Publications by authors named "Mauro Zaffaroni"

60 Publications

Fingolimod in pediatric-onset multiple sclerosis.

Authors:
Mauro Zaffaroni

Neurol Sci 2021 May 4. Epub 2021 May 4.

Multiple Sclerosis Centre, Hospital of Gallarate, ASST della Valle Olona, Via Pastori 4, 21013, Gallarate, Italy.

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http://dx.doi.org/10.1007/s10072-021-05294-zDOI Listing
May 2021

Risk of Persistent Disability in Patients With Pediatric-Onset Multiple Sclerosis.

JAMA Neurol 2021 May 3. Epub 2021 May 3.

Multiple Sclerosis Center, Gallarate Hospital, ASST Valle Olona, Gallarate (VA), Italy.

Importance: Availability of new disease-modifying therapies (DMTs) and changes of therapeutic paradigms have led to a general improvement of multiple sclerosis (MS) prognosis in adults. It is still unclear whether this improvement also involves patients with pediatric-onset MS (POMS), whose early management is more challenging.

Objective: To evaluate changes in the prognosis of POMS over time in association with changes in therapeutic and managing standards.

Design, Setting, And Participants: Retrospective, multicenter, observational study. Data were extracted and collected in May 2019 from the Italian MS Registry, a digital database including more than 59 000 patients. Inclusion criteria were MS onset before age 18 years, diagnosis before January 2014, and disease duration of at least 3 years. Exclusion criteria were primary progressive MS, Expanded Disability Status Scale (EDSS) score of at least 8 one year after onset, unavailability of diagnosis date, and less than 2 EDSS score evaluations. Eligible patients were 4704 patients with POMS. According to these criteria, we enrolled 3198 patients, excluding 1506.

Exposures: We compared time to reach disability milestones by epoch of MS diagnosis (<1993, 1993-1999, 2000-2006, and 2007-2013), adjusting for possible confounders linked to EDSS evaluations and clinical disease activity. We then analyzed the difference among the 4 diagnosis epochs regarding demographic characteristics, clinical disease activity at onset, and DMTs management.

Main Outcomes And Measures: Disability milestones were EDSS score 4.0 and 6.0, confirmed in the following clinical evaluation and in the last available visit.

Results: We enrolled 3198 patients with POMS (mean age at onset, 15.2 years; 69% female; median time to diagnosis, 3.2 years; annualized relapse rate in first 1 and 3 years, 1.3 and 0.6, respectively), with a mean (SD) follow-up of 21.8 (11.7) years. Median survival times to reach EDSS score of 4.0 and 6.0 were 31.7 and 40.5 years. The cumulative risk of reaching disability milestones gradually decreased over time, both for EDSS score of 4.0 (hazard ratio [HR], 0.70; 95% CI, 0.58-0.83 in 1993-1999; HR, 0.48; 95% CI, 0.38-0.60 in 2000-2006; and HR, 0.44; 95% CI, 0.32-0.59 in 2007-2013) and 6.0 (HR, 0.72; 95% CI, 0.57-0.90; HR, 0.44; 95% CI, 0.33-0.60; and HR, 0.30; 0.20-0.46). In later diagnosis epochs, a greater number of patients with POMS were treated with DMTs, especially high-potency drugs, that were given earlier and for a longer period. Demographic characteristics and clinical disease activity at onset did not change significantly over time.

Conclusions And Relevance: In POMS, the risk of persistent disability has been reduced by 50% to 70% in recent diagnosis epochs, probably owing to improvement in therapeutic and managing standards.
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http://dx.doi.org/10.1001/jamaneurol.2021.1008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094039PMC
May 2021

Switch from sequestering to anti-CD20 depleting treatment: disease activity outcomes during wash-out and in the first 6 months of ocrelizumab therapy.

Mult Scler 2021 Apr 15:13524585211005657. Epub 2021 Apr 15.

Department of Health Sciences, University of Genova, Genova, Italy.

Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity.

Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models.

Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse.

Discussion And Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.
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http://dx.doi.org/10.1177/13524585211005657DOI Listing
April 2021

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study.

J Neurol 2021 Feb 22. Epub 2021 Feb 22.

Clinica Neurologica, Centro Sclerosi Multipla, Azienda Ospedaliera di Padova, Padova, Italy.

Objective: To identify baseline factors associated with disease activity in patients with relapsing-remitting multiple sclerosis (RRMS) under teriflunomide treatment.

Methods: This was an independent, multi-centre, retrospective post-marketing study. We analysed data of 1,507 patients who started teriflunomide since October 2014 and were regularly followed in 28 Centres in Italy. We reported the proportions of patients who discontinued treatment (after excluding 32 lost to follow-up) and who experienced clinical disease activity, i.e., relapse(s) and/or confirmed disability worsening, as assessed by the Expanded Disability Status Scale (EDSS). Decision tree-based analysis was performed to identify baseline factors associated with clinical disease activity during teriflunomide treatment.

