Cost-effectiveness Analysis of Triptorelin, Goserelin, and Leuprolide in the Treatment of Patients with Metastatic Prostate Cancer: A Societal Perspective.

OBJECTIVES: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020. METHODS: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs. RESULTS: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes. CONCLUSIONS: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies.

The effect of BsmI (rs1544410) single nucleotide polymorphism of vitamin D receptor (VDR) on insulin resistance in healthy children and adolescents: a cross-sectional study.

The increasing prevalence of metabolic syndrome, type 2 diabetes, and insulin resistance are driven by complex interactions between genetic and environmental factors. One of the single nucleotide polymorphisms (SNPs) in the VDR gene associated with vitamin D levels is the rs1544410 SNP. This study examined the association of the rs1544410 polymorphism with insulin resistance to predict and screen for possible association with type 2 diabetes and target these individuals for appropriate treatment. This cross-sectional study examined 270 children and adolescents aged 9 to 18 years. Anthropometric and biochemical parameters were determined. Insulin resistance/sensitivity was determined using Quicki, HOMA-IR, MacAuley, Revised MacAuley, Bennetts, FIRI and insulin-to-glucose ratio. The BsmI single nucleotide polymorphism (rs1544410) was determined using the PCR-RFLP method after extracting DNA from peripheral blood collected from fasted subjects, and the resulting data were analyzed using SPSS software and statistical tests.According to linear regression analysis, a significant difference was found in Insulin to glucose ratio, FIRI and HOMA-IR indices between Bb / bb and BB genotypes and it was observed that individuals with BB genotype polymorphism of BsmI vitamin D receptor gene, after Adjustment of age, sex, BMI are at greater risk for insulin resistance and type 2 diabetes.This study demonstrated that those with the BB genotype of VDR BsmI polymorphism were at higher risk for insulin resistance and developing type 2 DM.

Evaluation and Comparison of the Effectiveness of Atropine Eye Drops, Ipratropium Bromide Nasal Spray, and Amitriptyline Tablet in the Management of Clozapine-Associated Sialorrhea in Patients With Refractory Schizophrenia: A Randomized Clinical Trial.

PURPOSE: Clozapine, a second-generation antipsychotic medication, is mainly indicated for managing treatment-resistant schizophrenia. Among all the nonthreatening adverse effects of clozapine, sialorrhea is a stigmatizing complication occurring in approximately 31.0% to 97.4% of patients. In this study, 2 topical agents (atropine eye drop and ipratropium nasal spray) and a systemic medication (amitriptyline) were compared simultaneously for the management of clozapine-associated sialorrhea. METHODS: We conducted a randomized, single-blinded, non-placebo-controlled clinical trial from June 2022 to January 2023. Eligible patients were randomly allocated into 3 mentioned groups. Patients were monitored for sialorrhea weekly based on scales, including the Toronto Nocturnal Hypersalivation Scale, Clinical Global Impression-Improvement, and Clinical Global Impression-Severity for 1 month. Possible adverse drug reactions and adherence were also recorded. RESULTS: Twenty-four patients, including 6, 10, and 8 individuals in ipratropium bromide nasal spray, atropine eye drop, and amitriptyline groups, completed the study, respectively. The cohort's demographic, baseline clinical, and sociocultural characteristics were comparable among the 3 groups. Within-group comparisons, between times baseline and week 4, demonstrated that significant differences were in groups atropine and amitriptyline based on Toronto Nocturnal Hypersalivation Scale, in 3 groups based on Clinical Global Impression-Improvement, and also in only-atropine group based on Clinical Global Impression-Severity. Likewise, between-group comparisons showed that atropine was significantly more effective in clozapine-associated sialorrhea management than amitriptyline and ipratropium, in the first 2 weeks and second 2 weeks of study, respectively. Regarding safety, the interventions were tolerated relatively well. CONCLUSIONS: Conclusively, atropine is more efficacious than amitriptyline, within the first 2 weeks of study and also relative to ipratropium, overall. As time effect was significant between atropine and amitriptyline, according to analysis of covariance test, further investigation with longer follow-up duration would be prudent. In addition, expanding patient population with larger sample size should be conducted for more precision.

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.

Moving toward a contemporary classification of drug-induced kidney disease.

