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Background: Multiple sclerosis has both high healthcare and social impacts., Objective: The purpose of this article is to analyse the available literature describing the economic burden of multiple sclerosis and to compare costs among studies examining main cost drivers., Methods: A literature search on studies published in English on cost-of-illness of multiple sclerosis included in this review using PubMed, the Cochrane Library, SCOPUS and Web of Science includes a retrospective horizon and it describes direct and indirect costs in patients categorized into severity groups., Results: Several papers were obtained from the database search (n=37). Additionally, results from "hand searching" were also included, where a wider horizon was considered. Cost estimates were compared among studies that used a societal perspective on costs, time-period studied, and year of price level used. The estimated total annual cost per patient in Europe is on average 40,300€ (n=20). In addition, differences by geographic areas and severity groups are also considered. All in all, the higher the severity, the higher the associated costs., Conclusions: This systematic review provides one clear finding: multiple sclerosis places a huge economic burden on healthcare models and societies due to productivity losses and caregiver burden. Moreover, costs of drugs were main cost determinants for less severe cases of multiple sclerosis and informal care and production losses for the most severe cases of multiple sclerosis., Competing Interests: Declaration of Competing Interest None of the authors has financial interest related to this study to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To determine the mediating effects of depression on health-related quality of life and fatigue in individuals with multiple sclerosis (MS)., Design: A cross-sectional study., Setting: Tertiary urban hospital., Participants: One hundred and eight patients (54% women) with MS participated in this study., Outcome Measures: Demographic and clinical data (weight, height, medication and neurological impairment), fatigue (Fatigue Impact Scale), depression (Beck Depression Inventory-II) and health-related quality of life (Short-Form Health Survey 36) were collected., Results: Fatigue was significantly associated with bodily pain, physical function, mental health and depression. Depression was associated with bodily pain and mental health. The path analysis found direct effects from physical function, bodily pain and depression to fatigue (all, P<0.01). The path model analysis revealed that depression exerted a mediator effect from bodily pain to fatigue (B=-0.04, P<0.01), and from mental health to fatigue (B=-0.16, P<0.01). The amount of fatigue explained by all predictors in the path model was 37%., Conclusions: This study found that depression mediates the relationship between some health-related quality of life domains and fatigue in people with MS. Future longitudinal studies focusing on proper management of depressive symptoms in individuals with MS will help determine the clinical implications of these findings., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)