Development and validation of a quantification method for direct oral anticoagulants from capillary blood using volumetric absorptive microsampling and online SPE-LC-MS.

The number of prescriptions for new direct oral anticoagulants (DOACs) apixaban, edoxaban, rivaroxaban and dabigatran has increased exponentially in recent years, increasingly replacing the old gold standard, vitamin-K-antagonists. Due to their wide therapeutic range, therapeutic drug monitoring (TDM) is not required, although it has been proven that this could significantly reduce side effects. In order to develop a cost-efficient and simple method for the simultaneous detection of the DOACs and phenprocoumon, a new technology for sample preparation from capillary blood in the ambulant sector named VAMS® was integrated and an LC-MS detector with on-line solid phase extraction (SPE) applying a Turboflow HTLC Cyclone 1.

Slow global motions in biosolids studied by the deuteron stimulated echo NMR experiment.

Recent 15N R1ρ-relaxation studies have shown that proteins in the solid state undergo slow, low amplitude global motion in the sub-millisecond time range. This range is at the edge of the time window for R1ρ experiments and, therefore, the motional parameters obtained by this method are not precise or reliable. In this paper, we present a 2H stimulated echo study of this type of molecular dynamics.

Prognostic significance of inferior vena cava volume defined by initial polytrauma CT-imaging: single-center experience of a level-1 trauma center.

Background: The significance of computed tomography (CT)-based volume measurement of the inferior vena cava (IVC) in the treatment and prognosis of trauma patients is not yet fully understood. The conflicting results that have been reported may be attributable to differences in injury severity and the use of different measurement methods, including IVC index and volumetry. The purpose of this study was to determine the relationship between IVC volume and red blood cell (RBC) transfusion and mortality in intubated trauma patients who were stable enough for initial CT imaging.

Development and Validation of a High-Performance Liquid Chromatography With Ultraviolet Detection Method to Facilitate Therapeutic Monitoring of Teicoplanin Using Dried Blood Spots.

Background: In neonatal and pediatric intensive care units, Gram -positive infections are a significant cause of morbidity and mortality. The increase in infections caused by methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococci have led to the increased use of glycopeptides, which treat invasive infections caused by Gram -positive organisms, particularly those resistant to beta-lactam antibiotics. Teicoplanin has bacteriostatic activity against Gram -positive bacteria, but its pharmacokinetics in children is highly variable, with most children failing to reach target levels at the recommended dose.

Rationalising Optimal Dosing of Phytotherapeutics For Use In Children: Current Status - Potential Solutions - Actions Needed.

"Children are not small adults with respect to the treatment with medicinal products." This statement of the WHO was the basis for the initiative of the European Commission for the establishment of a paediatric regulation in 2007 to improve the health of children by facilitating the development of medicines for children and adolescents. Seventeen years later, in the field of herbal medicinal products, results are still sobering.

Proof of concept of physiologically based pharmacokinetic modelling in paediatric acute lymphoblastic leukaemia.

Physiologically based pharmacokinetic (PBPK) modelling is an alternative modelling technique that is increasingly used in pharmacokinetics. Due to its nature, it can be complementarily employed to population pharmacokinetics, especially when it comes to small population size. Here, we report the proof of concept of its application to accurately describe the pharmacokinetics of a recombinant L-asparaginase in paediatric patients with acute lymphoblastic leukaemia.

Coronary artery calcification detected by initial polytrauma CT in severely injured patients: retrospective single-center cohort study.

Objectives: Coronary artery calcifications detected by computed tomography (CT) provide prognostic relevance for vascular disorders and coronary heart disease, whereas their prognostic relevance in severely injured trauma patients remains unclear.

Material And Methods: All consecutive trauma patients requiring emergency tracheal intubation before initial CT at a level-1 trauma center and admission to the intensive care unit (ICU) over a 12-year period (2008-2019) were reanalyzed. The Weston score, a semiquantitative method to quantify coronary calcifications, was evaluated as a prognostic variable based upon whole-body trauma CT analysis.

[Use of strongly acting sustained-release opioids in pediatrics : Pitfalls and solutions for morphine and hydromorphone].

Background: In pediatrics, adequate treatment with potent opioids requires the administration of sustained-release preparations for many patients; however, the dosing and administration of sustained-release morphine and hydromorphone preparations via gastrointestinal tubes confronts providers with a major hurdle, especially as the company Mundipharma GmbH has discontinued the production and distribution of the preparation MST retard granules in 2019, which has been proven for these purposes in pediatrics. The aim of this study was to establish a production technique for available sustained-release opioid preparations, which are particularly suitable for use in the low-dose range required in pediatrics and which can also be administered via gastrointestinal tubes.

Method: Low-dose preparations were produced by opening of morphine and hydromorphone capsules and weighing of the sustained-release pellets.

Development and validation of a bioanalytical method for the quantification of methotrexate from serum and capillary blood using volumetric absorptive microsampling (VAMS) and on-line solid phase extraction (SPE) LC-MS.

High-dose methotrexate is part of the polychemotherapy protocols for the treatment of Acute lymphoblastic leukaemia (ALL) with therapeutic drug monitoring (TDM) to adjust leucovorin rescue. An immunoassay is commonly used to analyse serum samples collected via venous blood sampling. However, immunoassays cannot distinguish between the parent drug and its metabolites.

Effects of the "ICU Support" team meeting concept on patient-centered and staff-centered outcomes: study protocol for a randomized controlled multicenter study.

