Although pregnancy in women with multiple sclerosis (MS) is not generally considered high risk, there are some associated therapeutic challenges. The pregnancy‐associated reduction in the relapse ...rate, especially in the third trimester, is followed by a sharp increase in the first few months postpartum. Nevertheless, retrospective evidence for pregnant women with and without MS followed for up to 10 years indicates that pregnancy has no perceptible effect on long‐term disease course or disability progression. Likewise, MS has no apparent effects on the pregnancy course or fetal outcomes. All disease‐modifying therapies (DMTs) have potential adverse effects on fertility and pregnancy outcomes, but the level of risk varies amongst agents. There is some support for continued use of interferon‐β and glatiramer acetate throughout pregnancy to reduce the risk of relapse. Use of DMTs during breastfeeding is best avoided if possible. Close evaluation of drug safety information is imperative when managing women with MS who are pregnant or wish to become pregnant. Decision‐making should be a shared experience between patient and physician, and the approach must be individualized for each patient.
Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences. It is the major cause of non‐traumatic disability in young ...adults. The social costs associated with MS are high because of its long duration, the early loss of productivity, the need for assistance in activities of daily living and the use of immunomodulatory treatments and multidisciplinary health care. Available MS epidemiological estimates are aimed at providing a measure of the disease burden in Europe. The total estimated prevalence rate of MS for the past three decades is 83 per 100 000 with higher rates in northern countries and a female:male ratio around 2.0. Prevalence rates are higher for women for all countries considered. The highest prevalence rates have been estimated for the age group 35–64 years for both sexes and for all countries. The estimated European mean annual MS incidence rate is 4.3 cases per 100 000. The mean distribution by disease course and by disability is also reported. Despite the wealth of epidemiological data on MS, comparing epidemiological indices among European countries is a hard task and often leads only to approximate estimates. This represents a major methodological concern when evaluating the MS burden in Europe and when implementing specific cost‐of‐illness studies.
Objective:
To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS).
Methods:
We performed a multicenter study ...including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes.
Results:
The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB.
Conclusion:
Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.
•Using genetic programming we identified models for the power output of a string.•Only the actual power and the time difference with respect to sunrise are necessary.•74 inputs were investigated, but ...no cloud information was considered.
In this paper we have identified several mathematical models for predicting the solar power output of a 1.05kWp Monocrystalline Silicon high-efficiency photovoltaic string located at the ENEL Catania site, Italy. The data we used corresponds to 15min of averaged power generated over a whole year (2010). A tool named the Brain Project was used. It follows a distributed genetic programming approach. Seventy-four inputs were investigated for our purposes, but no cloud information was considered. The accuracy of all the models was evaluated and compared to other approaches. Among these, the simpler models, that foresee only two inputs perform similarly to our more complex models and to several others in literature.
This paper is meant to provide guidance to anyone wishing to write a neurological guideline for diagnosis or treatment, and is directed at the Scientist Panels and task forces of the European ...Federation of Neurological Societies (EFNS). It substitutes the previous guidance paper from 2004. It contains several new aspects: the guidance is now based on a change of the grading system for evidence and for the resulting recommendations, and has adopted The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE). The process of grading the quality of evidence and strength of recommendations can now be improved and made more transparent. The task forces embarking on the development of a guideline must now make clearer and more transparent choices about outcomes considered most relevant when searching the literature and evaluating their findings. Thus, the outcomes chosen will be more critical, more patient‐oriented and easier to translate into simple recommendations. This paper also provides updated practical recommendations for planning a guideline task force within the framework of the EFNS. Finally, this paper hopes to find the approval also by the relevant bodies of our future organization, the European Academy of Neurology.
The Italian multiple sclerosis register Trojano, Maria; Bergamaschi, Roberto; Amato, Maria Pia ...
Neurological sciences,
01/2019, Letnik:
40, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to ...provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups.
Objective
To employ Artificial Intelligence to model, predict and simulate the amyotrophic lateral sclerosis (ALS) progression over time in terms of variable interactions, functional impairments, and ...survival.
Methods
We employed demographic and clinical variables, including functional scores and the utilisation of support interventions, of 3940 ALS patients from four Italian and two Israeli registers to develop a new approach based on Dynamic Bayesian Networks (DBNs) that models the ALS evolution over time, in two distinct scenarios of variable availability. The method allows to simulate patients’ disease trajectories and predict the probability of functional impairment and survival at different time points.