Drug-induced kidney disease (DIKD) accounts for about one-fourth of all cases of acute kidney injury (AKI) in hospitalized patients, especially in critically ill setting. There is no standard definition or classification system of DIKD. To address this, a phenotype definition of DIKD using expert consensus was introduced in 2015. Recently, a novel framework for DIKD classification was proposed that incorporated functional change and tissue damage biomarkers. Medications were stratified into four categories, including "dysfunction without damage," "damage without dysfunction," "both dysfunction and damage," and "neither dysfunction nor damage" using this novel framework along with predominant mechanism(s) of nephrotoxicity for drugs and drug classes. Here, we briefly describe mechanisms and provide examples of drugs/drug classes related to the categories in the proposed framework. In addition, the possible movement of a patient's kidney disease between certain categories in specific conditions is considered. Finally, opportunities and barriers to adoption of this framework for DIKD classification in real clinical practice are discussed. This new classification system allows congruencies for DIKD with the proposed categorization of AKI, offering clarity as well as consistency for clinicians and researchers.

Prevention and management of antibiotic associated acute kidney injury in critically ill patients: new insights.

PURPOSE OF REVIEW: Drug associated kidney injury (D-AKI) occurs in 19-26% of hospitalized patients and ranks as the third to fifth leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Given the high use of antimicrobials in the ICU and the emergence of new resistant organisms, the implementation of preventive measures to reduce the incidence of D-AKI has become increasingly important. RECENT FINDINGS: Artificial intelligence is showcasing its capabilities in early recognition of at-risk patients for acquiring AKI. Furthermore, novel synthetic medications and formulations have demonstrated reduced nephrotoxicity compared to their traditional counterparts in animal models and/or limited clinical evaluations, offering promise in the prevention of D-AKI. Nephroprotective antioxidant agents have had limited translation from animal studies to clinical practice. The control of modifiable risk factors remains pivotal in avoiding D-AKI. SUMMARY: The use of both old and new antimicrobials is increasingly important in combating the rise of resistant organisms. Advances in technology, such as artificial intelligence, and alternative formulations of traditional antimicrobials offer promise in reducing the incidence of D-AKI, while antioxidant medications may aid in minimizing nephrotoxicity. However, maintaining haemodynamic stability using isotonic fluids, drug monitoring, and reducing nephrotoxic burden combined with vigilant antimicrobial stewardship remain the core preventive measures for mitigating D-AKI while optimizing effective antimicrobial therapy.

Aminoglycosides: single- or multiple-daily dosing? An updated qualitative systematic review of randomized trials on toxicity and efficacy.

INTRODUCTION: Aminoglycosides are among the first-choice antibiotics for routine clinical use. However, dose-limiting factors such as ototoxicity and nephrotoxicity are considered as serious complications of aminoglycosides. OBJECTIVE: In this systematic review, the main goal was to investigate the efficacy and incidence of nephrotoxicity and ototoxicity of once-daily dosing (ODD) and multiple daily dosing (MDD) regimens of aminoglycosides through available randomized controlled trials (RCTs). METHODS: We performed a literature-based research in relevant databases, including EMBASE, MEDLINE, and SCOPUS published between 1987 and 2023 using the keywords "aminoglycosides", "pharmacokinetics", "ODD", "MDD", "once daily", "multiple daily", "dosing regimen", "nephrotoxicity", "ototoxicity", "efficacy", "safety", and "toxicity". As so told, the results of this article were limited to papers available in English. Our initial search yielded 1124 results. After a review of the titles and abstracts of the articles, 803 articles were excluded from this study because they did not address the toxicity and effectiveness of ODD versus MDD of aminoglycosides. A total number of 21 studies on gentamicin, tobramycin, netilmicin, and amikacin met the inclusion criteria for the efficacy of aminoglycosides and their role in ototoxicity and nephrotoxicity were included in this review. Studies recruited different age classes, and the age of relevant cohorts varied from only a few days to more than 70 years. RESULTS: The most common clinical condition in the included studies was cystic fibrosis. CONCLUSION: In most studies, there were no significant differences between the two regimens regarding ototoxicity. In addition, the ODD regimens were safer than MDD concerning nephrotoxicity.

