DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Cost minimization analysis of subcutaneous trastuzumab versus intravenous biosimilar trastuzumab: policy recommendations for breast cancer treatment in Malaysia.","authors":"Jin Ee Heng, Sivaraj Raman, Zhi Yen Wong, Valerine Jen Nin Beh","doi":"10.1007/s40199-023-00485-9","DOIUrl":"10.1007/s40199-023-00485-9","url":null,"abstract":"<p><strong>Purpose: </strong>Current clinical practice recommends switching innovator intravenous trastuzumab (IV-TZM_i) to subcutaneous trastuzumab (SC-TZM) to save healthcare resources. However, with the availability of biosimilar intravenous trastuzumab (IV-TZM_b), there is a need to re-evaluate the recommendation. Hence, this study aims to compare the cost and resource use of SC-TZM and IV-TZM_b in a Malaysian public healthcare facility.</p><p><strong>Methods: </strong>This activity-based costing study consists of (1) a retrospective medical record abstraction to determine patient details to estimate drug costs and (2) a time-motion study to quantify personnel time, patient time, and consumables used. The total cost of both SC-TZM and IV-TZM_b were then compared using a cost-minimization approach, while differences were explored using an independent t-test. A sensitivity analysis was also conducted to determine the impact of uncertainties in the analysis.</p><p><strong>Results: </strong>The mean total cost of SC-TZM and IV-TZM_b was USD 13,693 and USD 5,624 per patient respectively. The cost difference was primarily contributed by savings in drug cost of IV-TZM_b, a reduction of USD 8,546 (SD = 134), p < 0.001 compared to SC-TZM. Interestingly, SC-TZM had a significantly lower cost than IV-TZM_b for both the consumable and personnel cost, a reduction by USD 300 (SD = 17.6); p < 0.001 and USD 176 (SD = 7.3); p < 0.001 respectively. The sensitivity analysis demonstrated that the total cost difference between the formulation was mainly driven by drug costs.</p><p><strong>Conclusion: </strong>The study evidenced that IV-TZM_b was a more economically viable option in Malaysian public healthcare currently compared to SC-TZM.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"67-76"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chidamide inhibits cell glycolysis in acute myeloid leukemia by decreasing N6-methyladenosine-related GNAS-AS1.","authors":"Changmei Hu, Xiao Fu, Shujun Li, Cong Chen, Xielan Zhao, Jie Peng","doi":"10.1007/s40199-023-00482-y","DOIUrl":"10.1007/s40199-023-00482-y","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a hematopoietic malignancy. Chidamide has shown anti-cancer effect in different malignancies. The function of Chidamide in glycolysis in AML cells remains unclear.</p><p><strong>Methods: </strong>AML cells were treated with 1000 nM Chidamide for 48 h. The levels of long non-coding RNA-GNAS-AS1, miR-34a-5p, glycolysis-related proteins, and Ras homolog gene family (RhoA)/Rho-associated protein kinase (ROCK) signaling-related proteins were detected by qRT-PCR or western blot. Cell viability and apoptosis were measured by CCK-8 and flow cytometry. Glycolysis levels were measured by assay kits. GNAS-AS1 N6-methyladenosine (m6A) modification level was detected by methylated RNA immunoprecipitation sequencing. The combined targets of miR-34a-5p were validated using a dual-luciferase reporter assay. BALB/C nude mice were selected for subcutaneous tumor validation. Chidamide at a dosage of 25 mg/kg was used in the animal study.</p><p><strong>Results: </strong>GNAS-AS1 promoted glycolysis in AML cells by upregulating the expression of glycolysis-related proteins and increasing glucose consumption, lactate production, ATP generation, and the extracellular acidification rate. Chidamide treatment suppressed WT1-associated protein (WTAP)-mediated RNA m6A modification of GNAS-AS1. Chidamide downregulated GNAS-AS1 to inhibit glycolysis in AML cells. GNAS-AS1 targeted miR-34a-5p to promote insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) expression. IGF2BP2 inhibition reversed the promoting effect of miR-34a-5p knockdown on glycolysis and RhoA/ROCK pathway in Chidamide-treated cells. GNAS-AS1 overexpression abolished the inhibitory effect of Chidamide on AML tumorigenesis in vivo by modulating the RhoA/ROCK pathway.</p><p><strong>Conclusion: </strong>Chidamide inhibited glycolysis in AML by repressing WTAP-mediated GNAS-AS1 m6A modification and then regulating the miR-34a-5p/IGF2BP2 axis.