Results: At database lock (September 2020), approximately 29% of patients (430 out of 1,475) discontinued teriflunomide because of disease activity (~ 46%), adverse events (~ 37%), poor tolerability (~ 15%), pregnancy planning (~ 2%). Approximately 28% of patients experienced disease activity over a median follow-up of 2.75 years: ~ 9% had relapses but not disability worsening; ~ 13% had isolated disability worsening; ~ 6% had both relapses and disability worsening. The most important baseline factor associated with disease activity (especially disability worsening) was an EDSS > 4.0 (p < 0.001). In patients with moderate disability level (EDSS 2.0-4.0), disease activity occurred more frequently in case of ≥ 1 pre-treatment relapses (p = 0.025). In patients with milder disability level (EDSS < 2.0), disease activity occurred more frequently after previous exposure to ≥ 2 disease-modifying treatments (p = 0.007).

Conclusions: Our study suggests a place-in-therapy for teriflunomide in naïve patients with mild disability level or in those who switched their initial treatment for poor tolerability. Adverse events related with teriflunomide were consistent with literature data, without any new safety concern.
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http://dx.doi.org/10.1007/s00415-021-10455-3DOI Listing
February 2021

Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors.

Mult Scler 2021 03 19;27(3):430-438. Epub 2020 Nov 19.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy.

Background: No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available.

Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA).

Methods: Relapsing-onset MS patients ( = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models.

Results: SPMS identified by the DDA ( = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability ( < 0.0001), than those identified by the ND ( = 3868, 20.0%). In both groups, the most consistent risk factors ( < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0.

Conclusion: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.
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http://dx.doi.org/10.1177/1352458520974366DOI Listing
March 2021

Vaccinations in patients with multiple sclerosis: A Delphi consensus statement.

Mult Scler 2021 03 17;27(3):347-359. Epub 2020 Sep 17.

Multiple Sclerosis Center, IRCCS San Raffaele Hospital, Milan, Italy/Neurology Department, IRCCS San Raffaele Hospital, Milan, Italy.

Background: Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking disease-modifying drugs.

Methods: A modified Delphi consensus process (October 2017-June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017.

Results: Recommendations include the need for an 'infectious diseases card' of each patient's infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received.

Conclusion: Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.
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http://dx.doi.org/10.1177/1352458520952310DOI Listing
March 2021

The risk of infection in patients with multiple sclerosis treated with disease-modifying therapies: A Delphi consensus statement.

Mult Scler 2021 03 17;27(3):331-346. Epub 2020 Sep 17.

III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, University of Milan, Milan, Italy.

The risk of infection associated with immunomodulatory or immunosuppressive disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS) has been increasingly addressed in recent scientific literature. A modified Delphi consensus process was conducted to develop clinically relevant, evidence-based recommendations to assist physicians with decision-making in relation to the risks of a wide range of infections associated with different DMDs in patients with MS. The current consensus statements, developed by a panel of experts (neurologists, infectious disease specialists, a gynaecologist and a neuroradiologist), address the risk of iatrogenic infections (opportunistic infections, including herpes and cryptococcal infections, candidiasis and listeria; progressive multifocal leukoencephalopathy; human papillomavirus and urinary tract infections; respiratory tract infections and tuberculosis; hepatitis and gastrointestinal infections) in patients with MS treated with different DMDs, as well as prevention strategies and surveillance strategies for the early identification of infections. In the discussion, more recent data emerged in the literature were taken into consideration. Recommended risk reduction and management strategies for infections include screening at diagnosis and before starting a new DMD, prophylaxis where appropriate, monitoring and early diagnosis.
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http://dx.doi.org/10.1177/1352458520952311DOI Listing
March 2021

Disease-modifying drugs can reduce disability progression in relapsing multiple sclerosis.

Brain 2020 10;143(10):3013-3024

Ospedale Generale Regionale 'F. Miulli', Neurology Unit, Acquaviva delle Fonti (BA), Italy.

An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18-49 years) and late-onset multiple sclerosis (≥50 years). We included patients with a relapsing-remitting phenotype, ≥5 years follow-up, ≥3 Expanded Disability Status Scale (EDSS) evaluations and a first neurological evaluation within 3 years from the first demyelinating event. Multivariate Cox regression models (adjusted hazard ratio with 95% confidence intervals) were used to assess the risk of reaching a first 12-month confirmed disability worsening and the risk of reaching a sustained EDSS of 4.0. The effect of disease-modifying drugs was assessed as quartiles of time exposure. We found that disease-modifying drugs reduced the risk of 12-month confirmed disability worsening, with a progressive risk reduction in different quartiles of exposure in paediatric-onset and adult-onset patients [adjusted hazard ratios in non-exposed versus exposed >62% of the follow-up time: 8.0 (3.5-17.9) for paediatric-onset and 6.3 (4.9-8.0) for adult-onset, P < 0.0001] showing a trend in late-onset patients [adjusted hazard ratio = 1.9 (0.9-4.1), P = 0.07]. These results were confirmed for a sustained EDSS score of 4.0. We also found that relapses were a risk factor for 12-month confirmed disability worsening in all three cohorts, and female sex exerted a protective role in the late-onset cohort. This study provides evidence that sustained exposure to disease-modifying drugs decreases the risk of disability accumulation, seemingly in a dose-dependent manner. It confirms that the effectiveness of disease-modifying drugs is lower in late-onset patients, although still detectable.
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http://dx.doi.org/10.1093/brain/awaa251DOI Listing
October 2020

Mild COVID-19 infection in a group of teriflunomide-treated patients with multiple sclerosis.

