative analysis of language. RESULTS: Response rate was 71% (196/275). Our study results highlighted a variety of reasons that encourage students to begin a Nursing Degree Program: the feeling of usefulness (80%), the desire to help and to care people (78%), the interest in the sciences (71%), the compassion to the suffering people (66%). We also identified 4 categories that describe which characteristics a nurse should have according to the students' point of view: expertise; personal characteristics; to experience the professional life as a social function and to have interest in the health field. CONCLUSIONS: Students' answers indicate that often the choice to enter a Nursing Degree Program is not supported by clear ideas and strong motivations. We consider it crucial to provide a realistic image of the nursing role and opportunities for career development, so that students can have the right elements to make a conscious choice. There is a need for more qualitative research to explore the reasons why students choose the Nursing Degree Program; moreover, to identify, from the beginning of the course, those students who are in crisis of motivation, in order to adopt support strategies that could enable them to successfully achieve academic career.

Electrophysiological patterns of oropharyngeal swallowing in multiple sclerosis.

OBJECTIVE: We performed an electrophysiological study of swallowing (EPSS) in multiple sclerosis (MS) to describe oropharyngeal swallowing abnormalities and to analyze their correlations with dysphagia and with overall neurological impairment. METHODS: Neurological examinations were quantified using the Kurtzke Functional Systems and the Expanded Disability Status Scale (EDSS). Dysphagia was evaluated using the Dysphagia in Multiple Sclerosis (DYMUS) questionnaire, while fiberoptic endoscopic evaluation of swallowing (FEES) was used to establish the degree of aspiration and penetration, graded using the penetration-aspiration scale (PAS). The EPSS measured the duration of suprahyoid/submental muscle EMG activity (SHEMG-D), the duration of the laryngeal-pharyngeal mechanogram (LPM-D), and the duration of the pause in cricopharyngeal muscle EMG activity (CPEMG-PD); it also measured the interval between onset of the suprahyoid/submental muscle EMG activity (SHEMG) and onset of the laryngeal-pharyngeal mechanogram (I-SHEMG-LPM). RESULTS: 92% of patients showed at least one electrophysiological abnormality. I-SHEMG-LPM correlated positively with the DYMUS questionnaire. I-SHEMG-LPM, SHEMG-D, and DYMUS correlated positively with the PAS. Moderate to severe bladder sphincter dysfunction was associated with a significant reduction, or absence, of CPEMG-PD. CONCLUSION: EPSS improves our understanding of the pathophysiology of dysphagia in MS. SIGNIFICANCE: This investigation could be useful in MS patients with swallowing abnormalities.

Do they actually work across borders? Evaluation of two measures of psychological distress as screening instruments in a non Anglo-Saxon country.

Screening scales can be useful in searching for common mental disorders in primary care and in tracking relevant prevalence and correlates in community surveys. However, it is important to document their validity, before using them. We developed Italian versions of the widely-used K10 and K6 screening scales following the WHO forward-translation and back-translation protocol. To evaluate their effectiveness as screens for DSM-IV 12-month mood or anxiety disorders and "serious mental illness" (SMI), the scales were validated in a two-stage clinical reappraisal survey. In the first-phase, the scales were administered to 605 people. In the second-phase, a sub-sample of 147 first-phase respondents over-sampling screened positives was administered the 12-month version of the Structured Clinical Interview for DSM-IV Axis I Disorders as a clinical gold standard. Performance of the scales in screening for chosen disorders was assessed by calculating area under the receiver operating characteristic curve and stratum-specific likelihood ratios. Both the K10 and K6 performed well in detecting DSM-IV mood disorders, anxiety disorders, and serious mental illness (SMI), with areas under the curve (AUCs) (95% CIs) between 0.82 (0.75-0.89) and 0.91 (0.85-0.96). The Italian versions of the K6 and K10 scales have good psychometric properties, making them attractive inexpensive screens for mood disorders, anxiety disorders, and SMI.

