Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancies: A Pharmacokinetic Study.

PURPOSE: Children with hematological malignancies and chronic hepatitis C virus (HCV) infection are at a higher risk for rapid progression of liver disease and malignancy relapse due to multiple hepatitis flares and chemotherapy interruption. They are therefore potential candidates for microelimination of HCV infection. This study aimed to assess the effect of acute lymphoblastic leukemia (ALL) on the pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF) and the SOF major metabolite GS-331007. METHODS: This was a 24-week, prospective, controlled, open-label, 2-arm PK study of patients receiving 45/200 mg once-daily LDV/SOF orally for 12 weeks. Eligible patients were HCV-RNA-positive, treatment-naive children aged 6 to <12 years and/or weighing 17 to <35 kg with genotype 4 chronic HCV infection without cirrhosis. The primary efficacy and safety end points were the achievement of sustained virologic response for all patients with absence of any adverse events leading to permanent discontinuation of the study drug. Steady-state noncompartmental analysis was performed to determine the PK parameters of SOF, GS-331007, and LDV as the primary PK outcome. Dose suitability was based on the 90% CI of exposure geometric mean ratio percentage within 50% to 200% compared with adults. FINDINGS: Ten HCV-infected children with ALL (chemotherapy treatment group) and 12 eligible children with no malignancy (control group) were enrolled and completed the study period. All 22 patients achieved the sustained virologic response with no adverse events leading to interruption or permanent discontinuation of the study drug. Compared with the control group, the ALL group patients had similar SOF, GS-331007, and LDV exposure. Compared with adults, the AUCτ of GS-331007 was lower and the AUCτ and Cmax,ss of SOF and the Cmax,ss of LDV were modestly higher in the ALL group (acceptance limit, 50%-200%). However, the observed efficacy and favorable safety profile made these changes not clinically significant. IMPLICATIONS: Weight-based dosing of LDV/SOF (45/200 mg) is highly effective and safe among genotype 4 HCV-infected children weighing 17 to <35 kg and diagnosed with ALL undergoing maintenance chemotherapy. The similarity in the drug exposure, efficacy, and safety clinical end points between patients with and without hematological malignancy support their therapeutic equivalence. Further studies with a larger sample size may be required to confirm the safety of LDV/SOF in patients with ALL and to recommend appropriate dosing in children with hematological malignancies, if needed. CLINICALTRIALS: gov identifier: NCT03903185.

Effect of Metformin on Oxidative Stress and Left Ventricular Geometry in Nondiabetic Heart Failure Patients: A Randomized Controlled Trial.

Introduction: There is an increasing interest in using metformin in cardiovascular diseases and its potential new roles. Only two randomized controlled trials investigated the effect of metformin in nondiabetic heart failure (HF) patients. However, none of these studies assess the role of metformin in reducing oxidative stress. We hypothesized that metformin might improve oxidative stress and left ventricular remodeling in nondiabetic HF patients with reduced ejection fraction (HFrEF). Methods and Methods: Seventy HFrEF patients (EF 37% ± 8%; median age 66 years) were randomized to metformin (n = 35) or standard of care (SOC) for HF (n = 35) for 6 months in addition to standard therapy. Outcomes included the difference in the change (Δ) in total antioxidant capacity (TAC) and malondialdehyde (MDA), both assessed colorimetrically and left ventricular mass index (LVMI) assessed through transthoracic echocardiography. Results: Compared with the SOC, metformin treatment increased TAC [Δ = 0.12 mmol/L, confidence intervals (95% CIs): 0.03-0.21; P = 0.007]. TAC increased significantly only in the metformin group (0.90 ± 0.08 mmol/L at baseline vs. 1.04 ± 0.99 mmol/L at 6 months, P < 0.05). Metformin therapy preserved LVMI (Δ = -23 g/m2, 95% CI: -42.91 to -4.92; P = 0.014) and reduced fasting plasma glucose (Δ = -6.16, 95% CI: -12.31 to -0.02, P = 0.047) compared with the SOC. Results did not change after adjusting for baseline values. Changes in MDA left ventricular ejection fraction (LVEF) and blood pressure were not significantly different between groups. Conclusion: Metformin treatment in HF patients with reduced LVEF improved TAC and prevented the increase in LVMI compared with the SOC. These effects of metformin warrant further research in HF patients without diabetes to explore the potential benefits of metformin. Trial Registration Number: This protocol was registered in ClinicalTrials.gov under the number NCT05177588.

