Prevalence of Vitamin B12 and Folate Deficiencies and Homocysteinemia in Elderly Population of Shiraz, Southern Iran

Purpose: To investigate the prevalence of cobalamin and folate deficiencies among the elderly in the general population of Shiraz in southern Iran.Methods: This is a descriptive cross-sectional study including 340 individuals who are over 50 years old and were selected randomly from all the regions of Shiraz.Results: The study group was made up of 132 (38.8 %) males and 208 (61.2 %) females. In this group 174 (51.2 %) were aged 50 - 59 years and 166 (48.8 %) were aged ≥ 60 years. Cobalamin deficiency (< 200 pg/mL) was present in 124 (36.2 %) while 42 (12.4 %) had severe deficiency with levels < 100 pg/mL. Signs of metabolic deficiency at the cellular level were seen in 21 (5.25 %) of the samples. Serum folate deficiency (< 4 ng/mL) was present in 134 (39.4 %) while 19 (5.6 %) persons had severe folate deficiency (≤ 2 - 3 ng/mL). Correlation analysis showed that serum cobalamin and homocysteine in the study samples were not significant (p > 0.05).Conclusion: The prevalence of severe cobalamin deficiency with clinical significance is high in the elderly population of Shiraz, Iran.Keywords: Vitamin B12 deficiency, Folate deficiency, Homocysteinemia, Elderly populatio

Acute kidney injury in COVID-19 patients receiving remdesivir: A systematic review and meta-analysis of randomized clinical trials

Objectives: Remdesivir is an antiviral agent with positive effects on the prognosis of Coronavirus Disease (COVID-19). However, there are concerns about the detrimental effects of remdesivir on kidney function which might consequently lead to Acute Kidney Injury (AKI). In this study, we aim to determine whether remdesivir use in COVID-19 patients increases the risk of AKI. Methods: PubMed, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, medRxiv, and bioRxiv were systematically searched until July 2022, to find Randomized Clinical Trials (RCT) that evaluated remdesivir for its effect on COVID-19 and provided information on AKI events. A random-effects model meta-analysis was conducted and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. The primary outcomes were AKI as a Serious Adverse Event (SAE) and combined serious and non-serious Adverse Events (AE) due to AKI. Results: This study included 5 RCTs involving 3095 patients. Remdesivir treatment was not associated with a significant change in the risk of AKI classified as SAE (Risk Ratio [RR]: 0.71, 95% Confidence Interval [95% CI] 0.43‒1.18, p = 0.19, low-certainty evidence) and AKI classified as any grade AEs (RR = 0.83, 95% CI 0.52‒1.33, p = 0.44, low-certainty evidence), compared to the control group. Conclusion: Our study suggested that remdesivir treatment probably has little or no effect on the risk of AKI in COVID-19 patients

Utilization of Pharmacokinetic/Pharmacodynamic Modeling in Pharmacoepidemiological Studies:A Systematic Review on Antiarrhythmic and Glucose-Lowering Medicines

Introduction: In human pharmacology, there are two important scientific branches: clinical pharmacology and pharmacoepidemiology. Pharmacokinetic/pharmacodynamic (PK/PD) modeling is important in preclinical studies and randomized control trials. However, it is rarely used in pharmacoepidemiological studies on the effectiveness and medication safety where the target population is heterogeneous and followed for longer periods. The objective of this literature review was to investigate how far PK/PD modeling is utilized in observational studies on glucose-lowering and antiarrhythmic drugs. Method: A systematic literature search of MEDLINE, Embase, and Web of Science was conducted from January 2010 to 21 February 2020. To calculate the utilization of PK/PD modeling in observational studies, we followed two search strategies. In the first strategy, we screened a 1% random set from 95,672 studies on glucose-lowering and antiarrhythmic drugs on inclusion criteria. In the second strategy, we evaluated the percentage of studies in which PK/PD modeling techniques were utilized. Subsequently, we divided the total number of included studies in the second search strategy by the total number of eligible studies in the first search strategy. Results: The comprehensive search of databases and the manual search of included references yielded a total of 29 studies included in the qualitative synthesis of our systematic review. Nearly all 29 studies had utilized a PK model, whereas only two studies developed a PD model to evaluate the effectiveness of medications. In total, 16 out of 29 studies (55.1%) used a PK/PD model in the observational setting to study effect modification. The utilization of PK/PD modeling in observational studies was calculated as 0.42%. Conclusion: PK/PD modeling techniques were substantially underutilized in observational studies of antiarrhythmic and glucose-lowering drugs during the past decade

