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M Daumer

Publications and source records attributed to M Daumer.

11 recordsLinked to original sources
PubMed2006

Relapses and subsequent worsening of disability in relapsing-remitting multiple sclerosis.

OBJECTIVE: To investigate whether relapses contribute to the development of subsequent sustained increase of impairment and disability in patients with multiple sclerosis (MS). METHODS: In a random sampled subset of 256 relapsing-remitting MS (RRMS) patients from the placebo arms of 20 randomized, controlled clinical trials contained in the Sylvia Lawry Centre for MS Research (SLCMSR) open database (mean follow-up time 2.66 years), the authors tested whether time to an increase of the Expanded Disability Status Scale (EDSS) score (confirmed after 6 months) was related to the occurrence of prior relapses. In the primary analysis, EDSS progressions starting within the period used to calculate the on-study relapse rate (sacrifice period) were not counted. The result obtained was then validated in an independent validation part of the SLCMSR database (n = 320). RESULTS: Although in the first subset of 256 RRMS patients, occurrence of relapses in the first 4 months on study appeared to be the best predictor for a shorter time to subsequent sustained increase in the EDSS score (hazard ratio [HR] 2.26 [95% CI: 1.36 to 3.75]), this finding was not confirmed in the validation dataset (HR 1.35, one-sided Wald test, lower limit of the 95% CI: 0.90). CONCLUSION: Although relapses may result into permanent damage and Expanded Disability Status Scale (EDSS) progression, there is no consistent effect of on-study relapses on the subsequent development of sustained EDSS score increase during a typical clinical study observation period.

Adult↗
PubMed2006

MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability.

BACKGROUND: Previous studies have shown only modest correlation between multiple sclerosis (MS) lesions on MRI and clinical disability. OBJECTIVE: To investigate the relationship between proton density/T2-weighted (T2) burden of disease (BOD) quantitatively measured on MRI scans and clinical determinants including disability. METHODS: Using the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database, the authors studied baseline T2 BOD data from a pooled subsample of 1,312 placebo MS patients from 11 randomized controlled trials. Univariate comparisons guided development of multiple regression models incorporating the most important clinical predictors. RESULTS: Significant, although weak to moderate, correlations were found between T2 BOD and age at disease onset, disease duration, disease course, disability (as measured by the Expanded Disability Status Scale [EDSS]), relapse rate, certain presenting symptoms, and gadolinium enhancement. An unexpected but key finding that persisted in the multiple regression analyses was a plateauing relationship between T2 BOD and disability for EDSS values above 4.5. CONCLUSIONS: This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability.

Adult↗
PubMed2006

Survival, and time to an advanced disease state or progression, of untreated patients with moderately severe multiple sclerosis in a multicenter observational database: relevance for design of a clinical trial for high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation.

Despite prolonged survival, patients with multiple sclerosis (MS) experience considerable morbidity, which adversely impacts quality of life. To assess the risk-benefit of a clinical trial of high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation for MS, we sought to determine the natural history of the disease in a comparison group of untreated patients. We identified 285 individuals with 2132 combined observation years (median: 5.6 years; 5th to 95th percentile: 1-21 years), with Expanded Disability Status Scale (EDSS) scores of 3.0-5.5 at baseline observation. Disease-related mortality was zero at five years, 5.4% at 10 years, and 22% at 15 years (40 patients contributing to the data point; 95% confidence interval: 4-32%). Risk for progression to advanced disability, defined as an EDSS score of 8, was very low for the subgroup with a baseline EDSS score of 3-3.5; however, for those with a baseline EDSS score of 4-5.5, 3% had advanced disability after two years, 5% after three years, 6% after four years, 12% after five years, and 40% after 10 years. The estimated probability of disease progression, defined as an increase in EDSS score by > or = 1.0 sustained for at least 180 days, was 5% after one year, 14% after two years, 22% after three years, 38% after five years, 57% after 10 years, and >80% after 20 years of observation. The relevance of these features to the design of the clinical trial is discussed.

Clinical Trials as Topic↗
PubMed2005

Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials.

BACKGROUND: Gadolinium enhancement is often used in randomized clinical trials to evaluate the efficacy of new drugs in multiple sclerosis (MS). Knowledge about predictors of enhancement status is important for the selection of patients for MRI monitored trials. METHODS: Data from 17 trials were available in anonymized format through the Sylvia Lawry Centre for MS Research. In an open part containing 1,328 (non primary progressive) patients, two logistic regression analyses were explored, including demographic, clinical, and MRI predictors. The authors examined the area under the curve (AUC) and the increase in positive predictive value (PPV). The final selection of models was validated in a closed part of 848 comparable patients. RESULTS: Age at onset, disease duration, and disease course (CIS/RR/SP) were important predictors from the multivariate models. Further, a multivariate model including T2 burden of disease was more predictive than one with only clinical predictors (AUC 0.719 vs 0.625, p < 0.001). For the model with T2 burden of disease, the PPV was 66.8%, compared to 58.5% for the model without (a priori chance 46.4%). These findings were unequivocally confirmed in the closed part of the database. CONCLUSION: Gadolinium status can be predicted by a set of baseline variables, certainly when T2 burden of disease is included. These findings may benefit the design and statistical power of future randomized clinical trials.

Adult↗
PubMed2005

[MS registry in Germany--design and first results of the pilot phase].

In the summer of 2001, a nationwide epidemiological multiple sclerosis (MS) register was initiated under the auspices of the German MS Society (DMSG). This project aimed at collecting epidemiological data on the number of patients with MS, course of the disease, and their social situation in Germany. During the 2-year pilot phase, five MS centers with various regional differences and treatment methods participated, leading to a representative selection of patients. In December 2003, standardised data sets of 3,458 MS patients were available for evaluation. After examining the quality of the data, 3,223 sets remained for further analysis. The demographics were similar to those obtained from other epidemiological studies: 72% of the patients were female, mean age was 42.9+/-11.2 years, mean disease duration 12.6+/-8.7 years, and 64% suffered from the relapsing-remitting form of the disease. The median EDSS was 3.0, and 69% of patients had an EDSS </=4.0. The great effect of this disorder was underscored by the fact that one third of the patients had prematurely retired due to MS. After successful completion of the pilot phase, the MS register will provide reliable data and thus serve as an important tool to improve the overall situation of MS patients in Germany.

Adult↗
PubMed2005

A randomized, double-blind, placebo-controlled study of oral hydrolytic enzymes in relapsing multiple sclerosis.

Oral administration of hydrolytic enzymes (HE), such as bromelain, trypsin and rutosid, may have beneficial effects on the clinical course of neurological symptoms related to multiple sclerosis (MS). This is supported by a complete protection by HE from experimental allergic encephalomyelitis, an animal model related to MS. Three hundred and one patients with relapsing MS were enrolled in a double-blind, placebo-controlled trial. No treatment effect between the placebo and the HE groups was found either for clinical or MRI parameters.

Administration, Oral↗