COVID-19 vaccine hesitancy in Egypt: a cross-sectional study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) vaccine hesitancy is a major problem. This study aimed to determine the factors associated with COVID-19 vaccine acceptance. METHODOLOGY: A cross-sectional survey-based study was conducted on a sample of the Egyptian population using an online survey distributed through social media platforms, including Facebook, WhatsApp, and LinkedIn. The questionnaire was composed of five parts: part I describing the research questionnaire and its aim, part II assessing the demographic data, part III assessing knowledge and attitude towards COVID-19 infection, and part IV and V evaluating knowledge regarding COVID-19 vaccines, factors affecting vaccine acceptance and participants' attitude toward vaccination. Regression models were used to assess factors associated with vaccine acceptability. RESULTS: A total of 24376 responses were included in the statistical analysis. Females represented more than two-thirds of the study sample (70.5%,) and 18-24 years was the most commonly reported age group. Around one-third of the sample were healthcare professionals (HCPs). Only 14.3% of the participants received or registered to receive the vaccine, while 47% refused to be vaccinated. Regression analysis revealed that male gender, secondary education, older age, married or divorced status, presence of comorbidities, and higher level of knowledge regarding the vaccine were significantly associated with high vaccine acceptance. The most important vaccine attributes influencing vaccine selection in the current work were efficacy and safety. CONCLUSIONS: Vaccine hesitancy is currently a major challenge. Governments should design educational campaigns that provide trusted data related to vaccine efficacy and safety to encourage vaccination and enhance awareness.

Total Antioxidant Capacity and Prediabetes Are Associated with Left Ventricular Geometry in Heart-Failure Patients with Reduced Ejection Fraction: A Cross-Sectional Study.

Introduction: Few studies explored the association between total antioxidant capacity (TAC) and left ventricular (LV) geometry in patients with heart failure and reduced ejection fraction (HFrEF). The current study aimed to assess factors associated with LV geometry in HFrEF patients with particular emphasis on oxidative stress and glycemic status. Methods: A cross-sectional study was conducted from July 2021 to September 2022. All consecutive patients with HFrEF who were stabilized on optimal or maximally tolerated heart failure medications were recruited. Patients were classified into tertiles based on TAC and malondialdehyde for correlation with other parameters. Results: TAC was significantly associated with LV geometry (P = 0.01), with higher TAC levels observed in patients with normal LV geometry (0.95 ± 0.08) and concentric hypertrophy (1.01 ± 0.14) than in patients with eccentric hypertrophy (EH) (0.90 ± 0.10). There was a significant positive trend in the association between glycemic state and LV geometry (P = 0.002). TAC showed a statistically significant positive correlation with EF (r = 0.29, P = 0.0064) and a negative correlation with LV internal diameter at end diastole (r = -0.26, P = 0.014), LV mass index (r = -0.25, P = 0.016), and LV mass (r = -0.27, P = 0.009). After adjusting for multiple confounders, prediabetes [odds ratio (OR) = 4.19, P = 0.032] and diabetes (OR = 7.47, P = 0.008) were associated with higher odds of EH than normoglycemic patients. A significant inverse trend was also observed in the association between TAC tertile and the odds of LV geometry (OR = 0.51, P = 0.046). Conclusions: TAC and prediabetes are significantly associated with LV geometry. TAC can be used as an additional marker in HFrEF patients to reflect the severity of the disease. Interventions aimed at managing oxidative stress might be useful in HFrEF patients to reduce oxidative stress and improve LV geometry and quality of life. Trial Registration Number: This study is part of an ongoing randomized clinical trial (ClinicalTrials.gov identifier NCT05177588).

