Allopurinol versus Febuxostat: A New Approach for the Management of Hepatic Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) includes patients with hepatic steatosis and at least one of five cardiometabolic risk factors. Xanthine oxidase (XO) represents a treatment target for MASLD. We aimed to evaluate the effect of two xanthine oxidase inhibitors, allopurinol and febuxostat, plus lifestyle modifications compared to lifestyle modifications alone on improving steatosis. Ninety MASLD patients were assigned to one of three groups for three months. Patients with hyperuricemia were given either allopurinol 100 mg or febuxostat 40 mg daily, along with lifestyle modifications. The third control group was only given lifestyle modifications, excluding all patients with hyperuricemia due to ethical concerns. The primary outcome was to measure the change in the controlled attenuation parameter (CAP) score as an indicator of steatosis from baseline after three months. The secondary outcome was to measure the change in serum uric acid (SUA) three months from baseline. The study found that the CAP score decreased significantly in the allopurinol group (p = 0.009), but the decline in the febuxostat or lifestyle groups was non-significant (p = 0.189 and 0.054, respectively). The SUA levels were significantly reduced in both the allopurinol and febuxostat groups (p < 0.001), with no statistical difference between the two groups (p = 0.496).

Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers.

PURPOSE: The purpose of this study is to investigate the effect of sildenafil a CYP3A4 substrate and inhibitor on the pharmacokinetics and safety of saxagliptin. METHODS: Eighteen healthy volunteers were recruited in sequential; single-center study to determine pharmacokinetic parameters of saxagliptin and sildenafil, and (AUC0-∞), (AUC0-t); Cmax; tmax; t½, ke; ka were measured using validated LC-MS/MS method. Therapeutic doses were given as follows: Sildenafil 50 mg single dose on day one, then washout period from day two till day eight. Saxagliptin 5 mg once/day was given from day 9 till day 12; then on day 13, the two drugs were co-administered. Blood samples for pharmacokinetic analysis were collected on days 1 and 13 for sildenafil and on days 12 and 13 for saxagliptin. RESULTS: Saxagliptin ratios of T/R and 90% CI were 132.1% (122.7-142.3) for AUC0-t, and 167.6% (154.6-181.8) for Cmax. On the other hand, sildenafil pharmacokinetics were not affected. Gmax changed from 93.7 mg/dl to 95.6 mg/dl (P > 0.001) and AUCg0-t from 512.8 ng.h/ml to 532.75 ng.h/ml (P > 0.001) after co-administration of both drugs. CONCLUSION: Sildenafil significantly affected the pharmacokinetic parameters of saxagliptin when co-administered. REGISTRATION: This trial was registered at clinicaltrials.gov under identifier number: [NCT04170790] in November 2019.

Efficacy of High-Dose Vitamin C Infusion on Outcomes in Sepsis Requiring Mechanical Ventilation: A Double-Blind Randomized Controlled Trial.

Background: Critically ill patients have an increased requirement for vitamin C in sepsis and these patients have low levels of vitamin C. The researchers validated the efficacy of high-dose vitamin C intravenous infusion (IVI) in patients with sepsis requiring mechanical ventilation. Methods: Forty patients were randomly assigned to 2 groups (20 each) in a 1 : 1 ratio in accordance with the vitamin C treatment regimen: Group I (GI): patients received 1.5 g/6 h vitamin C in 50 ml of dextrose 5% in water (D5W) IVI over 30 minutes for 4 consecutive days; Group II (GII): patients received 100 mg vitamin C/day as a first single dose in 50 ml of D5W IVI over 30 minutes and the other three subsequent doses were 50 ml of plain D5W IVI over 30 minutes for 4 consecutive days. Primary outcomes were the change in sequential organ failure assessment (SOFA) score at day 7, the incidence of ventilator-associated pneumonia (VAP), and the plasma vitamin C level. The glutathione peroxidase (GPX) activity, C-reactive protein (CRP) level, duration of vasopressor therapy, and 28-day mortality were secondary outcomes. Results: The change in SOFA score at day 7 showed a significant difference between GI and GII (p < 0.001). The incidence of early VAP was significantly lower in GI (p=0.044). Vitamin C levels showed a significant rise in GI at day 1 and day 4 (p < 0.001 and p < 0.001, respectively). GPX activity of day 4 and day 7 was significantly higher in GI (p=0.005 and p=0.014, respectively). CRP levels of day 4 and day 7 were significantly higher in GII (p < 0.001 and p < 0.001, respectively). There was a significant difference in 28-day mortality (p=0.038) and duration of vasopressor therapy (p=0.033) in GI compared to GII. Conclusion: The early use of high-dose vitamin C intravenous infusion in patients with sepsis requiring mechanical ventilation in combination with the standard treatment for sepsis lowered the incidence of VAP, increased the antioxidant status, and improved the illness severity. Trial Registration. This trial is registered with ClinicalTrials.gov Identifier (NCT04029675).