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"11-24"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imiquimod as a new treatment in refractory idiopathic granulomatous mastitis: report of two cases.","authors":"Sadaf Alipour, Bardia Gholami, Marzieh Orouji, Samareh Heydari","doi":"10.1007/s40199-023-00501-y","DOIUrl":"10.1007/s40199-023-00501-y","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory lesion of the breast that mimics breast cancer or infection. Immunological pathogenesis is strongly suggested for the disease.</p><p><strong>Reason for the report: </strong>The treatment remains controversial, comprising a spectrum from observation or NSAIDs to immunosuppressive agents and surgery. Intractable cases are not uncommon and represent a major treatment challenge. Therefore in this study, we examine the effect of a topical immunomodulator agent, imiquimod, on refractory IGM. Patient 1 had IGM for 9 months and had not responded to the existing treatments. She responded to a 7-week course of imiquimod. In patient 2, the disease had begun 4 months sooner and had been resistant to all treatments; it responded to imiquimod after 4 weeks. Ulcers appeared on the skin of both patients but resolved safely.</p><p><strong>Outcome: </strong>Both patients were very satisfied with the results. Imiquimod can be an appropriate local treatment with limited adverse effects in refractory IGM. We propose similar studies to assess the efficacy of imiquimod in IGM further, paying attention to the possibility of developing skin wounds.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"443-447"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity of zinc oxide and zinc borate nanoparticles against resistant bacteria in an experimental lung cancer model.","authors":"Demet Celebi, Ozgur Celebi, Ali Taghizadehghalehjoughi, Sumeyye Baser, Elif Aydın, Daniela Calina, Ekaterina Charvalos, Anca Oana Docea, Aristidis Tsatsakis, Yaroslav Mezhuev, Serkan Yildirim","doi":"10.1007/s40199-024-00505-2","DOIUrl":"10.1007/s40199-024-00505-2","url":null,"abstract":"<p><strong>Background: </strong>Recent research indicates a prevalence of typical lung infections, such as pneumonia, in lung cancer patients. Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii stand out as antibiotic-resistant pathogens. Given this, there is a growing interest in alternative therapeutic avenues. Boron and zinc derivatives exhibit antimicrobial, antiviral, and antifungal properties.</p><p><strong>Objectives: </strong>This research aimed to establish the effectiveness of ZnO and ZB NPs in combating bacterial infections in lung cancer cell lines.</p><p><strong>Methods: </strong>Initially, this study determined the minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) of zinc oxide nanoparticles (ZnO NPs) and zinc borate (ZB) on chosen benchmark strains. Subsequent steps involved gauging treatment success through a lung cancer-bacteria combined culture and immunohistochemical analysis.</p><p><strong>Results: </strong>The inhibitory impact of ZnO NPs on bacteria was charted as follows: 0.97 µg/mL for K. pneumoniae 700603, 1.95 µg/mL for P. aeruginosa 27853, and 7.81 µg/mL for Acinetobacter baumannii 19,606. In comparison, the antibacterial influence of zinc borate was measured as 7.81 µg/mL for Klebsiella pneumoniae 700603 and 500 µg/mL for both P. aeruginosa 27853 and A.baumannii 19606. After 24 h, the cytotoxicity of ZnO NPs and ZB was analyzed using the MTT technique. The lowest cell viability was marked in the 500 µg/mL ZB NPs group, with a viability rate of 48.83% (P < 0.001). However, marked deviations appeared at ZB concentrations of 61.5 µg/mL (P < 0.05) and ZnO NPs at 125 µg/mL.</p><p><strong>Conclusion: </strong>A synergistic microbial inhibitory effect was observed when ZnO NP and ZB were combined against the bacteria under investigation.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"197-206"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of concerning excipients on animal safety: insights for veterinary pharmacotherapy and regulatory considerations.","authors":"Vanessa Cola Thomazini, Gabriel Mendes da Cunha, Nayhara Madeira Guimarães, Soraya Dias Saleme, Rita Cristina Gonçalves de Melo, Geanne Aparecida de Paula, Suzana Gonçalves Carvalho, Marlus Chorilli, Cristiane Dos Santos Giuberti, Janaina Cecília Oliveira Villanova","doi":"10.1007/s40199-023-00486-8","DOIUrl":"10.1007/s40199-023-00486-8","url":null,"abstract":"<p><strong>Objectives: </strong>Veterinarians and pharmacists are familiar with the efficacy and safety aspects attributed to active pharmaceutical ingredients included in medicines, but they are rarely concerned with the safety of excipients present in medicines. Although generally recognized as safe, excipients are not chemically inert and may produce adverse events in certain animal populations. This review aims to present excipients of concern to these populations and highlight their relevance for rational veterinary pharmacotherapy.