J Neurol 2020 Aug 31. Epub 2020 Aug 31.

Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

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http://dx.doi.org/10.1007/s00415-020-10196-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457441PMC
August 2020

Nabiximols discontinuation rate in a large population of patients with multiple sclerosis: a 18-month multicentre study.

J Neurol Neurosurg Psychiatry 2020 09 13;91(9):914-920. Epub 2020 Jul 13.

Department of Medical Sciences, Università degli Studi di Cagliari, Cagliari, Sardegna, Italy.

Introduction: Delta-δ-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray is used as an add-on therapy option for moderate to severe multiple sclerosis (MS) spasticity resistant to other medications. Aims of this study were to provide real-life data on long-term clinical outcomes in a large population of Italian patients treated with THC:CBD and to evaluate predictors of THC:CBD therapy continuation.

Materials And Methods: This prospective observational multicentre Italian study screened all patients with MS consecutively included in the Agenzia Italiana del Farmaco e-registry at the start of THC:CBD treatment (baseline), after 4 weeks (T1), 12±3 weeks (T2), 24±3 weeks (T3), 48±3 weeks (T4) and 72±3 weeks (T5) from baseline.

Results: A total of 1845 patients were recruited from 32 MS Italian centres. At T1, 1502 (81.4%) of patients reached a Numerical Rating Scale (NRS) improvement of ≥20%, with an NRS reduction of 26.9% at T1 and of 34.4% at T5. At T5, 725 patients (48.3% of 1502) discontinued treatment with highest discontinuation rate at T2 and T3. Daily number of puffs was generally stable through the observation period. The multivariate analysis showed that higher NRS scores at baseline (OR 2.28, 95% CI 1.15 to 6.36, p<0.01) and higher differences of NRS between T0 and T1 (OR 2.11, 95% CI 1.08 to 8.26, p<0.05) were associated with an increased probability to continue therapy after 18 months.

Discussion: THC:CBD effects were sustained for 18 months with a relatively stable number of puffs per day. About 50% of patients abandoned THC:CBD therapy for loss of efficacy or adverse events.
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http://dx.doi.org/10.1136/jnnp-2019-322480DOI Listing
September 2020

Effects of 2-year treatment with dimethyl fumarate on cognition and functional impairment in patients with relapsing remitting multiple sclerosis.

Neurol Sci 2020 Nov 1;41(11):3185-3193. Epub 2020 May 1.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.

Background: A significant proportion of patients with multiple sclerosis (MS) show cognitive impairment.

Objective: To evaluate the effect of 2-year treatment with oral dimethyl fumarate (DMF) on cognition in relapsing remitting MS (RRMS).

Methods: In this prospective single-arm study RRMS patients treated with DMF underwent a wide battery of tests, including an extensive neuropsychological evaluation, clinical and patient-reported outcomes (PROs) and quality of life (QoL). Primary endpoints were the proportion of patients with cognitive impairment at baseline and of patients with cognitive worsening over 2 years.

Results: Overall, 217 patients (74.2% females, mean age 37.3 years) receiving DMF were recruited, and 156 (67.2%) completed the study. Of the 49 patients with cognitive impairment at baseline, 34 had 2-year data: 15 (44.1%) patients worsened and 19 (55.9%) did not. The cognitive impairment index improved in one third of patients at 2 years. Less than 20% of patients had relapses at 2 years (annualized relapse rate: 0.190). Few patients had disability progression. PROs (fatigue, depression, impairment in work/social activities), QoL, and most of neuropsychological tests significantly improved vs. baseline.

Conclusion: The 2-year treatment with DMF was associated with slowing of cognitive impairment and with significant improvements in QoL and psychosocial function.
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http://dx.doi.org/10.1007/s10072-020-04320-wDOI Listing
November 2020

Clinical and patient determinants of changing therapy in relapsing-remitting multiple sclerosis (SWITCH study).

Mult Scler Relat Disord 2020 Jul 13;42:102124. Epub 2020 Apr 13.

Laboratory of Synaptic Immunopathology, Department of Systems Medicine, "Tor Vergata" University, Rome, Italy; Unit of Neurology - IRCCS Neuromed, Pozzilli, Isernia, Italy. Electronic address:

Background: clinical factors and frequency of disease-modifying therapy (DMT) changes/interruptions in relapsing-remitting multiple sclerosis (RRMS) patients have not been well defined. The aim of this study was to describe reasons of MS treatment modifications in a large cohort of Italian MS patients.

Methods: this multicenter, cross-sectional non interventional study (SWITCH) conducted at 28 Italian MS centers, screened, by visit/telephone contact between June 2016 and June 2017, all RRMS patients receiving stable DMT treatment and enrolled patients with change in DMT treatment.

Results: out of 13,657 recorded in the log, 409 (3%) changed therapy. Of these, 336 (2.5%), met the study criteria and were considered eligible. Among 303 (90.2% of 336) patients switching, the most common reason was "lack of efficacy" (58.4% of 303). Among 30 (8.9%) patients who interrupted treatment temporarily, the most common reason was pregnancy (40.0% of 30). Out of 3 (0.9%) patients who discontinued treatment permanently, 2 (66.7%) had as first reason as "patient decision". Multivariate analysis showed that EDSS was the only variable with statistically significant effect on changing treatments (r = 8.33; p-value of Type III Sum of Squares = 0.016).

