Drug-Related Problems in Coronary Artery Diseases

Coronary artery disease (CAD) remains the leading cause of mortality among cardiovascular diseases, responsible for 16% of the world’s total deaths. According to a statistical report published in 2020, the global prevalence of CAD was estimated at 1655 per 100,000 people and is predicted to exceed 1845 by 2030. Annually, in the United States, CAD accounts for approximately 610,000 deaths and costs more than 200 billion dollars for healthcare services. Most patients with CAD need to be treated over long periods with a combination of drugs. Therefore, the inappropriate use of drugs, or drug-related problems (DRPs), can lead to many consequences that affect these patients’ health, including decreased quality of life, increased hospitalization rates, prolonged hospital stays, increased overall health care costs, and even increased risk of morbidity and mortality. DRPs are common in CAD patients, with a prevalence of over 60%. DRPs must therefore be noticed and recognized by healthcare professionals. This chapter describes common types and determinants of DRPs in CAD patients and recommends interventions to limit their prevalence

The voices of youth in envisioning positive futures for nature and people

CITATION: Rana, S. et al. 2020. The voices of youth in envisioning positive futures for nature and people. Ecosystems and People, 16(1):326–344, doi:10.1080/26395916.2020.1821095.The original publication is available at https://www.tandfonline.comThe unpredictable Anthropocene poses the challenge of imagining a radically different, equitable and sustainable world. Looking 100 years ahead is not easy, and especially as millennials, it appears quite bleak. This paper is the outcome of a visioning exercise carried out in a 2-day workshop, attended by 33 young early career professionals under the auspices of IPBES. The process used Nature Futures Framework in an adapted visioning method from the Seeds of Good Anthropocene project. Four groups envisioned more desirable future worlds; where humanity has organised itself, the economy, politics and technology, to achieve improved nature-human well-being. The four visions had differing conceptualisations of this future. However, there were interesting commonalities in their leverage points for transformative change, including an emphasis on community, fundamentally different economic systems based on sharing and technological solutions to foster sustainability and human-nature connectedness. Debates included questioning the possibility of maintaining local biocultural diversity with increased connectivity globally and the prominence of technology for sustainability outcomes. These visions are the first step towards a wider galvanisation of youth visions for a brighter future, which is often missing in the arena where it can be taken seriously, to trigger more transformative pathways towards meeting global goals.Publisher's versio

Research Trends in Evidence-Based Medicine: A Joinpoint Regression Analysis of More than 50 Years of Publication Data

Background Evidence-based medicine (EBM) has developed as the dominant paradigm of assessment of evidence that is used in clinical practice. Since its development, EBM has been applied to integrate the best available research into diagnosis and treatment with the purpose of improving patient care. In the EBM era, a hierarchy of evidence has been proposed, including various types of research methods, such as meta-analysis (MA), systematic review (SRV), randomized controlled trial (RCT), case report (CR), practice guideline (PGL), and so on. Although there are numerous studies examining the impact and importance of specific cases of EBM in clinical practice, there is a lack of research quantitatively measuring publication trends in the growth and development of EBM. Therefore, a bibliometric analysis was constructed to determine the scientific productivity of EBM research over decades. Methods NCBI PubMed database was used to search, retrieve and classify publications according to research method and year of publication. Joinpoint regression analysis was undertaken to analyze trends in research productivity and the prevalence of individual research methods. Findings Analysis indicates that MA and SRV, which are classified as the highest ranking of evidence in the EBM, accounted for a relatively small but auspicious number of publications. For most research methods, the annual percent change (APC) indicates a consistent increase in publication frequency. MA, SRV and RCT show the highest rate of publication growth in the past twenty years. Only controlled clinical trials (CCT) shows a non-significant reduction in publications over the past ten years. Conclusions Higher quality research methods, such as MA, SRV and RCT, are showing continuous publication growth, which suggests an acknowledgement of the value of these methods. This study provides the first quantitative assessment of research method publication trends in EBM

A novel multi‐stage enrichment workflow and comprehensive characterization for HEK293F‐derived extracellular vesicles

Abstract Extracellular vesicles (EVs) are emerging as a promising drug delivery vehicle as they are biocompatible and capable of targeted delivery. However, clinical translation of EVs remains challenging due to the lack of standardized and scalable manufacturing protocols to consistently isolate small EVs (sEVs) with both high yield and high purity. The heterogenous nature of sEVs leading to unknown composition of biocargos causes further pushback due to safety concerns. In order to address these issues, we developed a robust quality‐controlled multi‐stage process to produce and isolate sEVs from human embryonic kidney HEK293F cells. We then compared different 2‐step and 3‐step workflows for eliminating protein impurities and cell‐free nucleic acids to meet acceptable limits of regulatory authorities. Our results showed that sEV production was maximized when HEK293F cells were grown at high‐density stationary phase in semi‐continuous culture. The novel 3‐step workflow combining tangential flow filtration, sucrose‐cushion ultracentrifugation and bind‐elute size‐exclusion chromatography outperformed other methods in sEV purity while still preserved high yield and particle integrity. The purified HEK293F‐derived sEVs were thoroughly characterized for identity including sub‐population analysis, content profiling including proteomics and miRNA sequencing, and demonstrated excellent preclinical safety profile in both in‐vitro and in‐vivo testing. Our rigorous enrichment workflow and comprehensive characterization will help advance the development of EVs, particularly HEK293F‐derived sEVs, to be safe and reliable drug carriers for therapeutic applications