Hope and fear; Paxlovid for COVID-19 treatment: A Letter to the Editor

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Prescription trends of antiseizure medications before and during the COVID-19 pandemic

IntroductionGiven the lack of evidence on how the COVID-19 pandemic impacted antiseizure medication (ASM) use, we examined the trends of ASMs before and during COVID-19.MethodsWe conducted a population-based study using provincial-level health databases from Manitoba, Canada, between 1 June 2016 and 1 March 2021. We used interrupted time series autoregressive models to examine changes in the prevalence and incidence of ASM prescription rates associated with COVID-19 public health restrictions.ResultsAmong prevalent users, the COVID-19 pandemic led to a significant increase in new-generation ASMs with a percentage change of 0.09% (p = 0.03) and a significant decrease in incidence use of all ASMs with a percentage change of −4.35% (p = 0.04). Significant trend changes were observed in the prevalent use of new-generation ASMs (p = 0.04) and incidence use of all (p = 0.04) and new-generation ASMs (p = 0.02). Gabapentin and clonazepam prescriptions contributed 37% of prevalent and 54% of incident use.ConclusionWith the introduction of public health measures during COVID-19, small but significant changes in the incident and prevalent use of ASM prescriptions were observed. Further studies are needed to examine whether barriers to medication access were associated with potential deterioration in seizure control among patients.Conference presentationThe results from this study have been presented as an oral presentation at the 38th ICPE, International Society of Pharmacoepidemiology (ISPE) annual conference in Copenhagen

Antioxidants and cisplatin nephrotoxicity; an updated review on current knowledge

Cisplatin is a first-line antitumor drug which is applied in the therapeutic field of numerous kinds of cancers. The main dose-dependent adverse effect of cisplatin is nephrotoxicity in approximately one-third of patients, who received this drug during their treatment. Oxidative stress is one of the most significant mechanisms in cisplatin nephrotoxicity. Cisplatin-induced oxidative stress stimulates apoptosis, inflammation, mitochondrial damage within cells, and endoplasmic reticulum (ER) stress. The administration of an antioxidant in this context could be a suitable approach for preventing of cisplatin nephrotoxicity. Antioxidants are categorized into four classes: dietary antioxidants, free radical scavengers, thiol-containing compounds, and iron chelators

COVID-19-associated glomerulopathy and high-risk apol1 genotype; basis for a two-hit mechanism of injury? A narrative review on recent findings

Kidney is one of the most common organs affected by coronavirus disease 2019 (COVID-19) after the respiratory and immune systems. Among the renal parenchymal components, the tubulointerstitial compartment is presumed to be the prime target of injury in COVID-19. The main mechanism of renal tubular damage by COVID-19 is considered to be indirect, i.e., cytokine-mediated injury. A proportion of infected individuals mount a strong inflammatory response to the virus by an exaggerated immune response of the body, namely cytokine storm. Sudden and massive release of cytokines may lead to serious systemic hyper-inflammation and renal tubular injury and inflammation resulting in acute renal failure. In addition, a number of cases of glomerulopathies, particularly collapsing glomerulopathy (CG) have been reported, predominantly in people of African ancestry, as a rare form of kidney involvement by SARS-CoV-2 that may originate from the background genetic susceptibility in this population complicated by the second hit of SARS-CoV-2 infection, either directly or indirectly. It is noteworthy that renal injury in COVID-19 could be severe in individuals of African origin due to the aforementioned genetic susceptibility, especially the presence of high-risk apolipoprotein L1 (APOL1) genotypes. Although the exact mechanism of kidney injury by SARS-CoV-2 is as yet unknown, multiple mechanisms are likely involved in renal damage caused by this virus. This review was aimed to summarize the salient points of pathogenesis of kidney injury, particularly glomerular injury in COVID-19 disease in the light of published data. A clear understanding of these is imperative for the proper management of these cases. For this review, a search was made of Google Scholar, Web of Science, Scopus, EBSCO and PubMed for finding English language articles related to COVID-19, kidney injury and glomerulopathy. From the information given in finally selected papers, the key aspects regarding glomerular involvement in COVID-19 were drawn out and are presented in this descriptive review

