Spatial and temporal characteristics of gait as outcome measures in multiple sclerosis (EDSS 0 to 6.5)

Background: Gait impairment represents one of the most common and disabling symptom of multiple sclerosis. Quantification of the gait is an important aspect of clinical trials. In order to identify which temporal or spatial parameters of gait could be used as outcome measures in interventional studies of patients with different levels of disability, we evaluated characteristics of these parameters in MS patients across the whole spectrum of mobility from EDSS 0 to 6.5. Methods: This is a cross-sectional study of spatial and temporal parameters of gait at self selected speed and at fast speed of walking in 284 patients with multiple sclerosis (108 men, mean age 38 years ± SD 10.8 years, range 18–64) divided into seven levels of disability (EDSS 0 to 1.5, EDSS 2.0 to 2.5, EDSS 3.0 to 3.5, EDSS 4.0 to 4.5, EDSS 5.0 to 5.5, EDSS 6.0, EDSS 6.5). Results: The velocity of gait decreases with increasing EDSS levels. Hovewer, the spatio-temporal parameters of gait that are involved in this process differ across the EDSS levels. The step length is decreased at higher EDSS levels up to the EDSS 6.0, but was not different between EDSS 6.0 and 6.5. The step time is significantly longer at EDSS 6.0 and 6.5, while the step length remains the same at those levels. The increase in percentage of double support time becomes statistically significant at EDSS 3.0-3.5 and continues to increase until EDSS 6.5. Variability of step time, step length or step width did not show significant difference between studied EDSS levels. Conclusions: There is no single spatio-temporal parameter of gait (other than velocity of gait) that would show significant differences among all levels of EDSS. The step length reflects shortening of steps at lower EDSS levels (2.0 to 6.0), and percentage of double support time better reflects changes at higher EDSS levels 3.0 – 6.5. Gait variability is not associated with disability in MS and therefore would not be a suitable outcome measure. T

Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study

© The Author(s), 2018. Background: Ozanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5. Objective: Evaluate efficacy, safety, and tolerability of ozanimod in relapsing multiple sclerosis. Methods: In the RADIANCE Part A phase II study (NCT01628393), participants with relapsing multiple sclerosis were randomized (1:1:1) to once-daily ozanimod hydrochloride (0.5 or 1 mg) or placebo. After 24 weeks, participants could enter a 2-year, dose-blinded extension. Ozanimod-treated participants continued their assigned dose; placebo participants were re-randomized (1:1) to ozanimod hydrochloride 0.5 or 1 mg (equivalent to ozanimod 0.46 and 0.92 mg). Results: A total of 223 (89.6%) of the 249 participants completed the blinded extension. At 2 years of the extension, the percentage of participants who were gadolinium-enhancing lesion-free ranged from 86.5% to 94.6%. Unadjusted annualized relapse rate during the blinded extension (week 24—end of treatment) was 0.32 for ozanimod hydrochloride 0.5 mg → ozanimod hydrochloride 0.5 mg, 0.18 for ozanimod hydrochloride 1 mg → ozanimod hydrochloride 1 mg, 0.30 for placebo → ozanimod hydrochloride 0.5 mg, and 0.18 for placebo → ozanimod hydrochloride 1 mg. No second-degree or higher atrioventricular block or serious opportunistic infection was reported. Conclusion: Ozanimod demonstrated sustained efficacy in participants continuing treatment up to 2 years and reached similar efficacy in participants who switched from placebo; no unexpected safety signals emerged

Data Descriptor: Ash leaf metabolomes reveal differences between trees tolerant and susceptible to ash dieback disease

CMS was funded by the ‘Nornex’ project jointly by UK BBSRC (BBS/E/J/000CA5323) and DEFRA and a BBSRC Tools and Resources grant (BB/N021452/1) awarded to M.G. and D.J.S