</p><p><strong>Evidence acquisition: </strong>A comprehensive review of the literature about the existence of adverse reactions in animals caused by pharmaceutical excipients was carried out based on an exploratory study. An overview of the correct conditions of use and safety of these excipients has also been provided, with information about their function, the proportion in which they are included in the different pharmaceutical dosage forms and the usual routes of administration.</p><p><strong>Results: </strong>We identified 18 excipients considered of concern due to their potential to cause harm to the health of specific animal populations: bentonite, benzalkonium chloride, benzoic acid, benzyl alcohol, ethanol, lactose, mannitol, mineral oil, monosodium glutamate, polyethylene glycol, polysorbate, propylene glycol, sodium benzoate, sodium carboxymethylcellulose, sodium lauryl sulfate, sulfites, polyoxyethylene castor oil derivatives, and xylitol. Among the 135 manuscripts listed, only 24 referred to studies in which the substances were correctly evaluated as excipients.</p><p><strong>Conclusions: </strong>Based on the information presented in this review, the authors hope to draw the attention of professionals involved in veterinary pharmacotherapy to the existence of excipients of concern in medicines. This information contributes to rational veterinary pharmacotherapy and supports veterinary pharmacovigilance actions. We hope to shed light on the subject and encourage studies and new manuscripts that address the safety of pharmaceutical excipients to the animal population.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"289-305"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71411061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ropivacaine suppresses the progression of renal cell carcinoma through regulating the lncRNA RMRP/EZH2/CCDC65 axis.","authors":"Yingfen Xiong, Xiaolan Zheng, Huangying Deng","doi":"10.1007/s40199-023-00492-w","DOIUrl":"10.1007/s40199-023-00492-w","url":null,"abstract":"<p><strong>Background: </strong>Renal cell carcinoma (RCC) is a common malignancy. Local anesthetics were displayed powerful effects against various cancers. This study aims to probe the functions and molecular mechanism of ropivacaine in RCC.</p><p><strong>Methods: </strong>Different concentrations of ropivacaine were performed to administrate RCC cells including 786-O and Caki-1 cells. Cell viability and cell apoptosis were examined using CCK-8 and flow cytometry, respectively. Cell migration and invasion were determined by transwell assay. RMRP and CCDC65 expression was firstly predicted using TCGA dataset and further validated in RCC cells using qRT-PCR and western blot. The interactions among RMRP, EZH2 and CCDC65 were verified by RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays.</p><p><strong>Results: </strong>Ropivacaine effectively suppressed RCC cell viability, migration and invasion and enhanced cell apoptosis rate. Aberrantly elevated RMRP expression in RCC tissues was predicted by TCGA database. Interestingly, overexpressed RMRP observed in RCC cells could be also blocked upon the administration of ropivacaine. Likewise, RMRP knockdown further strengthened ropivacaine-mediated tumor suppressive effects on RCC cells. In terms of mechanism, RMRP directly interacted with EZH2, thereby modulating the histone methylation of CCDC65 to silence its expression. Moreover, ropivacaine inhibited tumor growth in mice bearing RCC tumor through regulating RMRP/EZH2/CCDC65 axis.</p><p><strong>Conclusion: </strong>In sum up, our work revealed that ropivacaine suppressed capacities of RCC cell viability, migration and invasion through modulating the RMRP/EZH2/CCDC65 axis, which laid the experimental foundation of ropivacaine for clinical application in the future.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"121-132"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards greater impact in health technology assessment: System dynamic approach for new and emerging technologies in Iran.","authors":"Zahra Goudarzi, Milad Ahmadi Marzaleh, Shekoufeh Nikfar, Abbas Kebriaeezadeh, Reza Yousefi Zenouz, Akbar Abdollahiasl, Mojtaba Nouhi","doi":"10.1007/s40199-023-00483-x","DOIUrl":"10.1007/s40199-023-00483-x","url":null,"abstract":"<p><strong>Purpose: </strong>As classical health technology assessment models fail to predict the complexities of related impacts, the application of modeling techniques such as systems dynamics simulation (SD) is essential. This study aimed to develop an SD model to predict the outcomes of access to a new medicine in Iran.