Population-Based Analysis of 6534 Seizure Emergency Cases from Emergency Medical Services Data.

INTRODUCTION: Seizures are common reasons to call an ambulance, and this study aims to analyze the burden of seizures in the prehospital setting based on incidence, hospital admission rate, and costs. METHODS: This was a population-based, cross-sectional analysis of prehospital emergency medical services (EMS) data on suspected seizure cases from the federal state of Hesse, Germany, in 2019. RESULTS: A total of 6534 suspected seizure cases were identified, of which most were those with a known seizure disorder. Incidence rate for epilepsy-related seizures (ES; pediatric epilepsy, first seizure [1stS], seizure with known seizure disorder [SEPI]) was 205.7 per 100,000 inhabitants and incidence rate for pediatric febrile seizures (PFS) was 36.7 per 100,000 inhabitants, corresponding to 171,275 ES and 28,500 PFS (99.3% < 18 years) cases in Germany. A prehospital EMS physician was involved in 40.0% (SEPI) to 54.4% (PFS) of suspected seizure cases. Depending on the type of seizure, 70.7% (SEPI) to 80.9% (1stS) were admitted to hospital for inpatient stay of ≥ 24 h. An additional 4% (PFS) to 16% (1stS) of cases needed immediate intervention at hospital. Prehospital EMS staff needed 8:24 min:s (SD 7:24; n = 5004) after the emergency call to arrive at the scene of the ES and 10:58 min:s (SD 27:39; n = 321) for PFS. ES and PFS cases caused estimated costs of 48.5 and 8.1 million euros for Germany in 2019, respectively, not including hospital treatment-related costs. CONCLUSION: This study identified a high number of suspected seizure-related emergency cases and proportion of patients admitted to hospitals, as well as high associated costs in Germany.

Epidemiology and treatment of myasthenia gravis: a retrospective study using a large insurance claims dataset in Germany.

Myasthenia gravis (MG) is a rare, chronic autoimmune disease with symptoms of fluctuating muscular weakness and fatigability. The aim of this retrospective cohort study was to estimate the prevalence and incidence of MG in Germany, and to understand the burden of disease and treatment patterns, based on anonymized German claims data. Two patient samples were identified: (1) incident MG patients with newly onset disease between 2015 and 2019, and (2) prevalent MG patients in 2019. In total, 775 incident MG patients with a mean age of 66.9 years; and 1,247 prevalent MG patients with a mean age of 68.6 years were included. The prevalence for Germany was estimated to be 39.3/100,000 on 31/12/2019; the incidence in 2019 was 4.6 cases/100,000 persons. The 12-month mortality was 5.7. For 31.5% of the incident patients, no MG treatment was observed in the first year after the index date. Of all incident patients, 29.9% experienced an exacerbation, and 6.7% a myasthenic crisis during the observation. Our study indicates that a substantial proportion of MG patients remains untreated. Many MG patients still experience exacerbations / MG crises. MG seems to be associated with an excess mortality in comparison to the general non-MG population.

Essential steps in the ppGpp-dependent regulation of bacterial ribosomal RNA promoters can be explained by substrate competition.

Transcription of stable RNA genes is known to be dramatically reduced in the presence of guanosine tetraphosphate (ppGpp), the mediator of the stringent response. Using in vitro transcription systems with ribosomal RNA P1 promoters, we have analyzed which step of the initiation cycle is inhibited by the effector ppGpp. We show that formation of the ternary transcription initiation complex consisting of RNA polymerase holoenzyme, the promoter DNA, and the first initiating nucleotide triphosphate is the major step at which ppGpp exerts its regulation. Neither primary binding of RNA polymerase to the promoter nor isomerization to the open binary complexes or the subsequent promoter clearance steps contributes notably to the observed inhibition. The effect of ppGpp-dependent inhibition in the formation of the ternary transcription initiation complex could be mimicked by nucleotide derivatives known to bind to the RNA polymerase active center. Using these model compounds, almost identical inhibition characteristics were observed as seen with ppGpp. The results support the previously published model, which suggests that ppGpp-dependent inhibition is based on competition between the inhibitor molecules and NTP substrates for access to the active center of RNA polymerase.