Investigational immunosuppressants in early stage clinical trials for the treatment of multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale. Areas covered. The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS. The websites clinicaltrials.gov, clinicaltrialsregister.eu, and pubmed.gov were searched for phase 1, phase 2, and phase 3 trials starting from 2012. Twelve drugs were identified, including 7 monoclonal antibodies and 5 small molecules. Expert opinion. Current or recently completed trials of immunosuppressants for MS are mainly proof-of-concept studies enrolling patients with relapsing disease and using efficacy endpoints based on magnetic resonance imaging measures of inflammatory activity. Sphingosine 1-phosphate receptor modulators and B-cell depleting therapies represent the most commonly investigated drugs, suggesting that mechanisms of action that have already shown promise for MS treatment are being exploited to find new therapies with improved safety, tolerability, and convenience of dosing. Clinical trials of immunosuppressants for progressive MS are largely lacking

Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis.

BACKGROUND: Autoimmune disorders including nephropathies have been reported more frequently in alemtuzumab-treated multiple sclerosis (MS) patients than in the general population. OBJECTIVE: Describe instances of autoimmune nephropathy in alemtuzumab-treated MS patients. METHODS: Cases were identified from safety monitoring within the alemtuzumab relapsing-remitting multiple sclerosis (RRMS) clinical development program (CDP) or post-marketing, or following off-label use. RESULTS: As of 16 June 2017, 16 autoimmune nephropathies have occurred following alemtuzumab treatment for MS. The incidence of autoimmune nephropathies was 0.34% within the CDP (5/1485 patients). The five CDP cases (one of anti-glomerular basement membrane (anti-GBM) disease, two of membranous glomerulonephropathy, and two of serum anti-GBM antibody without typical anti-GBM disease) were identified early, responded to conventional therapy (where needed), and had favorable outcomes. Three of 11 cases outside the CDP occurred following off-label alemtuzumab use prior to approval for RRMS and were all anti-GBM disease. Diagnosis was delayed in one of these three cases and another did not receive appropriate treatment; all three cases resulted in end-stage renal failure. All anti-GBM disease cases with documented urinalysis demonstrated prior microscopic hematuria. CONCLUSION: Close monitoring of alemtuzumab-treated MS patients facilitates diagnosis and treatment early in the nephropathy course when preservation of renal function is more likely

Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study.

BackgroundOzanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5.ObjectiveEvaluate efficacy, safety, and tolerability of ozanimod in relapsing multiple sclerosis.MethodsIn the RADIANCE Part A phase II study (NCT01628393), participants with relapsing multiple sclerosis were randomized (1:1:1) to once-daily ozanimod hydrochloride (0.5 or 1 mg) or placebo. After 24 weeks, participants could enter a 2-year, dose-blinded extension. Ozanimod-treated participants continued their assigned dose; placebo participants were re-randomized (1:1) to ozanimod hydrochloride 0.5 or 1 mg (equivalent to ozanimod 0.46 and 0.92 mg).ResultsA total of 223 (89.6%) of the 249 participants completed the blinded extension. At 2 years of the extension, the percentage of participants who were gadolinium-enhancing lesion-free ranged from 86.5% to 94.6%. Unadjusted annualized relapse rate during the blinded extension (week 24-end of treatment) was 0.32 for ozanimod hydrochloride 0.5 mg → ozanimod hydrochloride 0.5 mg, 0.18 for ozanimod hydrochloride 1 mg → ozanimod hydrochloride 1 mg, 0.30 for placebo → ozanimod hydrochloride 0.5 mg, and 0.18 for placebo → ozanimod hydrochloride 1 mg. No second-degree or higher atrioventricular block or serious opportunistic infection was reported.ConclusionOzanimod demonstrated sustained efficacy in participants continuing treatment up to 2 years and reached similar efficacy in participants who switched from placebo; no unexpected safety signals emerged

Unraveling the carbohydrate count in the treatment of diabetes mellitus.