The ameliorating effect of limosilactobacillus fermentum and its supernatant postbiotic on cisplatin-induced chronic kidney disease in an animal model.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem affecting millions of people. Probiotics and postbiotics are associated with valuable compounds with antibacterial, anti-inflammatory, and immunomodulatory effects, preserving renal function in CKD patients. The current study is aimed to evaluate the efficacy of Limosilactobacillus fermentum (L. fermentum) and its postbiotic in an animal model of cisplatin-induced CKD. METHODS: The animals were divided into four experimental groups (normal mice, CKD mice with no treatment, CKD mice with probiotic treatment, and CKD mice with postbiotic treatment). CKD mice were induced by a single dose of cisplatin 10 mg/kg, intraperitoneally. For 28 days, the cultured probiotic bacteria and its supernatant (postbiotic) were delivered freshly to the related groups through their daily water. Then, blood urea nitrogen (BUN) and creatinine (Cr) of plasma samples as well as glutathione (GSH), lipid peroxidation, reactive oxygen species, and total antioxidant capacity of kidneys were assessed in the experimental mice groups. In addition, histopathological studies were performed on the kidneys. RESULTS: Application of L. fermentum probiotic, and especially postbiotics, significantly decreased BUN and Cr (P < 0.0001) as well as ROS formation and lipid peroxidation levels (P < 0.0001) along with increased total antioxidant capacity and GSH levels (P < 0.001). The histopathologic images also confirmed their renal protection effect. Interestingly, the postbiotic displayed more effectiveness than the probiotic in some assays. The improvement effect on renal function in the current model is mainly mediated by oxidative stress markers in the renal tissue. CONCLUSIONS: In conclusion, it was found that the administration of L. fermentum probiotic, and particularly its postbiotic in cisplatin-induced CKD mice, showed promising effects and could successfully improve renal function in the animal model of CKD. Therefore, probiotics and postbiotics are considered as probably promising alternative supplements to be used for CKD.

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.

Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Systematic Review of Economic Evaluations.

OBJECTIVES: Several studies have evaluated the economic evaluation of a group of medications known as novel oral anticoagulant drugs (NOACs) in recent years. The aim of this study is to review and systematically analyze the cost-utility studies results of warfarin compared with other NOAC drugs in atrial fibrillation patients. METHODS: A systematic review was performed to identify all studies evaluating the NOAC medications in comparison with warfarin. For this purpose, PubMed, Cochrane Library, ISI Web of Science, and Scopus were searched from 2013 to 2022. Articles were independently screened with inclusion criteria, and full texts were reviewed. First, the Consolidated Health Economic Evaluation Reporting Standards checklist was used to evaluate the quality of the articles. Then, the costs and outcomes of the studies were analyzed, and findings were appraised critically. RESULTS: A total of 84 costs-per-quality-adjusted life-year (QALY) cases were extracted from the studies in which the share of rivaroxaban, edoxaban, apixaban, and dabigatran were 31%, 13%, 29%, and 27%, respectively. The median cost per QALY of rivaroxaban, edoxaban, apixaban, and dabigatran was 21 910$/QALY, 22 096$/QALY, 17 765$/QALY, and 24 161$/QALY, respectively. Subgroup analysis based on perspective showed that dabigatran had the highest incremental cost-effectiveness ratio (ICER) and edoxaban had the lowest ICER value. Edoxaban and apixaban had the highest and the lowest cost per QALY from an insurance perspective, respectively. CONCLUSION: Despite the differences and variations in the economic evaluation studies of NOAC drugs, these drugs have shown acceptable cost-effectiveness in developed and developing countries. Among NOAC drugs, apixaban has the lowest ICER and the highest cost-effectiveness.

Genetic polymorphisms of glucocorticoid receptor and their association with new-onset diabetes mellitus in kidney transplant recipients.

