a-method-trigonometric-modelling-seasonal-variation-demonstrated-with

A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data

This report describes a novel Stata-based application of trigonometric regression modelling to  55 years of multiple sclerosis relapse data from 46 ...

Ulster Hospital

The Expanded Disability Status Scale (EDSS) is widely used to rate multiple sclerosis (MS) disability, but lack of disease duration information limits utility in assessing severity. EDSS ranking at specific disease durations was used to devise the MS Severity Score, which is gaining popularity for predicting outcomes. As this requires validation in longitudinal cohorts, we aimed to assess the utility of EDSS ranking as a predictor of 5-year outcome in the MSBase Registry.

The Kurtzke EDSS rank stability increases 4 years after the onset of multiple sclerosis: results from the MSBase Registry.

To analyze time-trends in age at disability milestones among MS patients who were enrolled into the MSBase International Registry during 1996-2010 period.

Increasing age at disability milestones among MS patients in the MSBase Registry.

To compare treatment persistence between two dosages of interferon Î²-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics.

Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon Beta 1a dosages for multiple sclerosis.

Pour comparer la persistance de traitement entre les deux doses d&#39;interf&eacute;ron &beta;-1 a, dans un registre de la scl&eacute;rose en plaques d&#39;observation grand et &eacute;valuer les r&eacute;sultats de la maladie de la 1&egrave;re ligne de traitement MS &agrave; ces dosages utilisant le score de propension &agrave; r&eacute;gler pour le d&eacute;s&eacute;quilibre de la base de caract&eacute;ristiques de la maladie.

Persistance sur la th&eacute;rapie et de la propension appari&eacute;s comparaison des r&eacute;sultats de deux dosages de 1 a b&ecirc;ta interf&eacute;ron sous-cutan&eacute;e pour la scl&eacute;rose en plaques.

Predictors and dynamics of postpartum relapses in women with multiple sclerosis.

The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10(-12)). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10(-12)). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.

Sex as a determinant of relapse incidence and progressive course of multiple sclerosis.

The aim was to analyse risk of relapse phenotype recurrence in multiple sclerosis and to characterise the effect of demographic and clinical features on this phenotype.

Risk of relapse phenotype recurrence in multiple sclerosis.

Previous studies assessing seasonal variation of relapse onset in multiple sclerosis have had conflicting results. Small relapse numbers, differing diagnostic criteria, and single region studies limit the generalizability of prior results. The aim of this study was to determine whether there is a temporal variation in onset of relapses in both hemispheres and to determine whether seasonal peak relapse probability varies with latitude.

Seasonal variation of relapse rate in multiple sclerosis is latitude dependent.

The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed.

Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing-remitting multiple sclerosis.

Multiple Sclerosis is more common in women than men and females have more relapses than men. In a large international cohort we have evaluated the effect of gender on disability accumulation and disease progression to determine if male MS patients have a worse clinical outcome than females.

Male Sex Is Independently Associated with Faster Disability Accumulation in Relapse-Onset MS but Not in Primary Progressive MS.

Symptomatic therapy in multiple sclerosis: Big pharma should do more - NO.

We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS).

The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis.

Prevention of irreversible disability is currently the most important goal of disease modifying therapy for multiple sclerosis. The disability outcomes used in most clinical trials rely on progression of Expanded Disability Status Scale score confirmed over 3 or 6 months. However, sensitivity and stability of this metric has not been extensively evaluated. Using the global MSBase cohort study, we evaluated 48 criteria of disability progression, testing three definitions of baseline disability, two definitions of progression magnitude, two definitions of long-term irreversibility and four definitions of event confirmation period. The study outcomes comprised the rates of detected progression events per 10 years and the proportions of the recorded events persistent at later time points. To evaluate the ratio of progression frequency and stability for each criterion, we calculated the proportion of events persistent over the five subsequent years once progression was achieved. Finally, we evaluated the clinical and demographic determinants characterising progression events and, for those that regressed back to baseline, determinants of their subsequent regression. The study population consisted of 16 636 patients with the minimum of three recorded disability scores, totalling 112 584 patient-years. The progression rates varied between 0.41 and 1.14 events per 10 years, with the length of required confirmation interval as the most important determinant of the observed variance. The concordance among all tested progression criteria was only 17.3%. Regression of disability occurred in 11-34% of the progression events over the five subsequent years. The most important determinant of progression stability was the length of the confirmation period. For the most accurate set of the progression criteria, the proportions of 3-, 6-, 12- or 24-month confirmed events persistent over 5 years reached 70%, 74%, 80% and 89%, respectively. Regression post progression was more common in younger patients, relapsing-remitting disease course, and after a smaller change in disability, and was inflated by higher visit frequency. These results suggest that the disability outcomes based on 3-6-month confirmed disability progression overestimate the accumulation of permanent disability by up to 30%. This could lead to spurious results in short-term clinical trials, and the issue may be magnified further in cohorts consisting predominantly of younger patients and patients with relapsing-remitting disease. Extension of the required confirmation period increases the persistence of progression events.

Article	Year
The Kurtzke EDSS rank stability increases 4 years after the onset of multiple sclerosis: results from the MSBase Registry. Journal of neurology, neurosurgery, and psychiatry\| PubMed ID: 22205675	2012
Increasing age at disability milestones among MS patients in the MSBase Registry. Journal of the neurological sciences\| PubMed ID: 22507751	2012
Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon Beta 1a dosages for multiple sclerosis. PloS one\| PubMed ID: 23704913	2013
Predictors and dynamics of postpartum relapses in women with multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England)\| PubMed ID: 24107309	2014
Sex as a determinant of relapse incidence and progressive course of multiple sclerosis. Brain : a journal of neurology\| PubMed ID: 24142147	2013
Risk of relapse phenotype recurrence in multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England)\| PubMed ID: 24777276	2014
Seasonal variation of relapse rate in multiple sclerosis is latitude dependent. Annals of neurology\| PubMed ID: 25283272	2014
Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing-remitting multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England)\| PubMed ID: 25480857	2015
Male Sex Is Independently Associated with Faster Disability Accumulation in Relapse-Onset MS but Not in Primary Progressive MS. PloS one\| PubMed ID: 26046348	2015
Symptomatic therapy in multiple sclerosis: Big pharma should do more - NO. Multiple sclerosis (Houndmills, Basingstoke, England)\| PubMed ID: 26084348	2015
The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England)\| PubMed ID: 26199347	2015
Defining reliable disability outcomes in multiple sclerosis. Brain : a journal of neurology\| PubMed ID: 26359291	2015

Orla Gray

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