1,721,297 research outputs found
Pharmacotherapy in Secondary Progressive Multiple Sclerosis: An Overview
Full text linkMultiple sclerosis is an immune-mediated inflammatory disease of the central nervous system characterised by demyelination, neuroaxonal loss and a heterogeneous clinical course. Multiple sclerosis presents with different phenotypes, most commonly a relapsing–remitting course and, less frequently, a progressive accumulation of disability from disease onset (primary progressive multiple sclerosis). The majority of people with relapsing–remitting multiple sclerosis, after a variable time, switch to a stage characterised by gradual neurological worsening known as secondary progressive multiple sclerosis. We have a limited understanding of the mechanisms underlying multiple sclerosis, and it is believed that multiple genetic, environmental and endogenous factors are elements driving inflammation and ultimately neurodegeneration. Axonal loss and grey matter damage have been regarded as amongst the leading causes of irreversible neurological disability in the progressive stages. There are over a dozen disease-modifying therapies currently licenced for relapsing–remitting multiple sclerosis, but none of these has provided evidence of effectiveness in secondary progressive multiple sclerosis. Recently, there has been some early modest success with siponimod in secondary progressive multiple sclerosis and ocrelizumab in primary progressive multiple sclerosis. Finding treatments to delay or prevent the courses of secondary progressive multiple sclerosis is an unmet and essential goal of the research in multiple sclerosis. In this review, we discuss new findings regarding drugs with immunomodulatory, neuroprotective or regenerative properties and possible treatment strategies for secondary progressive multiple sclerosis. We examine the field broadly to include trials where participants have progressive or relapsing phenotypes. We summarise the most relevant results from newer investigations from phase II and III randomised controlled trials over the past decade, with particular attention to the last 5 years
Interface of Multiple Sclerosis, Depression, Vascular Disease, and Mortality: A Population-Based Matched Cohort Study
No full textBACKGROUND AND OBJECTIVES: To assess whether the association among depression, vascular disease, and mortality differs in people with multiple sclerosis (MS) compared with age-, sex-, and general practice-matched controls. METHODS: We conducted a population-based retrospective matched cohort study between January 1, 1987, and September 30, 2018, that included people with MS and matched controls without MS from England, stratified by depression status. We used time-varying Cox proportional hazard regression models to test the association among MS, depression, and time to incident vascular disease and mortality. Analyses were also stratified by sex. RESULTS: We identified 12,251 people with MS and 72,572 matched controls. At baseline, 21% of people with MS and 9% of controls had depression. Compared with matched controls without depression, people with MS had an increased risk of incident vascular disease regardless of whether they had comorbid depression. The 10-year hazard of all-cause mortality was 1.75-fold greater in controls with depression (95% confidence interval [CI] 1.59-1.91), 3.88-fold greater in people with MS without depression (95% CI 3.66-4.10), and 5.43-fold greater in people with MS and depression (95% CI 4.88-5.96). Overall, the interaction between MS status and depression was synergistic, with 14% of the observed effect attributable to the interaction. Sex-stratified analyses confirmed differences in hazard ratios. DISCUSSION: Depression is associated with increased risks of incident vascular disease and mortality in people with MS, and the effects of depression and MS on all-cause mortality are synergistic. Further studies should evaluate whether effectively treating depression is associated with a reduced risk of vascular disease and mortality
Evaluating the Risk of Macrovascular Events and Mortality among People with Multiple Sclerosis in England
No full textImportance: People with multiple sclerosis (MS) are associated with an increased risk of cardiovascular disease and mortality; however, evidence from population-based studies is sparse. Objective: To assess whether the risk of macrovascular events and mortality differs among people with MS compared with a matched population without MS in England. Design, Setting, and Participants: A population-based retrospective matched cohort study was conducted in general practices registered with the Clinical Practice Research Datalink in England between January 1, 1987, and September 30, 2018, with a mean (SD) follow-up of 11.3 (6.5) years. A total of 12251 patients with MS were matched with up to 6 people without MS (n = 72572) by age, sex, and general practice. People with 3 or more diagnoses of MS recorded during the study period were included. The first MS diagnosis was considered as index date. Exposures: Multiple sclerosis status. Analyses were also stratified by sex. Main Outcomes and Measures: Main outcomes were acute coronary syndrome, cerebrovascular disease, any macrovascular disease (including peripheral arterial disease), and mortality (all-cause mortality and cardiovascular disease-specific mortality). Cox proportional hazards regression and Fine and Gray proportional subhazard regression models were used to assess differences in rates. Results: A total of 12251 people with MS (66.9% women; mean [SD] age, 44.9 [13.3] years) were matched with 72572 people without MS (69.8% women; mean [SD] age, 44.9 [13.3] years). As compared with people without MS, people with MS were associated with a 28% increased hazard of acute coronary syndrome (hazard ratio [HR], 1.28; 95% CI, 1.09-1.51), 59% increased hazard of cerebrovascular disease (HR, 1.59; 95% CI, 1.32-1.92), 32% increased hazard of any macrovascular disease (HR, 1.32; 95% CI, 1.15-1.52), 3.5-fold increased hazard of all-cause mortality (HR, 3.46; 95% CI, 3.28-3.65), and 1.5-fold increased hazard in cardiovascular disease mortality (HR, 1.47; 95% CI, 1.27-1.71). Differences in macrovascular events were more pronounced among women than men. Mortality risk was also higher for women than men. Treatment with lipid-lowering medications (mainly statins) was associated with lower mortality rates among people with MS. Conclusions and Relevance: This study suggests that MS is associated with an increased risk of cardiovascular and cerebrovascular disease that is not completely accounted for by traditional vascular risk factors. Given the adverse effects of these comorbidities on outcomes in patients with MS, further investigation is needed
Secondary Progressive Multiple Sclerosis: Definition and Measurement
Full text linkSecondary progressive multiple sclerosis (SPMS) is diagnosed retrospectively and involves a clinical course characterized by a progressive accumulation of neurological disability, independent of relapses, following an initial relapsing–remitting (RR) phase. Our incomplete understanding of the pathological mechanisms underlying neurodegeneration in multiple sclerosis (MS) may explain why, to date, there is no definitive imaging or laboratory test that is able to inform us when the disease is clearly entering into a progressive phase and why the vast majority of clinical trials testing immunosuppressant and immunomodulating drugs in SPMS patients has so far yielded disappointing or mixed results. Here we discuss the definition(s) of SPMS and how it may vary, outcome measurements (current and emerging) and modern trial design
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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