Conclusion: in our study, 303 (90.2% of eligible patients) switched treatment, 30 (8.9%) interrupted treatment temporarily, and 3 (0.9%) discontinued treatment permanently. Efficacy remains the main driving force behind switching behavior, as the primary aim of treatment is to be disease free or reduce disease activity.
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http://dx.doi.org/10.1016/j.msard.2020.102124DOI Listing
July 2020

Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study.

Neurol Sci 2020 Oct 25;41(10):2905-2913. Epub 2020 Apr 25.

Institute of Neurology, University "Magna Graecia", Germaneto, Catanzaro, Italy.

Introduction: The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice.

Materials And Methods: MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale [NRS] score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms.

Results: Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group.

Conclusion: Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients.
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http://dx.doi.org/10.1007/s10072-020-04413-6DOI Listing
October 2020

A method to compare prospective and historical cohorts to evaluate drug effects. Application to the analysis of early treatment effectiveness of intramuscular interferon-β1a in multiple sclerosis patients.

Mult Scler Relat Disord 2020 May 21;40:101952. Epub 2020 Jan 21.

IRCCS Mondino Foundation, Pavia, Italy.

Background: Disease modifying therapy have changed the natural evolution of multiple sclerosis (MS), with efficacy demonstrated in randomized clinical trials. Standard-of-care effectiveness is needed to complement clinical trial data and highlight outcomes in real-world practice, but comparing prospective patients with historical cohorts likely introduces biases. To address these potential biases, assigning a patient with a score that expresses his/her disease prognosis before starting a therapy may make it possible to evaluate the unbiased ability of the therapy to modify disease natural history. Thus, we aimed at analyzing the effectiveness of intramuscular interferon-β1a (im IFN-β1a) matching by BREMSO score (Bayesian Risk Estimate for Multiple Sclerosis at Onset) a prospective real-world cohort of treated patients with a historical cohort of untreated patients.

Material And Methods: We observed 108 newly diagnosed, treatment naïve MS patients over 12 months of treatment with im IFN-β1a. BREMSO score was used to assign a value to each patient, giving the real-world treated patients comparable with the Historical untreated patients, on the basis of the same risk to have unfavorable evolution.

Results: A significantly higher percentage of relapse-free patients is observed in IFN-β1a treated cohort vs. Historical untreated cohort (79.6% vs. 59.3%, p < 0.01). Clinical relapses risk is reduced by 2.2 times in treated patients (p = 0.01).

Conclusions: We propose a promising method to manage observational data in a relatively unbiased way, in order to analyze real-world treatment effectiveness.
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http://dx.doi.org/10.1016/j.msard.2020.101952DOI Listing
May 2020

Assessing measurement invariance of MSQOL-54 across Italian and English versions.

Qual Life Res 2020 Mar 9;29(3):783-791. Epub 2019 Nov 9.

Department of Psychology, University of Turin, Turin, Italy.

Purpose: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is a specific multiple sclerosis (MS) health-related quality of life inventory consisting of 52 items organized into 12 subscales plus two single items. No study was found in literature assessing its measurement invariance across language versions. We investigated whether MSQOL-54 items provide unbiased measurements of underlying constructs across Italian and English versions.

Methods: Three constrained levels of measurement invariance were evaluated: configural invariance where equivalent numbers of factors/factor patterns were required; metric invariance where equivalent factor loadings were required; and scalar invariance where equivalent item intercepts between groups were required. Comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR) fit indices and their changes between nested models were used to assess tenability of invariance constraints.

Results: Overall, the dataset included 3669 MS patients: 1605 (44%) Italian, mean age 41 years, 62% women, 69% with mild level of disability; 2064 (56%) English-speaking (840 [41%] from North America, 797 [39%] from Australasia, 427 [20%] from UK and Ireland), mean age 46 years, 83% women, 54% with mild level of disability. The configural invariance model showed acceptable fit (RMSEA = 0.052, CFI = 0.904, SRMR = 0.046); imposing loadings and intercepts equality constraints produced negligible worsening of fit (ΔRMSEA < 0.001, ΔCFI = - 0.002, ΔSRMR = 0.002 for metric invariance; ΔRMSEA = 0.003, ΔCFI = - 0.013, ΔSRMR = 0.003 for scalar invariance).

Conclusions: These findings support measurement invariance of the MSQOL-54 across the two language versions, suggesting that the questionnaire has the same meaning and the same measurement paramaters in the Italian and English versions.
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http://dx.doi.org/10.1007/s11136-019-02352-0DOI Listing
March 2020

Vitamin D deficiency in a population of migrant children: an Italian retrospective cross-sectional multicentric study.

Eur J Public Health 2020 06;30(3):551-556

Department of Woman and Child Health, Fondazione Policlinico Universitario "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.

Background: Vitamin D is a hot topic in the scientific community. Its deficiency and the implications for the children's health became increasingly discussed during the last 20 years. The main aim of this retrospective study was to determinate the prevalence of vitamin D metabolism disorders in a population of adopted children and their risk factors.