The Egyptian EQ-5D-5L Extensive Pilot Study: Lessons Learned.

OBJECTIVES: To investigate the effect of an extensive pilot phase in improving protocol compliance, face validity, reduction of interviewer effect and prediction errors in the composite time trade-off (cTTO) data elicited as part of the EQ-5D-5L valuation study in Egypt. METHODS: This study used the cTTO data and quality control (QC) reports from the Egyptian EQ-5D-5L valuation study. Three-level mixed models were estimated to test whether interviewer effects were reduced during the pilot phase and subsequent rounds of collected cTTO data. Ordinary least square (OLS) regression analysis was conducted for each interviewer separately to test whether the mean absolute error (MAE) improved as interviewers completed more interviews. Moreover, improvement in protocol compliance, face validity and reduction of prediction errors in the cTTO data were tested. RESULTS: 1180 interviews were conducted by nine interviewers and included in the final analysis, of which 206 interviews were pilot and 974 interviews were actual. There was substantial improvement in the face validity and reduction of prediction errors in the cTTO data where the MAE of the actual data was 0.37, which is much lower than that of the pilot data, which was 0.44. However, there was an initial high level of protocol compliance in terms of the four indicators of the QC tool and the variance attributed to the interviewers was small throughout the whole study. CONCLUSIONS: This study clarified the benefits of the pilot phase and the strict implementation of the QC tool in improving the face validity and the prediction accuracy of the cTTO data. However, a more extensive pilot phase may be more beneficial in EQ-5D-5L valuation studies that have issues initially with protocol compliance and interviewer effects.

Comparison between topical cetirizine with minoxidil versus topical placebo with minoxidil in female androgenetic alopecia: a randomized, double-blind, placebo-controlled study.

Androgenetic alopecia (AGA) is the most common cause of hair loss in both genders with a higher psychological impact on females. Currently, topical minoxidil is the only FDA-approved treatment for female AGA and it needs life-long application and causes side effects. Cetirizine is an antihistamine that may be effective in hair loss treatment. This study aimed to compare the efficacy and safety of topical cetirizine with minoxidil (group 1) versus topical minoxidil with placebo (group 2) in female patients with AGA. This was a double-blind, randomized, controlled, parallel study conducted at Dermatology Clinic, Cairo University Teaching Hospital (Kasr- Al- Ainy), Egypt. Sixty-six patients with female AGA, aged 20-50 years, Sinclair (II-IV), were randomly assigned to one of the 2 groups for 24 weeks. The trichoscopic parameters, patients' self-assessment, side effects and global photographic assessment were evaluated. There was a statistically significant change from baseline in frontal and vertex terminal and vellus hair density (P < 0.0005) with a significant increase in vertex hair shaft thickness and average number of hairs per follicular unit in group 1 (P < 0.05). Patients reported significantly better scores in patient self-assessment in group 1 (P < 0.05). Side effects were not significantly different between groups (P > 0.05). Topical cetirizine increases hair shaft thickness and results in a higher clinical improvement from patients' perspective with a good safety profile (NCT04481412, study start date: July 2020).

Effect of metformin on left ventricular mass and functional parameters in non-diabetic patients: a meta-analysis of randomized clinical trials.

