Trends in administrative prevalence of multiple sclerosis and utilization patterns of disease modifying drugs in Germany.

BACKGROUND: This study aimed to describe recent developments of multiple sclerosis (MS) prevalence in Germany and to assess utilization patterns of disease-modifying drugs (DMDs). METHODS: We used nationwide outpatient claims data of the statutory health insurance (SHI) from the years 2012 to 2019, covering 87% of the total German population. In annual cross-sectional analyses, MS prevalence was measured as the percentage of the SHI population affected by MS. Annual agent-specific prescription prevalence of DMDs was calculated by the number of patients receiving the DMD per 1.000 MS patients. RESULTS: From 2012 to 2019, the prevalence of MS increased gradually from 0.27% to 0.34%. The overall DMD prescription prevalence in MS patients rose from 436 per 1,000 MS patients (2012) to 483 (2019). From 2012 to 2019 the prescription prevalence of interferon-beta 1a and interferon-beta 1b decreased sharply from 180.2 to 70.8 (-61%) and 80.2 to 34.1 (-57%), respectively. In contrast, the prescription prevalence of teriflunomide (2012: 8.5; 2019: 54.5) and fingolimod (2012: 28.5; 2019: 63.8) exhibited a pronounced increase by factors of 5.4 and 2.2, respectively. CONCLUSION: MS prevalence in Germany steadily increased in recent years. MS treatment patterns changed markedly indicating a shifting predominance of DMD injectable drugs to oral medications.

Comparing stroke prevention therapy of direct oral anticoagulants and vitamin K antagonists in patients with atrial fibrillation: a nationwide retrospective observational study.

BACKGROUND: Direct oral anticoagulants (DOACs) are not only increasingly being used for the initial stroke prevention therapy but progressively also substitute vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (AF). DOACs have been compared regarding therapeutic efficacy and adverse outcomes to warfarin in several pivotal studies and showed non-inferiority in terms of stroke prevention and superiority in terms of bleeding complications. However, comprehensive comparative studies are lacking for phenprocoumon, a VKA prescribed frequently outside the USA and the UK and accounting for 99% of all VKA prescriptions in Germany. Patients treated with phenprocoumon seem to meet more often international normalized ratio values in the therapeutic range, which may have implications concerning their efficacy and safety. This study aims at comparing the risk of stroke and bleeding in phenprocoumon- and DOAC-treated patients with AF in an adequately powered observational study population. METHODS: Retrospective analysis of stroke and bleeding incidence of 837,430 patients (1.27 million patient years) treated with DOAC or phenprocoumon for stroke prevention in German ambulatory care between 2010 and 2017. Relative risks of stroke and bleeding were estimated by calculating cox regression-derived hazard ratios (HR) and 95% confidence intervals (CI) of propensity score-matched cohorts. RESULTS: Patients treated with DOAC had an overall higher risk for stroke (HR 1.32; CI 1.29-1.35) and a lower risk for bleeding (0.89; 0.88-0.90) compared to phenprocoumon. When analyzed separately, the risk for stroke was higher for dabigatran (1.93; 1.82-2.03), apixaban (1.52; 1.46-1.58), and rivaroxaban (1.13; 1.10-1.17) but not for edoxaban (0.88; 0.74-1.05). The risk for bleeding was lower for dabigatran (0.85; 0.83-0.88), apixaban (0.71; 0.70-0.73), and edoxaban (0.29; 0.17-0.51) but not for rivaroxaban (1.03; 1.01-1.04). CONCLUSIONS: This study provides a comprehensive view of the stroke and bleeding risks associated with phenprocoumon and DOAC use in Germany. Phenprocoumon may be preferable to DOAC treatment for the prevention of strokes in AF in a real-world population cared for in ambulatory care.

Patterns of the initiation of disease-modifying antirheumatic drugs in incident rheumatoid arthritis: a German perspective based on nationwide ambulatory drug prescription data.

This study aimed at providing a current and nearly complete picture of the patterns of the initiation of disease-modifying antirheumatic drugs (DMARDs) in patients with newly diagnosed RA. Based on ambulatory drug prescription data and physician billing claims data covering 87% of the German population, we assembled a cohort of incident RA patients aged 15-79 years (n = 54,896) and assessed the prescription frequency of total DMARDs, conventional synthetic (csDMARDs) and biologic DMARDs (bDMARDs) within the first year of disease. Using multiple logistic regression, we estimated the chance of early DMARD receipt based on age, sex, serotype and specialty of prescribing physician while controlling for region of residence. In total, 44% of incident RA patients received a DMARD prescription within the first year of disease. In multiple regression, younger patients (< 35 years) had 1.7-fold higher chances of receiving a csDMARD than patients aged ≥ 65 years [odds ratio (OR): 1.65 with 95% confidence interval (CI) 1.51-1.80] and almost tenfold higher chances to receive a bDMARD [OR (95% CI) 9.5 (8.0-11.3)]. Seropositivity and a visit to a rheumatologist were positively associated with DMARD initiation [OR (95% CI) 2.8 (2.6-2.9) and 5.9 (5.6-6.2) for csDMARDs, respectively]. Based on data covering 87% of the German population, the present study revealed that less than half of incident RA patients receive DMARDs within the first year of disease and that marked differences exist according to age. The study highlights the importance of involving a rheumatologist early in the management of RA.