INTRODUCTION: The variability in developing New-onset Diabetes Mellitus After Transplantation (NODAT), together with previously well-established interindividual variation in glucocorticoid sensitivity, led us to hypothesize that polymorphisms in the NR3C1 gene encoding glucocorticoid receptor may alter glucose balance in kidney transplant recipients. This study aimed to evaluate the association of three functional polymorphisms, BclI, N363S, and ER22/23EK, on the NR3C1 gene with NODAT in kidney allograft recipients. METHODS: From Jun 2020 to July 2022 in Shiraz, 52 patients with NODAT (case group) and 52 non-diabetic kidney transplant recipients (control group) were randomly screened and recruited in this case-control study. The PCR-RFLP technique determined the genotypes of BclI, N363S, and ER22/23EK polymorphisms. RESULTS: The allelic frequencies of the mutant alleles of BclI, N363S, and ER22/23EK polymorphisms in all patients were 0.36, 0.03, and 0.009, respectively. BclI mutant genotypes (CG and GG) were significantly associated with an increased risk of NODAT (P = 0.016), while the two other polymorphisms disclosed no significant association with NODAT development. In the case group, no significant association was detected between the onset time of NODAT and studied polymorphisms, including BclI (P = 0.43), N363S (P = 0.30), and ER22/23EK. P value was not reported for the last polymorphism because all patients with NODAT had the wild-type genotype (GG/GG) and performing statistical analysis was not feasible. Among studied demographic/clinical/paraclinical variables, factors such as higher mean trough level of tacrolimus during the first month after transplantation and higher mean daily dose of prednisolone significantly linked with NODAT development. CONCLUSION: Our data suggested that BclI polymorphism significantly affects NODAT development among Iranian kidney allograft recipients.

Evaluation of the Factors Associated with Prescribed and Non-Prescribed Medicine: A Population-Based Study.

OBJECTIVES: Several factors influence medication patterns. The purpose of this study was to look into the role of social determinants in the use of prescribed and non-prescribed medications in a population-based setting of people over 18 in a southern metropolis of Iran (Shiraz) for 2 years. STUDY DESIGN: Prospective population-based cross-sectional. METHODS: This descriptive and cross-sectional survey was done in 2018-2020. A total of 1016 participants were randomly selected based on their postal codes and recruited to the study. The demographic characteristics (age, sex, and education), social profiles (insurance, supplementary insurance, health status, and daily exercise plan), and outpatient visits (family/general physician or specialist/ subspecialist) were recorded by gathering sheets. Descriptive analyses and multinomial logistic analyses were carried out using SPSS software. RESULTS: The medication use pattern was classified into three categories: non-prescribed type I, non-prescribed type II, and prescribed. The mean age of participants was 45.54 ± 15.82 years. The results indicated that most of them took their medication without a prescription (non-prescribed type II). However, people who had insurance and referred to a family physician commonly used the prescribed medications. This study also found that patients who visited a family doctor or a general practitioner used fewer prescribed drugs than those who visited a specialist. CONCLUSION: This study describes social determinants as additional effective factors in health services that influence the use of prescribed and non-prescribed medications in Shiraz. These evidence- based findings can help policymakers to plan the best programs.

The clinical and paraclinical effectiveness of four-hour infusion vs. half-hour infusion of high-dose ampicillin-sulbactam in treatment of critically ill patients with sepsis or septic shock: An assessor-blinded randomized clinical trial.

PURPOSE: This study was conducted to determine whether critically ill patients admitted to the intensive care unit (ICU) with sepsis and septic shock may benefit from extended infusion of ampicillin/sulbactam compared with those receiving intermittent infusion. MATERIAL AND METHODS: This randomized assessor-blinded clinical trial was conducted in the ICUs of Nemazee and Shahid Rajaee hospital, Shiraz, Iran, from August 2019 to August 2021. The participants randomly received 9 g Ampicillin/Sulbactam every 8 h by either extended (infused over 4 h) or intermittent (infused over 30 min) intravenous infusion if their estimated glomerular filtration rate based on Cockrorft-Gault formula was higher than 60 ml/min. RESULTS: Totally, 136 patients were enrolled and allocated to the intervention and control groups, each with 68 patients. Clinical cure was significantly higher in the extended group (P = 0.039), but ICU and hospital length of stay did not differ between the groups (P = 0.87 and 0.83, respectively). The ICU (P = 0.031) and hospital (P = 0.037) mortality rates in the extended infusion group were significantly lower than those in the intermittent infusion group. CONCLUSION: These data should be replicated in larger clinical trials before providing any recommendation in favor of this method of administration in clinical practice.

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

Abstract 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 bio-Rxiv 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 metaanalysis 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.

Evaluation of factors that influenced the length of hospital stay using data mining techniques.

