Practices, Efficacy, and Reported Side Effects Associated with Isotretinoin Treatment in Palestine.

Background: Isotretinoin is a commonly prescribed medication for the treatment of acne. It is associated with serious side effects that require monitoring and adherence by patients and healthcare providers. No studies have been conducted in Palestine to explore isotretinoin prescribing and utilization. Objective: This study aims to evaluate the current clinical practices, adherence to clinical guidelines, efficacy, and reported side effects associated with Isotretinoin treatment in Palestine. Methods: A descriptive cross-sectional online questionnaire-based study using social media platforms (eg, Facebook and Telegram) was conducted among Birzeit University students in April 2023. This study included participants aged ≥ 18 years with a history of isotretinoin treatment; subjects with incomplete data were excluded. Statistical significance was set at P < 0.05. SPSS version 27 was used for data analysis. Results: A total of 548 participants were included in the study, the majority of most of whom were female (96%). The most predominant side effects were cracked, dry lips and xeroderma (96.2%). Moreover, 12% of participants had depression. Most respondents were educated about medication side effects and only 39.1% were counseled about blood donation. Of the 59 sexually active women, only 4 (6.8%) were asked for a recent pregnancy test. A total of 60.2% of dermatologists adhered to the American Academy of Dermatology (AAD) guidelines, and 48.7% ordered the required laboratory tests before initiating isotretinoin treatment. Only 1.7% of pharmacists followed the FDA-suggested protocols for dispensing isotretinoin to childbearing females. Conclusion: Adherence to isotretinoin safety prescribing protocols to provide patient education, monitoring, and ordering of laboratories to ensure patient safety can be improved by adapting policies and protocols in pharmacy and medical practice in Palestine to monitor and enforce adherence when prescribing, dispensing, or taking high-risk medications.

The Preparation and Evaluation of Cyanocobalamin Mucoadhesive Sublingual Tablets.

Cobalamin (vitamin B12), an essential vitamin with low oral bioavailability, plays a vital role in cellular functions. This research aimed to enhance the absorption of vitamin B12 using sublingual mucoadhesive tablets by increasing the residence time of the drug at the administration site. This research involved the preparation of different 50 mg placebo formulas using different methods. Formulas with disintegration times less than one minute and appropriate physical characteristics were incorporated into 1 mg of cyanocobalamin (S1-S20) using the direct compression method. The tablets obtained were evaluated ex vivo for residence time, and only those remaining for >15 min were included. The final formulas (S5, S8, S11, and S20) were evaluated in several ways, including pre- and post-compression, drug content, mucoadhesive strength, dissolution, and Permeapad® permeation test employed in the Franz diffusion cell. After conducting the evaluation, formula S11 (Eudragit L100-55) emerged as the most favorable formulation. It exhibited a mucoadhesive residence time of 118.2 ± 2.89 min, required a detachment force of 26 ± 1 g, maintained a drug content of 99.124 ± 0.001699%, and achieved a 76.85% drug release over 22 h, fitting well with the Peppas-Sahlin kinetic model (R2: 0.9949). This suggests that the drug release process encompasses the Fickian and non-Fickian kinetic mechanisms. Furthermore, Eudragit L100-55 demonstrated the highest permeability, boasting a flux value of 6.387 ± 1.860 µg/h/cm2; over 6 h. These findings indicate that including this polymer in the formulation leads to an improved residence time, which positively impacts bioavailability.

Quality of Life of Palestinian Patients on Hemodialysis: Cross-Sectional Observational Study.

Background: Hemodialysis is life-saving and life-altering, affecting patients' quality of life. The management of dialysis patients often focuses on renal replacement therapy to improve clinical outcomes and remove excess fluid; however, the patient's quality of life is often not factored in. Objective: This study aimed to explore the factors affecting the quality of life of patients on dialysis in Palestine using the Kidney Disease Quality of Life (KDQOL-SFTM) questionnaire. Methods: A multicenter cross-sectional observational study was conducted at multiple dialysis centers in Palestine, including 271 participants receiving renal replacement therapy. Demographics, socioeconomic, and disease status data were collected. The Arabic version of KDQOL-SFTM was used to assess dialysis patient quality of life. Statistical analysis was performed using SPSS to find correlations among patient factors and the questionnaire's three main domains, the kidney disease component summaries (KDCS), mental component summaries (MCS), and physical component summaries (PCS). Results: Mean KDCS, MCS, and PCS scores were 59.86, 47.10, and 41.15, respectively. KDC scores were lower among participants aged 40 years or older, with lower incomes, and with diabetes. PCS and MCS scores were lower among patients aged >40, less educated, and lower-income participants. There was a positive correlation between MCS and KDCS (r = 0.634, P-value <0.001), PCS and KDCS (r = 0.569, P-value <0.001), as well as MCS and PCS (r = 0.680, P-value <0.001). Conclusion: In this study, the KDQOL-SFTM questionnaire revealed lower PCS scores among hemodialysis patients in Palestine. Furthermore, the three domains of the questionnaire were adversely affected by patient income and education status. In addition, physical role, work status, and emotional role showed the lowest scores among the three main domains. Therefore, continuous assessment of patients' quality of life during their journey of hemodialysis using the KDQOL-SFTM along with the clinical assessment will allow the healthcare professionals to provide interventions to optimize their care.

