Background The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date. Method This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 h before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis. Results A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P value < 0.001) and Tocilizumab as an immunomodulator drug (P value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions. Conclusion The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in solid-organ transplant recipients could be promising treatments of choice to manage COVID-19.
Aging is correlated with several complex diseases, including type 2 diabetes, neurodegeneration diseases, and cancer. Identifying the nature of this correlation and treatment of age-related diseases has been a major subject of both modern and traditional medicine. Traditional Persian Medicine (TPM) embodies many prescriptions for the treatment of ARDs. Given that autophagy plays a critical role in antiaging processes, the present study aimed to examine whether the documented effect of plants used in TPM might be relevant to the induction of autophagy? To this end, the TPM-based medicinal herbs used in the treatment of the ARDs were identified from modern and traditional references. The known phytochemicals of these plants were then examined against literature for evidence of having autophagy inducing effects. As a result, several plants were identified to have multiple active ingredients, which indeed regulate the autophagy or its upstream pathways. In addition, gene set enrichment analysis of the identified targets confirmed the collective contribution of the identified targets in autophagy regulating processes. Also, the protein–protein interaction (PPI) network of the targets was reconstructed. Network centrality analysis of the PPI network identified mTOR as the key network hub. Given the well-documented role of mTOR in inhibiting autophagy, our results hence support the hypothesis that the antiaging mechanism of TPM-based medicines might involve autophagy induction. Chemoinformatics study of the phytochemicals using docking and molecular dynamics simulation identified, among other compounds, the cyclo-trijuglone of Juglans regia L. as a potential ATP-competitive inhibitor of mTOR. Our results hence, provide a basis for the study of TPM-based prescriptions using modern tools in the quest for developing synergistic therapies for ARDs.
Background: As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanism of SARS-CoV-2, the causing agent of COVID-19, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV as well as the comparable pattern of age-mortality relations suggest that some previous findings on SARS could be applicable for COVID-19. Objective: The aim of this study was to investigate the most important signaling pathways activated by coronaviruses to better understand the viral pathogenesis and host immune responses. Method: Here, a systems biology study was conducted on a SARS database. It was followed by a literature review on the cognate subject. Results: It was proved that interferons may possess a crucial role in the defense against coronavirus diseases. The literature supported the validity of the employed approach and the notion that interferon induction could play a key role in the body defense against coronavirus infections. Conclusion: Altogether, administration of interferons or interferon-inducing agents in a prophylactic manner or at early stages of the disease, could mimic the effective antiviral responses against SARS-CoV-2 and reduce the disease severity. At later stages of the disease, however, the balance of the immune reactions would be disrupted and the responses would shift toward immunopathogenic over-reactions, which could be exacerbated by interferon usage. Moderating the activity of the immune system by anti-inflammatory agents, might be the optimum approach in such conditions.
Background The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date. Method: This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 hours before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis. Results A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P-value˂0.001) and Tocilizumab as an immunomodulator drug (P-value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P-value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions. Conclusion The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in SOT recipients could be promising treatments of choice to manage COVID-19.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Purpose: Transplanted organ survival after solid organ transplantation highly correlates with the adherence levels of the patients to their immunosuppressive drugs. On the other hand, one of the main goals of liver transplantation is to increase the overall quality of life (QOL) for the patient. This study is aimed to analyze the relationship between adherence and QOL in adult liver transplant recipients of the biggest liver transplant center in Asia.Methods: All of the included patients were older than 18 years and at least 6 months had passed from their liver transplantation. The adherence level was measured with BAASIS method and the QOL was assessed by SF-36 questionnaire in real-time interviews. The relationship between adherence and different aspects of QOL in addition to qualitative and quantitative influential factors on these two outcomes was calculated with statistical analysis.Results: Among the 122 included patients, 41% of the were categorized in the non-adherent group. The most important reasons for non-adherence in these patients included forgetfulness (62%), lack of medication (12%), financial problems for drug supply (9%), and side effects (2%). According to the results of the multivariate linear regression model, rejection was the only influential factor in the occurrence of non-adherence among patients (OR = 8.226 CI (1.404-48.196)). The overall mean QOL score of patients was reported 51.09 ± 21.86. The lowest is given to social functioning, while mental health has achieved the highest score. The mean QOL scores in different dimensions in patients with adherence were higher than non-adherents, which was only significant in mental health (p-value = 0.01). Additionally, in total scores related to Physical Composite Score (PSC) and Mental Composite Score (MCS), the mean MSC scores in adherent patients were significantly higher than non-adherent patients (p-value: 0.02). Although adherent patients have an overall greater QOL, the only meaningful effect on QOL total score was from income level.Conclusion: The overall QoL score has been in all parameters higher in the adherent group compared with non-adherent patients. The difference in QoL was most meaningfully significant in mental composite score among other parameters of QoL.
Backgrounds: Transplanted patients receiving immunosuppressive agents are at a higher risk of Coronavirus-disease-2019 (COVID-19), and their polypharmacy state makes the choice of treatment challenging. This study aimed to evaluate the drug-related problems (DRP) and clinical pharmacists' interventions to manage transplanted patients and candidates for transplantation with COVID-19. Methods: This cross-sectional study was conducted from March 2020 to April 2021 at the COVID-19 intensive care unit of Shiraz-organ-transplant center, Iran. Patients were admitted to the COVID-19 intensive care unit based on clinical presentations or positive polymerase chain reaction (PCR) tests. The clinical pharmacist daily reviewed all medications and physicians' orders and evaluated DRPs regarding the pharmaceutical care network of Europe (PCNE) classification V8.01. The DRPs were informed to the treatment team, and the intervention acceptance or rejection was also recorded. Data were analyzed using SPSS V25.0. Descriptive statistics and logistic regression were performed to determine the proportion and determinants of drug-related problems, respectively. Results: A clinical pharmacist reviewed 631 individuals with 11770 medication orders, and 639 DRPs were identified from 69% of participants with an average of 1.01±1 per patient. Problems related to treatment effectiveness were the most commonly reported DRPs followed by adverse drug reactions (ADRs). A total of 982 interventions were provided at prescriber, patient, and drug levels, of which 801 were accepted, and 659 (82.27%) were fully implemented. Conclusion: There have been considerable drug-related problems in managing transplanted patients with COVID-19. Those with polypharmacy, more than three comorbidities, and Hydroxychloroquine regimens are more likely to manifest DRPs.
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