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.

Design, development, implementation, and evaluation of a severe drug-drug interaction alert system in the ICU: An analysis of acceptance and override rates.

BACKGROUND AND OBJECTIVE: The override rate of Drug-Drug Interaction Alerts (DDIA) in Intensive Care Units (ICUs) is very high. Therefore, this study aimed to design, develop, implement, and evaluate a severe Drug-Drug Alert System (DDIAS) in a system of ICUs and measure the override rate of this system. METHODS: This is a cross-sectional study that details the design, development, implementation, and evaluation of a DDIAS for severe interactions into a Computerized Provider Order Entry (CPOE) system in the ICUs of Nemazee general teaching hospitals in 2021. The patients exposed to the volume of DDIAS, acceptance and overridden of DDIAS, and usability of DDIAS have been collected. The study was approved by the local Institutional Review Board (IRB) and; the ethics committee of Shiraz University of Medical Science on date: 2019-11-23 (Approval ID: IR.SUMS.REC.1398.1046). RESULTS: The knowledge base of the DDIAS contains 9,809 severe potential drug-drug interactions (pDDIs). A total of 2672 medications were prescribed in the population study. The volume and acceptance rate for the DDIAS were 81 % and 97.5 %, respectively. The override rate was 2.5 %. The mean System Usability Scale (SUS) score of the DDIAS was 75. CONCLUSION: This study demonstrates that implementing high-risk DDIAS at the point of prescribing in ICUs improves adherence to alerts. In addition, the usability of the DDIAS was reasonable. Further studies are needed to investigate the establishment of severe DDIAS and measure the prescribers' response to DDIAS on a larger scale.

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.

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.

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.

A Brief Review of Pharmacokinetic Assessments of Vancomycin in Special Groups of Patients with Altered Pharmacokinetic Parameters.

Vancomycin is considered the drug of choice against many Gram-positive bacterial infections. Therapeutic drug monitoring (TDM) is essential to achieve an optimum clinical response and avoid vancomycin-induced adverse reactions including nephrotoxicity. Although different studies are available on vancomycin TDM, still there are controversies regarding the selection among different pharmacokinetic parameters including trough concentration, the area under the curve to minimum inhibitory concentration ratio (AUC24h/MIC), AUC of intervals, elimination constant, and vancomycin clearance. In this review, different pharmacokinetic parameters for vancomycin TDM have been discussed along with corresponding advantages and disadvantages. Also, vancomycin pharmacokinetic assessments are discussed in patients with altered pharmacokinetic parameters including those with renal and/or hepatic failure, critically ill patients, patients with burn injuries, intravenous drug users, obese and morbidly obese patients, those with cancer, patients undergoing organ transplantation, and vancomycin administration during pregnancy and lactation. An individualized dosing regimen is required to guarantee the optimum therapeutic responses and minimize adverse reactions including acute kidney injury in these special groups of patients. According to the pharmacoeconomic data on vancomycin TDM, pharmacokinetic assessments would be cost-effective in patients with altered pharmacokinetics and are associated with shorter hospitalization period, faster clinical stability status, and shorter courses of inpatient vancomycin administration.

Compliance with Antibiotics Prophylaxis Guideline in Surgical Patients in ICUs of a Teaching Referral Hospital.

Antimicrobial prophylaxis used for surgical procedures remains one of the measures for the prevention of surgical site infections (SSIs). The present study was designed to assess the compliance with clinical practice guideline for antimicrobial prophylaxis in variable surgeries conducted in the intensive care units (ICUs) of a major referral hospital. This cross-sectional investigation was carried out by prospective data collected from October 2017 to March 2018 in the intensive care unit (ICU) of Nemazi hospital in Shiraz. Demographic characteristics, surgery type as well as antibiotic treatment were gathered from medical records and entered in data collection forms. We reviewed compliance and adherence of prophylactic antibiotic administration to the Infectious Diseases Society of America (IDSA) guideline and evaluated the courses of antimicrobial drugs. If an antibiotic administrated for surgical prophylaxis was different from the guideline, the antibiotic was classified as non-guideline-based antibiotics. Most patients participated in this study were male (64.5%). Only 8.75% of the administrated antibiotics chosen for surgical prophylaxis were found to be appropriate antibiotic prescriptions; however, those patients receiving appropriate antibiotics prescribed an inappropriate dosage. In addition, the antibiotics were administrated with inappropriate durations in all cases. Our findings indicated that adherence to the IDSA international guideline seems to be far from ideal in Namazi hospital for antimicrobial prophylaxis, resulting in the unsuitable administration of a wide variety of antibiotics.

