Sara Mahmoud Shaheen

Non-responsive cycles during ovulation induction with letrozole (LZ) often necessitate the use of human menopausal gonadotropin (HMG), which may be associated with undesirable adverse effects. Therefore, strategies to improve the therapeutic outcomes of LZ are needed. This trial aimed to evaluate the impact of combining alpha-lipoic acid (ALA) with LZ on ovulation induction in women with polycystic ovary syndrome (PCOS). This randomized controlled trial included 151 infertile women with PCOS who were randomly allocated to either the LZ group ( n = 76) or the ALA group ( n = 75). The LZ group received LZ (2.5–7.5 mg) with lifestyle modification for up to three treatment cycles or until pregnancy occurred. The ALA group received the same regimen in addition to ALA (1800 mg/day), which was discontinued on the day of human chorionic gonadotropin (HCG) injection in ovulatory patients. Ovulation and pregnancy rates were assessed, along with hormonal parameters. Ovulation per cycle was significantly higher in the ALA group [153/166 (92.2%)] compared with the LZ group [146/203 (71.9%)] ( P = 0.035). Moreover, pregnancy per cycle was significantly higher in the ALA group than in the LZ group ( P = 0.033). Although serum estradiol, mid-luteal progesterone, and endometrial thickness showed numerically higher values in the ALA group, the differences between the groups were not statistically significant after Bonferroni adjustment. The addition of ALA to LZ improved ovulation and pregnancy outcomes and was associated with favorable metabolic and hormonal effects in women with PCOS.

Children undergoing chronic hemodialysis are exposed to persistent oxidative stress and systemic inflammation, contributing to long-term cardiovascular complications. Melatonin (MLT) is a pleiotropic hormone with potential antioxidant and anti-inflammatory effects. Due to scarcity of studies on pediatrics this study sought to investigate the effects of MLT on oxidative stress and inflammation in pediatric hemodialysis patients. This prospective, block-randomized, double-blinded, placebo-controlled study aimed at assessing the effect of 5 mg MLT on oxidative stress and inflammation in pediatric hemodialysis patients. Forty eligible patients were randomly allocated into either MLT or placebo group. Serum malondialdehyde (MDA), nuclear factor kappa B (NF-κB) levels and lipid profile were measured at baseline and at the end of the study after 12 weeks. MLT significantly reduced the median percent change of serum NF-κB − 5.404(− 58.25–129.7) with p-value = 0.027 in addition to reduction in median total cholesterol in the MLT group from 163.7(134.5–259.5) at baseline to 144(113–242) at the end of the study with p-value = 0.038 and reduction of low-density lipoprotein levels from 96(78–183) to 78.5(48–171) at the end of the 12 weeks with p-value = 0.002 while there was no significance in the placebo group. Although, there was no statistical significance in serum MDA levels in the MLT group but significant increase in MDA levels in the placebo group was detected. MDA levels increased from 11.79 ± 5.078 to 14.79 ± 4.257 at the end of the study in the placebo group with p-value = 0.048, supplementation appears to have beneficial effects on ameliorating inflammation and reducing serum lipids. Moreover, MLT may have a protective antioxidant effect by reduction and inhibition of elevation of serum MDA levels. Trial registration : The study was registered on ClinicalTrials.gov (identifier: NCT05570526 https://clinicaltrials.gov/study/NCT05570526 ), on 6th of October 2022

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).

Renal Organic Cation Transporter 2 (OCT2) plays a major role in metformin elimination. Daclatasvir, a Direct-Acting Antiviral (DAA), is an OCT2 inhibitor. Our study aimed to assess the potential interaction of daclatasvir with metformin pharmacokinetics and pharmacodynamics at two metformin doses. Twenty subjects were randomized in a two-period crossover study. The subjects received metformin 500 mg twice daily either alone (R1) or with daclatasvir 60 mg once daily (T1), followed by 1000 mg metformin twice daily either alone (R2) or with daclatasvir 60 mg once daily (T2). Metformin Cmax was higher in T1 and T2 than in R1 and R2 by 12% and 11%, respectively, with a geometric mean ratio (GMR) of 1.12 (90% CI: 0.98-1.26) and 1.12 (90% CI: 0.86-1.36), respectively. Renal clearance (Clr) was lower in T1and T2 compared to R1 and R2 by 15% and 11%, with a GMR of 0.85 (0.68-1.02) and 0.89 (0.69-1.09), respectively. The differences from baseline glucose level (ΔG %) and the area under the Δ G%-time curve (Δ AUG %) were higher for the 500 mg dose of metformin with daclatasvir (p < 0.05). Daclatasvir slightly altered the pharmacokinetics of metformin with a minor alteration of pharmacodynamics of the 500 mg dose.

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 (AUC_0-∞), (AUC_0-t); C_max; t_max; t_½, k_e; k_a 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 AUC_0–t, and 167.6% (154.6–181.8) for C_max. On the other hand, sildenafil pharmacokinetics were not affected. G_max changed from 93.7 mg/dl to 95.6 mg/dl (P > 0.001) and AUC_g0-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.

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).

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-naive 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.

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. 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. 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. Febuxostat appears to have a direct ameliorating effect on oxidative stress in hemodialysis patients with endothelial dysfunction.

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. 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. 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. 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.