A retrospective evaluation of drug-drug interactions in patients admitted to Internal Medicine Departments in Palestinian Hospitals.

Objective: To measure the prevalence and identify risk factors associated with drug-drug interactions among patients admitted to internal medicine departments in Palestinian hospitals. Methods: A retrospective cross-sectional observational study was conducted. Data were obtained from patient files from the internal medicine departments in Palestinian hospitals from 1 September 2017, to 31 March 2018. The data collected included patient gender, age, length of hospitalization, medications prescribed, and the number of medications. The digital clinical decision support system IBM Micromedex® was used to assess potential drug-drug interactions. Results: The number of patients included in this study is 513. The total number of potential drug-drug interactions detected in study participants is 1558. The average number of potential drug-drug interactions per patient was found to be 3 ± 3.9. Among study participants, 66.1% (n = 339) were found to have potential drug-drug interactions in their current medications. The most commonly encountered drug-drug interactions type was "major" drug-drug interaction, which was encountered in 43.6% (n = 681) of total detected drug-drug interactions. Other types of drug-drug interactions were encountered in 42% (n = 647), 14% (n = 224), and 0.4% (n = 6) which were moderate, minor, and contraindicated drug-drug interactions, respectively. Patients' age, number of medications, and length of hospitalization were associated with the increased risk of potential drug-drug interactions. Conclusion: The results indicated a high prevalence of potential drug-drug interactions in Palestinian hospitals, associated with polypharmacy, increased age, and increased length of hospitalization. Therefore, managing patient medication by a drug expert such as a clinical pharmacist to identify and resolve potential drug-drug interactions will possibly decrease the high prevalence of drug-drug interactions, prevent patient harm, and decrease the cost of hospitalization.

Novel Fusidic Acid Cream Containing Metal Ions and Natural Products against Multidrug-Resistant Bacteria.

BACKGROUND: Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the necessity for new treatments. Natural products have been used since the dawn of medicine to heal skin infections. The antimicrobial properties of fusidic acid, zinc sulfate, and copper sulfate have been studied and are well known. Furthermore, these compounds have different mechanisms of action in targeting microorganisms, either by inhibiting protein synthesis or bacterial cell walls. Therefore, their combination is expected to have synergistic activity in killing bacteria. However, the synergistic antimicrobial activity has not been evaluated in a cream formulation. Therefore, the objectives of this in vitro study were to develop and evaluate the synergistic efficacy of fusidic acid in combinations with natural products, including oleuropein, thyme oil, zinc sulfate, and copper sulfate, as a cream to eradicate fusidic-acid-resistant microorganisms in skin infections. METHODS: Three different cream formulations were developed, compared, and labeled F1, F2, and F3. The compounds were studied for their antibacterial activity. In addition, the stability of the cream was investigated at 25 °C and 40 °C in plastic jars over three months. RESULTS: The F2 formula has adequate physicochemical properties. Furthermore, it displays stable and better results than the marketed trade product and has potential inhibition zones (ZOI). Interestingly, considerable numbers (9.5%) of fusidic-acid-resistant Staphylococcus aureus (FRSA) isolates possessed a high resistance pattern with MIC ≥ 128 µg/mL. In contrast, most tested FRSA isolates (90.5%) had a low resistance pattern with MIC ≤ 8 µg/mL. CONCLUSION: In conclusion, the F2 cream made with fusidic acid, oleuropein, thyme oil, zinc sulfate, and copper sulfate in the right amounts has stable physical and chemical properties and has potential against FRSA as an antimicrobial agent.

Assessing Drug-Drug Interaction Potential among Patients Admitted to Surgery Departments in Three Palestinian Hospitals.