The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial.

Background: Empagliflozin is an SGLT2 inhibitor approved for use in patients with diabetes mellitus type 2 (DMT2) with or without other cardiovascular disease. Empagliflozin is taken once daily without rationale on the optimal timing for administration. This study aimed to determine the chronopharmacological effects of morning vs evening administration of empagliflozin (10 mg) in healthy Egyptian adults, by investigating the pharmacokinetics and pharmacodynamics parameters of empagliflozin depending on the intake time. Methods: An open label, sequential, two-way crossover trial comprised of two periods with a washout period of 7 days. All participants received a single oral dose of empagliflozin (JARDIANCE ®; 10 mg film coated tablet) in the evening, and after a seven-day washout period, the morning. Pharmacokinetics parameters (primary endpoints: t max (h), C max (ng/ml), AUC 0-t (ng.h/ml); secondary endpoints: AUC 0 to ∞(ng.h/ml)) were assessed. Method validation was done prior to injection in LC/MS/MS and samples were processed by Liquid-Liquid extraction. The pharmacodynamic profile (UGE 0-24) was determined after method validation (glucose hexokinase method). Results: T max increased by 35% in the evening phase compared to the morning phase, while C max decreased by -6.5% in the evening dose compared to the morning dose. Additionally, AUC 0 to ∞ increased in the evening phase by 8.25% compared to the morning phase. The mean cumulative amount of glucose excreted (UGE ( 0-24)) increased by 43% in the evening dose compared to the morning dose Conclusion: Despite the difference in pharmacokinetics parameters between evening and morning doses, C max, AUC 0-t, AUC 0-∞, didn't differ on the bioequivalence level. In addition, as UGE ( 0-24) didn't statistically differ, thus, we can conclude that there is no statistical significance between the morning and evening doses. Trial registration: Clinal Trials.gov, ID: NCT03895229 (registered on 29 th March 2019).

Clinical effects of simvastatin in chronic hepatitis C patients receiving sofosbuvir/daclatasvir combination. A randomized, placebo-controlled, double-blinded study.

AIM OF THE STUDY: Chronic hepatitis C (CHC) affects more than 71 million people worldwide. Many therapies containing different direct-acting antivirals (DAAs) are now used. However, lipid profile is considered an important outcome with DAAs. So, this study aimed to assess clinical effects of statins in CHC patients. MATERIAL AND METHODS: One hundred patients were recruited from Kobri El koba Armed Forces Hospital and randomly assigned to: the drug group (D;n = 50) receiving simvastatin 10 mg plus sofosbuvir 400 mg/daclatasvir 60 mg (SOF/DAC) daily for 12 weeks; and the placebo group (P; n = 50), receiving placebo plus the same (SOF/DAC) regimen. Sustained virological response at 12 weeks after treatment (SVR12), lipid profile, C-reactive protein (CRP) and fibrosis stage were assessed. RESULTS: One hundred treatment-naïve CHC patients completed 12 weeks of the protocol with no clinically significant side effects. There was an increase in SVR failure rate in P (10%) compared to D (only 2%) but not reaching statistical significant difference; SVR12 (p > 0.05). Logistic regression analysis showed that high baseline CRP, low baseline hemoglobin level and non-statin usage had an independent effect on increasing the probability of SVR failure in both groups; p = 0.03, p = 0.0028, p = 0.02, respectively. CONCLUSIONS: Statins could have an irreplaceable role in successful treatment of CHC patients receiving sofosbuvir/daclatasvir.

Evaluation of pharmacist-led educational interventions to reduce medication errors in emergency hospitals: a new insight into patient care.

BACKGROUND: Medication errors made by nurses are common in general practice and can lead to harm in patients. The aim of this study was to evaluate the impact of pharmacist-led educational implementations in reducing medication errors made by nurses in an emergency hospital in Cairo, Egypt. METHODS: A prospective pre-post-interventional study was conducted in an emergency hospital using direct observation for the detection of errors. The rate and severity of medication errors were determined before and after the implementation of educational tools. RESULTS: In total, 1025 and 1024 patients were examined pre- and post-intervention, respectively. Pharmacist interventions resulted in a significant reduction in the medication error rate from 351 (34.2%) in the pre-intervention phase to 157 (15.3%) in the post-intervention phase (P < 0.001). In both the pre- and post-intervention phases, none of the medication errors were associated with harm/death. Furthermore, all types of medication errors declined as a result of the interventions. CONCLUSION: Clinical pharmacists' interventions focusing on improving nurses' drug knowledge and awareness of errors were shown to be effective in reducing the rate and severity of medication administration errors among nurses in an emergency hospital environment.

Effect of febuxostat on oxidative stress in hemodialysis patients with endothelial dysfunction: a randomized, placebo-controlled, double-blinded study.