Background: Providing optimal care for critically ill patients is an extremely important but also highly demanding task, both emotionally and physically. The "ICU Support" team meeting concept aims to support intensive care unit (ICU) teams by promoting interprofessional communication, peer support, and patient safety by providing a structure for daily team meetings. This protocol describes a study to explore the effectiveness of "ICU Support" for patient- and staff-centered outcomes.

Voriconazole plasma concentrations and dosing in paediatric patients below 24 months of age.

Voriconazole (VCZ) is an important first-line option for management of invasive fungal diseases and approved in paediatric patients ≥24 months at distinct dosing schedules that consider different developmental stages. Information on dosing and exposures in children <24 months of age is scarce. Here we report our experience in children <24 months who received VCZ due to the lack of alternative treatment options.

How important are concurrent vehicle control groups in (sub)chronic non-human primate toxicity studies conducted in pharmaceutical development? An opportunity to reduce animal numbers.

Safety assessment of human pharmaceuticals demands extensive animal experiments before a compound can be tested in patients or released on the market. Such experiments typically include concurrent vehicle control groups. Reconsidering the need for concurrent controls could support the strive to reduce the use of animals for scientific purposes.

Rocking motion in solid proteins studied by the N proton-decoupled relaxometry.

Recently it has been revealed that proteins in solid samples undergo slow overall rocking. The parameters of this motion depend on intermolecular interactions. Therefore, the characterization of the rocking motion enables one to investigate protein-protein interactions.

Developing a Method for Quantifying Meropenem in Children-Volumetric Adsorptive Microsampling Versus Plasma Sampling.

Background: Meropenem is a carbapenem antibiotic often used in pediatric intensive care units due to its broad spectrum of activity. Therapeutic drug monitoring (TDM) is a useful tool to increase the effectiveness of meropenem by adjusting the dose based on plasma levels; however, the relatively large sample volume required for TDM can limit its use in children. Therefore, this study aimed to determine meropenem concentrations and consequently perform TDM effectively using the smallest possible sample volume.

Systematic Evaluation of Pharmacokinetic Models for Model-Informed Precision Dosing of Meropenem in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

The altered pharmacokinetics of renally cleared drugs such as meropenem in critically ill patients receiving continuous renal replacement therapy (CRRT) might impact target attainment. Model-informed precision dosing (MIPD) is applied to individualize meropenem dosing. However, most population pharmacokinetic (PopPK) models developed to date have not yet been evaluated for MIPD.

Validation of a liquid chromatography-tandem mass spectrometry method for simultaneous quantification of N,N-dimethylacetamide and N-monomethylacetamide in pediatric plasma.

N,N-dimethylacetamide is an excipient used in intravenous busulfan formulations, a drug used in hematopoietic stem cell transplantation conditioning. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry method for simultaneous quantification of N,N-dimethylacetamide, and its metabolite N-monomethylacetamide in plasma from children receiving busulfan. A 4 μl aliquot of patient plasma was extracted using 196 μl 50% methanol solution and quantified against calibrators prepared in the extraction solvent given negligible matrix effects across three concentrations.

Decision support software-guided medication reviews in elderly patients with polypharmacy: a prospective analysis of routine data from community pharmacies (OPtiMed study protocol).

Background: Pharmacist-led medication reviews are considered a valuable measure to address risks of polypharmacy. The software Medinspector is used in community pharmacies to assist the performance of this complex service by structuring the medication review process and supporting pharmacists in their decision-making with targeted clinical knowledge. Key feature is a computerized risk assessment of both the initial and adjusted medication regimen of a patient in multiple domains, thus aiming to support the identification and solving of drug-related problems.

Teaching Practical Skills in Anesthesia, Intensive Care, Emergency and Pain Medicine-What Is Really Relevant for Medical Students? Results of a German National Survey of Nearly 3000 Anesthesiologists.

As a part of a major reform of the medical curriculum in Germany, the national catalogue of learning objectives is being revised with the focus shifting from theory-based learning to teaching practical skills. Therefore, we conducted an online survey to answer the question, which practical skills are essential in anesthesia. Participants were asked to rate the relevance of several skills, that medical students should be able to perform at the time of graduation.

Safety management in times of crisis: Lessons learned from a nationwide status-analysis on German intensive care units during the COVID-19 pandemic.

Background: The status of Safety Management is highly relevant to evaluate an organization's ability to deal with unexpected events or errors, especially in times of crisis. However, it remains unclear to what extent Safety Management was developed and sufficiently implemented within the healthcare system during the COVID-19 pandemic. Providing insights of potential for improvement is expected to be directional for ongoing Safety Management efforts, in times of crisis and beyond.

Development and validation of a bioanalytical method for the quantification of axitinib from plasma and capillary blood using volumetric absorptive microsampling (VAMS) and on-line solid phase extraction (SPE) LC-MS.

For therapeutic drug monitoring (TDM) of axitinib, the new volumetric absorption microsampling technology (VAMS™) was applied to obtain capillary blood samples in an ambulatory setting and the results were compared to plasma samples as the gold standard. On-line solid phase extraction (SPE) applying a Turboflow HTLC Cyclone™ 1.0 × 500 mm column was used to reduce costs and working time.

[The cross-sectional field "pain medicine" in medical studies at the University of Leipzig-What has been achieved? : An analysis of self-estimation of students before, during and 5 years after establishment of the cross-sectional field].

Background: The field of pain medicine was established as an obligatory subject area of medical schools in Germany in 2016. No prior study has evaluated the effects of this curricular change on students' competences in the field of pain medicine.

Objective: The aim of this study was to find out to what extent the introduction of the additional subject "pain medicine" positively influenced the students' acquisition of competences measured via a self-assessment.