Dissolution enhancement of Gefitinib by solid dispersion and complexation with ß-cyclodextrins: In vitro testing, cytotoxic activity, and tablet formulation.

Cancer is the leading cause of mortality worldwide. In patients with metastatic non-small cell lung cancer, epidermal growth factor receptor (EGFR) is often overexpressed. Gefitinib (GEF), an inhibitor of EGFR, is approved for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the low solubility and dissolution of GEF limits its bioavailability. Numerous methods, including solid dispersion (SD) and complexation, have been reported to enhance the dissolution of poorly soluble drugs. In this study, GEF complexes were prepared using methyl-ß-cyclodextrin (MßCD) and hydroxypropyl-ß-cyclodextrin (HPßCD) in two molar ratios (1:1 and 1:2), furthermore, GEF SDs were prepared using polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and poloxamer-188(PXM) in three different ratios (1:2, 1:4 and 1:6 w/w). Dissolution studies were conducted on the prepared formulations. Dissolution results showed a 1.22-2.17-fold enhancement in drug dissolution after one hour compared to untreated GEF. Two formulations that showed higher dissolution enhancement were subsequently evaluated for in-vitro cytotoxicity and were formulated into tablets. The selected PVP-GEF (1:4 w/w) and MßCD-GEF (1:1M) formulas displayed improved cytotoxicity compared to untreated GEF. The IC50 values of the PVP-GEF and MßCD-GEF were 4.33 ± 0.66 and 4.84 ± 0.38 µM, respectively which are significantly lower (p < 0.05) than free GEF. In addition, the formulated tablets exhibited enhanced dissolution compared to pure GEF tablets. PVP-GEF SD tablets released (35.1 %±0.4) of GEF after one hour, while GEF-MßCD tablets released (42.2 % ± 0.7) after one hour. In the meantime, tablets containing pure GEF showed only 15 % ± 0.5 release at the same time. The findings of this study offer valuable insights for optimizing the dissolution and hence therapeutic capabilities of GEF while mitigating its limitations.

Dexamethasone versus methylprednisolone for multiple organ dysfunction in COVID-19 critically ill patients: a multicenter propensity score matching study.

BACKGROUND: Dexamethasone usually recommended for patients with severe coronavirus disease 2019 (COVID-19) to reduce short-term mortality. However, it is uncertain if another corticosteroid, such as methylprednisolone, may be utilized to obtain better clinical outcome. This study assessed dexamethasone's clinical and safety outcomes compared to methylprednisolone. METHODS: A multicenter, retrospective cohort study was conducted between March 01, 2020, and July 31, 2021. It included adult COVID-19 patients who were initiated on either dexamethasone or methylprednisolone therapy within 24 h of intensive care unit (ICU) admission. The primary outcome was the progression of multiple organ dysfunction score (MODS) on day three of ICU admission. Propensity score (PS) matching was used (1:3 ratio) based on the patient's age and MODS within 24 h of ICU admission. RESULTS: After Propensity Score (PS) matching, 264 patients were included; 198 received dexamethasone, while 66 patients received methylprednisolone within 24 h of ICU admission. In regression analysis, patients who received methylprednisolone had a higher MODS on day three of ICU admission than those who received dexamethasone (beta coefficient: 0.17 (95% CI 0.02, 0.32), P = 0.03). Moreover, hospital-acquired infection was higher in the methylprednisolone group (OR 2.17, 95% CI 1.01, 4.66; p = 0.04). On the other hand, the 30-day and the in-hospital mortality were not statistically significant different between the two groups. CONCLUSION: Dexamethasone showed a lower MODS on day three of ICU admission compared to methylprednisolone, with no statistically significant difference in mortality.

Clinical pharmacy services in acute care setting during mass gatherings (Hajj): Insights from a task force.

BACKGROUND: Hajj is the largest mass gathering worldwide that takes place every year in Makkah, Saudi Arabia. This paper aims to provide a comprehensive guide and expectations for delivering and optimizing clinical pharmacy services during one of the largest mass gatherings in the world, Hajj pilgrimage METHODS: A task force initiated and included members of clinical pharmacists who previously participated in delivering clinical pharmacy services during the Hajj pilgrimage, members of the Saudi Society of Clinical Pharmacy (SSCP), and policymakers from different sectors and representatives from pharmaceutical care of the Ministry of Health (MOH). The members established an expert task force to conceptualize and draft the proposed suggestions highlighting the roles and responsibilities of clinical pharmacists during the annual Hajj season. RESULTS: The task force determined the following key domains 1) pharmaceutical care (administration and strategic plan, resources, formulary management); 2) pharmacists' activities (clinical pharmacy services and documentation, professional training and development, and staff credentials, and qualifications); 3) challenges and proposed solutions. The task force was divided into groups to draft each domain and provide suggested statements and insights for each section. Finally, the group members of the task force issued 15 opinion statements. CONCLUSION: Mass gatherings such as Hajj pilgrimage, represent a unique opportunity to demonstrate the value of pharmacists in advancing health care delivery within a multidisciplinary team. These suggestions and insights could guide the implementation of clinical pharmacy services in acute settings during mass gatherings (Hajj). Future studies should focus on assessing the applicability and the impact of the provided suggestions.