An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment.

OBJECTIVES: Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. METHODS: Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). RESULTS: Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. CONCLUSIONS: This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

Validation of the DYMUS questionnaire for the assessment of dysphagia in multiple sclerosis.

Swallowing problems can complicate the course of multiple sclerosis (MS). However, no validated questionnaire for the assessment of dysphagia in MS is currently available. We previously developed a 10-item DYsphagia in Multiple Sclerosis questionnaire (DYMUS). In the present study, this questionnaire was submitted to a validation process. Thirteen Italian MS centres took part in this research in which DYMUS was administered to 1734 consecutive MS patients during routine checkups outside relapse. The questionnaire showed very good internal consistency (Cronbach's alpha = 0.914). It was then subdivided into two subscales, both of which also showed very good internal consistency: Cronbach's alpha was 0.885 for the 'dysphagia for solids' subscale and 0.864 for the 'dysphagia for liquids' subscale. The DYMUS questionnaire was found to be an easy and reliable tool for detecting dysphagia and also for the preliminary selection of patients requiring more specific instrumental analyses, and those suitable for aspiration prevention programmes.

[Bayesian statistics in medicine -- part II: main applications and inference]. / La statistica bayesiana in medicina -- parte II: le principali applicazioni e l'inferenza.

Bayesian statistics is not only used when one is dealing with 2-way tables, but it can be used for inferential purposes. Using the basic concepts presented in the first part, this paper aims to give a simple overview of Bayesian methods by introducing its foundation (Bayes' theorem) and then applying this rule to a very simple practical example; whenever possible, the elementary processes at the basis of analysis are compared to those of frequentist (classical) statistical analysis. The Bayesian reasoning is naturally connected to medical activity, since it appears to be quite similar to a diagnostic process.

[Bayesian statistics in medicine. Part I: The basic tools]. / La statistica bayesiana in medicina. Parte I: gli strumenti di base.

Bayesian statistics, so called after the British scientist Thomas Bayes who first used it in the 18th century, is a widely applied analytical tool in many branches of the applied sciences but is seldom mentioned in the medical literature. This paper aims to present a simple overview of the Bayesian method by introducing its basic mathematical tools (in particular the conditional probability) and then applying them to evaluate the characteristics of diagnostic tests.

The DYMUS questionnaire for the assessment of dysphagia in multiple sclerosis.

Swallowing problems can be relevant, even if underestimated, in Multiple Sclerosis (MS) patients. However, no specific questionnaire for the assessment of dysphagia in MS is available. We built a questionnaire (DYsphagia in MUltiple Sclerosis, DYMUS) that was administered to 226 consecutive MS patients (168 F, 58 M, mean age 40.5 years, mean disease duration 10.1 years, mean EDSS 3.1) during control visits in four Italian MS Centres. DYMUS was abnormal in 80 cases (35%). The patients who claimed to have swallowing problems had a significantly higher mean DYMUS score that the other patients (p<0.0001). Mean DYMUS scores were significantly higher in the progressive forms (p=0.003). DYMUS values were significantly correlated to EDSS (p=0.0007). DYMUS showed a very good internal consistency (Cronbach's alpha 0.877). Factor analysis allowed us to sub-divide DYMUS in two sub-scales, 'dysphagia for solid' and 'dysphagia for liquid', both of them had a very good internal consistency (Cronbach's alpha 0.852 and 0.870 respectively). DYMUS demonstrated to be an easy and consistent tool to detect dysphagia and its main characteristics in MS. It can be used for preliminary selection of patients to submit to more specific instrumental analyses, and to direct toward programs for prevention of aspiration.

