Assessment of patients’ awareness on drugs use and adherence to drug therapy as an element of Medication Review service

The administration of an excessive amount of or unnecessary drugs is a prerequisite for numerous drug-related problems, non-compliance, non-adherence to medicinal therapy, exacerbation and poor control of chronic diseases, and failure in achieving the treatment goals. The aim of this study was to assess patients’ awareness on drug use (administration, adherence to drug therapy) and to identify the possible drug-related problems with patients, using 5 or more medicines on Bulgarian territory. The data were collected implementing a structured study tool – a questionnaire for assessment of patients’ therapy using 5 or more drugs prescribed by a physician, including OTC and/or food supplements. The study provided an identification of factors affecting skipping of doses, modification of regime and analyzed the relationships and interdependencies between number of diagnoses and adverse drug effects rate; number of administered drugs and reported problems and unawareness of the medicinal product indications and health state. The results showed that it was necessary to introduce the Medication Review (MR) service in Bulgarian pharmaceutical practice. That will provide possibilities for development of pharmacists’ role in dispensing medical products, it will help in reducing drug-related problems and increasing the effectiveness of the treatment and adherence to medical therapy

Health Emergency Preparedness and Response Authority’s (HERA) role in dealing with the monkeypox emergency in the European Union

The current article examines and analyzes the actions taken by the European Commission, specifically through the Directorate-General Health Emergency Preparedness and Response Authority (HERA) – an organization that anticipates threats and potential health crises, through intelligence gathering and building the necessary response capacities), aimed at supporting member states in limiting the spread of MPOX (monkeypox – an infectious disease caused by the monkeypox virus). It explores specific pharmaceutical products and vaccines procured by HERA and how they have been distributed among member states. The article raises questions about the compliance in purchasing pharmaceutical products and vaccines lacking approval for use within the European Union, highlighting the potential new regulatory challenges for Bulgaria if it needs to secure medications for treatment of human smallpox disease such as Jynneos and TPOXX (Tecovirimat) for its citizens. In conclusion, the article notes the swift response of HERA through the procurement of the Jynneos vaccine and TPOXX medicinal product. This swift response may have contributed to the decline of MPOX cases in the European region, potentially due to collaborative efforts among health authorities at both European and national levels. This success underscores the importance of cooperation among health authorities at various levels in combating infectious diseases

Combination of Genetic Screening and Molecular Dynamics as a Useful Tool for Identification of Disease-Related Mutations: ZASP PDZ Domain G54S Mutation Case

Cypher/ZASP (<i>LDB3</i> gene) is known to interact with a network of proteins. It binds to α-actinin and the calcium voltage channels (LTCC) via its PDZ domain. Here we report the identification of a highly conserved ZASP G54S mutation classified as a variant of unknown significance in a sample of an adult with hypertrophic cardiomyopathy (HCM). The initial bioinformatics calculations strongly evaluated G54S as damaging. Furthermore, we employed accelerated and classical molecular dynamics and free energy calculations to study the structural impact of this mutation on the ZASP apo form and to address the question of whether it can be linked to HCM. Seventeen independent MD runs and simulations of 2.5 μs total were performed and showed that G54S perturbs the α2 helix position via destabilization of the adjacent loop linked to the β5 sheet. This also leads to the formation of a strong H-bond between peptide target residues Leu17 and Gln66, thus restricting both the α-actinin2 and LTCC C-terminal peptides to access their natural binding site and reducing in this way their binding capacity. On the basis of these observations and the adult’s clinical data, we propose that ZASP^G54S and presumably other ZASP PDZ domain mutations can cause HCM. To the best of our knowledge, this is the first reported ZASP PDZ domain mutation that might be linked to HCM. The integrated workflow used in this study can be applied for the identification and description of other mutations that might be related to particular diseases

Structural and Dynamical Insight into PPARγ Antagonism: In Silico Study of the Ligand-Receptor Interactions of Non-Covalent Antagonists

The structural and dynamical properties of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor have been broadly studied in its agonist state but little is known about the key features required for the receptor antagonistic activity. Here we report a series of molecular dynamics (MD) simulations in combination with free energy estimation of the recently discovered class of non-covalent PPARγ antagonists. Their binding modes and dynamical behavior are described in details. Two key interactions have been detected within the cavity between helices H3, H11 and the activation helix H12, as well as with H12. The strength of the ligand-amino acid residues interactions has been analyzed in relation to the specificity of the ligand dynamical and antagonistic features. According to our results, the PPARγ activation helix does not undergo dramatic conformational changes, as seen in other nuclear receptors, but rather perturbations that occur through a significant ligand-induced reshaping of the ligand-receptor and the receptor-coactivator binding pockets. The H12 residue Tyr473 and the charge clamp residue Glu471 play a central role for the receptor transformations. Our results also demonstrate that MD can be a helpful tool for the compound phenotype characterization (full agonists, partial agonists or antagonists) when insufficient experimental data are available

Cost analysis of neonates after prenatal corticosteroid prophylaxis of Respiratory Distress Syndrome

Preterm birth is a vital global health-economic problem. Health disorders provoked by it generate a high neonatal mortality rate. Prenatal corticosteroid prevention aims to reduce postnatal complications in premature infants. This survey covered two basic baby groups: work group of 89 premature infants that had been subjected to prenatal corticosteroid prophylaxis and a control group of 78 premature babies without prenatal prevention. The analysis of the pharmacoeconomic aspects of prenatal corticosteroid prevention enabled the comparison of clinical and therapeutic results, treatment costs, therapeutic expenditures, shortterm therapeutic effect, benefits and sequences from premature infants’ therapy. The analysis of clinical data obtained during this survey enabled the conclusion that when analyzing the combined effect of Dexamethasone prophylaxis, gestation week at birth and the age of the mother of premature infants with RDS, respiratory obstuction occurrence was mediated by the earlier gestation week at birth, older mother’s age and, at this background, it was restricted to a certain extent by prenatal corticosteroid administration. Conclusions: Prenatal corticosteroids cause reduction of premature infants’ treatment costs. The implementation of a smaller number of dexamethasone applications leads to smaller expenditures for premature infants’ treatment and care compared to those that have more dexamethasone applications