Changing lifestyle of persons with multiple sclerosis : development, feasibility and preliminary results of a novel high-impact collaborative intervention in leisure environments

Objective: Only a limited percentage of persons with MS (pwMS) participate to multidisciplinary rehabilitation (MDR) because of poor support, knowledge and motivation. We reasoned that pwMS should be more effectively prepared to increase their adherence. We implemented an innovative collaborative approach, called “brief highimpact preparatory experience” (b-HIPE), inspired by an overarching model based on the interplay between competence, motivation and opportunity to increase in a short time awareness and motivation of pwMS. Methods: B-HIPE integrates physiotherapy, mindfulness, sailing, healthy diet, and cultural activities to be experienced in a convivial form at a beautiful seaside location in Sardinia. Sixteen pwMS participated to 3 successive one-week editions of the b-HIPE, co-sponsored by the Rotary Club of Milan and supported by researchers of our Institute and of partner associations. The feasibility was assessed with structured questionnaires and free reports concerning accommodation, logistics, coordination, social climate and the specific activities proposed. For this pilot study we used a single-group design with repeated measurements at baseline and post-intervention. The SF-36 QoL scale was the main outcome measure, the Fatigue Severity Scale (FSS), the Berg Balance scale (BBS) and the 9 hole peg test (9HPT) were the secondary outcomes. Results: The approach was feasible. Scores on several FS-36 scales and secondary outcomes were significantly improved. Participants’ satisfaction with all aspects of the experience was above expectations. PwMS became more motivated and aware of physical and mental resources, all learned to sail adapted monohulls, strategies to master stress and to modify their diet according to specific recommendations. Conclusion: B-HIPE is safe and feasible. The interplay of multiple factors produced in a very short time the expected changes in participants’ attitude toward a healthier lifestyle. A monitoring program is ongoing to assess long-term effects including adherence to hospital-based MDR.Publisher PDFPeer reviewe

Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis

Introduction Natalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population. Materials and methods This retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the ’Italian MS Register’. All patients with MS were stratified into two groups based on NTZ administration schedule: standard interval dosing (SID) patients who received infusions on average from 28 to 32 days (median 30) and extended interval dosing (EID) including patients who have been infused with interval between 33 and 49 days (median 43). Clinical data were assessed at baseline (before starting NTZ), after 12 (T1) and 24 months (T2) of treatment. Results Out of 5231 patients with RR-MS screened, 2092 (mean age 43.2±12.0, 60.6% women) were enrolled. A total of 1254 (59.9%) received NTZ according to SID, and 838 (40.1%) according to EID. At 12 and 24 months, no differences in terms of annualised relapse rate and disability status were found between the two groups. Progression index and confirmed disability worsening were similar between the two groups. Discussion The use of NTZ with an extended interval schedule showed similar effectiveness compared with SID. Unchanged clinical efficacy of EID schedule may raise the question of a possible advantage in terms of tolerability and safety

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

HOW TO ENHANCE THEORY OF MIND IN MULTIPLE SCLEROSIS? FROM THE LITERATURE TO THE DEVELOPMENT OF A NOVEL CULTURAL INTERVENTION

La Teoria della Mente (ToM), la capacità cognitiva di riuscire a rappresentare ed interpretare gli stati mentali propri e altrui al fine di prevederne in comportamento, risulta essere deficitaria nella Sclerosi Multipla (SM), patologia cronica neurodegenerativa. La messa a punto e l’implementazione di un training di potenziamento di questa abilità sociale in questi pazienti è di rilevante importanza in quanto la ToM è strettamente connessa alla loro qualità della vita. Dato che ad oggi non esistono training di potenziamento della ToM nella SM, obiettivo primario della tesi è stata l’indagine relativa ai training di cognizione sociale attualmente esistenti in altre patologie croniche dell’età adulta. E’ stata effettuata una revisione sistematica ed una meta-analisi dei training attualmente esistenti per i soggetti con schizofrenia dato che questi soggetti presentano caratteristiche demografiche simili ai soggetti con SM. Si è quindi progettato un training di potenziamento della ToM da proporre ad un sample di soggetti con SM; prima di valutarne l’efficacia è stato condotto uno studio di accettabilità del suddetto training, al fine di superare potenziali barriere per la sua fattibilità. Si è infine proceduto all’esecuzione del terzo lavoro scientifico, ovvero la valutazione dell’efficacia del suddetto training sulla ToM in soggetti affetti da SM.Theory of Mind (ToM) is the ability of recognition and mental states' attribution to predict future behaviors. ToM deficit is well recognized in MS; hence, ToM training in this population is relevant because ToM is strictly connected with quality of life of people with multiple sclerosis (pwMS). To our knowledge, there is no training established for the treatment in this population. For this reason, we proposed to investigate the efficacy of social cognition training in other adults with chronic disease. We conducted a systematic review and a meta-analysis of SC training in schizophrenia, given that these subjects present demographic characteristics similar to pwMS. Hence, we design a rehabilitation ToM training for pwMS; before evaluating its efficacy, we conducted an acceptability study to overcome potential barriers for its feasibility. Lastly, we implement this novel rehabilitation training testing its efficacy on ToM in pwMS