Streptococcus suis cps7: an emerging virulent sequence type (ST29) shows a distinct, IgM-determined pattern of bacterial survival in blood of piglets during the early adaptive immune response after weaning.

Streptococcus (S.) suis is an important porcine pathogen causing meningitis, arthritis and septicemia. As cps7 emerged recently in Germany in association with severe herd problems, the objective of this study was to characterize the geno- and phenotype of invasive cps7 strains. Twenty cps7 strains were isolated from diseased pigs from different farms with S. suis herd problems due to meningitis and other pathologies. Eighteen of the cps7 isolates belonged to sequence type (ST) 29. Most of these cps7 strains secreted a short MRP variant in agreement with a premature stop codon. Expression of Ide Ssuis , an IgM specific protease, was variable in four further investigated cps7 ST29 isolates. Bactericidal assays revealed very high survival factors of these four cps7 ST29 strains in the blood of weaning piglets. In growing piglets, the increase of specific IgM led to efficient killing of cps7 ST29 as shown by addition of the IgM protease Ide Ssuis . Finally, virulence of a cps7 ST29 strain was confirmed in experimental infection of weaning piglets leading to meningitis and arthritis. In conclusion, this study characterizes cps7 ST29 as a distinct S. suis pathotype showing high survival factors in porcine blood after weaning, but IgM-mediated killing in the blood of older growing piglets. This underlines the relevance of IgM as an important host defense mechanism against S. suis.

Unusual Outbreak of Fatal Clostridiosis in a Group of Captive Brown Pelicans ( Pelecanus occidentalis).

Fatal clostridial infections and clostridial toxicoses are common in birds. Most fatalities are associated with toxin production and progress rapidly, often within 24 hours of infection. We describe an unusual and protracted course of disease in 6 captive brown pelicans ( Pelecanus occidentalis), which was believed to result from toxicosis by toxovar A produced by a mixed infection with Clostridium sordellii and Clostridium perfringens. Although the first death in the group occurred 3 days after signs of illness were documented, the remaining birds died over a 38-day period despite aggressive antibiotic and supportive therapy. Although the birds presented with classic signs of botulism, Clostridium botulinum was not identified in any tissues or environmental samples. Postmortem findings in all pelicans included extensive subacute myonecrosis, enteritis, and nonsuppurative hepatitis. Alpha-toxins and sordellilysin genes from C perfringens and C sordelli isolates, respectively, were detected via polymerase chain reaction. The source of the pathogenic bacteria was sediment within a water basin inside the affected birds' enclosure.

P2X(7) receptor-mRNA and -protein in the mouse retina; changes during retinal degeneration in BALBCrds mice.

A combined real-time PCR/immunohistochemistry study was carried out to investigate whether P2X(7) receptors, known to induce apoptosis and necrosis, may be causally related to the process of retinal degeneration in BALBCrds mice. In the retinae of BALBCrds mice, P2X(7) receptor-mRNA was the highest at an age of 20-40 days, and declined afterwards. At the same time, the P2X(7) receptor-message was constantly low in the retina of control BALBC mice until postnatal day 100. The receptor-mRNA in total brain tissue of both strains of mice was comparable with that of BALBCrds retinae. Double immunofluorescence in combination with laser scanning microscopy was used to study the distribution of P2X(7) receptor-immunoreactivity (IR) on neurons and different glial cell types of the retina. An exclusively neuronal localization of P2X(7)-IR in the ganglion cell layer was found by using either anti-neuronal nuclei or microtubule associated protein-2 as neuronal markers. There was a slight age-dependent decrease in the abundance of neuronal P2X(7)-IR both in BALBCrds or BALBC mice. P2X(7)-IR failed to co-localize with any of the non-neuronal markers used to stain microglial or Müller glial cells. No P2X(7) receptor-IR was found in the retinal ganglion cell layer of P2X(7)(-/-) animals, when compared with the control littermates. Hence, we suggest that, in BALBCrds mice, an early up-regulation of neuronal P2X(7) receptors may cause injury of retinal neurons and thereby functionally contribute to the retinal damage.