A qualitative study on the working experiences of clinical pharmacists in fighting against COVID-19.

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19) has overwhelmed healthcare systems across the world. Along with the medical team, clinical pharmacists played a significant role during the public health emergency of COVID-19. This study aimed to explore the working experience of clinical pharmacists and provide reference for first-line clinical pharmacists to prepare for fighting against COVID-19. METHODS: A qualitative study based on descriptive phenomenology was employed with face-to-face and audio-recorded interviews to study the working experience of 13 clinical pharmacists (including two clinical nutritional pharmacists). All interviews were transcribed verbatim, and the interview data were analyzed thematically using NVivo software. RESULTS: Four themes emerged from interview data, including roles of clinical pharmacists, working experiences of clinical pharmacists, psychological feelings of clinical pharmacists, and career expectations of clinical pharmacists. CONCLUSIONS: The results contributed to a deeper understanding of the clinical pharmacists' work experiences in COVID-19 and offered guidance to better prepare clinical pharmacists in participating in a public health crisis.

Exploring the experiences and expectations of pharmacist interns in large general hospitals in China: from the perspective of interns.

BACKGROUND: Hospital-based pharmacy internship (HBPI) is critical for the transition from "pharmacy students" to "professional pharmacists". This study explores the pharmacist interns' experiences and expectations for HBPI from their personal experiences intending to provide references for future hospital pharmacy education reform and policy development. METHODS: This is a multicenter qualitative study applying focus group discussions. Pharmacist interns were invited as participants from large teaching hospitals in Henan, China. A thematic analysis was conducted to qualitatively analyze this data. Nvivo 12 was utilized for data management and processing. RESULTS: Three focus group discussions were conducted, involving 16 interns as participants. Three themes were summarized regarding interns' expectations and experiences: (1) positive experiences of the HBPI; (2) negative experiences of the HBPI; (3) expectations and suggestions for the HBPI. CONCLUSION: This study finds that the HBPI improves the professional knowledge, professional skills, and core competencies of interns. Therefore, the HBPI is an important preparation and transition stage for pharmacy students. However, the current pharmacy internship in China still has imperfections such as the insufficient ability of clinical teachers, unreasonable internship models, and unscientific internship content.

Lower Platelet Aggregation Is a Risk Factor for Dual Antiplatelet Therapy-Associated Bleeding: A Preliminary Retrospective Study with Genotype Analysis.

BACKGROUND The purpose of this study was to investigate factors influencing bleeding in patients with acute coronary syndrome (ACS) who are on aspirin and ticagrelor as dual antiplatelet therapy. MATERIAL AND METHODS This retrospective case-control study included 50 patients with ACS (25 with reported bleeding events and 25 without) on aspirin and ticagrelor. Adenosine diphosphate (ADP)- and arachidonic acid (ACA)-induced platelet aggregation rates were measured using light transmission aggregometry. Single-nucleotide polymorphisms (SNPs) in PEAR1, GP1BA, and GSTP1 were genotyped. RESULTS ACA-induced platelet aggregation rates were obviously lower in patients with bleeding events than in those without (13.28±8.46% vs. 24.93±9.89%, P<0.001). No significant differences in ADP-induced platelet aggregation rates were observed between the 2 groups (16.17±9.74% vs. 16.88±12.69%, P>0.05). Among those with bleeding events and among controls, 70% and 80% had an ACA-induced platelet aggregation rate of 0-18% and 18-50%, respectively. Mutation rates of rs6065 in GP1BA and rs1695, rs4891, and rs8191439 in GSTP1 also differed significantly between the 2 groups. CONCLUSIONS Lower ACA-induced platelet aggregation rates are associated with increased risk of bleeding in patients with ACS who are on aspirin and ticagrelor. An ACA-induced platelet aggregation rate of 18% may be considered the cutoff point for identifying high risk of aspirin-associated bleeding events in patients with ACS. SNP genotyping may also help predict the risk of bleeding in patients with ACS.

Population pharmacokinetics and pharmacodynamics of ticagrelor and AR-C124910XX in Chinese healthy male subjects.

