Vaccination Training for Pharmacy Undergraduates as a Compulsory Part of the Curriculum?-A Multicentric Observation.

In order to increase vaccination rates, the Government of Germany introduced vaccination against influenza and COVID-19 into the regular care administered by pharmacists. However, vaccination training is yet not integrated into the German pharmacy curriculum. Therefore, the Institute for Clinical Pharmacy and Pharmacotherapy in Duesseldorf had developed an innovative vaccination course using high-fidelity simulation for students. To investigate the acceptance further, the course was carried out at three different German universities (Bonn, Duesseldorf, Greifswald). Students were asked to give their self-assessment before and after and satisfaction only after the training course. Responses from 33 participants from the University of Bonn, 42 from the University of Duesseldorf and 49 from the University of Greifswald were analyzed. Every participant at the respective universities showed a significant increase in their self-assessment and indicated a high level of satisfaction with the course. The results also did not differ significantly between the respective universities. Consequently, the results lead to the hypothesis that the satisfaction of pharmacy students with this kind of training using high-fidelity simulation is very high and attractive, and can be recommended for other German universities. The integration of such vaccination training into the German pharmacy curriculum might be a future step.

[Fostering medication safety by and for patients]. / Verbesserung der Arzneimitteltherapiesicherheit mit und für den Patienten.

The overall goal of all measures for medication safety is the optimization of drug treatment and the prevention of unnecessary risk that potentially endangers patients. Per definition, the goal of medication safety is a beneficial patient outcome. Particularly in primary care, the success of many medication safety strategies will depend on the active participation of patients, as in this healthcare sector the patient is responsible for many substeps of the medication process.From a healthcare systems perspective, a number of medication safety strategies have been developed that aim to support the patient in their active role in the medication process. These strategies intend to safeguard the processes of care including transfer of information, but also aim to prevent intentional and unintentional nonadherence. The prerequisites for successful implementation are targeted awareness-raising measures to sensitize all participants for potential risks in the medication process. Moreover, readily available medication safety strategies must be easily accessible and promoted both to patients and healthcare providers.

Prospective systemic risk analysis of the dispensing process in German community pharmacies.

BACKGROUND: Medicine dispensing represents an error-prone activity, carrying a considerable risk for patients. OBJECTIVE: To prospectively identify and prioritize potential failure modes in the medicine dispensing process as well as to develop corrective actions for patient safety improvement in German community pharmacies. METHOD: Failure mode and effects analysis was performed in 2 community pharmacies in North Rhine-Westphalia, Germany, in October 2016. A 9-member team was assembled, comprising of a leader and process experts who prospectively assessed the medicine dispensing process by brainstorming, quantified the attributed risks, proposed corrective actions, and reassessed the risks. RESULTS: The analysis identified 39 failure modes, out of which the highest criticality scores were assigned to inadequate assessment of therapy appropriateness (Risk Priority Number 45), reluctance to deviate from rebate contracts (36), and dispensing the wrong medicine (30). The corrective actions proposed demonstrated a considerable potential for risk reduction in most failure modes, the most effective of which were introducing obligatory continuous education for pharmacists, organizing communication training, and implementing electronic prescribing. CONCLUSION: This analysis not only detected various potential safety issues concerning the dispensing in Germany but also strongly indicated that application of failure mode and effects analysis could be highly effective in prospective risk reduction in community pharmacies.

Localization of the gate and selectivity filter of the full-length P2X7 receptor.

The P2X7 receptor (P2X7R) belongs to the P2X family of ATP-gated cation channels. P2X7Rs are expressed in epithelial cells, leukocytes, and microglia, and they play important roles in immunological and inflammatory processes. P2X7Rs are obligate homotrimers, with each subunit having two transmembrane helices, TM1 and TM2. Structural and functional data regarding the P2X2 and P2X4 receptors indicate that the central trihelical TM2 bundle forms the intrinsic transmembrane channel of P2X receptors. Here, we studied the accessibility of single cysteines substituted along the pre-TM2 and TM2 helix (residues 327-357) of the P2X7R using as readouts (i) the covalent maleimide fluorescence accessibility of the surface-bound P2X7R and (ii) covalent modulation of macroscopic and single-channel currents using extracellularly and intracellularly applied methanethiosulfonate (MTS) reagents. We found that the channel opening extends from the pre-TM2 region through the outer half of the trihelical TM2 channel. Covalently adducted MTS ethylammonium+ (MTSEA+) strongly increased the probability that the channel was open by delaying channel closing of seven of eight responsive human P2X7R (hP2X7R) mutants. Structural modeling, as supported by experimental probing, suggested that resulting intraluminal hydrogen bonding interactions stabilize the open-channel state. The additional decrease in single-channel conductance by MTSEA+ in five of seven positions identified Y336, S339, L341C, Y343, and G345 as the narrowest part of the channel lumen. The gate and ion-selectivity filter of the P2X7R could be colocalized at and around residue S342. None of our results provided any evidence for dilation of the hP2X7R channel on sustained stimulation with ATP4.

Working together to enhance medication safety: working group 'medication safety' of the Aktionsbündnis Patientensicherheit e.V. / Gemeinsam für mehr Arzneimitteltherapiesicherheit Die AG AMTS im Aktionsbündnis Patientensicherheit e. V.