BACKGROUND: Left ventricular hypertrophy is a common finding in patients with ischemic heart disease and is associated with mortality in patients with cardiovascular disease (CVD). Metformin, an antidiabetic drug, has been shown to reduce oxidative stress and left ventricular mass index (LVMI) in animal hypertrophy models. We summarized evidence regarding the effect of metformin on LVMI and LVEF. METHODS: Electronic databases were searched for randomized clinical trials (RCTs) that used metformin in non-diabetic patients with or without pre-existing CVD. The standardized mean change using change score standardization (SMCC) was calculated for each study. The random-effects model was used to pool the SMCC across studies. Meta-regression analysis was used to assess the association of heart failure (HF), metformin dose, and duration with the SMCC. RESULTS: Data synthesis from nine RCTs (754 patients) showed that metformin use resulted in higher reduction in LVMI after 12 months (SMCC = -0.63, 95% CI - 1.23; - 0.04, p = 0.04) and an overall higher reduction in LVMI (SMCC = -0.5, 95% CI - 0.84; - 0.16, p < 0.01). These values equate to absolute values of 11.3 (95% CI 22.1-0.72) and 8.97 (95% CI 15.06-2.87) g/m2, respectively. The overall improvement in LVEF was also higher in metformin users after excluding one outlier (SMCC = 0.26, 95% CI 0.03-0.49, P = 0.03) which translates to a higher absolute improvement of 2.99% (95% CI 0.34; 5.63). Subgroup analysis revealed a favorable effect for metformin on LVEF in patients who received > 1000 mg/day (SMCC = 0.28, 95% CI 0.04; 0.52, P = 0.04), and patients with HF (SMCC = 0.23; 95% CI 0.1; 0.36; P = 0.004). These values translate to a higher increase of 2.64% and 3.21%, respectively. CONCLUSION: Results suggest a favorable effect for metformin on LVMI and LVEF in patients with or without pre-existing CVD. Additional trials are needed to address the long-term effect of metformin. Registration The study was registered on the PROSPERO database with the registration number CRD42021239368 ( https://www.crd.york.ac.uk/prospero ).

A pharmacoeconomic study comparing the use of mycophenolate mofetil or cyclophosphamide as induction therapy in lupus nephritis patients in Egypt.

INTRODUCTION/OBJECTIVES: Lupus nephritis (LN) is a major and serious complication of systemic lupus erythematosus (SLE) and is associated with morbidity and mortality. The difference in drug cost between mycophenolate mofetil (MMF) and cyclophosphamide (CYC) inducing regimens becomes a relevant and realistic issue, especially in developing countries. Thus, this study aims to estimate and compare the costs and outcomes of CYC and MMF for better allocation of resources to reduce the burden on the Egyptian healthcare system. METHODS: A prospective, parallel observational study was conducted at Kasr Al-Aini Hospital between 2018 and 2020. One hundred and twenty-two LN patients were followed up monthly during the study period. Remission and maintenance of renal remission were assessed at 6 and 12 months from the start of therapy. Total direct medical costs associated with both regimens were examined. We applied the cost-minimization analysis method from governmental perspective. Besides, a prospective evaluation of reported changes in health-related quality of life using SF-36 was included in our study. RESULTS: There was no statistically significant difference in treatment response at 6 and 12 months (RR 0.6 [0.26;1.43] and 0.8 [0.27;2.33]), respectively, as well as the incidence of infection episodes between MMF and CYC group (71.4% versus 70.45%, p > 0.05). The average direct medical expenditures per patient in the MMF group were approximately one and half times more than the CYC group (2339.69 $ versus 1329.03 $, p <0.001). CONCLUSION: The CYC arm was associated with lower costs than the MMF arm, with equally effective outcomes indicating that CYC is an attractive treatment option.

Determinants of Health Preferences Using Data from the Egyptian EQ-5D-5L Valuation Study.

OBJECTIVE: The aim of this study was to explore the impact of sociodemographic characteristics and illness experience on time trade-off (TTO)-based utility scores using data from the EQ-5D-5L Egyptian valuation study. METHODS: Data were from the Egyptian valuation study that was conducted using the adapted translated version of the EQ-VT to develop the Egyptian Tariff for the EQ-5D-5L based on preferences of the Egyptian population. Data were analysed using a series of univariate and multivariable censored linear regression models adjusted for severity of health states where the dependent variable was the TTO scores and the independent variables included age, sex, education, geographical region, dwelling, marital status, number of people in the household, employment status, having health insurance, number of chronic conditions, previous experience with illness, and self-rated health. RESULTS: Age, sex, education, marital status, dwelling, region of residence, health insurance and multimorbidity were significantly associated with health state valuations, while employment status, number of people in a household, religion, and previous experience with illness had non-significant associations. CONCLUSION: Age, sex and marital status are the main determinants of health state valuation in the Egyptian population, a finding consistent with those from other countries. Knowing these factors will help tailor health services provided and improve patient-centered care.