BACKGROUND: Ticagrelor, the first reversible P2Y12 receptor antagonist, exhibits faster onset and offset of antiplatelet effects and more consistent platelet inhibition than clopidogrel in both healthy subjects and patients with stable coronary artery disease. OBJECTIVE: The objectives of this study were to establish a population pharmacokinetics (PK) and pharmacodynamics (PD) model of ticagrelor and to provide a theoretical basis for the optimization of ticagrelor treatment in clinic. METHODS: A single oral dose of 180 mg ticagrelor was administered to 14 healthy male subjects in a randomized study. Common single-nucleotide polymorphisms (SNPs) in biotransformation enzymes CYP3A4 and CYP3A5 (CYP3A4*1G and CYP3A5*3) were genotyped by PCR-direct sequencing. Blood samples were collected to measure plasma concentrations of ticagrelor and its active metabolite AR-C124910XX and maximal platelet inhibition. Various models were evaluated to characterize the pharmacokinetics of ticagrelor and AR-C124910XX as well as their PK-PD relationship. Covariates that may potentially affect PK or PD of ticagrelor and AR-C124910XX were included and assessed. Simulation for dosage regimen was performed based on the final PK-PD model. RESULTS: Ticagrelor and AR-C124910XX PK were best described by a two-compartment model with first-order transit absorption model. CYP3A4*1G increased clearance for AR-C124910XX, but had no significant effect on ticagrelor clearance. The relationship between concentration and platelet response of ticagrelor was best described by a turnover model. Simulation results indicated that a lower dosage regimen of 30 mg maintenance dose (MD) could produce an anticipated anti-platelet response in comparison to the routine clinical dosage regimen (180 mg loading dose (LD), 90 mg MD). CONCLUSION: Our study developed a population PK-PD model for ticagrelor and further simulation for dosage regimen was performed based on the final model. Compared to the current recommended dosage regimen (180 mg LD, 90 mg MD), our simulation result of a relatively lower dose (30 mg MD) could also obtain an acceptable anti-platelet response, which may provide a reference for further dosage regimen design in Chinese population.

New sesquiterpenoids and a diterpenoid from Alpinia oxyphylla.

The new compounds 2-methyl-6-isopropyl-7-hydroxymethyl naphthalene (1), oxyphyllenone H (2), epi-oxyphyllenone (6), (E)-labda-12,14-dien-15(16)-olide-17-oic acid (3), and two new natural products 4 and 5 were isolated from the ethyl acetate part of 95% ethanol extract of Alpinia oxyphylla, together with six known compounds 7-12. The inhibitory effects of compounds 1-12 on α-glucosidase were evaluated, and compounds 1, 3 and 6 showed moderate bioactive effect, with inhibitory rates of 10.3%, 10.0% and 11.5%, respectively, compared to the positive control acarbose (41.9%) at 20 µg/mL.

Identification of Potential Biological Factors Affecting the Treatment of Ticagrelor After Percutaneous Coronary Intervention in the Chinese Population.

BACKGROUND: Generally, many individual factors can affect the clinical application of drugs, of which genetic factors contribute more than 20%. Ticagrelor is a new class of receptor inhibitors receptor antagonist of P2Y12 and is used as an antiplatelet agents. But it is not affected by the influence of CYP2C19 polymorphism. With lack of predicted biomarkers, especially the research data of Chinese, it has the important significance in studying individual differences of ticagrelor in the antiplatelet efficacy and safety, through pharmacogenomics research. METHODS: Whole-exome sequencing (WES) was performed in 100 patients after PCI with ticagrelor treatment. Clinical characteristics and WES of patients were used to performed genome-wide association analysis (GWAS), region-based tests of rare DNA variant to find the influencing factors of antiplatelet effect to ticagrelor and bleeding events. Co-expression, protein-protein interaction (PPI) network and pathway enrichment analysis were then used to find possible genetic mechanisms. Atlas of GWAS (https://atlas.ctglab.nl/) were used for external data validation. RESULTS: DNAH17, PGS1 and ABCA1 as the potential variant genes are associated with the expected antiplatelet effect to ticagrelor. The affected pathways may include the synthesis and metabolism of lipoprotein cholesterol and the catabolic process of pyrimidine-containing compound (GO:0072529). Age, sex and PLT were found may be potential factors for ticagrelor bleeding events. CONCLUSION: We systematically identified new genetic variants and some risk factors for reduced efficacy of ticagrelor and highlighted related genes that may be involved in antiplatelet effects and bleeding event of ticagrelor. Our results enhance the understanding of the absorption and metabolic mechanisms that influence antiplatelet response to ticagrelor treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03161002. First Posted: May 19, 2017. https://clinicaltrials.gov/ct2/show/study/NCT03161002.

Current Status and Trends in Peptide Receptor Radionuclide Therapy in the Past 20 Years (2000-2019): A Bibliometric Study.