Soft tissue regeneration in animal models using grafts from adipose mesenchymal stem cells and peripheral blood fibrin gel

OBJECTIVE: Our study aimed to evaluate the effect of soft tissue regeneration in nude mice using grafts made from the combination of adipocytes from fat tissue mesenchymal stem cells and fibrin gel from peripheral blood. MATERIALS AND METHODS: Mesenchymal stem cells were isolated from adipose tissue and identified according to ISCT criteria. The scaffold used was fibrin obtained from peripheral blood. The grafts in this study were generated by transferring mesenchymal stem cells onto a fibrin scaffold. Two types of grafts, the research sample (fibrin scaffold containing adipocytes differentiated from mesenchymal stem cells) and the control sample (fibrin scaffold only), were grafted under the dorsal skin of the same mouse. After each research period, samples were collected and evaluated by histological methods to observe the existence and growth of cells inside the grafts. RESULTS: The results showed that the study group’s graft integrated better within the tissue when compared with the control group. In addition, the grafts in the study group showed the presence of cells with characteristic morphology of adipocytes one week after transplantation. In contrast, control samples showed dimorphous shapes and features mainly composed of non-homogenous fragments. CONCLUSIONS: These initial conclusions might be considered a first step in generating safe bio-compatible engineered grafts specifically usable in post-traumatic tissue regeneration procedures

A study survey on molnupiravir treatment in COVID-19 patients at home in Ninh Thuan province, Vietnam

Objective: Molnupiravir (MOV) is an oral antiviral drug that received use authorization in Vietnam for the treatment of mild COVID-19 (F0). There was a need to develop alternative approaches that allowed patients to access medication, decongest hospitals, clinics, and facilities, and protect people from infection. During the COVID-19 crisis, the Ninh Thuan Health Authorities implemented the home delivery of medication by community health workers. This study conducted in collaboration with two important Italian entities [the Aldo Moro University of Bari City and the 118 Department of Territorial Emergency System (118 SET) of Taranto City] aimed to evaluate the implementation of home delivery F0 treatment package assessing the rate of infection recovering during the coronavirus pandemic in Ninh Thuan province, Vietnam. Patients and methods: A convergent mixed methods research, based on a longitudinal study with quantitative research and qualitative assessments, evaluated four implementation outcomes: the feasibility, fidelity, coverage, sustainability, and effectiveness of the initiative. Data sources included routinely collected data, a telephonic survey of patients, an analysis of set-up and recurrent costs, as well as descriptive exploratory qualitative and quantitative analysis. Results: After taking the MOV for 5 days, only 35 out of the initial 400 F0 patients remained positive, while 365 patients (91.2%) were negative (CT≥30). Whilst, the successful rate after using the drug during the course accounted for 99.85% and 100% after the entire treatment course, without any death. After 5 days of taking the drug, a positive test result (CT<30) was associated with age group ≥60 (OR=2.7) and comorbidities (OR=3.0) (p<0.05) compared to negative and positive results (CT≥30). Negative factors impacting F0 at home include a shortage of healthcare workers, inadequate supply of thermometers and SpO2 meters, and insufficient financial support for healthcare workers. Conclusions: MOV caused a reduction in the risk of hospitalization or death in mild COVID-19 patients, and molnupiravir was also found to be well tolerated and safe without any major adverse events during the administration period

Spindle checkpoint factors Bub1 and Bub2 promote DNA double-strand break repair by nonhomologous end joining

The nonhomologous end-joining (NHEJ) pathway is essential for the preservation of genome integrity, as it efficiently repairs DNA double-strand breaks (DSBs). Previous biochemical and genetic investigations have indicated that, despite the importance of this pathway, the entire complement of genes regulating NHEJ remains unknown. To address this, we employed a plasmidbased NHEJ DNA repair screen in budding yeast (Saccharomyces cerevisiae) using 369 putative nonessential DNA repair-related components as queries. Among the newly identified genes associated with NHEJ deficiency upon disruption are two spindle assembly checkpoint kinases, Bub1 and Bub2. Both observation of resulting phenotypes and chromatin immunoprecipitation demonstrated that Bub1 and -2, either alone or in combination with cell cycle regulators, are recruited near the DSB, where phosphorylated Rad53 or H2A accumulates. Large-scale proteomic analysis of Bub kinases phosphorylated in response to DNA damage identified previously unknown kinase substrates on Tel1 S/T-Q sites. Moreover, Bub1 NHEJ function appears to be conserved in mammalian cells. 53BP1, which influences DSB repair by NHEJ, colocalizes with human BUB1 and is recruited to the break sites. Thus, while Bub is not a core component of NHEJ machinery, our data support its dual role in mitotic exit and promotion of NHE