Drug Utilization Evaluation of Erythropoietin at a Referral Teaching Hospital in Iran.

Objectives: Drug utilization evaluation (DUE) studies aim to survey the appropriateness of drug use. DUE is an executive approach used to improve the use of medications as well as reduce the cost of treatment, ensure drug adequacy, and improve patient safety. The aim of this study was to evaluate the pattern of erythropoietin use, according to standard guidelines, in patients admitted to Namazi Hospital in Shiraz, Iran. Methods: In this descriptive, retrospective study, 230 patients were assessed. All patients who were hospitalized in different wards of Namazi Hospital, affiliated to Shiraz University of Medical Sciences, and received at least three doses of erythropoietin from September 2019 to March 2020 participated in this study. The following standard indicators of erythropoietin use were evaluated through reviewing medical charts of the cohort: drug dose, dosing intervals, route of administration, indication, monitoring of laboratory parameters, drug dose adjustment based on the response rate as well as target hemoglobin ≥12 g/dl, attention to major drug interactions, and administration of injectable or oral iron supplementation during treatment. Results: Most (65.2%) of the participants were male. The mean ± SD age of the patients was 47.55 ± 22.71 years. More than half (51.3%) of the included subjects were hospitalized in the nephrology ward. PDpoetin® and Cinnapoietin® were given to 52.6% and 47.4% of the study participants, respectively. Treatment of anemia due to chronic kidney disease was the most frequent indication of erythropoietin. The time interval of erythropoietin administration was three times a week for 68.3% of the patients. The most frequently administered weekly dose of erythropoietin was 12,000 units. The weekly dose, dose interval, and route of administration of erythropoietin were appropriate in 52.6%, 77.4%, and 100% of the patients, respectively. Dose adjustment based on the response rate, attention to major drug interactions as well as absolute-relative contraindications, and attention to the target hemoglobin ≥12 g/dl to decide whether or not to continue treatment were based on standard guideline in 98.1%, 98.7%, and 93% of the patients, respectively. The sum indexes of erythropoietin use were in line with standard guidelines in 75.84% of the cases. Conclusion: According to our results, in the setting of erythropoietin use in hospitals, physicians need more attention and education in areas such as selecting the proper dose of medication, correct indication of the drug, temporal arrangement of monitoring laboratory items, and the patient's need for iron supplements.

An Expert Overview on Therapies in Non-Transfusion-Dependent Thalassemia: Classical to Cutting Edge in Treatment.

The thalassemia issue is a growing worldwide health concern that anticipates the number of patients suffering from the disease will soon increase significantly. Patients with ß-thalassemia intermedia (ß-TI) manifest mild to intermediate levels of anemia, which is a reason for it to be clinically located between thalassemia minor and ß-thalassemia major (ß-TM). Notably, the determination of the actual rate of ß-TI is more complicated than ß-TM. The leading cause of this illness could be partial repression of ß-globin protein production; accordingly, the rate of ß-globin gene repression is different in patients, and the gene repression intensity creates a different clinical status. This review article provides an overview of functional mechanisms, advantages, and disadvantages of the classic to latest new treatments for this group of patients, depending on the disease severity divided into the typical management strategies for patients with ß-TI such as fetal hemoglobin (Hb) induction, splenectomy, bone marrow transplantation (BMT), transfusion therapy, and herbal and chemical iron chelators. Recently, novel erythropoiesis-stimulating agents have been added. Novel strategies are subclassified into molecular and cellular interventions. Genome editing is one of the efficient molecular therapies for improving hemoglobinopathies, especially ß-TI. It encompasses high-fidelity DNA repair (HDR), base and prime editing, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 procedure, nuclease-free strategies, and epigenetic modulation. In cellular interventions, we mentioned the approach pattern to improve erythropoiesis impairments in translational models and patients with ß-TI that involve activin II receptor traps, Janus-associated kinase 2 (JAK2) inhibitors, and iron metabolism regulation.

Antibiotic stewardship implementation at the largest solid organ transplantation center in Asia: a retrospective cohort study.

BACKGROUND: Using Antimicrobial stewardship programs (ASP) to monitor the use of antibiotics can lead to improved antibiotic use and reduced costs. METHODS: This retrospective cohort study was done at Shiraz Organ Transplant Center, the largest transplant center in Asia. Antimicrobial use, cost, clinical outcomes, and antibiotic resistance pattern were evaluated before and after ASP. RESULTS: This study included 2791 patients, 1154 of whom were related to the time before ASP and 1637 to the time after ASP. During the period of the research, a total of 4051 interventions were done. The use of all classes of antibiotics was significantly reduced by ASP, with 329 DDD/100PD before the intervention compared to 201 DDD/100PD after it (p = 0.04). In addition, the overall cost of antibiotics purchased was much lower after the ASP measures were implemented ($43.10 per PD) than before implementation of the ASP measures ($60.60 per PD) (p = 0.03). After the implementation of ASP, the number of MDR isolates was significantly reduced. CONCLUSION: The results of our study showed that the implementation of ASP significantly reduced the number and costs of antibiotics and also the number of resistant pathogens, but did not affect the patients' length of stay.

The effects of beraprost sodium on renal function and cardiometabolic profile in patients with diabetes mellitus: a systematic review and meta-analysis of clinical trials.

