Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis

Rationale: While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges. Objectives: Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders. Methods: The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated. Results: Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120-270 ng/ml and 180-380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders. Conclusions: High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers

Sprachwelten: Vier Vorträge

Der vorliegende Band präsentiert die Druckfassungen der Vorträge zum Thema ‚Sprachwelten‘, die anlässlich der Erlanger Universitätstage vom 07. März bis zum 04. April 2017 in Amberg und vom 26. Oktober bis zum 30. November 2017 in Ansbach gehalten wurden. Die sechs Erlanger Wissenschaftlerinnen und Wissenschaftler, Professor Dr. Andrea Büttner, Prof. Dr. Jessica Freiherr, Professor Dr. Andreas Grüner, Prof. Dr. Thomas Herbst, Prof. Dr. Norbert Oettinger und Prof. Dr. André Reis – aus den fünf Disziplinen Lebensmittelchemie, Archäologie, Englische Sprachwissenschaft, Indogermanistik und Humangenetik – verstanden es auf ebenso anregende wie informative Weise, das Thema ‚Sprachwelten‘ aus ihrer jeweiligen Fachperspektive heraus zu interpretieren

Initial Risk Assessment in Patients with Alveolar Echinococcosis—Results from a Retrospective Cohort Study

Background: Alveolar echinococcosis (AE) is a potentially lethal parasitosis with a broad spectrum of disease dynamics in affected patients. To guide clinical management, we assessed initial prognostic factors for both progressive and controlled AE based on initial staging. Methods: A retrospective cohort study was conducted, examining 279 patients assigned to different clinical groups: cured, stable with and without the need for benzimidazole treatment, and progressive disease. Univariate analysis compared demographic and clinical variables. Significant variables were subsequently entered into two separate logistic regression models for progressive and controlled disease. Results: Based on the multivariate analysis, a large AE lesion (OR = 1.02 per millimetre in size; 95%CI 1.004–1.029), PNM staging (OR = 2.86; 95%CI 1.384–5.911) and especially the involvement of neighbouring organs (OR = 3.70; 95%CI 1.173–11.653) remained significant risk factors for progressive disease. A negative Em2+ IgG (OR = 0.25; 95%CI 0.072–0.835) and a small AE lesion (OR = 0.97; 95%CI 0.949–0.996) were significant protective factors. Conclusions: Patients with large lesions and advanced stages should be monitored closely and most likely require long-term treatment with benzimidazoles if curative resection is not feasible. Patients with small lesions and negative Em2+ IgG seem able to control the disease to a certain extent and a less strict treatment regimen might suffice

Prediction of COVID-19 deterioration in high-risk patients at diagnosis: an early warning score for advanced COVID-19 developed by machine learning

Purpose!#!While more advanced COVID-19 necessitates medical interventions and hospitalization, patients with mild COVID-19 do not require this. Identifying patients at risk of progressing to advanced COVID-19 might guide treatment decisions, particularly for better prioritizing patients in need for hospitalization.!##!Methods!#!We developed a machine learning-based predictor for deriving a clinical score identifying patients with asymptomatic/mild COVID-19 at risk of progressing to advanced COVID-19. Clinical data from SARS-CoV-2 positive patients from the multicenter Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) were used for discovery (2020-03-16 to 2020-07-14) and validation (data from 2020-07-15 to 2021-02-16).!##!Results!#!The LEOSS dataset contains 473 baseline patient parameters measured at the first patient contact. After training the predictor model on a training dataset comprising 1233 patients, 20 of the 473 parameters were selected for the predictor model. From the predictor model, we delineated a composite predictive score (SACOV-19, Score for the prediction of an Advanced stage of COVID-19) with eleven variables. In the validation cohort (n = 2264 patients), we observed good prediction performance with an area under the curve (AUC) of 0.73 ± 0.01. Besides temperature, age, body mass index and smoking habit, variables indicating pulmonary involvement (respiration rate, oxygen saturation, dyspnea), inflammation (CRP, LDH, lymphocyte counts), and acute kidney injury at diagnosis were identified. For better interpretability, the predictor was translated into a web interface.!##!Conclusion!#!We present a machine learning-based predictor model and a clinical score for identifying patients at risk of developing advanced COVID-19

HORIZON 2020 EuPRAXIA Design Study

The Horizon 2020 Project EuPRAXIA (European Plasma Research Accelerator with eXcellence In Applications) aims at producing a design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020

Status of the Horizon 2020 EuPRAXIA Conceptual Design Study

The Horizon 2020 Project EuPRAXIA (European Plasma Research Accelerator with eXcellence In Applications) is producing a conceptual design report for a highly compact and cost-effective European facility with multi-GeV electron beams accelerated using plasmas. EuPRAXIA will be set up as a distributed Open Innovation platform with two construction sites, one with a focus on beam-driven plasma acceleration (PWFA) and another site with a focus on laser-driven plasma acceleration (LWFA). User areas at both sites will provide access to FEL pilot experiments, positron generation and acceleration, compact radiation sources, and test beams for HEP detector development. Support centres in four different countries will complement the pan-European implementation of this infrastructure