</p><p><strong>Methods: </strong>This study extracted the important and influential variables in providing access to new pharmaceutical technologies by comprehensively reviewing previous research and combining the technical knowledge of experts in this field. The variables were incorporated into the systems thinking framework and modeled using dynamic systems tools, followed by simulation and testing in VENSIM. The model was piloted for deferoxamine and deferasirox in thalassemia. Various tests were used to evaluate the validity and reliability of the model. The model was designed for a ten-year horizon (2018-2028) for medicines selected as the pilot.</p><p><strong>Results: </strong>The variables extracted from the panel of experts encompassed the primary and short-term impacts of access to newly emerged medicine and long-term impacts regarding the economy, health, and society. After modeling, the leverage points presented for the problem with the greatest impact or effectiveness in access to new medicine included the policy determining the amount of medicine supply, the import and production of medicine, the prevalence and incidence of disease, insurance coverage, and treatment adherence.</p><p><strong>Conclusion: </strong>The SD models allow the researchers to evaluate the efficiency and health outcomes of a new pharmaceutical more precisely in the health system in Iran.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"25-45"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrochemical evaluation of nivolumab used in cancer treatment with differential pulse voltammetry: A novel approach with single-use pencil graphite electrode.","authors":"Mehmet Aslan, Fırat Aydın, Abdulkadir Levent","doi":"10.1007/s40199-023-00491-x","DOIUrl":"10.1007/s40199-023-00491-x","url":null,"abstract":"<p><strong>Objectives: </strong>Nivolumab is used in a treatment called immunotherapy, which helps the immune system cells to attack cancer cells. The electrochemical properties and quantification of this drug were performed using single-use pencil tips.</p><p><strong>Evidence acquisition: </strong>Here, a selective voltammetric method for the determination and electrochemical characterization of Nivolumab used in cancer therapy was developed for the first time using a disposable pencil electrode by cyclic voltammetry and differential pulse voltammetry techniques. Nivolumab exhibited an anodic signal at +0.879 V (vs. Ag/AgCl) in PBS (pH 3.0, 0.02 M NaCl) medium.</p><p><strong>Results: </strong>This procedure showed a linear response in phosphate buffer solutions (pH 3.0, 0.02 M NaCl) media within the concentration range of 0.01 mg mL^-1 to 0.07 mg mL^-1 and limit of detection and the limit of quantification values were determined to be 2.49 μg mL^-1 and 8.30 μg mL^-1, respectively.</p><p><strong>Conclusions: </strong>The developed method offers an important analytical approach for the detection and characterization of NIVO. Precisely measuring and monitoring the levels of such drugs in real sample analyses or biological samples is critical for evaluating response to treatment, optimizing treatment strategies. Therefore, the method was applied to real sample analyses. Voltammetric results developed using PG electrode were compared with UV-Vis results. It has been determined that the results obtained are compatible with each other.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"109-120"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Screening Using a Combination of Ligand-Based Machine Learning and Molecular Docking Methods for the Repurposing of Antivirals Targeting the SARS-CoV-2 Main Protease.","authors":"Gusti Putu Wahyunanda Crista Yuda, Naufa Hanif, Adam Hermawan","doi":"10.1007/s40199-023-00484-w","DOIUrl":"10.1007/s40199-023-00484-w","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 is an infectious disease caused by SARS-CoV-2, a close relative of SARS-CoV. Several studies have searched for COVID-19 therapies. The topics of these works ranged from vaccine discovery to natural products targeting the SARS-CoV-2 main protease (M^pro), a potential therapeutic target due to its essential role in replication and conserved sequences. However, published research on this target is limited, presenting an opportunity for drug discovery and development.