Background: Peptide receptor radionuclide therapy (PRRT) is an emerging therapeutic option for the treatment of neuroendocrine tumors (NETs), and the number of publications in this field has been increasing in recent years. The aim of the present study was to present the research status and summarize the key topics through bibliometric analysis of published PRRT literature. Methods: A literature search for PRRT research from 2000 to 2019 was conducted using the Science Citation Index Expanded of Web of Science Core Collection (limited to SCIE) on August 4, 2020. The VOSviewer, R-bibliometrix, and CiteSpace software were used to conduct the bibliometric analysis. Results: From 2000 to 2019, a total of 681 publications (523 articles and 158 reviews) were retrieved. Annual publication outputs grew from three to 111 records. Germany had the largest number of publications, making the largest contribution to the field (n = 151, 22.17%). Active cooperation between countries/regions was observed. Kwekkeboom from the Erasmus Medical Center is perhaps a key researcher in the field of PRRT. The European Journal of Nuclear Medicine and Molecular Imaging and Journal of Nuclear Medicine ranked first for productive (n = 84, 12.33%) and co-cited (n = 3,438) journals, respectively. Important topics mainly included matters related to the efficacy of PRRT (e.g., 90Y-dotatoc and 177Lu-dotatate), the long-term adverse effects of PRRT (e.g., hematologic and renal toxicities), standardization of NETs and PRRT in practice, the development of medical imaging techniques, and the individual dose optimization of PRRT. Conclusion: Using bibliometric analysis, we gained deep insight into the global status and trends of studies investigating PRRT for the first time. The PRRT field is undergoing a period of rapid development, and our study provides a valuable reference for clinical researchers and practitioners.

[Determination of the fingerprint attribution ratio and process recovery of medicinal effectiveness components for TCM-compound prescription with quantified fingerprint method].

By setting up the organic additive model of chemical fingerprints of TCM-compound, the quantified fingerprint method had been established to solve the qualitative and quantitative analyses problems for both the fingerprint attribution ratio and process recovery of medicinal effective components in TCM-compound prescription. The method firstly performs the qualitative analyses of the attribution ratios, and then the quantitative analyses, which can successfully disclose the results of attribution ratio and determine the process recovery of the medicinal effective components for TCM-compound prescription. Three optional methods were represented to assess the amount and distribution proportion of chemical compositions for single crude drug to compound prescription. In terms of components absorbed ultraviolet light, S5 (Radix Scutellariae) was assessed to be the most important crude drug containing much more effective components, and S7 (Radix Gentianae), S4 (Flos Lonicerae Japonica), S8 (Rhizome Anemarrhena) and S9 (Fructus Gardeniae) were second important crude drugs. The results showed lower process recovery of the medicinal effective components for eight batches of marketed preparations. Above all, the quantified fingerprint method can objectively and accurately reflect how high is the contribution of a single crude drug to the compound prescription, and quantitatively evaluate the process recovery of medicinal effectiveness components.

Effect of CYP3A4∗1G and CYP3A5∗3 Polymorphisms on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Healthy Chinese Subjects.

Ticagrelor is the first reversible, direct-acting, potent P2Y12 receptor antagonist in management of acute coronary syndromes. It is rapidly absorbed and extensively metabolized. AR-C124910XX, the major active metabolite, antagonizes the P2Y12 receptor at approximately equal potency. The metabolism of ticagrelor to AR-C124910XX involves CYP3A4 and CYP3A5. CYP3A polymorphisms have been well documented, and CYP3A4∗1G (g.20230G>A, rs2242480) and CYP3A5∗3 (g.6986A>G, rs776746) are the most important single nucleotide polymorphisms in Chinese. Genetic differences in CYP3A4 and CYP3A5 expression in human volunteers and patients might affect the clearance of ticagrelor or AR-C124910XX in vivo resulting in subsequent variable patient response. Thus, this study is designed to explore the effects of CYP3A4∗1G and CYP3A5∗3 polymorphisms on the pharmacokinetics and pharmcodynamics of ticagrelor in healthy Chinese subjects. The results indicated that the CYP3A4∗1G polymorphism significantly influenced the pharmacokinetics of AR-C124910XX, and it may be more important than CYP3A5∗3 with respect to influencing ticagrelor pharmacokinetics by increasing CYP3A4 activity. However, the significant effect of CYP3A4∗1G polymorphism on AR-C124910XX plasma levels did not translate into detectable effect on inhibition of platelet aggregation. Therefore, it seems not necessary to adjust the dosage of ticagrelor according to the CYP3A4 or 3A5 genotype.