Characteristics of Critical Care Pharmacy Services in Saudi Arabia.

Purpose: Critical care pharmacists (CCPs) in intensive care units (ICUs) are associated with improved patient outcomes, reduced adverse events (ADEs), and reduced mortality rates. This study aimed to describe the activities and pharmacy services provided by CCP in ICUs in hospitals in Saudi Arabia (SA). Methods: In this cross-sectional prospective study, a questionnaire was electronically sent to CCPs practicing in SA between September 2022 and January 2023. A modified version of a previously published and validated survey was sent to the Saudi Critical Care and Emergency Specialty Network. The questionnaire focused on four CCP activities: clinical, educational, scholarly, and administrative. The level of services was similarly classified into three domains: fundamental, optimal, and desirable. The responses were analyzed using descriptive statistics. Results: The study surveyed 44 CCPs in SA, with a response rate of 52.3%. These CCPs were predominantly located in the central (47.8%) and eastern (30.4%) regions. Hospitals' ICU bed capacity ranged from 10 to 100, with 82% reporting mixed medical and surgical ICUs. Most CCPs had 4-10 years of critical care experience, and 60% held advanced degrees, with a substantial portion having completed PGY-1 and PGY-2 pharmacy residencies. CCPs were actively involved in patient care, with 86.9% participating in multidisciplinary rounds five days a week. They were engaged in clinical, educational, and administrative activities, with 82.6% involved in retrospective research and educational activities. Furthermore, 78.2% were engaged in pharmacy and therapeutic committees, 56.5% in critical care committees, and 56.5% in pharmacy department policy development. Conclusion: The study reveals that CCPs in SA play integral roles in ICU patient care and contribute significantly to clinical, educational, and administrative activities. The study highlights the need for standardized CCP-to-patient ratios and further support for CCPs to expand their services, thus contributing to enhanced healthcare quality.

Effectiveness and safety of edoxaban versus warfarin in patients with nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia type. Patients with AF are often administered anticoagulants to reduce the risk of ischemic stroke due to an irregular heartbeat. We evaluated the efficacy and safety of edoxaban versus warfarin in patients with nonvalvular AF by conducting an updated meta-analysis of real-world studies. Methods: In this comprehensive meta-analysis, we searched two databases, PubMed and EMBASE, and included retrospective cohort observational studies that compared edoxaban with warfarin in patients with nonvalvular AF from 1 January 2009, to 30 September 2023. The effectiveness and safety outcomes were ischemic stroke and major bleeding, respectively. In the final analysis, six retrospective observational studies involving 87,236 patients treated with warfarin and 40,933 patients treated with edoxaban were included. To analyze the data, we used a random-effects model to calculate the hazard ratio (HR). Results: Patients treated with edoxaban had a significantly lower risk of ischemic stroke [hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.61-0.70; p < 0.0001] and major bleeding (HR = 0.58; 95% CI = 0.49-0.69; p < 0.0001) than those treated with warfarin. The sensitivity analysis results for ischemic stroke and major bleeding were as follows: HR = 0.66; 95% CI = 0.61-0.70; p < 0.0001 and HR = 0.58; 95% CI = 0.49-0.69; p < 0.0001, respectively. Conclusion: Our findings revealed that edoxaban performed better than warfarin against major bleeding and ischemic stroke.

The clinical characteristics and quality of life of 248 pediatric and adult patients with Congenital Adrenal Hyperplasia.