Estrogen receptor alpha and APOEepsilon4 polymorphisms interact to increase risk for sporadic AD in Italian females.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects both sexes, with a higher prevalence in women. Declining estrogen levels after menopause may render estrogen target neurons in the brain more susceptible to age or disease-related processes such as AD. To investigate the role of two single nucleotide polymorphisms in the first intron of the ER-alpha gene, denominated PvuII and XbaI, and their interaction with the known AD susceptibility gene APOE, we examined 131 patients with sporadic AD and 109 healthy control subjects. In multinomial logistic regression analysis, a significantly increased risk of sporadic AD because of interaction between the ER-alpha p allele and APOE epsilon4 allele was observed in women, taking subjects who had neither the p allele nor epsilon4 as reference [odds ratio (OR) 7.24; 95% CI, 2.22-23.60]. For women carrying the ER-alpha x allele together with APOE epsilon4, the risk of sporadic AD was similarly elevated (OR 8.33; 95% CI, 1.73-40.06). The data suggest that the p and x alleles of polymorphic ER-alpha gene interact synergistically with the APOE epsilon4 allele to increase the risk of AD in women but not in men in this Italian cohort.

Bayesian mapping of multiple sclerosis prevalence in the province of Pavia, northern Italy.

The geographical analysis of a disease risk is particularly difficult when the disease is non-frequent and the area units are small. The practical use of the Bayesian modelling, instead of the classical frequentist one, is applied to study the geographical variation of multiple sclerosis (MS) across the province of Pavia, Northern Italy. 464 MS-affected individuals resident in the province of Pavia were identified on December 31st 2000. The overall prevalence was 94 per 100,000 inhabitants. This estimate indicates an increasing MS prevalence in the province, in accordance with the vast majority of the Italian areas where prevalence studies have been repeated. We mapped the geographical variation of MS prevalence across the 190 communes of the province both with a classical approach and a Bayesian approach. The frequentist approach produced an extremely dishomogeneous map, while the Bayesian map was much smoother and more interpretable. Our study underlines the usefulness of Bayesian methods to obtain reliable maps of disease prevalence and to identify possible clusters of disease where to carry out further epidemiological investigations.

A functional assessment methodology for alcohol dependent patients undergoing rehabilitative treatments.

PURPOSE: We propose a functional assessment approach for patients with alcoholic dependence of working age undergoing aerobic training. The background is the WHO indication (ICIDH-2) to use measurable 'activities' as a means to assess the individual 'participation' in social life which also implies work capacity. Defining sustainable energetic levels for the individual is an important issue for both the quantification of an effective training and the evaluation of possible improvements following training. METHODS: Fifty-six 'alcohol dependent' patients, as defined by DSM IV (Diagnostic and Statistical Manual of Mental Disorders), admitted to our Unit in a 16 month-period participated in the study. Eighteen healthy subjects served as controls (Group C). Out of all the 56 patients, 33 (Group A) underwent an aerobic training and 23 subjects (Group N) underwent the same pharmacological and psychological therapy but without aerobic training. Patients were assigned to the treatment (A) or no treatment (N) group according to a 'quasi-experimental' design (i.e. temporal selection criteria). The evaluation protocol consisted of submaximal symptom-limited tests. The tests consisted of bouts of 'basic' activities (walking, lifting, arm-work) to be performed at different intensities. We estimated the total energetic work (TW) performed in the tests by means of formulas available in the literature. The maximal energetic intensity (EI) reached during the tests was also estimated and expressed in MET (multiple of the basal metabolism). RESULTS: Significant differences in work capacity were observed between patients and healthy subjects at baseline. Group A significantly increased TW after rehabilitation, while Group N did not increment their performance at the re-test. CONCLUSIONS: The proposed approach could be useful in the functional assessment of deconditioned subjects with alcohol dependence in working age, and could monitor the changes in work capacity following training.

An ecologic study of geographical variation in multiple sclerosis risk in central Sardinia, Italy.