PURPOSE: This systematic review and meta-analysis aimed to assess renal function and cardiometabolic biomarkers after treatment with beraprost sodium in patients with diabetes mellitus. METHODS: We systemically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library up to August 2020. Statistical heterogeneities were computed using Cochrane's Q test and I2 test. A fixed- or random-effects model was used to calculate the weighted mean difference (WMD) and corresponding 95% confidence intervals (CI). RESULTS: From 341citations, seven trials were included into our meta-analysis. Our findings demonstrated that beraprost sodium intake significantly decreased blood urea nitrogen (BUN) (WMD = -5.62, 95% CI [-8.49, -2.74], P < 0.001) and cystatin C (WMD = -0.57, 95% CI [-0.68, -0.46], P < 0.001). Beraprost sodium intake had no significant effect on fasting blood sugar (FBS), hemoglobin A1c (HbA1c), cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, systolic blood pressure (SBP), diastolic blood pressure (DBP), and creatinine (Cr) in patients with diabetes receiving beraprost sodium in comparison with the controls. CONCLUSION: Our meta-analysis revealed that beraprost sodium administration significantly decreased BUN and cystatin C levels in patients with diabetes. However, no significant effect was observed on the cardiometabolic profile.

Nitric Oxide and Immune Responses in Cancer: Searching for New Therapeutic Strategies.

In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, and EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low/moderate levels may favor tumorigenesis, while higher levels would exert antitumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this "doubleedged sword" in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.

The Effects of Vitamin D Supplementation on Anthropometric and Biochemical Indices in Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Background: Vitamin D was reported to be associated with non-alcoholic fatty liver disease (NAFLD). This systematic review and meta-analysis aimed to investigate the effects of the vitamin D supplementation on anthropometric and biochemical indices in patient with NAFLD. Methods: PubMed, Web of science, Scopus, and Embase databases were explored to identify all randomized controlled trial (RCT) investigating the effects of vitamin D supplementation on anthropometric and biochemical indices in patients with NAFLD. A random-effects model was used to pool weighted mean difference (WMD) and corresponding 95% confidence intervals (CIs). The statistical heterogeneity among the studies was assessed using I2 statistic (high ≥ 50%, low < 50%) and Cochran's Q-test. Results: Sixteen RCTs were included in this meta-analysis. The results identified that high-density lipoprotein-cholesterol (HDL-C) level significantly increased following vitamin D supplementation (P = 0.008). Vitamin D reduced body weight (P = 0.007), body mass index (P = 0.002), waist circumstance (WC) (P = 0.02), serum alanine transaminase (ALT) (P = 0.01), fasting blood sugar (FBS) (P = 0.01), homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.004), and calcium (P = 0.01). No significant changes were found on body fat, triglyceride (TG), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, and adiponectin following vitamin D supplementation. Conclusion: Vitamin D had significant effects on anthropometric and biochemical indices including HDL-C, body weight, BMI, WC, serum ALT, serum FBS, HOMA-IR, and calcium. Vitamin D supplementation can be considered as an effective strategy in management of patients with NAFLD. Systematic Review Registration: [website], identifier [registration number].

Effect of Liraglutide on Cardiometabolic Risk Profile in People with Coronary Artery Disease with or without Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Whether liraglutide use improves cardiometabolic risk factors in different subsets of subjects with coronary artery disease (CAD) remains unclear. In a systematic review and meta-analysis, we quantified the effects of liraglutide on cardiometabolic risk profile in subjects with CAD with or without type 2 diabetes mellitus (T2D). Methods: Online database searches were conducted in PubMed, Scopus, EMBASE, Web of Science, Cochrane library, and Google Scholar from incept up to 15th January 2021. We identified randomized controlled trials (RCTs) assessing the effects of liraglutide compared to placebo on cardiometabolic risk profile. We used the random- or fixed-effect models to pool the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results: Out of a total of 7,320 citations, six articles (seven RCTs) with 294 subjects with CAD (mean age, 61.21 years; 19% women) were included. Our findings presented as WMD and 95% CI showed a statistical significant decrease in hemoglobin A1c (HbA1c) [-0.36%; -0.47; -0.26, p < 0.001; I 2 = 0.0% (with 6 RCTs)], body mass index (BMI) [-0.61 kg/m2; -1.21; -0.01, p = 0.047; I 2 = 72.2% (with five RCTs)], and waist circumference [-2.41 cm; -3.47; -1.36, p < 0.001; I 2 = 0.0% (with three RCTs)]. Through a set of subgroup analyses, we found a significant reduction in BMI in CAD patients with T2D [WMD = -1.06; 95% CI, -1.42, -0.70, p < 0.001; I 2 = 0.0% (with three RCTs)] compared to CAD only patients [WMD = -0.08; 95% CI, -0.45, 0.29, p = 0.66; I 2 = 0.0% (with two RCTs)] in the liraglutide group compared with the placebo group. No significant changes in heart rate, blood pressure, and lipid profiles were observed. Conclusions: Among people with established CAD, liraglutide significantly improved HbA1c, BMI, and waist circumference values. The effect of liraglutide on BMI was more robust in individuals with T2D compared to those without.