Efficacy and safety of azithromycin in Covid-19 patients: A systematic review and meta-analysis of randomized clinical trials.

Azithromycin (AZM) is commonly used in Covid-19 patients based on low-quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta-analysis investigated the safety and efficacy of AZM in treating Covid-19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random-effects model was used to pool estimates using the Paule-Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as 'low' for five of the seven mortality results and as 'some concerns' and 'high' in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid-19 patients (OR = 0.96, 95% CI 0.88-1.05, p = 0.317 based on the random-effect meta-analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49-1.87, p = 0.85) and length of stay (Δ = 1.11, 95% CI -2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid-19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.

The EQ-5D-5L Valuation Study in Egypt.

INTRODUCTION: No value sets exist for either the EQ-5D-3L or the EQ-5D-5L in Egypt, despite local pharmacoeconomic guidelines recommending the use of the EQ-5D to derive utility. Most published Egyptian economic evaluation studies have used utility values from other published studies and systematic reviews. OBJECTIVE: Our objective was to develop an Egyptian EQ-5D-5L value set using the international EuroQol standardized protocol (EQ-VT-2.1). This study is a revision of a previous EQ-5D-5L value set for Egypt retracted by the authors. METHODS: Adult Egyptian participants were recruited from public places using multi-stratified quota sampling based on age, sex, and geographical distribution. Two elicitation techniques were applied: the composite time trade-off (cTTO) and discrete-choice experiments (DCEs). Before actual data collection, interviewers' performance was assessed in a pilot phase. Data were modelled using generalized least squares, Tobit, heteroskedastic, logit, and hybrid models, and the best fitting model was selected based on logical consistency of the parameters, significance level, prediction accuracy, and model parsimony. RESULTS: A total of 1378 interviews were conducted, of which 188 were excluded because they were incomplete and did not comply with the protocol, 216 were pilot interviews, and 974 were included in the final analysis. The heteroskedastic model with constraints (model 4) based on the cTTO data was selected as the preferred model to generate the value set. Values ranged from - 0.964 for the worst health state (55555) to 1 for full health (11111) and 0.948 for 11211, with 1123 of all predicted health states (35.94%) being worse than dead. Mobility had the largest impact on health state preference values. CONCLUSION: This is the first value set for the EQ-5D-5L based on social preferences obtained from a nationally representative sample in Egypt or any Arabic-speaking country. The value set can be used as a scoring system for economic evaluation and to improve the quality of health technology assessment in the Egyptian healthcare system.

EQ-VT protocol: one-size-fits-all? Challenges and innovative adaptations used in Egypt: a cross-sectional study.

