Characteristics, Risk Factors, and Outcomes in Acute Kidney Injury Patients: A Retrospective Cross-Sectional Study, Palestine.

Background: Acute kidney injury (AKI) is a major medical problem affecting patients' quality of life and healthcare costs. Objectives: This study evaluated the severity, risk factors, and outcomes of patients diagnosed with acute kidney injury (AKI), including community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), who were admitted to tertiary institutions in Palestine. Methods: This retrospective cross-sectional study was conducted at multiple tertiary care hospitals in Palestine by reviewing patient charts from January 2020 to March 2023. The study included all patients aged ≥18 years who were admitted to the hospital and diagnosed with AKI at admission (CA-AKI) or who developed AKI 48 hours after admission (HA-AKI). Patients with incomplete medical records and those with no reported creatinine levels during their stay, pregnant women, kidney transplant patients, and end-stage renal disease patients were excluded. Data were analyzed using SPSS v22.0. The incidence of AKI in each group was compared using the chi-squared test. Results: This study included 259 participants. HA-AKI was present in 27.3% of the patients, while CA-AKI was 72.7%. The most common stage among patients was stage 3 (55.7%, HA-AKI) (42.9%, CA-AKI), and the most common comorbidity contributing to AKI was CKD. NSAIDs, ACE-I/ARBs, and DIURETICs were the most nephrotoxic drugs contributing to AKI. Patients with hyperphosphatemia, hyperkalemia, severe metabolic acidosis, or stage 3 AKI require renal replacement therapy. In addition, our findings revealed a significant association among AKI mortality, age, and heart disease. Conclusion: CA-AKI was more prevalent than HA-AKI in Palestinian patients admitted for AKI. Risk factors for AKI included diabetes, CKD, and medications (antibiotics, NSAID, diuretics, and ACE-I/ARB). Preventive measures, medication management, and disease state management are necessary to minimize AKI during hospital admission or in the community.

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.

Side effects of Pfizer/BioNTech (BNT162b2) COVID-19 vaccine reported by the Birzeit University community.

BACKGROUND: The Pfizer BioNTech COVID-19 vaccine was the first to receive emergency authorization and approval from the FDA. Therefore, it is preferred by most recipients; however, many people are concerned about the vaccine's side effects. At the time of the study, December 2021, Palestine lacked a national reporting system for monitoring adverse vaccine effects. Therefore, this study investigates the post-vaccine adverse events following the Pfizer/BioNTech COVID-19 Vaccine administration in Palestine and identifies the occurrence, extent, and severity among university staff, employees, and students at Birzeit University. METHOD: A questionnaire-based retrospective cross-sectional study was conducted using a university website (Ritaj), social media platforms (e.g., Facebook and Telegram), and in-person interviews. The Chi-square, Fisher's exact, and McNemar's tests were used to investigate significant relationships. Data were analyzed using SPSS version 22. RESULTS: In total, 1137 participants completed the questionnaire, 33.2% were males, and the mean age was 21.163 years. All participants received at least one dose of the Pfizer-BioNTech COVID-19 vaccine. Approximately one-third of participants reported no adverse effects after receiving the first, second, or third doses (34%, 33.6%, and 32.5%, respectively). The most commonly reported adverse events were fever, chills, headache, fatigue, pain and swelling at the injection site, muscle pain, and joint pain. Allergic reactions were reported by 12.7% of the participants; furthermore, participants with a history of allergy or anaphylaxis before vaccination had a significantly higher tendency for post-vaccination allergic reactions. Eight participants reported rare side effects, including 7 (0.6%) cases of thrombocytopenia and one (0.1%) case of myocarditis. Males aged less than 20 years and smokers were significantly less likely to complain of adverse events. The number of reported side effects was significantly higher after the second vaccine dose than after the first dose. Finally, participants infected with COVID-19 before vaccination was significantly associated with side effects such as fever, chills, shortness of breath, and persistent cough. CONCLUSION: In this study, the most common post- BNT162b2 Vaccination reported self-limiting side effects similar to those reported by Pfizer/BioNTech Company. However, higher rates of allergic reactions were reported in this sample. Rare side effects, such as thrombocytopenia and myocarditis, were reported by 8 participants. COVID vaccines have been developed at an accelerated pace, and vaccine safety is a top priority; therefore, standard monitoring through a national adverse event reporting system is necessary for safety assurance. Continuous monitoring and long-term studies are required to ensure vaccine safety.