Background: Congenital Adrenal Hyperplasia (CAH) is a chronic disease that requires lifelong treatment. Patients may face stigmatization, which may affect their quality of life (QoL). Therefore, we assessed the clinical characteristics and QoL of patients with CAH in the Middle East. Methods: This case-control study included patients with CAH aged >5 years from two tertiary centers (2020-2021). The patients were matched to a healthy control group and were then divided into pediatric and adult groups. Data were collected from their electronic medical records. Additionally, the EQ-5D-5L QoL questionnaire was completed by both the patients and control group to assess five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Results: The study included 248 patients with CAH (females: 58.8%), with a family history of the condition (57.3%) and/or parental consanguinity (68.1%). The most frequently reported gene defect was CYP21A2, while the most commonly reported symptoms/signs were ambiguous genitalia and obesity. Almost all female patients had received corrective surgery. The questionnaire response rate was 86.3% (n=214/248). The CAH patient group's mean total QoL score was 85.2 compared with 99.8 in the control. Further, CAH patients had lower QoL scores in all domains compared to those in the control group (p ≤ 0.0001-0.0023). The pain/discomfort and anxiety/depression domains were affected significantly more than the other domains were, with 47.7% and 44.4% participants, respectively, p<0.0001. Additionally, obesity was found to be a predictor of reduced mobility following a logistic regression analysis (p ≤ 0.04, OR (0.18-0.98)). Conclusion: Patients with CAH reported lower QoL overall, particularly in the pain/discomfort and anxiety/depression domains. Based on this, we recommend the early involvement of psychologists in a multidisciplinary team approach, pre-marital screening, and the implementation of awareness programs for people diagnosed with CAH in communities with high consanguineous mating.

Leaf anatomy explains the strength of C4 activity within the grass species Alloteropsis semialata.

C4 photosynthesis results from anatomical and biochemical characteristics that together concentrate CO2 around ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), increasing productivity in warm conditions. This complex trait evolved through the gradual accumulation of components, and particular species possess only some of these, resulting in weak C4 activity. The consequences of adding C4 components have been modelled and investigated through comparative approaches, but the intraspecific dynamics responsible for strengthening the C4 pathway remain largely unexplored. Here, we evaluate the link between anatomical variation and C4 activity, focusing on populations of the photosynthetically diverse grass Alloteropsis semialata that fix various proportions of carbon via the C4 cycle. The carbon isotope ratios in these populations range from values typical of C3 to those typical of C4 plants. This variation is statistically explained by a combination of leaf anatomical traits linked to the preponderance of bundle sheath tissue. We hypothesize that increased investment in bundle sheath boosts the strength of the intercellular C4 pump and shifts the balance of carbon acquisition towards the C4 cycle. Carbon isotope ratios indicating a stronger C4 pathway are associated with warmer, drier environments, suggesting that incremental anatomical alterations can lead to the emergence of C4 physiology during local adaptation within metapopulations.

Development and Optimization of Ciprofloxacin HCl-Loaded Chitosan Nanoparticles Using Box-Behnken Experimental Design.

Various chitosan (CS)-based nanoparticles (CS-NPs) of ciprofloxacin hydrochloride (CHCl) have been investigated for therapeutic delivery and to enhance antimicrobial efficacy. However, the Box-Behnken design (BBD)-supported statistical optimization of NPs of CHCl has not been performed in the literature. As a result, the goal of this study was to look into the key interactions and quadratic impacts of formulation variables on the performance of CHCl-CS-NPs in a systematic way. To optimize CHCl-loaded CS-NPs generated by the ionic gelation process, the response surface methodology (RSM) was used. The BBD was used with three factors on three levels and three replicas at the central point. Tripolyphosphate, CS concentrations, and ultrasonication energy were chosen as independent variables after preliminary screening. Particle size (PS), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), and in vitro release were the dependent factors (responses). Prepared NPs were found in the PS range of 198-304 nm with a ZP of 27-42 mV. EE and drug release were in the range of 23-45% and 36-61%, respectively. All of the responses were optimized at the same time using a desirability function based on Design Expert® modeling and a desirability factor of 95%. The minimum inhibitory concentration (MIC) of the improved formula against two bacterial strains, Pseudomonas aeruginosa and Staphylococcus aureus, was determined. The MIC of the optimized NPs was found to be decreased 4-fold compared with pure CHCl. The predicted and observed values for the optimized formulation were nearly identical. The BBD aided in a better understanding of the intrinsic relationship between formulation variables and responses, as well as the optimization of CHCl-loaded CS-NPs in a time- and labor-efficient manner.

Point prevalence of delirium among critically ill patients in Saudi Arabia: A multicenter observational study.

