Samar Farid

In type 2 diabetes mellitus (T2DM), hyperglycemia leads to oxidative insult. Vitamins A and E have antioxidant potentials and may help in managing diabetes. The combined effect of high-dose vitamin A plus E supplementation with and without zinc on T2DM, has never been examined. Thus, this study aimed to evaluate and compare the effect of high-dose vitamin A plus E supplementation (AE) versus high-dose vitamin A plus E with zinc (AEZ), on different diabetic parameters. Ninety-eight patients with T2DM were randomized to receive either: 50,000 IU vitamin A and 100 mg vitamin E (AE group, N = 36), an equivalent dose of vitamin A and E combined with 25 mg zinc (AEZ group, N = 35), or no supplements (control group, N = 27) for three months. Compared to control, AEZ group showed significant reductions in fasting blood glucose, 2 h postprandial blood glucose, and glycated hemoglobin (HbA1c) with significant increases in homeostasis model assessment of beta-cell function and difference value of fasting insulin. Two hair loss cases were recorded in both treated groups. Although vitamin A needs dose moderation, these results suggest that, high-dose vitamin A plus E supplementation combined with zinc may improve glycemic control, β-cell function, and insulin secretion in adults with T2DM.

BACKGROUND: Iron overload-induced oxidative stress and transfusion-acquired hepatitis C viral (HCV) infection are the main reasons of liver damage in beta thalassemia major (β-TM).

OBJECTIVES: Based on metformin's hepatic benefits in non-diabetic populations, the study aims to investigate the safety and the potential hepatoprotective effect of metformin in HCV-infected β-TM adolescent patients.

METHODS: This was a prospective, randomized, parallel, controlled, open label study in which 60 HCV-infected β-TM adolescent patients aged 11 to 18 years and receiving no antiviral therapy; were selected and randomly assigned to treatment or control group in 1:1 allocation. Both groups were receiving β-TM standard of care regimen while metformin (500 mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed-up for six months with assessment of liver biochemical profile, oxidative stress markers, liver fibrosis, clinical symptoms improvement and metformin's adverse effects.

RESULTS: Aspartate aminotransferase serum level decreased significantly over time in the treatment group only (P= 0.013). However, improvement was not clinically significant and did not attain normality. Change in total antioxidant capacity and malondialdehyde serum levels indicated significantly improved oxidative stress status in the treatment group versus significant deterioration in the control group (P ˂ 0.001). Fibrosis grade improvement was observed in 14 patients in the treatment group versus one improved case in the control group.

CONCLUSION: Use of metformin in HCV-infected β-TM adolescent patients as an adjuvant antioxidant hepatoprotective agent is promising and can improve liver damage.

PURPOSE: Vitamin D deficiency is highly prevalent in critically ill patients, and has been associated with more prolonged length of hospital stay and poor prognosis. Patients undergoing open-heart surgery are at higher risk due to the associated life-threatening postoperative complications. This study investigated the effect of alfacalcidol treatment on the length of hospital stay in patients undergoing valve-replacement surgery.

METHODS: This single-center, randomized, open-label, controlled trial was conducted at El-Demerdash Cardiac Academy Hospital (Cairo, Egypt), from April 2017 to January 2018. This study included adult patients undergoing valve-replacement surgery who were randomized to the intervention group (n = 47; alfacalcidol 2 μg/d started 48 h before surgery and continued throughout the hospital stay) or to the control group (n = 42). The primary end points were lengths of stay (LOS) in the intensive care unit (ICU) and in the hospital. Secondary end points were the prevalence of postoperative hospital-acquired infections, cardiac complications, and in-hospital mortality.

FINDINGS: A total of 86 patients were included in the final analysis, with 51 (59.3%) being vitamin D deficient on hospital admission. Treatment with alfacalcidol was associated with a statistically significant decrease in ICU LOS (hazard ratio = 1.61; 95% CI, 1.77-2.81; P = 0.041) and hospital LOS (hazard ratio = 1.63; 95% CI, 1.04-2.55; P = 0.034). Treated patients had a significantly lower postoperative infection rate than did the control group (35.5% vs 56.1%; P = 0.017). The median epinephrine dose was lower in the intervention group compared to that in the control group (5.9 vs 8.2 mg; P = 0.019). The rate of in-hospital mortality was not significantly different between the 2 groups.