Evaluation of Proton Pump Inhibitors Prescribing Among Hospitalized Patients: A Cross-Sectional Study.

Background: Proton pump inhibitors (PPIs) are the most effective agents for managing acid-related disorders. However, inappropriate prescribing of PPIs is becoming an issue of concern. Objective: This study aimed to assess the appropriate utilization of PPIs in terms of indication, dose, frequency, and route of administration during admission and discharge. Furthermore, direct costs associated with inappropriate PPI use were calculated. Methods: A descriptive cross-sectional study was conducted at the internal medicine department of a tertiary hospital in Palestine from January 1, 2021, to June 30, 2021. The medical records of patients aged 18 years or older, hospitalized for 48 hours or more, and receiving oral or intravenous (IV) PPIs during their stay were collected and evaluated for the appropriateness of PPIs prescribed according to clinical guidelines. Results: Of 262 patients, 80.2% had an appropriate indication for prophylaxis (67.6%) or treatment (12.6%). A total of 230 patients were prescribed IV pantoprazole.182 (79.1%) had an appropriate indication, whereas 122/182 (67%) received IV PPI instead of oral without an appropriate indication. Of the 32 patients who received 20 mg of oral omeprazole, 28 (87.5%) had an appropriate indication, dose, and route of administration, whereas 16/28 (57.1%) had an inappropriate frequency. At discharge, 32.5% of patients were discharged with unnecessary PPI prescriptions. The total direct cost of inappropriate PPI Indications and route of administration in 188 patients over six months was $1518. Conclusion: This study showed that most patients received a PPI for an appropriate indication with the correct dose. However, a high prevalence of inappropriate IV pantoprazole administration was observed, resulting in the highest costs, demonstrating the importance of correctly ordering IV medications. Adherence to clinical guidelines, such as those of the American College of Gastroenterology (ACG), will improve the appropriateness of PPI prescribing, prevent complications, and reduce healthcare costs.

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.

Vitamin D Deficiency Association with Comorbid Diseases in Palestine: "A Cross-Sectional Observation Study".

Background: Vitamin D deficiency (VDD) is a global health concern. This study aimed to determine the prevalence of vitamin D deficiency and its associated comorbidities in Palestine, such as diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular and autoimmune diseases. Methods: A retrospective, descriptive study retrieved medical data from the Nat Health insurance processor database from 2014 to 2020. Patient information included age, sex, vitamin D laboratory order, symptoms, and comorbidities. This study included patients prescribed vitamin D at a dose of 50000IU for vitamin D deficiency confirmed by a serum vitamin D laboratory test. The collected data were analyzed using IBM SPSS. In addition, a chi-square test was conducted to assess the association between vitamin D deficiency, symptoms, and comorbidities. Results: Data of 3011 patients were collected; 639 patients were diagnosed with osteoporosis, and 39 patients prescribed vitamin D without a laboratory test were excluded. Approximately, 1837 (78%) participants had vitamin D deficiency. A total of 1330 women (81.3%) were significantly more likely to have vitamin D deficiency than males, 507 (72.7%; P < 0.001). Joint pain, back pain, and cervicalgia were significantly associated with vitamin D deficiency (P < 0.001). Asymptomatic participants (2.1%) were significantly less likely to have vitamin D deficiency than symptomatic participants (9.5%, p < 0.001). Hypothyroidism is significantly associated with vitamin D deficiency (p = 0.048). Conclusion: In this retrospective study, the prevalence of vitamin D was high and alarming. There was a significant association between VDD, patients who presented with back pain, arthritis, and cervicalgia symptoms, and patients diagnosed with hypothyroidism. Therefore, health initiative programs are warranted to increase awareness regarding screening, prevention, and treatment. Further studies are needed to confirm the relationship between vitamin D supplementation and the reduced risk of comorbid diseases.

