Enhanced skin targeting of retinoic acid spanlastics: in vitro characterization and clinical evaluation in acne patients.

Acne vulgaris is the most common dermatological disorder affecting millions of individuals. Acne therapeutic solutions include topical treatment with retinoic acid (RA) which showed a good efficacy in treatment of mild and moderate cases. However, the high prevalence of adverse events, such as skin dryness, shedding and skin irritation affects the patient convenience and obstruct the acne treatment. Thus, the objective of this paper was to produce Span 60 based elastic vesicles enriched with penetration enhancers, and study their influence on the delivery of RA and its skin irritation. RA-loaded nanovesicles, enriched with Transcutol®/Labrasol®, were made using the thin film hydration technique, and assessed for entrapment efficiency, particle size and zeta potential. The optimized RA-loaded nanovesicles (composed of Span 60-Tween 20, and Transcutol®) were morphologically assessed via transmission electron microscopy. Moreover, RA deposition into newborn mice skin was assessed in vitro under non-occlusive conditions, where the optimized RA-loaded nanovesicles showed 2-fold higher RA deposition in the skin compared to the corresponding one lacking Transcutol. The optimized RA-loaded nanovesicles incorporated into 1% carbopol gel was evaluated for in-vivo clinical performance in acne patients, and showed appreciable advantages over the marketed formulation (Acretin®) in the treatment of acne regarding skin tolerability and patient's compliance.

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.

Validation of pharmacogenetic algorithms and warfarin dosing table in Egyptian patients.

BACKGROUND: Warfarin remains a difficult drug to use due to the large variability in dose response. Clear understanding of the accuracy of warfarin pharmacogenetic dosing methods might lead to appropriate control of anticoagulation. OBJECTIVE: This study aims to evaluate the accuracy of warfarin dosing table and two pharmacogenetic algorithms, namely the algorithms of Gage et al. (Clin Pharmacol Ther 84:326-331, 2008), and the International Warfarin Pharmacogenetics Consortium algorithm (IWPC) in a real Egyptian clinical setting. Additionally, three non-pharmacogenetic dosing methods (the Gage, IWPC clinical algorithms and the empiric 5 mg/day dosing) were evaluated. SETTING: Sixty-three Egyptian patients on a stable therapeutic warfarin dose were included. Patients were recruited from the outpatient clinic of the critical care medicine department. METHODS: CYP2C9 and VKORC1 polymorphisms were genotyped by real time PCR system. Predicted doses by all dosing methods were calculated and compared with the actual therapeutic warfarin doses. RESULTS: The Gage algorithm (adjusted R(2) = 0.421, and mean absolute error (MAE) = 3.3), and IWPC algorithm (adjusted R(2) = 0.419, MAE = 3.2) produced better accuracy than did the warfarin dosing table (adjusted R(2) = 0.246, MAE = 3.5), the two clinical algorithms (R(2) = 0.24, MAE = 3.7) and the fixed dose approach (MAE = 3.9). However, all dosing models produced comparable clinical accuracy with respect to proportion of patients within 1 mg/day of actual dose (ideal dose). Non-pharmacogenetic methods severely over-predicted dose (defined as ≥2 mg/day more than actual dose) compared to the three pharmacogenetic models. In comparison to non-pharmacogenetic methods, the three pharmacogenetic models performed better regarding the low dose group in terms of percentage of patients within ideal dose. In the high dose group, none of the dosing models predicted warfarin doses within ideal dose. CONCLUSION: Our study showed that genotype-based dosing improved prediction of warfarin therapeutic dose beyond that available with the fixed-dose approach or the clinical algorithms, especially in the low-dose group. However, the two pharmacogenetic algorithms were the most accurate.

Efficacy and safety of pegylated interferon in children and adolescents infected with chronic hepatitis C: a preliminary study.

This study researches the efficacy and safety of pegylated interferon alpha-2a (pegIFNα-2a) in Egyptian children and adolescents diagnosed with hepatitis C virus. Thirty patients were enrolled to receive pegIFN once a week with ribavirin twice daily for 12 weeks; viral load and experienced adverse effects were then assessed. Of the 30 patients, 16 (53.33%) were cleared from the virus, showing early virologic response (EVR). Three patients (10%) showed a 2-log reduction by week 12, with an overall early response rate of 63.33%. Three patients who showed EVR after 4 weeks relapsed by week 12. Levels of serum alanine aminotransferase (ALT) normalized at week 12. Adverse events included fever, myalgia, headache, flu-like symptoms, fatigue, anemia, and leucopenia; 63.33% of the patients showed significant reduction in their body weight. Although the patients showed a reduction in average body mass index, this reduction was not significant. Hemoglobin values decreased within the first 2 weeks and then stabilized but not back to baseline. A significant reduction in the level of absolute neutrophil count (ANC) was observed by the 4th week and started to improve by the 12th week. Of the recruited patients, 29.4% were subjected to IFN dose reduction. None of the patients with neutropenia developed serious infection or sepsis. The authors concluded that pegIFN plus ribavirin therapy is promising when tested on Egyptian children.