Methods: We gathered data from 2140 children observed in five different National Working Group for the Migrant Children of the Italian Society of Pediatrics centers, variously located in Italy. Serum 25-hydroxy (OH)-D concentration was used to determine every child's vitamin D status, defined as severely deficient (serum 25-OH-D < 10 ng/ml), moderately deficient (serum 25-OH-D {≥10 ng/ml U < 20 ng/ml}), mildly deficient (serum 25-OH-D {≥20 ng/ml U < 30 ng/ml}) and normal (serum 25-OH-D ≥ 30 ng/ml).

Results: Mean value of serum 25-OH-D was 22.7 ng/ml (SD ± 12.1). Vitamin D status was deemed as normal in 483 (22.6%) children, mildly deficient in 718 (33.6%) children, moderately deficient in 730 (34.1%) children and severely deficient in 209 (9.8%) children.

Conclusions: A very high percentage of migrant children is affected by hypovitaminosis D, with a strong association with age, geographic origin, season of blood sample collection and time spent in Italy after the arrival. This finding highlights the need for corrective measures. However, these measures cannot be applied without increasing the access of migrant populations to healthcare services.
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http://dx.doi.org/10.1093/eurpub/ckz182DOI Listing
June 2020

Retrospectively acquired cohort study to evaluate the long-term impact of two different treatment strategies on disability outcomes in patients with relapsing multiple sclerosis (RE.LO.DI.MS): data from the Italian MS Register.

J Neurol 2019 Dec 18;266(12):3098-3107. Epub 2019 Sep 18.

Multiple Sclerosis Center, Hospital of Gallarate, Gallarate, Italy.

Background: The increase in disease-modifying drugs (DMDs) allows individualization of treatment in relapsing multiple sclerosis (RMS); however, the long-term impact of different treatment sequences is not well established. This is particularly relevant for MS patients who may need to postpone more aggressive DMD strategies.

Objective: To evaluate different therapeutic strategies and their long-term outcomes, measured as relapses and confirmed disability progression (CDP), in MS 'real-world' settings.

Methods: Multicentre, observational, retrospectively acquired cohort study evaluating the long-term impact of different treatment strategies on disability outcomes in patients with RMS in the Italian MS Register.

Results: We evaluated 1152 RMS-naïve patients after propensity-score adjustment. Patients included were receiving: interferon beta-1a (IFN-β1a) 44 µg switching to fingolimod (FTY; IFN-switchers; n = 97); FTY only (FTY-stayers; n = 157); IFN-β1a only (IFN-stayers; n = 849). CDP and relapses did not differ between FTY-stayers and IFN-switchers [HR (95% CI) 0.99 (0.48-2.04), p = 0.98 and 0.81 (0.42-1.58), p = 0.55, respectively]. However, IFN-stayers showed increased risk of relapses compared with FTY-stayers [HR (95% CI) 1.46 (1.00-2.12), p = 0.05].

Conclusion: The ideal treatment option for MS is becoming increasingly complex, with the need to balance benefit and risks. Our results suggest that starting with FTY affects the long-term disease outcome similarly to escalating from IFN-β1a to FTY.
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http://dx.doi.org/10.1007/s00415-019-09531-6DOI Listing
December 2019

Impact of natural menopause on multiple sclerosis: a multicentre study.

J Neurol Neurosurg Psychiatry 2019 11 12;90(11):1201-1206. Epub 2019 Jun 12.

Multiple Sclerosis Centre, Gallarate Hospital, ASST Valle Olona, Gallarate, Italy.

Objective: To study the effect of natural menopause on multiple sclerosis clinical course.

Methods: This was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status.

Results: 148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059).

Conclusion: Natural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.
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http://dx.doi.org/10.1136/jnnp-2019-320587DOI Listing
November 2019

Different MRI patterns in MS worsening after stopping fingolimod.

Neurol Neuroimmunol Neuroinflamm 2019 07 16;6(4):e566. Epub 2019 Apr 16.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics (C.L., M.C., G.B., M.P., G.N., G.L.M., A.U., M.I.), Maternal and Child Health (DiNOGMI), University of Genoa; Multiple Sclerosis Centre (D.B., A.G., M.Z.), Gallarate Hospital, ASST of Valle Olona, Gallarate; Department of Neurology (M.C., G.B., M.P., G.L.M., A.U.), Ospedale Policlinico San Martino-Sistema Sanitario Regione; Liguria -Istituto di Ricovero e Cura a Carattere Scientifico per l'Oncologia; IRCCS Foundation C. Mondino National Neurological Institute (I.C.), Pavia; Department of Health Sciences (DISSAL) (M.P.S., L. R.), Ospedale Policlinico San Martino IRCCS, Genoa, Italy; Department of Radiology and Neuroscience (M.I.), Icahn School of Medicine at Mount Sinai, New York; and Department of Neuroradiology (L.R.), Ospedale Policlinico San Martino IRCCS, Genoa, Italy.

Objective: To analyze MRI images in patients with MS who experienced worsening of neurologic status (WNS) after stopping fingolimod (FTY).

Methods: In this retrospective study, demographic, clinical, and radiologic data of patients with MS who experienced WNS after stopping FTY were retrospectively collected. We introduced the "δExpanded Disability Status Scale (EDSS)-ratio" to identify patients who, after FTY withdrawal, showed an inflammatory flare-up exceeding the highest lifetime disease activity level. Patients with δEDSS-ratio > 1 were enrolled in the study.