BACKGROUND: Drug-drug interactions (DDIs) are a common issue that leads to adverse drug reactions in hospitals. Patients in the surgical department are expected to have potential DDIs that may lead to morbidity and mortality. OBJECTIVES: To study potential DDI prevalence in the surgery departments in 3 hospitals in Palestine. Moreover, to identify pertinent factors that are associated with drug-drug interactions. METHOD: A cross-sectional study in 3 governmental Palestinian hospitals: Palestine Medical Complex, Rafidia Hospital, and Beit Jala Hospital. Patients who are 20 years old or above and admitted to the surgical wards between September 2017 and February 2018 were included in the study. Patient demographics, all medications given in the hospital, and hospitalization period were obtained from medical files. The digital clinical decision support system Micromedex® was used for analysis and classification of possible drug interactions. Bivariate analysis and logistic regression were used to study the risk factors for developing DDIs. RESULTS: 502 patients were included in this report. The prevalence of potential DDIs among patients admitted to surgery wards in three Palestinian hospitals was 56%. The number of detected potential DDIs per patient was 2.22 ± 3.76. The number of prescribed medications (P < 0.001) was found to increase the possibility of having drug interactions. CONCLUSIONS: DDIs in Palestinian hospitals are a prevalent problem, and caution should be taken when ordering medications to hospitalized patients in surgery departments.

Gender effect on the pharmacokinetics of thymoquinone: Preclinical investigation and in silico modeling in male and female rats.

Thymoquinone is the most biologically active constituent of Nigella sativa (black seed). A monoterpene compound chemically known as 2-methyl-5-isopropyl-1, 4-quinone. In this study, the gender-dependent pharmacokinetic behavior of thymoquinone in rats was investigated. Thymoquinone was administered orally (20 mg/kg) and intravenously (5 mg/kg) to male and female rats and blood samples were collected at specific time points. Plasma concentration-time curves were plotted and pharmacokinetic parameters were determined using the non-compartmental analysis. In addition, simulations of steady state concentrations of thymoquinone in male and female rats were performed using GastroPlus PK software. After oral administration, the maximum plasma concentration (Cmax) of thymoquinone was 4.52 ±â€¯0.092 µg/ml in male rats and 5.22 ±â€¯0.154 µg/ml in female rats (p = 0.002). Similarly, after intravenous administration, the Cmax was 8.36 ±â€¯0.132 µg/ml in males and 9.51 ±â€¯0.158 µg/ml in females (p = 0.550). The area under the plasma concentration-time curve (AUC)0-∞ following oral dosing was 47.38 ±â€¯0.821 µg/ml·h in females and 43.63 ±â€¯0.953 µg/ml·h in males (p = 0.014). Pharmacokinetics and plasma concentration vs. time profiles for multiple oral doses of thymoquinone in rats were predicted using a simulation model to compare the simulation results with the experimental plasma pharmacokinetic data. The differences observed in thymoquinone pharmacokinetics between male and female rats after a single dose were not evident for the simulated steady-state parameters. The findings suggest that the gender difference does not seem to play a significant role in thymoquinone disposition at steady state.

Excipients enhance intestinal absorption of ganciclovir by P-gp inhibition: assessed in vitro by everted gut sac and in situ by improved intestinal perfusion.

In rats we examined the effects of some common excipients on the intestinal absorption of ganciclovir (GCV), a BCS-III drug and substrate of P-gp, by assessing its in vitro transfer from mucosa to serosa and in situ transepithelial permeation. In vitro, all selected excipients (concentration range 0.1-1% [w/v]) could increase the transport amount of GCV in the everted gut sac model. Whereas enhancement by F-68 demonstrated regional differences like verapamil, PEG-400, Tween-80 and EL-35 exhibited no regional differences. In situ studies were performed by an improved perfusion model, single-pass perfusion with whole small intestine, to determine more accurately the permeability of lipophobic compounds. The permeability of GCV was significantly increased by all excipients. The effects of EL-35 and F-68 were dose-dependent but those of PEG-400 and Tween-80 were not. The results suggest that enhancements of intestinal absorption of GCV by these excipients are probably due to inhibition of P-gp-mediated drug efflux. It could be deduced from their different properties that both blocking binding sites of P-gp and altering membrane fluidity were involved in their P-gp-inhibition. The former mechanism might be involved for F-68, while the latter one might account for the effects of PEG-400, Tween-80 and EL-35.