OBJECTIVES: To present the challenges and adaptations done to the EuroQol Valuation Technology (EQ-VT) protocol to fit the Egyptian culture during the extensive pilot phase of the Egyptian EuroQol 5 Dimension five level (EQ-5D-5L) valuation study DESIGN: This study was a cross-sectional, interviewer-administered face-to-face survey of representative Egyptians using the Arabic version of the EuroQol Group Valuation Technology (EQ-VT-2.1) and a country specific questionnaire pertaining to participants' demographics and opinions about health, life and death SETTING: Participants were recruited from workplaces, university campuses, sporting clubs, shopping malls and other public areas from different Egyptian governorates representing all geographical areas of the country. PARTICIPANTS: A total of 1378 participants were interviewed from July 2019 to March 2020 by 12 interviewers to select a representative sample in terms of: geographical distribution, age and gender, of which 75 participants did not complete the interview, 298 interviews were pilot and 1005 interviews were real of which 974 interviews were used for the valuation study. Two participants did not complete the country-specific questionnaire but completed the valuation protocol; therefore, 1301 interviews were included in the final analysis of country specific questions. RESULTS: Some modifications were applied to the protocol. The 'wheelchair example' was modified to 'migraine example' since most of the participants in the pilot interviews considered being in a wheelchair 'worse than dead'. There was some ambiguity in the Egyptian translated version for the EQ-5D-5L between levels 4 and 5 of the pain and depression dimensions. This was overcome by using colour coding to express the different levels of severity. A pictorial representation for the EQ-5D-5L health states was used to interview illiterate and less educated participants. CONCLUSION: In the Egyptian valuation study, the modifications made to the EQ-VT protocol made it feasible and culturally acceptable to the Egyptian participants.

Analysis of activities undertaken by ward-based clinical pharmacy technicians during patient hospital journey.

INTRODUCTION: Previous studies recognise insufficient time as an obstacle to pharmacists expanding their clinical-based activities and services. For such a reason, the role of well-trained ward-based clinical pharmacy technicians (CPTs) is to work as an integral part of the pharmacy team to achieve the best patient outcomes and medicines optimisation, releasing pharmacist time to complete more complex clinical-related activities. OBJECTIVE: To demonstrate quantitatively the range and extent of daily activities undertaken by CPTs during a patient's hospital journey. METHOD: A prospective-based study has been designed. All daily working services and activities undertaken by ward-based CPTs within a 450-bed Acute District General hospital were quantitatively collected and documented. Data were collected from five medical, two surgical and one cardiology wards of 30 beds in each over a period of 2 weeks for each ward representing a total of 70 working days (14 weeks, excluding weekends). RESULTS: Results showed the breakdown of seven different ward-based activities throughout a typical working day with the main working load being reviews of the patients' medication charts in order to supply new medicines and refer medicines-related issues to the ward pharmacist, with an average number reviewed of (23.17±0.85) representing 77.23% of the total patients in a 30-bed ward. The CPTs' highest workload was on Mondays and Fridays, mainly during the morning working hours (09:00-12:00). Also, statistically significant differences (p<0.05; Kruskal-Wallis test) existed between the workload of the three different ward specialties (medical, surgical and cardiology) in five clinical activities out of seven undertaken by CPT per day. CONCLUSION: CPTs are completing more than seven different ward pharmacy-related activities which enhance medicines optimisation, medicines management and patient care. They are a valuable resource carrying out many roles which were previously completed by junior pharmacists. Their prioritising of patients for review ensures pharmacists focus their efforts on the most vulnerable patients.

Pharmacoeconomics Education in the Middle East and North Africa Region: A Web-Based Research Project.

OBJECTIVES: Pharmacoeconomics (PE) is a relatively new science that is gaining special attention in many countries of the Middle East and North Africa (MENA) region that have limited healthcare resources. Therefore, education is crucial for capacity building in PE in the region. This study aimed to assess the current status of PE education in schools of pharmacy in the MENA region and shed some light on the role played by ISPOR chapters in PE education. METHODS: A survey containing 5 questions about PE education in 14 MENA countries was self-answered by 2 investigators after screening information available on college or school of pharmacy official websites. RESULTS: Of 176 schools of pharmacy in the MENA region, only 80 offer PE educational courses. Egypt and Jordan have the highest number of schools offering PE teaching, especially on the professional level for undergraduates. The graduate level of PE education was offered mostly in Iran and Egypt. The fundamentals of PE was the topic most taught, whereas decision analysis and modeling topics were the least taught topics. Different ISPOR chapters were found to play a crucial role in developing focused health economics education for better healthcare decision making. CONCLUSIONS: There has been an increase in the number of schools of pharmacy offering PE education in the MENA region; however, PE education and research need improvement. Providing structured PE education should be encouraged to establish the infrastructure needed for allocation of limited healthcare resources. Furthermore, updating websites of schools of pharmacy is essential to obtain a complete picture of the PE education in the MENA region.