O diabetes mellitus é uma condição crônica que requer gerenciamento continuo, trata-se de um grupo heterogêneo de distúrbios metabólicos que apresenta em comum a hiperglicemia. A terapia nutricional é um dos componentes fundamentais da abordagem terapêutica do diabetes, em virtude disso no contexto de alimentação saudável a contagem de carboidratos torna-se uma estratégia chave para o tratamento da doença. Logo, neste estudo objetivou-se realizar uma revisão de literatura com os principais pontos relacionados ao diabetes a fim de compreender a repercussão da contagem de carboidratos como dietoterapia, analisando e fornecendo informações a respeito destas repercussões. Foram pesquisados artigos por meio de bancos de dados PUBMED, LILACS-BIREME e SCIELO, com o fim de realizar uma leitura criteriosa e objetiva do material que serviu de base para análise da relação entre contagem de carboidratos como estratégia para o tratamento do diabetes mellitus. A alimentação do paciente diabético demanda bastante atenção, por ser um aspecto conflitante para o indivíduo e para a sua família. O método de contagem pode ser amplamente utilizado por todos os tipos de diabetes, é uma estratégia de planejamento alimentar com foco nos carboidratos, por este ser o principal nutriente a afetar a resposta glicêmica pós prandial, além de ser um método que proporciona inserção social e que respeita as necessidades nutricionais e hábitos alimentares do indivíduo com diabetes. Com isso qualquer indivíduo com diabetes pode utilizar contagem de carboidrato como um plano de refeição.Diabetes mellitus is a chronic condition that requires ongoing management. It is a heterogeneous group of metabolic disorders, which presents, in common, the hyperglycemia. Nutritional therapy is one of the fundamental components of the therapeutic approach to diabetes. Thus, in the healthy eating context, carbohydrate counting becomes a key strategy for the treatment of diabetes. Therefore, this study aimed to conduct a literature review with the main points related to diabetes in order to understand the impact of carbohydrate counting and diet therapy, analyzing and providing information about these repercussions. Articles from the databases PUBMED, LILACS-BIREME and SCIELO were collected in order to conduct a careful and objective reading of the material that formed the basis for the analysis of the relationship between carbohydrate counting and diabetes mellitus. The diet of the diabetic patient demands close attention, because it is a conflicting issue for the individual and his family. The counting method can be widely used by all types of diabetes, being also a meal planning strategy focused on carbohydrate, which is the main nutrient that affects the postprandial glycemic response. In addition, the counting method provides social integration, and respects the nutritional needs and eating habits of the individual with diabetes. With that anyone with diabetes can use carbohydrate counting as a meal plan

Efficacy and safety of ozanimod in multiple sclerosis : Dose-blinded extension of a randomized phase II study

Altres ajuts: The study was sponsored by Celgene Corporation.Ozanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5. Evaluate efficacy, safety, and tolerability of ozanimod in relapsing multiple sclerosis. In the RADIANCE Part A phase II study (NCT01628393), participants with relapsing multiple sclerosis were randomized (1:1:1) to once-daily ozanimod hydrochloride (0.5 or 1 mg) or placebo. After 24 weeks, participants could enter a 2-year, dose-blinded extension. Ozanimod-treated participants continued their assigned dose; placebo participants were re-randomized (1:1) to ozanimod hydrochloride 0.5 or 1 mg (equivalent to ozanimod 0.46 and 0.92 mg). A total of 223 (89.6%) of the 249 participants completed the blinded extension. At 2 years of the extension, the percentage of participants who were gadolinium-enhancing lesion-free ranged from 86.5% to 94.6%. Unadjusted annualized relapse rate during the blinded extension (week 24-end of treatment) was 0.32 for ozanimod hydrochloride 0.5 mg → ozanimod hydrochloride 0.5 mg, 0.18 for ozanimod hydrochloride 1 mg → ozanimod hydrochloride 1 mg, 0.30 for placebo → ozanimod hydrochloride 0.5 mg, and 0.18 for placebo → ozanimod hydrochloride 1 mg. No second-degree or higher atrioventricular block or serious opportunistic infection was reported. Ozanimod demonstrated sustained efficacy in participants continuing treatment up to 2 years and reached similar efficacy in participants who switched from placebo; no unexpected safety signals emerged