We carried out an ecological study in the most archaic area of Sardinia to obtain a reliable estimate of the prevalence of multiple sclerosis (MS) and to investigate the geographical variation in the prevalence across the 100 administrative communes. To estimate the area-specific prevalence rate, we adopted a Bayesian approach that makes it possible to filter out the random variation from the estimates and to obtain a map that reflects the true geographical variation in MS prevalence. 428 resident cases were identified by the case register, including 69 multiplex families. The overall prevalence was 157 per 100,000 inhabitants. The Bayesian area-specific prevalence ranged from 143 to 262/100,000. The high prevalence and its moderate geographical variation in a genetically homogeneous population, as well as the high number of multiplex families observed in the communes with the highest prevalence, could be interpreted as representing a high susceptibility of the population to MS.

Association between the ancestral haplotype HLA A30B18DR3 and multiple sclerosis in central Sardinia.

Association and linkage studies have established the importance of the major histocompatibility complex (MHC) in the susceptibility for multiple sclerosis (MS). We carried out a case-control study to investigate the ancestral haplotype A30B18DR3 and MS in the Nuoro population of Sardinia, which is isolated and genetically distinct from other populations in the Mediterranean basin and characterized by genetic homogeneity, high level of inbreeding, low migration, high prevalence of MS, high frequency of the relevant haplotype, and high past malaria prevalence. Cases and controls were serologically typed for the currently recognized HLA-A, B, and DR antigens. We used a log-linear approach to fit a wide class of models. We tested our hypothesis comparing different models via a likelihood ratio test. We overcame the complication due to unknown gametic phase using expectation-maximization (EM) algorithm as the estimation method. We estimated confidence intervals for odds ratio by using a profile likelihood approach. We found that: (1) the ancestral haplotype A30B18DR3 was associated to MS after allowing for a possible stratification in cases and controls; (2) DR3 allele was conditional independent on disease status, given A30B18 haplotype; (3) there was a tendency for ORs for the high-risk haplotypes to be higher in the high malaria strata; however, this indication did not achieve statistical significance (P = 0.11).

An Italian epidemiological multicentre study of nocturnal enuresis.

OBJECTIVE: To estimate the prevalence of enuresis in schoolchildren in Italy. SUBJECTS AND METHODS: The Italian Club of Nocturnal Enuresis promoted a prevalence study of nocturnal enuresis using a self-administered questionnaire in seven cities in Northern, Central and Southern Italy. The association between enuresis and potential risk factors, e.g. a family history of enuresis, stress, socio-economic status and abnormal diurnal voiding habits, was investigated. The perceived impact on the child and on the family was also evaluated. A random-cluster sampling scheme was used to obtain a sample of primary and secondary schoolchildren from each city. One primary school and one secondary school for each socio-economic level was sampled in each city, giving a total of 42 schools surveyed; 9086 children were covered by the survey. In a cluster sampling method, the variance of prevalence is divided into two components, binomial and extra-binomial variability. Both the DSM III and DSM IV definitions of enuresis were used because at present, there is no consensus on the diagnostic criteria. RESULTS: Completed questionnaires were received from 7012 children, an overall response rate of 77.2%. Those aged 6-14 years were analysed, restricting the sample to 6892 children. There were 250 enuretic children using the DSM III definition of enuresis and 112 using the DSM IV definition. The overall prevalence was 3.88% and showed a decreasing trend with increasing age. Bedwetting was more frequent in boys than in girls. The prevalence of enuresis was higher when the child was from a family of low socio-economic status despite the child's age group. The logistic analysis showed that familiality, stress, birthweight, age of attaining diurnal continence, soiling and, for girls, menstruation, were statistically significant variables and thus contributed to predicting the probability of bedwetting, confirming the findings of previous studies. There was a large difference in prevalence using the two DSM definitions; a high percentage of DSM III enuretic children had more than two wet nights per week. CONCLUSION: It is important that a consensus about the 'working definitions' of enuresis is reached to avoid bias in the recruitment step, to carry out comparable epidemiological studies and to obtain adequate therapeutic responses.