Effective and Safe Daclatasvir Drug Exposures Predicted in Children Using Adult Formulations.

BACKGROUND: Sofosbuvir (SOF)/daclatasvir (DCV) is the direct-acting antiviral regimen of choice in many low- and middle-income countries for curative treatment of chronic hepatitis C virus (HCV) infection in adults, but data on the use of DCV in children are lacking. We performed a population pharmacokinetic (PK) analysis to predict DCV exposure in children treated with available adult formulations. METHODS: DCV concentration data from HCV-infected adolescents receiving SOF/DCV [400/60 mg, once daily (OD)] who participated in a PK study in Egypt were used for model development. PK parameters were estimated using a population approach. Monte Carlo simulations were run for virtual children weighing 10 to <35 kg receiving 60 or 30 mg OD, and DCV exposures were compared with adults ranges. RESULTS: Seventeen HCV-infected adolescents (13 males) provided 151 DCV concentrations. Median (range) age was 14 (11-18) years and weight 50 (32-63) kg. In these adolescents receiving 60 mg DCV, median (interquartile range) DCV area under the concentration time curve 0 to 24 hours, maximum concentrations, and minimum concentrations were 11,130 (8140-14,690) ng·h/mL, 1030 (790-1220) ng/mL and 130 (110-220) ng/mL, respectively, compared with 10,343 (7661-14,095) ng·h/mL, 1132 (876-1518) ng/mL and 110 (55.7-192) ng/mL predicted in children 10 to <35 kg receiving 30 mg. The proportion of children with DCV exposures above the adult range rapidly increased for children <30 kg using 60 mg OD, similarly for children 10-14 kg using 30 mg. CONCLUSIONS: DCV 30 mg OD was predicted to achieve effective and safe exposures in children 14 to <35 kg, perhaps down to 10 kg. These results should be validated clinically. Low-cost available adult DCV formulations together with approved pediatric doses of SOF would expand global access to HCV treatment for children.

A prospective, randomised clinical study comparing triple therapy regimen to hydrocortisone monotherapy in reducing mortality in septic shock patients.

OBJECTIVES: This prospective, comparative and randomised clinical study evaluated the effectiveness of triple therapy regimen (hydrocortisone, thiamine and vitamin C) versus hydrocortisone alone in reducing the mortality rate and preventing progressive organ dysfunction in septic shock patients. METHODS: A total of 94 patients were randomly assigned to one of two groups: the first group received hydrocortisone 50 mg/6-h IV for 7 days or till intensive care unit (ICU) discharge, if sooner, followed by tapering. The second group received hydrocortisone 50 mg/6-h IV for 7 days or ICU discharge followed by tapering, vitamin C 1.5 g/6-h IV for 4 days or till ICU discharge and thiamine 200 mg/12-h IV for 4 days or till ICU discharge. RESULTS: The triple therapy regimen showed a non-significant reduction in 28-day mortality compared to hydrocortisone alone (17 [36.2%] vs. 21 [44.7%]; P = .4005), but it was significantly lower than the control group regarding shock time and the duration of vasopressor use in days (4.000 [3.000-7.000]; 5.000 [4.000-8.000], [P = .0100]). The patients in the control group were likely to get 0.59 more in SCr level than those in the intervention group by a linear regression model which was significant (P < .05). Also, the number of patients who developed a fever after 216 hours was significantly higher in the control group (P value = .0299). CONCLUSION: Vitamin C, thiamine, and hydrocortisone regimen for septic shock management showed non-significant efficacy in decreasing 28-day mortality when compared to hydrocortisone monotherapy. On the other hand, it showed significant efficacy in decreasing the shock time and duration on vasopressors.

The EQ-5D-5L Valuation Study in Egypt.

