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Background: Bolus administration of adrenaline during cardiopulmonary resuscitation (CPR) results in only short-term increases in systemic and cerebral perfusion pressure (CePP) with unclear effects on cerebral oxygenation. The aim of this study was to investigate the effects of bolus compared to continuous adrenaline administration on cerebral oxygenation in a porcine CPR model. Methods: After five minutes of cardiac arrest, mechanical CPR was performed for 15 min. Adrenaline (45 μg/kg) was administered either as a bolus every five minutes or continuously over the same period via an infusion pump. Main outcome parameter was brain tissue oxygen tension (PbtO2), secondary outcome parameters included mean arterial pressure (MAP), intracranial pressure (ICP), CePP and cerebral regional oxygen saturation (rSO2) as well as arterial and cerebral venous blood gases. Results: During CPR, mean MAP (45 ± 8 mmHg vs. 38 ± 8 mmHg; p = 0.0827), mean ICP (27 ± 7 mmHg vs. 20 ± 7 mmHg; p = 0.0653) and mean CePP (18 ± 8 mmHg vs. 18 ± 8 mmHg; p = 0.9008) were similar in the bolus and the continuous adrenaline group. Also, rSO2 (both 24 ± 6 mmHg; p = 0.9903) and cerebral venous oxygen saturation (18 ± 12% versus 27.5 ± 12%; p = 0.1596) did not differ. In contrast, relative PbtO2 reached higher values in the continuous group after five minutes of CPR and remained significantly higher than in the bolus group until the end of resuscitation. Conclusion: Continuous administration of adrenaline improved brain tissue oxygen tension compared with bolus administration during prolonged CPR.

The typical approach to account for non-stationarity in the generalized extreme value distribution (GEV) is to model the temporal behavior of the GEV parameters, e.g.,with linear relationships between the parameters and e.g.,the year. When in addition, seasonality, i.e., sub-yearly patterns are of interest, this relationship needs to be more complex. A natural candidate for nonstationary analysis of precipitation extremes is the metastatistical extreme value distribution (MEVD) assuming the ordinary rainfall events being Weibull distributed. It uses all ordinary events of the underlying rainfall distribution and implicitly considers temporal nonstationary changes in the Weibull parameters by a blockwise estimation. However, the MEVD still does not make use of the sub-yearly evolution of the distribution parameters and thus discards a significant part of information. In this paper a modification of the MEVD is proposed. The temporal MEVD (TMEV) relaxes the assumption of constant coefficients of the underlying distribution. The MEVD in each block estimates the Weibull parameters using the number of wet events in that block, regardless whether an individual wet day contributes much or less to the yearly rainfall sum. The newly proposed TMEV weights the single wet days contributions during parameter estimation and is therefore able to explicitly account for seasonal differences of rainfall events. It is shown that the TMEV provides a very similar error characteristic to the simplified MEVD for the estimation of quantiles with different sample lengths. In addition, we demonstrate the ability of the TMEV to identify longterm trends and seasonal variations of extreme precipitation in Austria and discuss possible implications for general trend estimations. We also present a spatio-temporal TMEV model, which is able to reproduce known patterns of a 50-year return level map of daily rainfall in Austria, thereby lending credence to the TMEV approach.

Background: Sertraline is a selective serotonin reuptake inhibitor with specific indications in child and adolescent psychiatry. Notwithstanding its frequent use and clinical benefits, the relationship between pharmacokinetics, pharmacodynamics, efficacy, and tolerability of sertraline across indications, particularly in non-adult patients, is not fully understood. Method: This naturalistic therapeutic drug monitoring (TDM) study was conducted in a transdiagnostic sample of children and adolescents treated with sertraline (n = 78; mean age, 14.22 ± 2.39; range, 7–18 years) within the prospective multicenter “TDM-VIGIL” project. Associations between dose, serum concentration, and medication-specific therapeutic and side effects based on the Clinical Global Impression scale were examined. Tolerability was measured qualitatively with the 56-item Pediatric Adverse Event Rating Scale. Results: A strong linear positive dose–serum concentration relationship (with dose explaining 45% of the variance in concentration) and significant effects of weight and co-medication were found. Neither dose nor serum concentration were associated with side effects. An overall mild-to-moderate tolerability profile of sertraline was observed. In contrast with the transdiagnostic analysis that did not indicate an effect of concentration, when split into depression (MDD) and obsessive-compulsive disorder (OCD) diagnoses, the probability of clinical improvement significantly increased as both dose and concentration increased for OCD, but not for MDD. Conclusions: This TDM–flexible-dose study revealed a significant diagnosis-specific effect between sertraline serum concentration and clinical efficacy for pediatric OCD. While TDM already guides clinical decision-making regarding compliance, dose calibration, and drug–drug interactions, combining TDM with other methods, such as pharmacogenetics, may facilitate a personalized medicine approach in psychiatry.