BACKGROUND: length of stay (LOS) is the time between hospital admission and discharge. LOS has an impact on hospital management and hospital care functions. METHODS: A descriptive, retrospective study was designed on about 27,500 inpatients between March 2019 and 2020. Required data were collected from six wards (CCU, ICU, NICU, General, Maternity, and Women) in a teaching hospital. Clinical data such as demographic characteristics (age, sex), type of ward, and duration of hospital stay were analyzed by the R-studio program. Violin plots, bar charts, mosaic plots, and tree-based models were used to demonstrate the results. RESULTS: The mean age of the population was 40.8 ± 19.2 years. The LOS of the study population was 2.43 ± 4.13 days. About 60% of patients were discharged after staying one day in the hospital. After staying one day in the hospital, 67% of women were discharged. However, 23% of men were discharged within this time frame. The majority of LOS in the CCU, ICU, and NICU ranged from 5 to 9 days.; In contrast, LOS was one day in General, Maternity, and Woman wards. Due to the tree plot, there was a different LOS pattern between Maternity-Women and the CCU-General-ICU-NICU wards group. CONCLUSION: We observed that patients with more severe diseases hospitalized in critical care wards had a longer LOS than those not admitted to critical care wards. The older patient had longer hospital LOS than the younger. By excluding Maternity and Woman wards, LOS in the hospital was comparable between males and females and demonstrated a similar pattern.

Evaluation of the Costs and Outcomes of COVID-19 Therapeutic Regimens in Hospitalized Patients in Shiraz.

COVID-19 patients in critical conditions are hospitalized and treated with various protocols including antiviral drugs, which have been updated repeatedly. This study was aimed to analyze the demographics, costs, and outcomes of drug regimens in COVID-19 patients hospitalized in "Ali Asghar" hospital, affiliated with Shiraz University of Medical Sciences, from March 2019 to December 2020 as a retrospective study, approved by the ethics committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1399.1003) on Dec. 28, 2020. Using hospital information system (HIS) data, 2174 patients receiving favipiravir, remdesivir, interferon-ß, and Kaletra® were analyzed. Descriptive, univariate, and regression analyses were used. The costs and consequences of different drug regimens were significantly different (P value < 0.05); the highest and lowest costs belonged to remdesivir and Kaletra®, respectively. The highest and lowest mean length of stay and mortality were related to remdesivir and favipiravir, respectively. Mortality did not differ significantly with various regimens. Length of stay was significantly shorter with favipiravir and Kaletra® than interferon-ß. Remdesivir had significantly the highest cost. Age presented a significantly positive relationship with mortality and length of stay. Besides, ICU admission significantly increased mortality, length of stay, and costs. Underlying diseases and low blood oxygen saturation contributed to mortality. COVID-19 correlation with age and underlying diseases is accordant with the published data. Given the highest costs and broad usage of remdesivir, besides controversies regarding its outcomes and side effects, a stricter evaluation of remdesivir benefits seems essential. Totally, COVID-19 therapeutic protocols should be selected carefully to optimize costs and outcomes.

Pharmacokinetic assessment of vancomycin in critically ill patients and nephrotoxicity prediction using individualized pharmacokinetic parameters.

Introduction: Therapeutic drug monitoring (TDM) and pharmacokinetic assessments of vancomycin would be essential to avoid vancomycin-associated nephrotoxicity and obtain optimal therapeutic and clinical responses. Different pharmacokinetic parameters, including trough concentration and area under the curve (AUC), have been proposed to assess the safety and efficacy of vancomycin administration. Methods: Critically ill patients receiving vancomycin at Nemazee Hospital were included in this prospective study. Four blood samples at various time intervals were taken from each participated patient. Vancomycin was extracted from plasma samples and analyzed using a validated HPLC method. Results: Fifty-three critically ill patients with a total of 212 blood samples from June 2019 to June 2021 were included in this study. There was a significant correlation between baseline GFR, baseline serum creatinine, trough and peak concentrations, AUCτ, AUC24h, Cl, and Vd values with vancomycin-induced AKI. Based on trough concentration values, 66% of patients were under-dosed (trough concentration <15 µg/ml) and 18.9% were over-dosed (trough concentration ≥20 µg/ml). Also, based on AUC24h values, about 52.2% were under-dosed (AUC24h < 400 µg h/ml), and 21.7% were over-dosed (AUC24h > 600 µg h/ml) that emphasizes on the superiority of AUC-based monitoring approach for TDM purposes to avoid nephrotoxicity occurrence. Conclusion: The AUC-based monitoring approach would be superior in terms of nephrotoxicity prediction. Also, to avoid vancomycin-induced AKI, trough concentration and AUCτ values should be maintained below the cut-off points.