IMPLICATIONS: Early treatment with 2 μg of alfacalcidol in patients undergoing valve-replacement surgery is promising and well tolerated. This effect may be attributed to its immunomodulatory and cardioprotective mechanisms. ClinicalTrials.gov identifier: NCT04085770.

BACKGROUND: Coagulopathy and thromboembolic events are common in Covid-19 patients and are poor prognostic factors. Controversy exists regarding the potential of anticoagulation (AC) to reduce mortality and incidence of thromboembolic events in Covid-19 patients. The current systematic review and meta-analysis investigated the association between anticoagulants and mortality in adult hospitalized COVID-19 patients using the available published non-randomized studies.

METHODS: Google Scholar, PubMed, Scopus, the Cochrane Library and Clinical Trials.gov were searched for relevant studies. A meta-analysis of adjusted and unadjusted estimates was performed. The relative risk was used as a measure of effect. The random-effects model was used to pool estimates using the generic inverse variance method.

RESULTS: Sixteen studies were included in the quantitative data synthesis. Results showed a statistically significant association between AC and mortality (RR = 0.56, 95% CI 0.36; 0.92, p = 0.02). Both therapeutic (Relative risk [RR] = 0.4, 95% CI 0.27; 0.57) and prophylactic AC (RR = 0.54, 95% CI 0.41; 0.71) were associated with lower risk of mortality. Pre-admission AC was not associated with mortality (RR = 0.84, 95% CI 0.49; 1.43, p > 0.05) while prophylactic AC was associated with higher risk of mortality compared to therapeutic AC (RR = 1.58, 95% CI 1.34; 1.87, p < 0.001).

CONCLUSION: Findings support the association of AC with mortality in Covid-19 patients. The results, synthesized from mostly low-quality studies, show that prophylactic and therapeutic AC might reduce mortality in Covid-19 patients. Findings suggest that therapeutic doses might be associated with better survival compared to prophylactic doses.

BACKGROUND: Daclatasvir has potent antiviral activity against HCV infection when used in combination with sofosbuvir, however, its pharmacokinetics have not been described in adolescents. The aim is to determine the pharmacokinetic parameters of daclatasvir in adolescents, and to develop a population pharmacokinetic (PopPK) model.

METHODS: Seventeen adolescent patients with genotype-4 chronic HCV infection received once daily oral daclatasvir 60 mg in combination with 400 mg sofosbuvir for 12 weeks. Steady state concentrations were determined. Non-compartmental and population PK were determined.

RESULTS: The average PK parameters calculated by non-compartmental analysis (NCA): maximum plasma concentration (C), area under the curve (AUC), apparent oral volume of distribution (V/F), apparent oral clearance (CL/F) and half-life (T) were 1,092 ng/ml, 11,178 ng/ml•h, 55 l, 4.5 l/h and 8.5 h, respectively. Daclatasvir was best described by one compartment structural PK model with zero order absorption and first-order elimination. The absorption rate constant (K), V/F, and CL/F of the final PopPK model of daclatasvir were 1.5/h, 52 l and 4.7 l/h, respectively. Body weight and serum albumin had significant effect on the V/F parameter.

CONCLUSIONS: Body weight and serum albumin were the major determinants of daclatasvir V/F in this population. PK parameters were comparable to those reported in adult HCV patients, demonstrating that 60 mg daclatasvir is an appropriate dose for adolescents. ClinicalTrials.gov NCT03540212.