</p><p><strong>Method: </strong>This study aims to repurpose 10692 drugs in DrugBank by using ligand-based virtual screening (LBVS) machine learning (ML) with Konstanz Information Miner (KNIME) to seek potential therapeutics based on M^pro inhibitors. The top candidate compounds, the native ligand (GC-376) of the M^pro inhibitor, and the positive control boceprevir were then subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) characterization, drug-likeness prediction, and molecular docking (MD). Protein-protein interaction (PPI) network analysis was added to provide accurate information about the M^pro regulatory network.</p><p><strong>Results: </strong>This study identified 3,166 compound candidates inhibiting M^pro. The random forest (RF) molecular access system ML model provided the highest confidence score of 0.95 (bromo-7-nitroindazole) and identified the top 22 candidate compounds. Subjecting the 22 candidate compounds, the native ligand GC-376, and boceprevir to further ADMET property characterization and drug-likeness predictions revealed that one compound had two violations of Lipinski's rule. Additional MD results showed that only five compounds had more negative binding energies than the native ligand (- 12.25 kcal/mol). Among these compounds, CCX-140 exhibited the lowest score of - 13.64 kcal/mol. Through literature analysis, six compound classes with potential activity for M^pro were discovered. They included benzopyrazole, azole, pyrazolopyrimidine, carboxylic acids and derivatives, benzene and substituted derivatives, and diazine. Four pathologies were also discovered on the basis of the M^pro PPI network.</p><p><strong>Conclusion: </strong>Results demonstrated the efficiency of LBVS combined with MD. This combined strategy provided positive evidence showing that the top screened drugs, including CCX-140, which had the lowest MD score, can be reasonably advanced to the in vitro phase. This combined method may accelerate the discovery of therapies for novel or orphan diseases from existing drugs.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"47-65"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Educational interventions in pharmacovigilance to improve the knowledge, attitude and the report of adverse drug reactions in healthcare professionals: Systematic Review and Meta-analysis.","authors":"Mónica J Cervantes-Arellano, Osvaldo D Castelán-Martínez, Yolanda Marín-Campos, Juan L Chávez-Pacheco, Olga Morales-Ríos, Laura M Ubaldo-Reyes","doi":"10.1007/s40199-024-00508-z","DOIUrl":"10.1007/s40199-024-00508-z","url":null,"abstract":"<p><strong>Objectives: </strong>Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this systematic review with meta-analyses was to synthesize the evidence of educational interventions (EIs) efficacy in health professionals to increase ADR reporting, attitudes, and knowledge of pharmacovigilance.</p><p><strong>Evidence acquisition: </strong>A systematic literature review was carried out to identify randomized clinical trials evaluating the efficacy of EI in pharmacovigilance in health professionals to improve ADR reports, knowledge, and attitude toward pharmacovigilance. ADR reports were pooled by calculating Odds Ratio (OR) with a 95% confidence interval (95%CI), while pharmacovigilance knowledge and attitude were pooled by calculating a mean difference (MD) with 95%CI. In addition, the subanalysis was performed by EI type. Meta-analysis was performed with RevMan 5.4 software. PROSPERO registry CRD42021254270.</p><p><strong>Results: </strong>Eight hundred seventy-five articles were identified as potentially relevant, and 11 were included in the systematic review. Metanalysis showed that EI increased ADR reporting in comparison with control group (OR = 4.74, [95%CI, 2.46 to 9.12], I² = 93%, 5 studies). In subgroup analysis, the workshops (OR = 6.26, [95%CI, 4.03 to 9.73], I² = 57%, 3 studies) increased ADR reporting more than telephone-based interventions (OR = 2.59, [95%CI, 0.77 to 8.73], I² = 29%, 2 studies) or combined interventions (OR = 5.14, [95%CI, 0.97 to 27.26], I² = 93%, 3 studies). No difference was observed in pharmacovigilance knowledge. However, the subanalysis revealed that workshops increase pharmacovigilance knowledge (SMD = 1.85 [95%CI, 1.44 to 2.27], 1 study). Only one study evaluated ADR reporting attitude among participants and showed a positive effect after the intervention.</p><p><strong>Conclusion: </strong>EI improves ADR reports and increases pharmacovigilance knowledge. Workshops are the most effective EI to increase ADR reporting.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":" ","pages":"421-434"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}