Results: Eight patients were identified. The mean (SD) age of the 8 (7 female) patients was 35.3 (4.9) years. The mean FTY treatment duration was 3.1 (0.8) years. The mean FTY discontinuation-WNS interval was 4 (0.9) months. The 4 patients with δEDSS-ratio ≥ 2 developed severe monophasic WNS (EDSS score above 8.5), characterized by clinical features and MRI findings not typical of MS, which we classified as "tumefactive demyelination pattern" (TDL) and "Punctuated pattern" (PL). Conversely, patients whose δEDSS-ratio was between 1 and 2 had clinical features and brain MRI compatible with a more typical, even if aggressive, MS relapse. In patients with TDL and PL, the flare-up of inflammatory activity led to severe tissue damage resulting in T2 but also T1 lesion volume increase at 6-month follow-up.

Conclusions: Peculiar MRI features (TDL and PL), different from a typical MS flare-up, might occur in some patients who experienced WNS after stopping FTY. Further studies, also involving immunologic biomarkers, are necessary to investigate TDL or PL pathophysiology.
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http://dx.doi.org/10.1212/NXI.0000000000000566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481223PMC
July 2019

Ein weiblicher Säugling mit papulovesikulären Läsionen.

J Dtsch Dermatol Ges 2018 Nov;16(11):1383-1386

Dermatologic Clinic, Dept. of Health Science, University of Eastern Piedmont, Novara, Italy.

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http://dx.doi.org/10.1111/ddg.13643_gDOI Listing
November 2018

A female newborn with papulovesicular lesions.

J Dtsch Dermatol Ges 2018 Nov 29;16(11):1383-1386. Epub 2018 Aug 29.

Dermatologic Clinic, Dept. of Health Science, University of Eastern Piedmont, Novara, Italy.

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http://dx.doi.org/10.1111/ddg.13643DOI Listing
November 2018

Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis.

Front Immunol 2018 21;9:571. Epub 2018 Mar 21.

Laboratorio de Neuroinmunología, Fundación Ciencia and Vida, Santiago, Chile.

The dual potential to promote tolerance or inflammation to self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of dopamine receptor D5 (DRD5) in DCs potentiates their inflammatory behaviour, favouring the development of experimental autoimmune encephalomyelitis (EAE). Here, we aimed to decipher the underlying mechanism and to test its relevance in multiple sclerosis (MS) patients. Our data shows that DRD5-deficiency confined to DCs in EAE mice resulted in reduced frequencies of CD4 T-cell subsets with inflammatory potential in the central nervous system, including not only Th1 and Th17 cells but also granulocyte-macrophage colony-stimulating factor producers. Importantly, depletion of dopamine from DCs resulted in a dramatic reduction of EAE severity, highlighting the relevance of an autocrine loop promoting inflammation . Mechanistic analyses indicated that DRD5-signalling in both mouse DCs and human monocytes involves the attenuation of signal transducer and activator of transcription 3-activation, a transcription factor that limits the production of the inflammatory cytokines interleukin (IL)-12 and IL-23. Furthermore, we found an exacerbated expression of all dopamine receptors in peripheral blood pro-inflammatory monocytes obtained from MS patients. These findings illustrate a novel mechanism by which myeloid antigen-presenting cells may trigger the onset of their inflammatory behaviour promoting the development of autoimmunity.
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http://dx.doi.org/10.3389/fimmu.2018.00571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871671PMC
May 2019

Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks.

Neurology 2018 03 7;90(10):e823-e831. Epub 2018 Feb 7.

From IRCCS Don Gnocchi Foundation (E.P.), Florence; Multiple Sclerosis Study Center (P.A., A.G., M.Z.), ASST Valle Olona, Gallarate Hospital (VA); Scientific Institute University Vita-Salute San Raffaele (L.M., V.M., G.C.), Milan; Department of Neurosciences, Reproductive and Odontostomatological Sciences (R.L., V.B.M.), Federico II University of Naples; Department of Neurosciences (F.R., P.G.), Multiple Sclerosis Centre-Veneto Region (CeSMuV), University Hospital of Padova; Department of Neurology (C.T., D.P., M.T.), University of Bari; Department of Neurology and Psychiatry (C.P., L.D.G.), "La Sapienza" University, Rome; Department of Neurology (P.C.), University of Torino; Department of Medical Sciences and Public Health (E.C., M.G.M.), University of Cagliari; Department of Neurology (F.P.), University of Catania; Department of Neurology (C.S.), ASL3 Genovese; Multiple Sclerosis Center (P.B.), IRCCS Neuromed, Pozzilli; Department of Neurology (A.U., A.L.), University of Genova; and Department of NEUROFARBA (L.P., M.G., M.P.A.), University of Florence, Italy.

Objective: To assess fetal risk after pregnancy exposure to natalizumab in women with multiple sclerosis (MS), with a specific focus on spontaneous abortion (SA) and congenital anomalies (CA).

Methods: Data of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. Rates of SA and CA were also compared with those reported in the Italian population. Multivariable logistic and linear regression models were performed.