Background: Delirium in critically ill patients is independently associated with poor clinical outcomes. There is a scarcity of published data on the prevalence of delirium among critically ill patients in Saudi Arabia. Therefore, we sought to determine, in a multicenter fashion, the prevalence of delirium in critically ill patients in Saudi Arabia and explore associated risk factors. Methods: A cross-sectional point prevalence study was conducted on January 28, 2020, at 14 intensive care units (ICUs) across 3 universities and 11 other tertiary care hospitals in Saudi Arabia. Delirium was screened once using the Intensive Care Delirium Screening Checklist. We excluded patients who were unable to participate in a valid delirium assessment, patients admitted with traumatic brain injury, and patients with documented dementia in their medical charts. Results: Of the 407 screened ICU patients, 233 patients were enrolled and 45.9% were diagnosed with delirium. The prevalence was higher in mechanically ventilated patients compared to patients not mechanically ventilated (57.5% vs. 33.6%; P < 0.001). In a multivariate model, risk factors independently associated with delirium included age (adjusted odds ratio [AOR], 1.021; 95% confidence interval [CI], 1.01-1.04; P = 0.008), mechanical ventilation (AOR, 2.39; 95% CI, 1.34-4.28; P = 0.003), and higher severity of illness (AOR, 1.01; 95% CI, 1.001-1.021; P = 0.026). Conclusion: In our study, delirium remains a prevalent complication, with distinct risk factors. Further studies are necessary to investigate long-term outcomes of delirium in critically ill patients in Saudi Arabia.

Off-Label Drug Use in Pediatric Out-Patient Care: A Multi-Center Observational Study.

OBJECTIVE: Prescribing a drug for a child is not an easy task and requires using the best available evidence as a guide, especially when a drug is used off-label. The practice of prescribing a drug for off-label use is fairly widespread worldwide. The FDA does not regulate prescribing patterns or practices of individual practitioners and, therefore, allows off-label use. The main objective of this study is to evaluate off-label prescribing among the pediatric population in the Kingdom of Saudi Arabia (KSA). METHOD: This is a retrospective, simple random selection observational study of children (≤15 years) who visited pediatric clinics and had at least 1 drug prescribed over a 12-month period (January to December 2018). RESULTS: A total of 865 drugs (mean 1 and SD 0.24) were prescribed to 326 children. Off-label was identified in 39.4% of the drugs with a frequency of 512 (as 1 drug may belong to more than 1 off-label category). The most common reason for off-label prescribing was related to doses that were "higher or lower than the recommended use" (48.6%), and the most frequently identified drug class prescribed for off-label use was anti-infective drugs for systemic use (39.9%). The percentage of off-label drug use was found to be higher in girls and in the age group of 1 month to 2 years (P = .001) for both variables. In addition, a significant association was found between off label drug use and the total number of drugs prescribed, P < .001. CONCLUSION: The findings of this study showed a high incidence of off-label prescribing mainly related to dosing and indication. The results of this observational study support the need to establish a unified national pediatric dosing formulary guide to ensure safe drug use in pediatrics.

Predicting Patients' Intention to Use a Personal Health Record Using an Adapted Unified Theory of Acceptance and Use of Technology Model: Secondary Data Analysis.

BACKGROUND: With the rise in the use of information and communication technologies in health care, patients have been encouraged to use eHealth tools such as personal health records (PHRs) for better health and well-being services. PHRs support patient-centered care and patient engagement. To support the achievement of the Kingdom of Saudi Arabia's Vision 2030 ambitions, the National Transformation program provides a framework to use PHRs in meeting the 3-fold aim for health care-increased access, reduced cost, and improved quality of care-and to provide patient- and person-centered care. However, there has been limited research on PHR uptake within the country. OBJECTIVE: Using the Unified Theory of Acceptance and Use of Technology (UTAUT) as the theoretical framework, this study aims at identifying predictors of patient intention to utilize the Ministry of National Guard-Health Affairs PHR (MNGHA Care) app. METHODS: Using secondary data from a cross-sectional survey, data measuring the intention to use the MNGHA Care app, along with its predictors, were collected from among adults (n=324) visiting Ministry of National Guard-Health Affairs facilities in Riyadh, Jeddah, Dammam, Madinah, Al Ahsa, and Qassim. The relationship of predictors (main theory constructs) and moderators (age, gender, and experience with health apps) with the dependent variable (intention to use MNGHA Care) was tested using hierarchical multiple regression. RESULTS: Of the eligible population, a total of 261 adult patients were included in the analysis. They had a mean age of 35.07 (SD 9.61) years, 50.6 % were male (n=132), 45.2% had university-level education (n=118), and 53.3% had at least 1 chronic medical condition (n=139). The model explained 48.9% of the variance in behavioral intention to use the PHR (P=.38). Performance expectancy, effort expectancy, and positive attitude were significantly associated with behavioral intention to use the PHR (P<.05). Prior experience with health apps moderated the relationship between social influence and behavioral intention to use the PHR (P=.04). CONCLUSIONS: This study contributes to the existing literature on PHR adoption broadly as well as in the context of the Kingdom of Saudi Arabia. Understanding which factors are associated with patient adoption of PHRs can guide future development and support the country's aim of transforming the health care system. Similar to previous studies on PHR adoption, performance expectancy, effort expectancy, and positive attitude are important factors, and practical consideration should be given to support these areas.

