Alia Alshammari

Levofloxacin (LFX) is widely prescribed to treat bacterial ocular infections. However, its topical application as eyedrops faces rapid precorneal clearance and poor ocular surface residence. These limitations often require frequent administration. In this project, ocular inserts loaded with LFX were developed using hot-melt extrusion (HME) to address these shortcomings. A D-optimal mixture design was applied to study the effects of hydroxypropyl cellulose (HPC-JXF), polyethylene oxide (PEO-N10), and sorbitol on LFX-release behavior. Sixteen insert formulations were prepared and evaluated for their physicochemical characteristics and in vitro dissolution performance. All developed inserts showed adequate weight uniformity, thickness, surface pH, and drug content. Statistical analysis results revealed that formulation composition had a marked influence on LFX release at both 0.5 and 8 h time points. PEO-N10 played a key role in improving LFX release; however, HPC-JXF contributed to release retardation and preservation of matrix integrity. Numerical optimization identified a formulation containing 90% polymer content of HPC-JXF and 10% LFX as the optimal extended-release system. The optimized formulation released ~18% of LFX within the first 30 min and ~64% at 8 h, indicating close agreement between the experimental results and model-predicted values. Differential Scanning Calorimetry thermograms suggested that HME processing helped in the molecular dispersion of LFX throughout the polymeric carrier, resulting in an amorphous drug distribution within the insert matrix. The Korsmeyer–Peppas release exponent, determined via DDSolver modeling, indicated anomalous transport, where drug diffusion and polymer relaxation contributed to the release process. Overall, the project outcomes prove the potential of HME for the fabrication of LFX-loaded ocular inserts with tunable release characteristics that range from immediate to extended release. The optimized insert formulation could be a promising alternative platform to conventional ophthalmic eyedrops for the management of bacterial ocular infections.

Background: Remdesivir is associated with hepatotoxicity and acute kidney injury (AKI). The objective of this study was to assess the hepatotoxicity and AKI with remdesivir. Method: This is a multicenter, retrospective cohort study for adult patients who used remdesivir for COVID-19 from 3/2020 to 10/2021. The study was conducted at Rhode Island Hospital, Rhode Island, United States. Data were analyzed with descriptive statistics as well as logistic regression analysis using STATA 18. Results: A total of 1635 patients were evaluated for hepatotoxicity: 337 developed hepatotoxicity, and 1298 had normal hepatic function. The overall median frequency of hepatotoxicity occurred in 319 patients (19.5%). Patient age (OR 1.02, 95% CI: 1–1.04, p = 0.02) and selective serotonin reuptake inhibitors (SSRIs) use (OR 1.7, 95% CI: 1.1–2.6, p = 0.01) were potential risk factors for remdesivir-associated hepatotoxicity. In contrast, being male gender was protective against remdesivir-associated hepatotoxicity (OR 0.63, 95% CI: 0.47–0.87, p = 0.02). The frequency of AKI with remdesivir occurred in 280 patients (17.3%). Conclusions: The frequency of hepatotoxicity was 19.5%, and the frequency of AKI was 17.3%. Increasing age and using SSRIs were risk factors for remdesivir-associated hepatotoxicity, while male gender was a protective factor. Clinicians should vigilantly monitor hepatic and renal functions for patients using remdesivir, especially in elderly patients.

Aim: This study aimed to explore the relationships between burnout, emotional intelligence (EI), and work engagement (WE) among hospital nurses. Specifically, it examined the mediating role of burnout in the relationship between EI and WE. Background: Nurses are frequently exposed to emotionally and physically demanding environments, which may lead to sustained occupational stress. Prolonged exposure to such conditions can contribute to burnout, adversely affecting both personal well-being and professional performance. EI is increasingly recognised as a protective factor that may alleviate burnout and enhance WE. Methods: A quantitative, cross-sectional correlational design was employed. A quota sampling technique was used to select 336 nurses working in public healthcare facilities in Ha’il, Saudi Arabia. Data were collected using standardised self-report instruments: the 14-item Shirom–Melamed Burnout Questionnaire (SMBM), the short-form Genos Emotional Intelligence Inventory (Genos EI), and the 9-item Utrecht Work Engagement Scale (UWES-9). Structural equation modelling examined associations and the mediating role of burnout between EI and WE. Results: EI was positively associated with WE and negatively with burnout. Burnout, in turn, was negatively associated with WE. Mediation analysis confirmed that burnout partially mediated the effect of EI on WE, indicating that EI nurses were less likely to experience burnout and more likely to remain engaged in their roles. Discussion: The results emphasise the role of EI in reducing burnout and enhancing WE among nurses. Burnout partially mediates this relationship, suggesting that EI influences WE both directly and indirectly. Conclusions and Implications for Nursing: Integrating EI training into professional development and implementing measures to reduce burnout may improve WE and retention. Policy efforts should ensure supportive work environments and adequate staffing to sustain nurse well-being.