The effect of nanocurcumin on the incidence of atrial fibrillation, and markers of inflammation and oxidative stress level after coronary artery bypass graft surgery: A randomized, double-blind, placebo-controlled clinical study.

Objective: Postoperative atrial fibrillation (POAF) is the most frequent dysrhythmias observed following coronary artery bypass graft (CABG) surgery. Several studies have shown the beneficial effects of curcumin on cardiovascular diseases; however, there is no clinical trial to examine its effect on POAF. This randomized, double-blind, placebo-controlled clinical study was designed to evaluate the prophylactic effects of a nano-formulation of curcumin (SinaCurcumin™) versus placebo on POAF and levels of biomarkers of inflammation and oxidative stress in patients undergoing CABG surgery. Materials and Methods: A total of 234 eligible patients were randomized to receive 240 mg curcumin nano-formulation or placebo three days prior to the surgery and on the first four postoperative days. The occurrence of POAF was monitored for at least 96 hr after the surgery. Also, C-reactive protein (hs-CRP), malondialdehyde (MDA) and glutathione (GSH) levels were assessed at baseline and the end of the study. Results: Analyses were done in the intention-to-treat population. No significant difference was observed in the occurrence of POAF between the treatment (9.5%) and placebo (11.5%) groups. Also, curcumin intervention did not alter serum concentration of the hs-CRP, MDA, or GSH in comparison with placebo. Conclusion: In conclusion, it seems that perioperative treatment with SinaCurcumin™ did not prevent POAF after CABG surgery.

The effect of taurine supplementation on delirium post liver transplantation: A randomized controlled trial.

BACKGROUND & AIMS: Delirium is a prevalent complication of liver transplantation (LT). It may enhance the risk of morbidity and mortality. Taurine is considered to have antioxidant and neuroprotective activities. The aim of this study was to evaluate taurine supplementation effect on post-LT delirium. METHODS: Patients older than 18 years old who had received LT in Abu-Ali Sina transplantation center in Shiraz, Iran from September 2020 to June 2021, were enrolled in this double-blinded randomized clinical trial. Exclusion criteria was known hypersensitivity to taurine, pregnancy or breast-feeding and death within 72 h post-LT. Patients were randomly divided into two groups, each received 2 g/day placebo or taurine from the first day post-LT for 30 days. Delirium was assessed using Confusion Assessment Method-Intensive Care Unit (CAM-ICU). Mortality and rejection rates and length of Intensive Transplantation Unit (ITU) and hospital stays were evaluated within one month after transplantation. RESULTS: Two hundred and seven patients were divided into two groups. Twenty-eight and 23 patients were excluded due to their refuse to participate in the study and death within 72 h post-LT, respectively. Delirium rate within the first month was 23.08% and was significantly lower in taurine group (9.46%) compared with placebo (35.36%, P = 0.012). Length of ITU stay was significantly higher among delirious patients (P = 0.015) in this analysis. CONCLUSION: we reached to the result that taurine can prevent post-LT delirium, dramatically. Placebo receiving and longer stay in ITU were the only independent risk factors in this trial. REGISTRATION NUMBER OF CLINICAL TRIAL: The study was registered at the Iranian Registry of Clinical Trials (IRCT20200312046755N1; http://www.irct.ir/).

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.

Immune Targeted Therapies for COVID-19 Infection: A Narrative Review.

In December 2019, the coronavirus disease-2019 (COVID-19) outbreak emerged in Wuhan, China. The World Health Organization officially declared it a pandemic on March 11, 2020. Reports indicated that the associated mortality of the infection is quite higher in the elderly, individuals with specific comorbidities (such as diabetes mellitus), and generally the ones with a compromised immune system. A cohort study in Wuhan, China, reported a dysregulated immune response in 452 patients with laboratory-confirmed COVID-19. As a result of this suppressed immune response, an increase in neutrophil to lymphocyte ratio, T lymphopenia, and a decrease in CD4+ T cells were all common laboratory findings, especially in severe cases. On the other hand, there is substantial evidence of T cell exhaustion in critically ill patients. Accordingly, the immune system seems to play an important role in the prognosis and pathogenesis of the disease. Therefore, this study aims to review the evidence on the immune response dysregulation in COVID-19 infection and the potential role of immunoregulatory treatments such as immune checkpoint inhibitors, interferons, and CD200 inhibitors in altering disease prognosis, especially in critically ill patients.