The World Health Organization (WHO) promotes health systems strengthening as a means of improving population health, especially in low- and middle-income countries. The United Nations Sustainable Development Goals highlight the importance of investing in workforce development to improve population health and economic well-being. In relation to pharmaceuticals, health systems face challenges in terms of i) guaranteeing access to needed drugs, ii) rationalizing medicines use, and iii) avoiding harm from adverse events. There is a pressing need to better understand the relationships between technology and pharmacy practice when strengthening pharmaceutical care systems. In response, this paper examines ways in which harnessing new technologies can change pharmacy practice and strengthen pharmaceutical systems for the benefit of patients. The paper will present a conceptual framework as well as exploring case studies.

BACKGROUND: Egypt faces many challenges when matching patient needs with available resources. Consequently, there has been an increasing interest in pharmacoeconomics as an aid tool in health decision-making to better allocate resources.

OBJECTIVES: To review and evaluate the volume and the quality of published pharmacoeconomic studies in Egypt.

METHODS: A literature search was conducted in August 2018 using PubMed, Google Scholar, and Cochrane library to identify published Egyptian pharmacoeconomic studies. Articles were included if they were original economic studies, written and published in English, and conducted in Egypt. Each article was assessed independently by two reviewers using the 100-point Quality of Health Evaluation Studies (QHES) scale.

RESULTS: Fifteen studies published between 2002 and 2017 were included in the review. Most of them were cost-effectiveness analyses (60%). The minority used secondary data (33.3%) or adopted modeling techniques (40%). The mean QHES score of the included studies was 70.1 ± 21.8, and approximately 40% of them had a QHES score of more than 80.

CONCLUSION: Pharmacoeconomic evaluations in Egypt are still in their infancy. The Egyptian guidelines for economic evaluation should be adopted and the EQ-5D-5L value sets should be developed to increase the quality of economic research.

INTRODUCTION: Vitamin D binding protein (VDBP) is a potential modulator of immune response and is associated with clinical progression of many diseases. Our aim was to assess influence of baseline 25-hydroxyvitamin D levels and VDBP single nucleotide polymorphisms (SNPs), rs4588 (C > A) and rs7041 (G > T), on baseline clinical parameters and response to interferon based therapy in chronic hepatitis C patients in Egypt.

METHODOLOGY: Genotyping was performed by RFLP (Restriction Fragment Length Polymorphism) in 112 treatment naïve hepatitis C patients and 50 healthy controls. Vitamin D levels were assessed by ELISA. HCV RNA quantification was performed by PCR to assess therapy outcome.

RESULTS: Patients with VDBP WT+ diplotype (3 or 4 VDBP major alleles) had higher viral response rates at weeks 12, 48, and 72 (p = 0.046, 0.034 and 0.029, respectively) and lower base line viral load (p = 0.016). Multivariate logistic regression identified VDBP WT+ diplotype as an independent predictor of sustained viral response (SVR; p = 0.014, RR = 4.716, 95% CI = 1.371 - 16.609). Interestingly, WT- diplotype (less than 3 VDBP major alleles) was associated with significant liver fibrosis (p = 0.045).

CONCLUSIONS: VDBP WT+ diplotype is associated with lower baseline viral load and better therapy outcome in HCV treatment naïve patients. The rs4588 genotype is associated with SVR in the Egyptian population.

AIM: Compare the safety and efficacy of intermittent fenofibrate versus simvastatin in chronic hemodialysis patients.

PATIENTS & METHODS: Sixty patients received either fenofibrate 100 mg or simvastatin 20 mg after their dialysis session (parallel study). The safety and efficacy of drugs on lipid profile, oxidized low-density lipoprotein (Ox-LDL), glutathione peroxidase and C-reactive protein were compared before and after 16-week treatment.

RESULTS: After treatment, significant increase in glutathione peroxidase, significant decrease in total cholesterol, triglycerides, low density lipoprotein (LDL) and ox-LDL (p < 0.05) and no significant changes in C-reactive protein (p > 0.05) were observed in both groups. Both drugs were well tolerated with no serious side effects reported by the patients.

CONCLUSION: Both drugs have comparable efficacy and safety when used as intermittent low dose regimen in hemodialysis. Larger studies with longer follow-up periods are needed to confirm our new findings.