Psychiatric Adverse Drug Reactions and Potential Anti-COVID-19 Drug Interactions with Psychotropic Medications.

Coronavirus disease 2019 (COVID-19) management in patients with predisposing psychiatric disorders would be challenging due to potential drug-drug interactions (PDDIs) and precipitation of their disease severity. Furthermore, COVID-19 itself might precipitate or induce unpredicted psychiatry and neuropsychiatry complications in these patients. In this literature review study, the psychological impacts of COVID-19 and major psychiatric adverse drug reactions (ADRs) of COVID-19 treatment options have been discussed. A detailed Table has been provided to assess potential drug-drug interactions of COVID-19 treatment options with psychotropic medications to avoid unwanted major drug-drug interactions. Finally, potential mechanisms of these major drug-drug interactions and possible management of them have been summarized. The most common type of major PDDIs is pharmacokinetics. Hydroxychloroquine/chloroquine and lopinavir/ritonavir were the most involved anti-COVID-19 agents in these major PDDIs.

Association between the Three Polymorphisms of the Glucocorticoid Receptor Gene and the Early Clinical Outcome in Kidney Transplantation Patients.

Background: Glucocorticoids are pivotal components of immunosuppressive regimens in solid organ transplantations. This study aimed to assess the possible association between the ER22/23EK, N363S, and Bcl1 polymorphisms, and short-term clinical outcomes, including acute rejection and delayed graft function (DGF), in kidney transplantation recipients. Methods: A case-control study was conducted in a two-year period on adults with transplanted kidneys, comprised of subjects without rejection (n=50, control) and those with documented rejection within one year after transplantation (n=50, case), between April 2017 and September 2018, in Shiraz, Iran. Demographic characteristics and clinical and paraclinical findings were gathered. The genotyping of the ER22/23EK, N363S, and Bcl1 polymorphisms was carried out via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The association between the genotypes and DGF as well as rejection types was evaluated using either the Chi square test or Fisher exact test. A stepwise logistic regression analysis was conducted to determine the independent factors of acute rejection within the first year after transplantation. Results: The study population consisted of 64 men and 36 women. The frequency of mutated alleles was 0.32 for G (Bcl1), 0.02 for S (N363S), and 0.065 for A (ER22/23EK). There was no significant association either between the studied polymorphisms and acute rejection or between the Bcl1 (P=0.17), N363S (P=0.99), and ER22/23EK (P=0.99) genotypes and DGF. The length of hospital stay after kidney transplantation was slightly more in N363N and ER22/23EK wild allele carriers. However, this difference was not statistically significant. Conclusion: Our data suggested no statistically significant association between the genotypes of the studied polymorphisms and early clinical outcomes after kidney transplantation.

Assessing the Performance of Community Pharmacies in Iran by Measuring Responsiveness to Non-Medical Needs: An Application of WHO Responsiveness Framework.

OBJECTIVE: Despite growing debates about the health systems' nonmedical performance, there has not been any empirical research on nonmedical performance and patients' rights consideration as a driver of human rights in the pharmaceutical sector. This study's main objective was to assess the nonmedical performance of community pharmacies of Shiraz, Iran. METHODS: A cross-sectional study was conducted using two self-administrated Likert-based questionnaires based on the World Health Organization (WHO) responsiveness framework and the legal charter communicated by the Ministry of Health and Medical Education of Iran. The population was patients older than 18 years who took a prescription from community pharmacies located in Shiraz and willing to answer the questions voluntarily, from 2018 to 2019. Considering the weights of subdimensions of responsiveness provided by the WHO framework, the total score of responsiveness was calculated ranging from 0 to 100. FINDINGS: The response rate was 80.5%. The mean (standard deviation) overall score of responsiveness was 57.18 (21.61), with a median of 56.71. The mean score of client orientation was lower in respondents with a high education level than those with a diploma and under diploma (P = 0.028). CONCLUSION: Nonmedical pharmacy performance was considered either medium or high in more than half of the cases based on the participants' views. Regarding client, orientation was seen less often in patients with high education level compared to those with a lower education level.