Premature ejaculation among men with erectile dysfunction-findings from a real-life cross-sectional study

: Concomitant sexual disorders have progressively shown increased prevalence in men at first outpatient presentation. We sought to i) estimate the prevalence of unreported premature ejaculation (PE) in a homogenous cohort of 1258 men seeking first medical help for erectile dysfunction (ED) as their primary compliant; ii) compare the baseline sociodemographic and clinical characteristics of men with only ED(ED-only) compared to those with ED and PE(ED + PE); and, iii) investigate the likelihood of detecting PE among men self-reporting only ED over a 16-year period at a single tertiary-referral centre. Descriptive statistics compared sociodemographic and clinical characteristics between ED-only patients and those with unreported concomitant primary/secondary PE(ED + PE). Logistic regression models predicted the risk of having ED + PE at baseline. Local polynomial regression models graphically explored the probability of reporting PE among ED men with ≤40 vs. 41-60 vs. >60 years over the analysed timeframe. Of all, 932 (74.1%) were ED-only and 326 (25.9%) ED + PE patients, respectively. ED + PE patients were younger, presented with fewer comorbidities, and lower rates of severe ED (all p ≤ 0.04). At multivariable logistic regression analysis, younger age (OR:0.98) and low sexual desire/interest (OR:1.54) were independently associated with ED + PE at first clinical assessment (all p = 0.03). The likelihood of detecting unreported concomitant primary/secondary PE among patients complaining of only ED at first presentation worrisomely increased among younger and middle-aged men over the last 16 years

Cancer risk for multiple sclerosis patients treated with azathioprine and disease-modifying therapies: an Italian observational study

BACKGROUND: The risk of malignancy associated with sequential disease-modifying therapies (DMTs) for patients with multiple sclerosis (MS) is uncertain. The aim of this study was to analyze the risk of cancer in patients with MS treated with azathioprine (AZA) and the influence of sequential DMTs on the risk.METHOD: We retrospectively enrolled a cohort of AZA-treated MS patients followed in two Italian centers from 1987 to 2019. The ratio between observed and expected cancers in the Italian general population was calculated as standardized incidence ratio (SIR). Associations between AZA and DMTs and cancer were estimated by Cox proportional hazards model.RESULTS: We identified 500 AZA-treated MS patients, followed for a median time of 9.7 (0.1-45.7) years: 61.8% of them were treated with DMTs. We found 22 cases of cancer (4.4%). The SIR was 1.14 (95% CI 0.98-1.29), not significantly increased in comparison with the general population. However, the risk was significantly higher in the quintiles of age 32-45, SIR 1.21 (95% CI 1.21-1.42), and 46-51, SIR 1.11 (95% CI 1.11-1.32) than in older cases. Age at AZA treatment onset was the only covariate significantly related to cancer incidence (HR = 1.049, 95% CI 1.007-1.093). The exposure to other DMTs did not modify the risk.CONCLUSION: The risk of malignancy in MS patients after AZA was similar to that of the general population and did not change with other DMTs sequential treatments. The increased risk in the younger ages should be considered in treatment assessment

The symptomatic burden of Peyronie's disease at presentation according to patient age: A critical analysis of the Peyronie's disease questionnaire (PDQ) domains