PURPOSE: Oxidative stress, which is most likely a key mediator in the development of cardiovascular disease, is implicated in the progression and deterioration of chronic kidney disease. Patients on hemodialysis exhibit the excessive generation of oxidative stressors, which may also be responsible for the endothelial dysfunction prevalent in these patients. Febuxostat, an inhibitor of xanthine oxidase enzyme, is emerging as a novel drug in the amelioration of oxidative stress status. However, studies regarding its effect among hemodialysis patients are still lacking. METHODS: This prospective, block-randomized, double-blinded, placebo-controlled study was carried out to assess the effect of oral 40 mg febuxostat on oxidative stress in hemodialysis patients. In total, fifty-seven eligible patients were randomly assigned to either a drug group or a placebo group for the 2-month study period. Serum malondialdehyde (MDA) and serum superoxide dismutase (SOD) were assessed at baseline and at the end of the study. A correlation analysis between previously reported serum asymmetric dimethylarginine (ADMA), serum MDA and serum SOD was performed. RESULTS: Febuxostat significantly decreased the serum MDA and significantly increased the serum SOD, while no significant results were observed in the placebo group. A highly positive correlation between the MDA levels and ADMA levels at baseline was noticed in both groups, while there was a highly negative correlation between the SOD levels and ADMA levels at baseline in both groups. A positive correlation between the change in ADMA levels and MDA levels from baseline was observed only in the drug group. CONCLUSION: Febuxostat appears to have a direct ameliorating effect on oxidative stress in hemodialysis patients with endothelial dysfunction.

Effect of Omega-3 Fatty Acids on Serum Lipid Profile and Oxidative Stress in Pediatric Patients on Regular Hemodialysis: A Randomized Placebo-Controlled Study.

OBJECTIVE: We sought to evaluate the effects of omega-3 fatty acids supplementation on serum lipid profile and oxidative stress markers in pediatric patients with end-stage renal disease on regular hemodialysis (HD). DESIGN: This study was a double-blinded, randomized, placebo-controlled trial conducted on 49 pediatric patients on regular HD for at least 6 months. INTERVENTION: Patients were randomly divided into either omega-3 group (n = 25) who received 1-g oral omega-3 capsule once daily for 16 weeks or placebo group (n = 24) who received 1-g matching oral placebo capsule once daily for 16 weeks. MAIN OUTCOME MEASURE: Lipid profile markers including: total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and oxidative stress markers including the following: malondialdehyde, glutathione peroxidase, and superoxide dismutase were measured at baseline and after 16 weeks of supplementation. RESULTS: By the end of the study, children in omega-3 group showed a highly significant reduction in total cholesterol and a highly significant increase in glutathione peroxidase and superoxide dismutase levels. CONCLUSION: The administration of omega-3 has a beneficial effect on serum lipid profile and oxidative stress in children undergoing HD.

FAS and FASL genetic polymorphisms impact on clinical outcome of malignant pleural mesothelioma.

BACKGROUND: FAS-670 A>G (rs1800682) and FASL-844 C>T (rs763110) polymorphisms have been previously correlated with clinical outcome of non-small cell lung cancer (NSCLC) and breast and bladder cancers. We investigated the influence of these polymorphisms on clinical outcome of malignant pleural mesothelioma (MPM) patients. PATIENTS AND METHODS: In this cohort study (NCT02269878), 68 epithelioid MPM Egyptian patients treated with first-line platinum-based chemotherapy were recruited in the period between April 2014 and May 2015. The genotype analysis was performed using TaqMan® single-nucleotide polymorphism genotyping assay. The association between the selected polymorphisms and response rate, progression-free survival (PFS) and overall survival (OS) at 18 months was evaluated. RESULTS: The median age of patients was 55 years and 45.6% of them received platinum in combination with pemetrexed, while 54.4% received platinum in combination with gemcitabine. FASL-844 CC genotype was more common than expected in early-stage tumor (P=0.042). It was found that there was no association between the investigated polymorphisms and response rate or 18-month OS. However, the PFS rate at 18 months for FASL-844 CC genotype carriers was 45% versus 10.6% for FASL-844 CT/TT genotypes carriers (log-rank: 6.2; P=0.013). Also, the number of platinum-based cycles and tumor stage were found to be significant variables for PFS by univariate analysis (P≤0.001 and P=0.006, respectively). Stratified Cox regression showed that the carriers of FASL-844 CT/TT genotypes were still more susceptible to disease progression than carriers of FASL-844 CC genotype (adjusted HR =3.77, 95% CI: 1.34-10.62, P=0.012). CONCLUSION: The results of this study suggest that FASL-844 C/T polymorphism could predict PFS in MPM patients receiving platinum-based chemotherapy; therefore, this should be further evaluated as a potential marker for the prediction of clinical outcome in patients with MPM.