Molecular-based detection of Leishmania tropica isolates among sensitive, resistant, and relapsed patients treated with Meglumine Antimoniate.

The appearance of resistance to pentavalent antimony, as the mainline of treatment for Cutaneous Leishmaniasis (CL) has been reported from Iran. According to the patients' laboratory and clinical history, 96 archived slides of patients infected with Leishmania tropica (L. tropica) treated with Meglumine Antimoniate (Glucantime®) were selected. After microscopic examination, Nested Polymerase Chain Reaction (Nested-PCR) and Restriction Fragment Length Polymorphism (RFLP) assays were done for each sample. In Nested-PCR, all positive samples were characterized as L. tropica. Additionally, some positive products of sensitive, resistant, and recidivans cases were selected to check their differentiations by sequencing software. In RFLP, various patterns of schizodemes were detected according to the reference patterns. Most sensitive cases of L. tropica (treated with Glucantime®) were categorized as schizodeme B, and most resistant cases were identified as schizodeme B and D. In recidivans cases, 91% of specimens categorized as schizodeme A and B. However, study on the type of L. tropica isolates that are resistant or sensitive to Glucantime® could be helpful before drug therapy.

Pharmacological agents for the prevention of colistin-induced nephrotoxicity.

BACKGROUND: Colistin is a polymyxin antibiotic which has been used for treatment of Gram-negative infections, but it was withdrawn due to its nephrotoxicity. However, colistin has gained its popularity in recent years due to the reemergence of multidrug resistant Gram-negative infections and drug-induced toxicity is considered as the main obstacle for using this valuable antibiotic. RESULTS: In total, 30 articles, including 29 animal studies and one clinical trial were included in this study. These compounds, including aged black garlic extract, albumin fragments, alpha lipoic acid, astaxanthin, baicalein, chrysin, cilastatin, colchicine, curcumin, cytochrome c, dexmedetomidine, gelofusine, grape seed proanthocyanidin extract, hesperidin, luteolin, lycopene, melatonin, methionine, N-acetylcysteine, silymarin, taurine, vitamin C, and vitamin E exhibited beneficial effects in most of the published works. CONCLUSIONS: In this review, the authors have attempted to review the available literature on the use of several compounds for prevention or attenuation of colistin-induced nephrotoxicity. Most of the studied compounds were potent antioxidants, and it seems that using antioxidants concomitantly can have a protective effect during the colistin exposure.

Usability of Venous Thromboembolism Prophylaxis Recommender System: A Pilot Study.

Poor usability of clinical decision support system impact negative on healthcare professionals, decrease usage and quality of clinical decision support system and result in a negative effect on patient outcome. Therefore, the objective of this study was the usability evaluation of the venous thromboembolism prophylaxis recommendation system. This study design is a pilot study. Totally seven individuals participate in the study that 4 out of 7 were ICU attending and 3 out of 7 were Residents in ICUs setting. System Usability Scale (SUS) was used to assess the usability of the clinical decision support system (venous thromboembolism prophylaxis recommendation system) integrated into the medication order entry system in the ICU setting. This study has shown that the mean System Usability Scale (SUS) score was 74.64. Summing up the results, it can be concluded that the usability quality of the venous thromboembolism prophylaxis recommendations system is good. Further research requires to evaluate the usability of the venous thromboembolism prophylaxis recommendation system by quantitative and qualitative methods in large scale.

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.

A focused review on technologies, mechanisms, safety, and efficacy of available COVID-19 vaccines.

>20 months has been passed since the detection of the first cases of SARS-CoV-2 infection named COVID-19 from Wuhan city of China. This novel coronavirus spread rapidly around the world and became a pandemic. Although different therapeutic options have been considered and approved for the management of COVID-19 infection in different stages of the disease, challenges in pharmacotherapy especially in patients with moderate to severe COVID-19 and with underlying diseases have still remained. Prevention of infection through public vaccination would be the only efficient strategy to control the morbidity and mortality caused by COVID-19. To date, several COVID-19 vaccines using different platforms including nucleic acid-based vaccines, adenovirus-based vaccines, protein-based vaccines, and inactivated vaccines have been introduced among which many have received approval for prevention against COVID-19. In this comprehensive review, available COVID-19 vaccines have been discussed. The mechanisms, safety, efficacy, dosage, dosing intervals, possible adverse reactions, storage, and coverage of these four different vaccine platforms against SARS-CoV-2 variants have been discussed in detail and summarized in tabular format for ease of comparison and conclusion. Although each COVID-19 vaccine has various advantages and disadvantages over the others, accessibility and affordability of approved vaccines by the official health organizations, especially in developing countries, would be essential to terminate this pandemic. The main limitation of this study was the lack of access to the clinical data on available COVID-19 vaccines developed in Eastern countries since the data on their efficacy, safety, and adverse reactions were limited.