Background: Peyronie's disease (PD) has a huge impact on patients' physical and psychological wellbeing. Objectives: To investigate whether patients' age has an impact on PD symptomatic burden at first presentation. Materials and methods: Data from 129 consecutive heterosexual patients seeking first medical attention for PD at a single andrological tertiary-referral centre were collected. All patients completed the International Index for Erectile Function (IIEF) and the PD questionnaire (PDQ). Descriptive statistics were used to compare clinical features between younger (≤40years) and older (>40 years) patients. Multivariable linear model assessed the impact of age, the degree of penile curvature and their impact on PDQ (total scores and its domains), after adjusting for PD duration and IIEF-erectile function domain scores. Results: Of 129, 24 (18.6%) patients were ≤40 years old. Young patients presented with a less severe curvature than older patients (median [interquartile ranges] 20° [15-36] vs. 50° [40-80]; p = 0.04). However, younger age was associated with higher psychological and physical symptoms, PDQ-penile pain and PDQ-symptom bother scores (Coeff -0.11, -0.21 and -0.17, respectively) (all p < 0.05). Moreover, the greater the degree of curvature, the higher the PDQ-psychological and physical symptoms and the PDQ-symptom bother scores (Coeff. 0.21 and 0.22, respectively; all p < 0.05). Conclusion: Around one in five men seeking first medical help for PD is younger than 40 years at presentation in the real-life setting. PD-related distress varies according to patients' age, with younger men presenting with a greater risk of penile pain and symptom bother despite lower curvature

Unrecognised orgasmic phase disorders in men presenting with new-onset erectile dysfunction-Findings from a real-life, cross-sectional study

Background: Orgasmic phase disorders in men worsen the burden of erectile dysfunction on sexual satisfaction. Objectives: To investigate the prevalence of and predictors of unreported orgasmic phase disorder in a cohort of men looking for their first urological assessment for new-onset erectile dysfunction in a real-life setting. Materials and methods: Data from 1107 heterosexual, sexually active men consecutively assessed for new-onset erectile dysfunction were analysed. Throughout a comprehensive medical and sexual history, all patients were asked to self-report any orgasmic phase disorder and to complete the International Index of Erectile Function and the Beck's Inventory for Depression (depressive symptoms scored as Beck's Inventory for Depression ≥11). Men self-reporting orgasmic phase disorder during the interview were excluded from further analyses. The median value of the International Index of Erectile Function-orgasmic function domain was arbitrarily used to categorise men with (International Index of Erectile Function-orgasmic function ≤5) and without unreported orgasmic phase disorder (International Index of Erectile Function-orgasmic function >5). Circulating hormones were measured in every patient. Descriptive statistics and logistic regression models were used to test the association between clinical variables and unreported orgasmic phase disorder. Results: Of 1098 patients with non-self-reporting orgasmic phase disorder, 314 (28.6%) had International Index of Erectile Function-orgasmic function ≤5. Patients with erectile dysfunction + unreported orgasmic phase disorder were older (median [interquartile range]: 58 [44-66] years vs. 51 [40-60] years), had higher body mass index [25.8 (23.7-28.1) kg/m2 vs. 25.2 (23.3-27.4) kg/m2 ], higher prevalence of type 2 diabetes (36 [11.5%] vs. 45 [5.7%]) and lower International Index of Erectile Function-erectile function scores (6 [2-10] vs. 18 [11-24]) than men with erectile dysfunction-only (all p < 0.05). Patients with erectile dysfunction + unreported orgasmic phase disorder depicted higher rates of severe erectile dysfunction (75.5% vs. 25%) and Beck's Inventory for Depression ≥11 (22.6% vs. 17.9%) (all p < 0.05). In the multivariable logistic regression analysis, older age (odds ratio: 1.02) and lower International Index of Erectile Function-erectile function scores (odds ratio: 0.83) were independently associated with unreported orgasmic phase disorder (all p < 0.05). Conclusions: Almost one in three men seeking first medical help for erectile dysfunction depicted criteria suggestive of unreported orgasmic phase disorder. Men with unreported orgasmic phase disorder were older and had higher rates of severe erectile dysfunction and concomitant depressive symptoms. These real-life findings outline the clinical relevance of a comprehensive investigation of concomitant sexual dysfunction in men only complaining of erectile dysfunction to more effectively tailor patient management