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Tuberous sclerosis complex (TSC) is a rare genetic disease that is, besides cutaneous and visceral organ manifestations, typically associated with a severe, usually drug refractory epilepsy at a very early stage of the disease. Due to its direct effect on the mTOR signaling pathway dysregulated by TSC and its synergistic effects on other organ manifestations, the rapamycin derivative everolimus (EVE) is increasingly being used. The aim of this systematic review is to evaluate the efficacy, safety and tolerability of EVE in patients with TSC-associated, refractory epilepsy.
Background: Patients with epilepsy often require a specialized treatment, which may differ because of the responsibility of the federal states for healthcare policy in Germany.
Objective: State-specific differences in healthcare structures based on inpatient hospital cases of epilepsy patients between 2000 and 2020 in relation to specialized treatment offers.
Material and methods: The inpatient hospital cases of the German federal states were evaluated using the Friedman test and time series trend analysis. A state-specific inpatient undertreatment or overtreatment of inpatient hospital cases outside the registered state was analyzed by comparing residence-related and treatment site-related case numbers with a threshold of ±5%.
Results: After age adjustment, significantly more inpatient cases were found in the “new states” compared to the “old states” (p < 0.001); the highest number of cases nationwide was found in Saarland with 224.8 ± 11.5 cases per 100,000 inhabitants. The trend analysis showed an increase in cases until the end of 2016 with a trend reversal from 2017 and a further significant decrease in hospital cases in the COVID year 2020. A relative inpatient undertreatment was shown for Brandenburg, Lower Saxony, Rhineland-Palatinate, Saxony-Anhalt, Schleswig-Holstein and Thuringia. Additional, possibly compensatory, inpatient care was found for all city states (Hamburg, Bremen and Berlin) and Baden-Wuerttemberg. In federal states with a relative inpatient undertreatment and/or high inpatient hospital case numbers, there was often a lower availability of specialized epilepsy centers, specialized outpatient clinics and epilepsy outpatient clinics.
Conclusion: In Germany there are state-specific differences in the structure of care, with higher inpatient hospital care in the “new states” and Saarland. In addition, there were federal states with disproportionately higher treatment of patients not registered in this federal state. A potential influencing factor may be the availability of centers with specialized treatment for epilepsy patients.
Background: Multiple studies have focused on medical and pharmacological treatments and outcome predictors of patients with status epilepticus (SE). However, a sufficient understanding of recurrent episodes of SE is lacking. Therefore, we reviewed recurrent SE episodes to investigate their clinical characteristics and outcomes in patients with relapses.
Methods: In this retrospective, multicenter study, we reviewed recurrent SE patient data covering 2011 to 2017 from the university hospitals of Frankfurt and Marburg, Germany. Clinical characteristics and outcome variables were compared among the first and subsequent SE episodes using a standardized form for data collection.
Results: We identified 120 recurrent SE episodes in 80 patients (10.2% of all 1177 episodes). The mean age at the first SE episode was 62.2 years (median 66.5; SD 19.3; range 21–91), and 42 of these patients were male (52.5%). A mean of 262.4 days passed between the first and the second episode. Tonic–clonic seizure semiology and a cerebrovascular disease etiology were predominant in initial and recurrent episodes. After subsequent episodes, patients showed increased disability as indicated by the modified Rankin Scale (mRS), and 9 out of 80 patients died during the second episode (11.3%). Increases in refractory and super-refractory SE (RSE and SRSE, respectively) were noted during the second episode, and the occurrence of a non-refractory SE (NRSE) during the first SE episode did not necessarily provide a protective marker for subsequent non-refractory episodes. An increase in the use of intravenous-available anti-seizure medication (ASM) was observed in the treatment of SE patients. Patients were discharged from hospital with a mean of 2.8 ± 1.0 ASMs after the second SE episode and 2.1 ± 1.2 ASMs after the first episode. Levetiracetam was the most common ASM used before admission and on discharge for SE patients.
Conclusions: This retrospective, multicenter study used the mRS to demonstrate worsened outcomes of patients at consecutive SE episodes. ASM accumulations after subsequent SE episodes were registered over the study period. The study results underline the necessity for improved clinical follow-ups and outpatient care to reduce the health care burden from recurrent SE episodes.
Measurements of the production of electrons from heavy-flavour hadron decays in pp collisions at s√=13 TeV at midrapidity with the ALICE detector are presented down to a transverse momentum (pT) of 0.2 GeV/c and up to pT=35 GeV/c, which is the largest momentum range probed for inclusive electron measurements in ALICE. In p−Pb collisions, the production cross section and the nuclear modification factor of electrons from heavy-flavour hadron decays are measured in the pT range 0.5<pT<26 GeV/c at sNN−−−√=8.16 TeV. The nuclear modification factor is found to be consistent with unity within the statistical and systematic uncertainties. In both collision systems, first measurements of the yields of electrons from heavy-flavour hadron decays in different multiplicity intervals normalised to the multiplicity-integrated yield (self-normalised yield) at midrapidity are reported as a function of the self-normalised charged-particle multiplicity estimated at midrapidity. The self-normalised yields in pp and p−Pb collisions grow faster than linear with the self-normalised multiplicity. A strong pT dependence is observed in pp collisions, where the yield of high-pT electrons increases faster as a function of multiplicity than the one of low-pT electrons. The measurement in p−Pb collisions shows no pT dependence within uncertainties. The self-normalised yields in pp and p−Pb collisions are compared with measurements of other heavy-flavour, light-flavour, and strange particles, and with Monte Carlo simulations.