Results: A total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with SA (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.9-8.5, < 0.001). However, the rate of SA (17.4%) was within the estimates for the general population, as well as the rate of major CA (3.7%). Moreover, exposure to natalizumab and interferon-β (IFN-β) was associated with lower length and weight of the babies ( < 0.001).

Conclusion: Our results showed that natalizumab exposure to up 12 weeks of gestation is associated with an increased risk of SA, although within the limits expected in the general population, whereas the risk of CA needs further investigation. Taking into account the high risk of disease reactivation after natalizumab suspension, pregnancy could be planned continuing natalizumab while strictly monitoring conception.

Classification Of Evidence: This study provides Class III evidence that in women with MS, natalizumab exposure increases the risk of spontaneous abortion as compared to IFN-β-exposed or untreated patients (OR 3.9, 95% CI 1.9-8.5).
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http://dx.doi.org/10.1212/WNL.0000000000005067DOI Listing
March 2018

Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: II: Maternal risks.

Neurology 2018 03 7;90(10):e832-e839. Epub 2018 Feb 7.

From IRCCS Don Gnocchi Foundation (E.P.), Florence; Scientific Institute University Vita-Salute San Raffaele (L.M., V.M., G.C.), Milan; Multiple Sclerosis Study Center (P.A., A.G., M.Z.), ASST Valle Olona, Gallarate Hospital (VA); Department of Neurosciences, Reproductive and Odontostomatological Sciences (R.L., V.B.M.), Federico II University of Naples; Department of Neurosciences (F.R., P.G.), Multiple Sclerosis Centre-Veneto Region (CeSMuV), University Hospital of Padova; Department of Neurology (C.T., D.P., M.T.), University of Bari; Department of Neurology and Psychiatry (C.P., L.D.G.), "La Sapienza" University, Rome; Department of Neurology (P.C.), University of Torino; Department of Medical Sciences and Public Health (E.C., M.G.M.), University of Cagliari; Department of Neurology (C.S.), ASL3 Genovese; Department of Neurology (A.U., A.L.), University of Genova; and Department of NEUROFARBA (L.P., M.G., M.P.A.), University of Florence, Italy.

Objective: To assess the risk of disease reactivation during pregnancy after natalizumab suspension in women with multiple sclerosis (MS).

Methods: Data of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents through a 2-factor repeated measures analysis. Predictors of disease activity were assessed through stepwise multivariable logistic regression models.

Results: A total of 92 pregnancies were tracked in 83 women receiving natalizumab. Among these pregnancies, 74 in 70 women resulted in live births, with a postpartum follow-up of at least 1 year, and were compared with 350 previously published pregnancies. Relapse rate during and after pregnancy was higher in women treated with natalizumab ( < 0.001). In multivariable analysis, longer natalizumab washout period was the only predictor of relapse occurrence during pregnancy ( = 0.001). Relapses in the postpartum year were related to relapses during pregnancy ( = 0.019) and early reintroduction of disease-modifying drugs (DMD; = 0.021). Disability progression occurred in 16.2% of patients and was reduced by early reintroduction of DMD ( = 0.024).

Conclusions: Taken as a whole, our findings indicate that the combination of avoiding natalizumab washout and the early resumption of DMD after delivery could be the best option in the perspective of maternal risk. This approach must take into account possible fetal risks that need to be discussed with the mother and require further investigation.

Classification Of Evidence: This study provides Class IV evidence that in women with MS, the risk of relapses during pregnancy is higher in those who had been using natalizumab as compared to those who had been using interferon-β or no treatment.
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http://dx.doi.org/10.1212/WNL.0000000000005068DOI Listing
March 2018

Italian multicentre study found infectious and vaccine-preventable diseases in children adopted from Africa and recommends prompt medical screening.

Acta Paediatr 2018 Jan 24. Epub 2018 Jan 24.

Division of Pediatrics, Department of Health Sciences, IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), University of Piemonte Orientale Amedeo Avogadro, Novara, Italy.

Aim: This study evaluated the prevalence of infectious diseases and immunisation status of children adopted from Africa.

Methods: We studied 762 African children referred to 11 Italian paediatric centres in 2009-2015. Clinical and laboratory data were retrospectively collected and analysed.

Results: The median age of the children (60.3% males) was 3 years and 6 months, 52.6% came from Ethiopia and 50.1% had at least one infectious disease. Parasitic infections accounted for the majority of the infectious diseases (409 of 715), and the most common were Giardia lamblia (n = 239), Toxocara canis (n = 65) and skin infections (n = 205), notably Tinea capitis/corporis (n = 134) and Molluscum contagiosum (n = 56) Active tuberculosis (TB) was diagnosed in nine children (1.2%). Latent TB infections were diagnosed in 52 (6.8%) children, and only 23 had concordant positive tuberculin skin tests and Quantiferon Gold In-Tube results. Discordant results were associated with Bacille de Calmette-Guérin vaccinations (odd ratio 6.30 and 95% confidence interval of 1.01-39.20, p = 0.011). Nonprotective antitetanus or antihepatitis B antibody titres were documented in 266 (34.9%) and 396 (51.9%) of the 762 children.