For 12 years, the 'Aktionsbündnis Patientensicherheit e.V. (APS)' has been developing tools for improving patient safety. Experts with different professional backgrounds are working alongside patients and self-help associations in different working groups to develop and publish problem-oriented best-practice recommendations. Since its foundation in 2005, APS has published more than 20 best-practice recommendations and is one of the most important institutions for patient safety in Germany. In this article, the aims and initiatives of one working group of the APS, i.e. the medication safety working group, are presented. The standardized concept for the development of best-practice recommendations is illustrated by the example of the recommendations for medication safety in hospitals.

Risk of renal dysfunction in an elderly patient with chronic heart failure. / Belastung der Nieren bei älterer Patientin mit Herzinsuffizienz.

The treatment of elderly multimorbid patients according to clinical guidelines often results in polypharmacy. An individual risk assessment is required to consider the possibility of deprescribing especially potentially inappropriate medication in the elderly. This exemplary case report describes a medication review of a patient with multiple chronic cardiovascular diseases taking into account the impact on renal function.

ATP binding site mutagenesis reveals different subunit stoichiometry of functional P2X2/3 and P2X2/6 receptors.

The aim of the present experiments was to clarify the subunit stoichiometry of P2X2/3 and P2X2/6 receptors, where the same subunit (P2X2) forms a receptor with two different partners (P2X3 or P2X6). For this purpose, four non-functional Ala mutants of the P2X2, P2X3, and P2X6 subunits were generated by replacing single, homologous amino acids particularly important for agonist binding. Co-expression of these mutants in HEK293 cells to yield the P2X2 WT/P2X3 mutant or P2X2 mutant/P2X3 WT receptors resulted in a selective blockade of agonist responses in the former combination only. In contrast, of the P2X2 WT/P2X6 mutant and P2X2 mutant/P2X6 WT receptors, only the latter combination failed to respond to agonists. The effects of α,ß-methylene-ATP and 2-methylthio-ATP were determined by measuring transmembrane currents by the patch clamp technique and intracellular Ca(2+) transients by the Ca(2+)-imaging method. Protein labeling, purification, and PAGE confirmed the assembly and surface trafficking of the investigated WT and WT/mutant combinations in Xenopus laevis oocytes. In conclusion, both electrophysiological and biochemical investigations uniformly indicate that one subunit of P2X2 and two subunits of P2X3 form P2X2/3 heteromeric receptors, whereas two subunits of P2X2 and one subunit of P2X6 constitute P2X2/6 receptors. Further, it was shown that already two binding sites of the three possible ones are sufficient to allow these receptors to react with their agonists.

Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor.

P2X7 is the largest member of the P2X subfamily of purinergic receptors. A typical feature is the carboxyl tail, which allows formation of a large pore. Recently a naturally occurring truncated P2X7 splice variant, isoform B (P2X7B), has been identified. Here we show that P2X7B expression in HEK293 cells, a cell type lacking endogenous P2X receptors, mediated ATP-stimulated channel activity but not plasma membrane permeabilization, raised endoplasmic reticulum Ca(2+) content, activated the transcription factor NFATc1, increased the cellular ATP content, and stimulated growth. In addition, P2X7B-transfected HEK293 cells (HEK293-P2X7B), like most tumor cells, showed strong soft agar-infiltrating ability. When coexpressed with full-length P2X7 (P2X7A), P2X7B coassembled with P2X7A into a heterotrimer and potentiated all known responses mediated by this latter receptor. P2X7B mRNA was found to be widely distributed in human tissues, especially in the immune and nervous systems, and to a much higher level than P2X7A. Finally, P2X7B expression was increased on mitogenic stimulation of peripheral blood lymphocyte. Altogether, these data show that P2X7B is widely expressed in several human tissues, modulates P2X7A functions, participates in the control of cell growth, and may help understand the role of the P2X7 receptor in the control of normal and cancer cell proliferation.

The P2X7 carboxyl tail is a regulatory module of P2X7 receptor channel activity.

P2X(7) receptors are ATP-gated cation channels composed of three identical subunits, each having intracellular amino and carboxyl termini and two transmembrane segments connected by a large ectodomain. Within the P2X family, P2X(7) subunits are unique in possessing an extended carboxyl tail. We expressed the human P2X(7) subunit as two complementary fragments, a carboxyl tail-truncated receptor channel core (residues 1-436 or 1-505) and a tail extension (residues 434-595) in Xenopus laevis oocytes. P2X(7) channel core subunits efficiently assembled as homotrimers that appeared abundantly at the oocyte surface, yet produced only approximately 5% of the full-length P2X(7) receptor current. Co-assembly of channel core subunits with full-length P2X(7) subunits inhibited channel current, indicating that the lack of a single carboxyl tail domain is dominant-negative for P2X(7) receptor activity. Co-expression of the tail extension as a discrete protein increased ATP-gated current amplitudes of P2X(7) channel cores 10-20-fold, fully reconstituting the wild type electrophysiological phenotype of the P2X(7) receptor. Chemical cross-linking revealed that the discrete tail extension bound with unity stoichiometry to the carboxyl tail of the P2X(7) channel core. We conclude that a non-covalent association of crucial functional importance exists between the carboxyl tail of the channel core and the tail extension. Using a slightly shorter P2X(7) subunit core and subfragments of the tail extension, this association could be narrowed down to include residues 409-436 and 434-494 of the split receptor. Together, these results identify the tail extension as a regulatory gating module, potentially making P2X(7) channel gating sensitive to intracellular regulation.