Fluorescence spectroscopy as a novel technique for premarital screening of sickle cell disorders.

Spectral diagnostic screening for sickle cell disease was carried out on volunteer blood samples (N = 100). The samples were subjected to different diagnostic methods including conventional complete blood count (CBC), hemoglobin electrophoresis (HBE) and spectral diagnosis. For the spectral diagnostic method, we discriminated three different characteristic spectral features. In total, 15 samples were sickle cell trait (SCT), 34 samples were sickle cell disease (SCD), and the rest of the samples (N = 51) were normal controls. The spectral discrimination of the three different sets of samples was distinguished on the quantification of fluorescent biomolecules such as tyrosine, tryptophan, NADH, FAD, and porphyrins. The results were compared with the conventional standard CBC and capillary electrophoresis findings. The spectral diagnosis method exhibited a sensitivity and specificity greater than 90 % for the tested samples. This technique requires only 5 mL blood samples, has an analysis time of 20 min, exhibits high accuracy and may be used in small clinics in remote villages.

Safety of Peripheral Administration of 3% Hypertonic Saline in Critically Ill Patients: A Literature Review.

BACKGROUND: Hyponatremia and neurocritical injury are life-threatening conditions requiring immediate management with consideration of the safety concerns related to peripheral intravenous administration of hypertonic solutions. Although a central intravenous catheter is the preferred route of administration, central intravenous catheters have many complications and can potentially delay medication administration in urgent situations. OBJECTIVE: To evaluate the safety and efficacy of continuous infusion of 3% hypertonic saline via peripheral intravenous administration in critically ill adult patients. METHODS: Data were collected from PubMed and Web of Science from database inception to April 7, 2019. Included studies involved adult patients with hyponatremia and/or neurocritical situations and compared administration of 3% hypertonic saline via peripheral administration with standard supportive care (administration through a central intravenous catheter). RESULTS: Of 502 articles identified, 7 were included in the review. Three articles were retrospective studies, 2 were prospective studies, 1 was a case series, and 1 was a case report. Infusion-related adverse events and electrolyte abnormalities due to 3% hypertonic saline administration through a peripheral intravenous catheter were minimal and were limited to phlebitis, erythema, edema, hyperchloremia, and hypokalemia with administration at a high infusion rate (83.3 mL/h) and for a prolonged duration (≥ 6 hours). Infusion rate, duration, catheter gauge, and catheter placement may have a role in infusion-related adverse events. CONCLUSIONS: Current recommendations to administer continuous infusions of 3% hypertonic saline through a central intravenous catheter should be reassessed. Peripheral intravenous administration can be used safely and effectively in patients in critical situations.

Adoption of a Personal Health Record in the Digital Age: Cross-Sectional Study.

BACKGROUND: As health care organizations strive to improve health care access, quality, and costs, they have implemented patient-facing eHealth technologies such as personal health records to better engage patients in the management of their health. In the Kingdom of Saudi Arabia, eHealth is also growing in accordance with Vision 2030 and its National Transformation Program framework, creating a roadmap for increased quality and efficiency of the health care system and supporting the goal of patient-centered care. OBJECTIVE: The aim of this study was to investigate the adoption of the personal health record of the Ministry of National Guard Health Affairs (MNGHA Care). METHODS: A cross-sectional survey was conducted in adults visiting outpatient clinics in hospitals at the Ministry of National Guard Health Affairs hospitals in Riyadh, Jeddah, Dammam, Madinah, and Al Ahsa, and primary health care clinics in Riyadh and Qassim. The main outcome measure was self-reported use of MNGHA Care. RESULTS: In the sample of 546 adult patients, 383 (70.1%) reported being users of MNGHA Care. MNGHA Care users were more likely to be younger (P<.001), high school or university educated (P<.001), employed (P<.001), have a chronic condition (P=.046), use the internet to search for health-related information (P<.001), and use health apps on their mobile phones (P<.001). CONCLUSIONS: The results of this study show that there is substantial interest for the use of MNGHA Care personal health record with 70% of participants self-reporting use. To confirm these findings, objective data from the portal usage logs are needed. Maximizing the potential of MNGHA Care supports patient engagement and is aligned with the national eHealth initiative to encourage the use of technology for high-quality, accessible patient-centered care. Future research should include health care provider perspectives, incorporate objective data, employ a mixed-methods approach, and use a theoretical framework.