Conclusion: The prevalence of infectious conditions and not-protective titres for vaccine-preventable diseases observed in our population underlines the need for prompt and complete medical screening of children adopted from Africa.
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http://dx.doi.org/10.1111/apa.14237DOI Listing
January 2018

Long-term follow-up of pediatric MS patients starting treatment with injectable first-line agents: A multicentre, Italian, retrospective, observational study.

Mult Scler 2019 03 24;25(3):399-407. Epub 2018 Jan 24.

Multiple Sclerosis Study Center, Gallarate Hospital, ASST Valle Olona, Via Eusebio Pastori 4, 21013 Gallarate, Italy.

Background: Few data are available on very long-term follow-up of pediatric multiple sclerosis (MS) patients treated with disease modifying treatments (DMTs).

Objectives: To present a long-term follow-up of a cohort of Pediatric-MS patients starting injectable first-line agents.

Methods: Data regarding treatments, annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and serious adverse event were collected. Baseline characteristics were tested in multivariate analysis to identify predictors of disease evolution.

Results: In total, 97 patients were followed for 12.5 ± 3.3 years. They started therapy at 13.9 ± 2.1 years, 88 with interferons and 9 with copaxone. During the whole follow-up, 82 patients changed therapy, switching to immunosuppressors/second-line treatment in 58% of cases. Compared to pre-treatment phase, the ARR was significantly reduced during the first treatment (from 3.2 ± 2.6 to 0.7 ± 1.5, p < 0.001), and it remained low during the whole follow-up (0.3 ± 0.2, p < 0.001). At last observation, 40% had disability worsening, but EDSS score remained <4 in 89%. One patient died at age of 23 years due to MS. One case of natalizumab-related progressive multifocal encephalopathy (PML) was recorded. Starting therapy before 12 years of age resulted in a better course of disease in multivariate analysis.

Conclusion: Pediatric-MS patients benefited from interferons/copaxone, but the majority had to switch to more powerful drugs. Starting therapy before 12 years of age could lead to a more favorable outcome.
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http://dx.doi.org/10.1177/1352458518754364DOI Listing
March 2019

Cerebrospinal fluid analysis and the determination of oligoclonal bands.

Neurol Sci 2017 Oct;38(Suppl 2):217-224

IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.

This document presents the guidelines for the cerebrospinal fluid (CSF) analysis and the determination of oligoclonal bands (OCBs) as pivotal tests in neuroinflammatory pathologies of the central nervous system. The guidelines have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on the pathologies in which the CSF analysis is indicated, and, particularly, on those characterized by the presence of OCBs in the intrathecal compartment, indications and limits of CSF analysis and OCB determination, instructions for result interpretation, and agreed laboratory protocols (Appendix) are reported for the communicative community of neurologists and clinical pathologists.
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http://dx.doi.org/10.1007/s10072-017-3034-2DOI Listing
October 2017

Vitamin D status in internationally adopted children: the experience in Northwest Italy.

Minerva Pediatr 2017 Sep 15. Epub 2017 Sep 15.

Unit of Pediatrics, Castelli Hospital, Verbania, Italy.

Background: The majority of internationally adopted children, before adoption, might have experienced malnutrition, exposure to infectious diseases, environmental deprivation and neglect; they could also develop medical problems such as vitamin D deficiency. Scantly data are available about vitamin D status in internationally adopted children and, to our knowledge, no report exists on Italian adoptees.

Methods: We carried out a prospective multicenter study, involving three Pediatric Centers in Piedmont, Italy, in order to collect information about 25-hydroxyvitamin D [25(OH)D] profile in adoptees, shortly after their arrival in Italy.

Results: In 142/158 internationally adopted children 25(OH)D was measured: 75 males and 67 females, with a mean age of 4.22 ± 2.2 years (range 0.7-14.6 years). Fifty-three (37.3%) of them came from Asia, 48 (33.8%) from Africa, 24 (16.9%) from Eastern Europe, and 17 (12%) from Latin America. The median level of 25(OH)D in serum was 21.5 ng/mL (IQR range 14.3-29.7 ng/mL): 26 (18.2%) of the examined children had an insufficiency of 25-OHD, whereas 36 (25.2%) had a deficiency. Adoptees with longer time of institution stay had a significant risk to develop 25(OH)D deficiency. The Asian origin proved to be a risk factor to develop 25(OH)D deficiency, whereas the age >1 year was significantly associated with 25(OH)D insufficiency.

Conclusions: Our survey showed that vitamin D deficiency and insufficiency, in internationally adoptees, are frequent and relevant health problems.
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http://dx.doi.org/10.23736/S0026-4946.17.04883-6DOI Listing
September 2017

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

PLoS One 2017 1;12(8):e0180651. Epub 2017 Aug 1.

Department of Medical Sciences, Institute of Neurology-University "Magna Graecia", Catanzaro, Italy.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180651PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538735PMC
October 2017

Hypomagnesaemia as a trigger of relapsing non-alcoholic Wernicke encephalopathy: a case report.

Neurol Sci 2017 11 20;38(11):2069-2071. Epub 2017 Jul 20.

Multiple Sclerosis Study Center, Gallarate Hospital, ASST Valle Olona, Gallarate, Italy.

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http://dx.doi.org/10.1007/s10072-017-3062-yDOI Listing
November 2017