Results
DBNs explicitly represent the relationships between the variables and the pathways along which they influence the disease progression. Several notable inter-dependencies were identified and validated by comparison with literature. Moreover, the implemented tool allows the assessment of the effect of different markers on the disease course, reproducing the probabilistically expected clinical progressions. The tool shows high concordance in terms of predicted and real prognosis, assessed as time to functional impairments and survival (integral of the AU-ROC in the first 36 months between 0.80–0.93 and 0.84–0.89 for the two scenarios, respectively).
Conclusions
Provided only with measurements commonly collected during the first visit, our models can predict time to the loss of independence in walking, breathing, swallowing, communicating, and survival and it can be used to generate in silico patient cohorts with specific characteristics. Our tool provides a comprehensive framework to support physicians in treatment planning and clinical decision-making.
Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system unsurpassed for variability in disease outcome. A cohort of sporadic MS cases (n = 163), taken from opposite ...extremes of the distribution of long-term outcome, was used to determine the role of the HLA-DRB1 locus on MS disease severity. Genotyping sets of benign and malignant MS patients showed that HLA-DRB1*01 was significantly underrepresented in malignant compared with benign cases. This allele appears to attenuate the progressive disability that characterizes MS in the long term. The observation was doubly replicated in (i) Sardinian benign and malignant patients and (ii) a cohort of affected sibling pairs discordant for HLA-DRB1*01. Among the latter, mean disability progression indices were significantly lower in those carrying the HLA-DRB1*01 allele compared with their disease-concordant siblings who did not. The findings were additionally supported by similar transmission distortion of HLA-DRB1*04 subtypes closely related to HLA-DRB1*01. The protective effect of HLA-DRB1*01 in sibling pairs may result from a specific epistatic interaction with the susceptibility allele HLA-DRB1*1501. A high-density (>700) SNP examination of the MHC region in the benign and malignant patients could not identify variants differing significantly between the two groups, suggesting that HLA-DRB1 may itself be the disease-modifying locus. We conclude that HLA-DRB1*01, previously implicated in disease resistance, acts as an independent modifier of disease progression. These results closely link susceptibility to long-term outcome in MS, suggesting that shared quantitative MHC-based mechanisms are common to both, emphasizing the central role of this region in pathogenesis.
Objective
In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS ...cases in Emilia Romagna Region (ERR), Italy.
Methods
A registry for ALS has been collecting all incident cases in ERR since 2009. Detailed clinical data from all patients diagnosed with ALS between 1.1.2009 and 31.12.2014 have been analyzed for this study, with last follow up date set at 31.12.2015.
Results
During the 6 years of the study, there were 681 incident cases with a median tracheostomy-free survival of 40 months (95% CI 36–44) from onset and of 26 months (95% CI 24–30) from diagnosis; 573 patients (84.14%) were treated with riluzole, 207 (30.39%) patients underwent gastrostomy, 246 (36.12%) non invasive ventilation, and 103 (15.15%) invasive ventilation. Patients who took treatment for ≥ 75% of disease duration from diagnosis had a median survival of 29 months compared to 18 months in patients with < 75% treatment duration. In multivariable analysis, factors independently influencing survival were age at onset (HR 1.04, 95% CI 1.02–1.05,
p
< 0.001), dementia (HR 1.56, 95% CI 1.05–2.32,
p
= 0.027), degree of diagnostic certainty (HR 0.88, 95% CI 0.78–0.98,
p
= 0.021), gastrostomy (HR 1.46, 95% CI 1.14–1.88,
p
= 0.003), NIV (HR 1.43, 95% CI 1.12–1.82,
p
= 0.004), and weight loss at diagnosis (HR 1.05, 95% CI 1.03–1.07,
p
< 0.001), diagnostic delay (HR 0.98, 95% CI 0.97–0.99,
p
= 0.004), and % treatment duration (HR 0.98, 95% CI 0.98–0.99,
p
< 0.001).
Conclusions
Independently from other prognostic factors, patients who received riluzole for a longer period of time survived longer, but further population based studies are needed to verify if long-tem use of riluzole prolongs survival.
•Nineteen questionnaires from European MS registries were analysed.•Aim and focus as well as number of patients and inclusion criteria vary considerably.•Most of the MS registries collect data within ...common general categories.•There are more pronounced differences regarding specific subcategories.
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