Factors facilitating and hindering development of a medication use review service in Eastern Europe and Iran - cross-sectional exploratory study

Funding Information: European Association of Faculties of Pharmacy PRD 2019 grant for the project ?Develop-ment and Implementation of Medication Use Review Services at Community Pharmacy in Eastern European countries?. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Polypharmacy is a common issue in patients with chronic diseases. Eastern-European countries and Iran are exploring possibilities for implementing the Medication Use Review (MUR) as a measure for optimizing medication use and ensuring medication safety in polypharmacy patients. The aim of this study was to gain insights into the development of the community pharmacy sector and map facilitators and barriers of MUR in Eastern Europe and Iran. The representatives of the framework countries received a questionnaire on community pharmacy sector indicators, current and future developments of pharmacies, and factors encouraging and hindering MUR. To answer the questionnaire, all representatives performed document analysis, literature review, and qualitative interviews with key stakeholders. The socio-ecological model was used for inductive thematic analysis of the identified factors. Current community pharmacist competencies in framework countries were more related to traditional pharmacy services. Main facilitators of MUR were increase in polypharmacy and pharmaceutical waste, and access to patients’ electronic list of medications by pharmacists. Main barriers included the service being unfamiliar, lack of funding and private consultation areas. Pharmacists in the framework countries are well-placed to provide MUR, however, the service needs more introduction and barriers mostly on organizational and public policy levels must be addressed.publishersversionPeer reviewe

Synthesis and Cytotoxicity Study of New Cyclopenta [b] quinoline-1,8-dione Derivatives

Abstract DNA intercalators belong to aromatic heterocyclic compounds interacting reversibly with DNA. These compounds have been used extremely as cytotoxic agents against cancer. In this study, the synthesis and biological activity of some novel derivatives of cyclopenta [b] quinoline-1, 8-dione as new intercalating agent were investigated. Twenty novel derivatives of cyclopenta [b] quinoline-1, 8-dione were synthesized by molecular condensation of equivalent amount of 3-imino cyclopentanone, corresponding aldehyde and cyclohexane-1, 3-dione. Then, their cytotoxic activity was evaluated against HeLa, LS180, MCF-7 and Raji cancer cell lines by MTT assay. The results of cytotoxic activity evaluation indicate that the most of synthesized compounds show weak cytotoxic effect on the different cell lines (IC 50 of these compounds is higher than 50 or 100 m ). According to previous studies, in the case of compounds with the weak biological activity, it is more suitable to use IC 15 and IC 30 instead of IC 50 as the indicator of biological activity. Since most of compounds have weak cytotoxic effect, we also calculated IC 15 and IC 30 for evaluating the cytotoxic activity of synthesized compounds. The most potent compound, 6 h (9-(3-Bromo-phenyl)-4-pheny l-2, 3, 5, 6, 7, 9-hexahydro-4H-cyclopenta [b] quinoline-1, 8-dione), containing bromophenyl moiety and phenyl substitute on nitrogen of central quinoline ring, show significant cytotoxic activity especially in Raji and HeLa cell lines (IC 30 : 82 and 24.4 m M respectively) comparing to other compounds. Although the results of cytotoxic activity evaluation demonstrated that the in-vitro anti-cancer effect of synthesized compounds are mainly low, it seems that this structure can be used as a novel cytotoxic scaffold for further modification and design of novel potent compounds