Health care situation of patients with relapsing-remitting multiple sclerosis receiving immunomodulatory therapy: a retrospective survey of more than 9000 German patients with MS.

BACKGROUND AND PURPOSE: First-line immunomodulatory treatment with interferon-beta or glatiramer acetate is accepted as effective basic therapy in patients with relapsing-remitting multiple sclerosis (RRMS). However, a considerable portion of patients does not benefit from treatment. METHOD: To test basic immunomodulatory treatment under real-life conditions, we retrospectively analyzed clinical and subclinical disease activity within the last 12 months in a cohort of 9916 patients with RRMS, of which 7896 patients were receiving immunomodulatory treatment. In addition, factors associated with treating physicians' consideration of a switch of current treatment were assessed. RESULTS: The majority of treated patients (approximately 66%) experienced no relapse during the last 12 months. However, in line with common clinical study findings, about one-third (approximately 34%) of patients had relapses. When MRI data were taken into account, approximately one-quarter (24%) of patients would qualify for therapy escalation to monoclonal antibody natalizumab. Relapse rate in the preceding year (the year directly prior to the start of retrospective data collection) was strongly associated with considering a switch of current treatment. In addition, therapy switch was more often considered in younger patients. The relationship between MRI findings in the absence of clinical symptoms and consideration of a treatment switch was not as clear. CONCLUSIONS: This analysis confirms that disease progression occurs in a considerable proportion of patients with RRMS. These patients should be considered for therapy escalation.

Quality of life in 1000 patients with early relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: To examine the quality of life (QoL) in a large cohort of untreated patients with relapsing-remitting multiple sclerosis (RRMS) and to investigate the impact of intramuscular (IM) interferon beta-1a (IFNbeta-1a) treatment. METHODS: Prospective, observational, open-label, multicentre study conducted in Germany. Untreated patients with RRMS who initiated treatment with IM IFNbeta-1a were included and followed for 12 months. QoL was measured using the EQ-5D questionnaire. Clinical response was assessed by relapse rate and disability (Expanded Disability Status Scale; EDSS). RESULTS: A total of 1157 patients were included [mean age 37.6 years, median disease duration 13 months, mean relapse rate 1.7 (95%CI: 1.58-1.73), median EDSS score 2.0]. Relapse rate was reduced to 0.6 at 12 months (95%CI: 0.51-0.69, P < 0.0001). EDSS did not change significantly. At baseline, QoL was considerably lower in MS patients compared with the general German population, but was improved after treatment initiation [utilities of EQ-5D: 0.77 (95%CI: 0.75-0.78) vs. 0.75 (95%CI: 0.74-0.76) at baseline, 95%CI for difference: 0.01-0.03, P = 0.0046]. Higher disease activity and inability to work were negative predictors of QoL. 14.7% of patients were incapable of working for MS-related reasons. CONCLUSIONS: Quality of life is considerably impaired in early stages of MS. Treatment initiation with IM IFNbeta attenuates MS disease activity and improves QoL. Inability to work early during the disease is a major challenge for the social security systems.

Molecular characterization and module composition of P22-related Salmonella phage genomes.

Genomes of newly isolated Salmonella phages were analysed by comparison of their EcoRI restriction patterns and by hybridization. Characteristic hybridization probes from reference phages P22, ES18 and E. coli phage lambda were chosen. Four probes selected from the lysis region examined the dispersal of the lambdoid lysis genes. Other probes characterized were the replication genes and part of the structural genes. The complex immunity region was investigated by means of hybridization as well as biological tests. The results showed the relationship of the isolated phages to the P22 branch of the lambdoid phages and revealed their modular genome organization consisting of different proportions of P22-related sequences. DNA restriction patterns of phages released from Salmonella strains sampled in limited geographical areas were significantly less heterogeneous than those of phages released from the worldwide sampled SARA collection. The use of prophage restriction patterns as a tool for the typing of Salmonellae to support the epidemiologic classification of pathogenic strains is discussed.

Transduction of multiple drug resistance of Salmonella enterica serovar typhimurium DT104.

Epidemic strain Salmonella typhimurium DT104 is characterized by various multiresistance patterns. At least some of the resistance genes are organized as integrons. Resistance genes of DT104 isolates can be efficiently transduced by P22-like phage ES18 and by phage PDT17 which is released by all DT104 isolates so far analyzed. Cotransduction tests demonstrate that the resistance genes, although not organized in a unique integron, are tightly clustered on the Salmonella chromosome. The spread of resistance genes in this strain by generalized transduction is discussed.

A comparative study on the frequency of prophages among natural isolates of Salmonella and Escherichia coli with emphasis on generalized transducers.

Several collections of natural isolates of the genus Salmonella and of the species Escherichia coli were studied for the release of viable temperate phages. The results indicated that functional prophage genomes may be a common constituent of all bacterial genomes of the investigated strains. About 99% of the Salmonella phages are capable of generalized transduction of chromosomal host markers and plasmids. The ratio of transducing E. coli phages is significantly lower.

Sequence comparison of the genes for immunity, DNA replication, and cell lysis of the P22-related Salmonella phages ES18 and L.

Complementation and hybridization experiments with the generalized transducing Salmonella phages P22, ES18 and L revealed strong similarity between the phages L and P22; the genome of ES18 shows a mosaic structure. About half of its genome, including the early genes, is similar or completely homologous to P22; the other half of the morphologically different ES18 does not show any similarity to P22 nor to E. coli phage lambda. Sequence comparison of the early genes has confirmed that the C-immunity region of ES18 is identical with that of P22, whereas the same region of phage L shows poor (repressor gene) or no similarity. The 5'-terminus of the DNA replication gene 12 of ES18, however, is homologous to the same section of gene O of phage lambda. The lysis genes of ES18 again are identical to those of P22; only gene 15 is mosaic-like and has more similarity to gene Rz of phage lambda. These results will be discussed in terms of the theory of modular genome organization.

Frequency of generalized transducing phages in natural isolates of the Salmonella typhimurium complex.

From 85 natural isolates of the Salmonella typhimurium complex, including the Salmonella reference collection A (P. Beltran, S. A. Plock, N. H. Smith, T. S. Whittam, D. C. Old, and R. K. Selander, J. Gen. Microbiol. 137:601-606, 1991), 65 strains (76.5%) released 71 different temperate phages. Forty-three (93.5%) of 46 tested phages were able to transduce the chromosomal markers his+ and trp+ and the cloning vector pBR325.