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Background: Pharmacogenetic testing in routine care could provide benefits for patients, doctors and statutory health insurances. Therefore, the aim of the retrospective, observational study Einfluss metabolischer Profile auf die Arzneimitteltherapiesicherheit in der Routineversorgung (EMPAR) was to analyze the relationship between pharmacogenetic profiles, the risk of adverse drug reactions, and patients' perceptions of drug therapy in 10748 adult (≥18 years) participants in Germany., Methods: A questionnaire was used to assess views and beliefs about medicines and participants individual perception of sensitivity to drug therapies. The questionnaire consisted of the Beliefs about Medicines Questionnaire (BMQ)-General scales (Overuse, Harm, Benefit), the Perceived Sensitivity to Medicines (PSM), Natural Remedy, and Gene Testing scales. The influence of gender, age, study collective, genotype and phenotype of relevant pharmacogenes on participant's perception were evaluated., Results: Overuse, PSM and Benefit scores were significantly higher among patients of the collective International Classification of Diseases and Health Related Disorders (ICD)-10 Y57.9! diagnosis, which indicates complications related to drugs, compared to the anticoagulant/antiplatelet and cholesterol-lowering drug collective. Age and gender also played a significant role in patients' perceptions, with younger patients and female participants more likely to believe in medication overuse according to the Overuse scale score compared to older and male participants. Female participants compared to male participants and the old age group compared to the young and/or middle-age subgroup, scored higher in PSM and/or Harm scales, respectively. Only a tendency of increased Harm, Overuse and PSM scores was observed in the participant group with five or more relevant actionable variants compared to subgroups with 0 up to 4 variants., Conclusions: In conclusion, patients' beliefs about medicines and their drug sensitivity perceptions are influenced by various factors including age, gender, previous complications with medicines, and with some tendency also pharmacogenetic profiles. The higher association with more negative views related to treatment indicates that there is a need to target the underlying issues in affected patient groups in order to improve compliance to treatment and outcomes in routine care. Trial registration: EMPAR was registered in the German Clinical Trials Register (DRKS) on 06 July 2018 (DRKS00013909)., Competing Interests: The authors declare no conflict of commercial or financial interests., (Copyright: © 2024 Atemnkeng Ntam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The impact of genetic variability of pharmacogenes as a possible risk factor for adverse drug reactions is elucidated in the EMPAR (Einfluss metabolischer Profile auf die Arzneimitteltherapiesicherheit in der Routineversorgung/English: influence of metabolic profiles on the safety of drug therapy in routine care) study. EMPAR evaluates possible associations of pharmacogenetically predicted metabolic profiles relevant for the metabolism of frequently prescribed cardiovascular drugs. Based on a German study population of 10,748 participants providing access to healthcare claims data and DNA samples for pharmacogenetic assessment, first analyses were performed and evaluated. The aim of this first evaluation was the characterization of the study population with regard to general parameters such as age, gender, comorbidity, and polypharmacy at baseline (baseline year) as well as important combinations of cardiovascular drugs with relevant genetic variants and predicted metabolic phenotypes. The study was registered in the German Clinical Trials Register (DRKS) on July 6, 2018 (DRKS00013909)., (© 2022. The Author(s).)

Introduction: Pre-emptive testing of pharmacogenetically relevant single-nucleotide polymorphisms can be an effective tool in the prevention of adverse drug reactions and therapy resistance. However, most of the tests are not used as standard in routine care in Germany because of lacking evidence for the clinical and economical benefit and their impact on the usage of healthcare services. We address this issue by investigating the influence of pharmacogenetic profiles on the use of healthcare services over an extended period of several years using routine care data from a statutory health insurance company. The goal is to provide clinical evidence whether pre-emptive pharmacogenetic testing of metabolic profiles in routine care in Germany is beneficial and cost-effective., Methods and Analysis: The EMPAR (Einfluss metabolischer Profile auf die Arzneimitteltherapiesicherheit in der Routineversorgung) study is a non-interventional cohort study conducted to analyse pharmacogenetic risk factors that are important for drug therapy by means of endpoints relevant for healthcare. The analysis is based on pharmacogenetic profiles and statutory health insurance data. We perform pharmacogenetic, pharmacoepidemiological and pharmacoeconomic analyses using health care utilisation scores and machine learning techniques. Therefore, we aim to include about 10 000 patients (≥18 years) insured by the health insurance provider Techniker Krankenkasse. The study focuses on patients with prescriptions of anticoagulants and prescriptions of cholesterol-lowering drugs. Also, a screening for special pharmacogenetic characteristics will be performed in patients with at least one Y57.9! diagnosis (Complication of medical and surgical care: drug or medicament, unspecified). Outcomes include the utilisation of health insurance services, the incidence of incapacity for work and costs for drugs and treatment., Ethics and Dissemination: The protocol was approved by the Ethics Committee of the Medical Faculty, University of Bonn (Lfd. Nr. 339/17). The results of this research project will be published in scientific open access journals and at conferences., Trial Registration Number: German Clinical Trials Register, DRKS00013909., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Time-correlated Förster resonance energy transfer (FRET) probes molecular distances with greater accuracy than intensity-based calculation of FRET efficiency and provides a powerful tool to study biomolecular structure and dynamics. Moreover, time-correlated photon count measurements bear additional information on the variety of donor surroundings allowing more detailed differentiation between distinct structural geometries which are typically inaccessible to general fitting solutions., Results: Here we develop a new approach based on Monte Carlo simulations of time-correlated FRET events to estimate the time-correlated single photon counts (TCSPC) histograms in complex systems. This simulation solution assesses the full statistics of time-correlated photon counts and distance distributions of fluorescently labeled biomolecules. The simulations are consistent with the theoretical predictions of the dye behavior in FRET systems with defined dye distances and measurements of randomly distributed dye solutions. We validate the simulation results using a highly heterogeneous aggregation system and explore the conditions to use this tool in complex systems., Conclusion: This approach is powerful in distinguishing distance distributions in a wide variety of experimental setups, thus providing a versatile tool to accurately distinguish between different structural assemblies in highly complex systems.