Evaluation of Self-Medication with Antibiotics in Primary Care Clinics in Palestine.

Background: Antibiotics are highly effective medications and essential in curing infectious diseases; however, their inappropriate use, such as self-medication, is a significant factor in developing antimicrobial resistance. Objective: This study aimed to evaluate the level of antibiotic self-medication among patients who visited primary care clinics in Palestine. Methods: Data were collected via a self-administered questionnaire, either printed or electronically, using google forms (Google Inc., USA). The sample size needed to provide a 95% confidence level and 5% margin error and assuming a prevalence of 50% of SM with antibiotics was 377 patients. A total of 700 questionnaires were randomly distributed to patients aged 18 years or older. However, 87 were excluded due to duplication, incomplete responses, or participants under 18 years old. Finally, 423 patients were included in this study, with 254 patients completing the electronic Google Forms and 181 completing the written survey. The questionnaire consists of patients' demographics, antibiotics knowledge, and self-medication behavior. In addition, descriptive statistics and knowledge scales were performed using SPSS 22 IBM to measure and assess the scope of the problem and find the association between self-medication demographics, education, and socioeconomic status. Results: Approximately 50% of participants reported self-medication with antibiotics, with a very high use among participants with medical knowledge. Most people have adequate awareness of antibiotics, whereas out of 423 respondents, (40.2%, n = 170) had GKL, (50.4%, n= 213) had AKL, and only (9.5%, n=40) presented PKL. The primary source for self-treatment with antibiotics was community pharmacies (87.1%, n=223), whereas (14.1%, n=36) got antibiotics from family and friends. Convenience, easy access, and experience with community pharmacists contributed to self-medications. The most commonly used antibiotic for self-medication was amoxicillin/clavulanic acid. Conclusion: Self-medication with antibiotics is a common practice in Palestine, regardless of socioeconomic or educational status. Patients' educations about complications from inappropriate use and the possibility of side effects are essential steps to decrease patients' demands for antibiotics. Furthermore, compliance and adherence of community pharmacists in dispensing antibiotics only with a prescription is necessary.

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.

In Situ intestinal perfusion of irinotecan: application to P-gp mediated drug interaction and introduction of an improved HPLC assay.

PURPOSE: To determine experimentally the intestinal permeability of the anticancer prodrug irinotecan, and to quantify the amount of its cytotoxic metabolite SN-38 that is intestinally excreted (exsorped) as a predictor of intestinal toxicity, and to assess the effect of p-glycoprotein (p-gp) inhibitors (verapamil as a model) on the permeability and toxicity of irinotecan. METHODS: Single pass intestinal perfusion of rat's whole length small intestines is applied to assess the permeability of the parent drug and quantify the intestinally excreted metabolite. The perfusion solution contained 30µg/ml of irinotecan (control group) without or with verapamil (verapamil group). A simple reversed phase HPLC method with UV detection is developed and validated for simultaneous determination of irinotecan and SN-38 using camptothecin as an internal standard. RESULTS: HPLC-UV method found to be simple, specific, accurate, and precise. Effective permeability coefficient of irinotecan found to be 4.9±1.7 10-3 mm/min and was doubled in verapamil group (P=0.007). Average cumulative amount of SN-38 exsorped found to be 29 ng/cm over 2 hours perfusion time which was decreased to 15 ng/cm in verapamil group (P=0.016). CONCLUSIONS: in situ intestinal perfusion method was successfully applied to quantify the permeability of irinotecan and the exsorption of SN-38 in the same experiment, in a manner that robustly reflects real in vivo situation. P-gp inhibition using verapamil found to significantly enhance the intestinal permeability of irinotecan and potentially decrease the intestinal toxicity due to SN-38 exposure.

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.