INTRODUCTION: No value sets exist for either the EQ-5D-3L or the EQ-5D-5L in Egypt, despite local pharmacoeconomic guidelines recommending the use of the EQ-5D to derive utility. Most published Egyptian economic evaluation studies have used utility values from other published studies and systematic reviews. OBJECTIVE: Our objective was to develop an Egyptian EQ-5D-5L value set using the international EuroQol standardized protocol (EQ-VT-2.1). METHODS: Adult Egyptian participants were recruited from public places using multi-stratified quota sampling based on age, sex, and geographical distribution. Two elicitation techniques were applied: the composite time trade-off (cTTO) and discrete-choice experiments (DCEs). Before actual data collection, interviewers' performance was assessed in a pilot phase. Data were modelled using generalized least square, Tobit, heteroskedastic, logit, and hybrid models, and the best fitting model was selected based on the value range between observed and predicted values, logical consistency of the parameters, significance level, and prediction accuracy. RESULTS: A total of 1378 interviews were conducted, of which 188 were excluded because they were incomplete or did not comply with protocol, 216 were pilot interviews, and 974 were included in the final analysis. The heteroskedastic model (model 4) based on the cTTO data was selected as the preferred model to generate the value set. Values ranged from - 0.93 for the worst health state (55555) to 1 for full health (11111), with 1136 (36.3%) of all predicted health states being worse than dead. Mobility had the largest impact on health state preference values. CONCLUSION: This is the first value set for the EQ-5D-5L based on social preferences obtained from a nationally representative sample in Egypt or any Arabic-speaking country. The value set can be used as a scoring system for economic evaluations and to improve the quality of health technology assessment in the Egyptian healthcare system.

Awareness of the Egyptian public about COVID-19: what we do and do not know.

To survey the health-seeking behaviors and perspectives of the Egyptian population toward the COVID-19 pandemic. A descriptive survey was designed and disseminated via social media platforms. The survey consisted of 32 questions addressing respondent's demographics, knowledge, practice, and attitude toward the COVID-19 pandemic. A total of 25,994 Egyptians participated in the survey from the 29 Egyptian governorates. More than 99% of the respondents were aware of the COVID-19 pandemic. Responses showed split opinions regarding whether people should wear gloves or masks to prevent COVID-19 infection (47.7% and 49.5% replied with "False", respectively). Almost one-quarter (23.1%) of the respondents went to crowded places during the last 14 days. Calling the emergency hotline and self-isolation at home were the most frequent practices to deal with COVID-19 symptoms (34.1% and 44.5%, respectively). A total of 85% of respondents reported their confidence in the Egyptian healthcare system to win the battle against COVID-19 despite the challenges. A vast majority of this large population sample reported reasonable knowledge levels and potentially appropriate practices toward COVID-19.

The potential hepatoprotective effect of metformin in hepatitis C virus-infected adolescent patients with beta thalassemia major: Randomised clinical trial.

BACKGROUND: Iron overload-induced oxidative stress and transfusion-acquired hepatitis C virus (HCV) infection are the main reasons of liver damage in beta thalassemia major (ß-TM). OBJECTIVES: Based on metformin's hepatic benefits in nondiabetic populations, the study aims to investigate the safety and the potential hepatoprotective effect of metformin in HCV-infected ß-TM adolescent patients. METHODS: This was a prospective, randomised, parallel, controlled, open-label study in which 60 HCV-infected ß-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 ß-TM standard-of-care regimen, whereas metformin (500 mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed up for 6 months with assessment of liver biochemical profile, oxidative stress markers, liver fibrosis, clinical symptom improvement and metformin's adverse effects. RESULTS: Aspartate aminotransferase serum level decreased significantly over time in the treatment group only (P = .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 < .001). Fibrosis grade improvement was observed in 14 patients in the treatment group versus one improved case in the control group. CONCLUSION: The use of metformin in HCV-infected ß-TM adolescent patients as an adjuvant antioxidant hepatoprotective agent is promising and can improve liver damage.