Administration of COVID-19 vaccines in immunocompromised patients.

Since the beginning of vaccination programs against COVID-19 in different countries, several populations such as patients with specific immunological conditions have been considered as the priorities for immunization. In this regard, patients with autoimmune diseases or those receiving immunosuppressive agents and anti-cancer therapies, need special attention. However, no confirmed data is presently available regarding COVID-19 vaccines in these populations due to exclusion from the conducted clinical trials. Given the probable suppression or over-activation of the immune system in such patients, reaching a consensus for their vaccination is critical, besides gathering data and conducting trials, which could probably clarify this matter in the future. In this review, besides a brief on the available COVID-19 vaccines, considerations and available knowledge about administering similar vaccines in patients with cancer, hematopoietic stem cell transplantation, solid organ transplantation, multiple sclerosis (MS), inflammatory bowel disease (IBD), and rheumatologic and dermatologic autoimmune disorders are summarized to help in decision making. As discussed, live-attenuated viruses, which should be avoided in these groups, are not employed in the present COVID-19 vaccines. Thus, the main concern regarding efficacy could be met using a potent COVID-19 vaccine. Moreover, the vaccination timing for maximum efficacy could be decided according to the patient's condition, indicated medications, and the guides provided here. Post-vaccination monitoring is also advised to ensure an adequate immune response. Further studies in this area are urgently warranted.

The effect of silymarin on liver enzymes and antioxidant status in trauma patients in the intensive care unit: a randomized double blinded placebo-controlled clinical trial.

AIM OF THE STUDY: This study was conducted to investigate the positive effect of silymarin on liver enzymes and antioxidant status in trauma patients with elevated liver enzymes due to trauma-induced liver injury, admitted to the intensive care unit. MATERIAL AND METHODS: This one-year, randomized, double-blinded, placebo-controlled clinical trial was conducted on 90 trauma patients. The participants were assigned to either receiving Livergol tablets containing 140 mg of silymarin or 140 mg of placebo three times daily for 14 days. Liver enzymes, including aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), were measured at baseline and days 3, 7, 9 and 14 after intervention. Also, antioxidant markers were measured at baseline and day 14 after treatment. RESULTS: Receiving silymarin supplement significantly lowered the liver enzymes, compared to placebo (p < 0.05). The mean serum level of malondialdehyde (MDA) was significantly decreased and the mean serum levels of total antioxidant capacity (TAC) and thiol groups were significantly increased in the silymarin group from baseline to day 14. In the placebo group, mean serum levels of MDA and thiol groups were significantly increased, while serum level of TAC was not significantly changed at day 14, compared to baseline. Also, the mean serum level of MDA was significantly lower, while the serum levels of thiol groups and TAC were significantly higher in the silymarin group. CONCLUSIONS: Silymarin supplementation significantly improved some antioxidant markers (TAC and thiol) and decreased liver enzymes in patients with trauma-induced liver injury.

Major Neurologic Adverse Drug Reactions, Potential Drug-Drug Interactions and Pharmacokinetic Aspects of Drugs Used in COVID-19 Patients with Stroke: A Narrative Review.

Stroke has been considered as one of the underlying diseases that increases the probability of severe infection and mortality. Meanwhile, there are ongoing reports of stroke subsequent to COVID-19 infection. In this narrative paper, we reviewed major neurologic adverse drug reactions (ADRs) and pharmacokinetics of drugs which are routinely used for COVID-19 infection and their potential drug-drug interactions (PDDIs) with common drugs used for the treatment of stroke. It is highly recommended to monitor patients on chloroquine (CQ), hydroxychloroquine (HCQ), antiviral drugs, and/or corticosteroids about initiation or progression of cardiac arrhythmias, delirium, seizure, myopathy, and/or neuropathy. In addition, PDDIs of anti-COVID-19 drugs with tissue plasminogen activator (tPA), anticoagulants, antiaggregants, statins, antihypertensive agents, and iodine-contrast agents should be considered. The most dangerous PDDIs were interaction of lopinavir/ritonavir or atazanavir with clopidogrel, prasugrel, and new oral anticoagulants (NOACs).