Background: Diabetic nephropathy (DN) represents one of the most severe complications associated with type 2 diabetes (T2D), often leading to kidney failure and significantly affecting patients’ quality of life. Early detection and monitoring of DN are essential to prevent its progression. Midkine and copeptin, two biomarkers associated with inflammatory and metabolic processes, have shown promise in reflecting the underlying changes associated with DN, thus offering hope for improved diagnosis and management. The objective of this study was to investigate the clinical relevance of midkine and copeptin levels in T2D patients and their associations with insulin resistance and albuminuria status, evaluating their potential as predictive tools to detect the progression of DN. Methods: A case–control study was carried out with 360 participants, grouped into 90 healthy controls and T2D patients categorized by different stages of albuminuria (normoalbuminuric, microalbuminuric, and macroalbuminuric, with 90 individuals in each category). Serum levels of midkine, copeptin, fasting insulin, and other biochemical analytes were measured. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR), while renal function was evaluated using the albumin–creatinine ratio (ACR) and the estimated glomerular filtration rate (eGFR). Results: Elevated levels of midkine and copeptin were found in T2D patients, with the highest levels observed in the macroalbuminuric group ( p < 0.001). Both biomarkers were positively correlated with glycemic parameters (fasting glucose, HbA1c), insulin resistance (HOMA-IR), and markers of DN (ACR, eGFR) ( p < 0.001). ROC (receiver operating characteristic) analysis showed strong diagnostic performance for both biomarkers, with midkine yielding an area under the curve (AUC) of 0.96 (95% CI: 0.94–0.99, sensitivity: 96.7%, specificity: 91.1%) and copeptin yielding an AUC of 0.98 (95% CI: 0.97–1.0, sensitivity: 97.8%, specificity: 88.9%). Multivariate linear regression analysis identified midkine ( p = 0.039) and copeptin ( p = 0.027) as significant predictors of albuminuria. Conclusion: Serum levels of midkine and copeptin are elevated in T2D patients, with a strong association with the onset and progression of DN. These biomarkers may serve as early indicators for diabetic kidney disease, facilitating timely detection and management of renal complications. Their role in predicting insulin resistance and cardiovascular risk further underscores their potential as clinical tools for managing DN.

Background: Brucellosis is a major zoonotic infection that warrants treatment with antibiotic therapy. Current treatment recommendations include using either dual or triple therapy with antibiotics active against brucella species. This study aims to evaluate the effectiveness and safety of dual and triple antibiotic therapy for treating brucellosis. Methods: This is a retrospective cohort study for patients with confirmed Brucellosis infection from 2015 to 2024. The primary outcome was the achievement of a favorable response. Secondary outcomes were treatment failure, 90-day mortality, relapse of brucella infection, hospital re-admission, and adverse drug reactions (ADRs). Baseline characteristics were reported as means with standard deviations. All the statistical tests are shown as odds ratios (ORs) with 95% confidence intervals (CIs). Results: In total, 966 patients were screened and 287 met the inclusion criteria: 164 patients in the dual therapy group and 123 patients in the triple therapy group. Achievement of a favorable response was not statistically different between the dual therapy and triple therapy groups; 87.3% vs. 90.5%, OR 1.2 (0.48–3.02, p = 0.42). No patient died in either treatment group. Treatment failure, mean duration of hospitalization, brucella relapse, hospital re-admission, and the mean time to defervescence were not statistically different between dual and triple therapy groups. Adverse drug reactions were numerically higher in the triple therapy group. Conclusions: Dual therapy was equally effective for the treatment of patients with brucellosis compared to the triple therapy regimens. Although not statistically significant, there more ADRs in the triple therapy group compared to those receiving dual therapy. Thus, dual antibiotic therapy is efficacious, less costly, and associated with fewer ADRs compared to triple antibiotic therapy.

Sulpiride (Sul) is a medication that blocks dopamine D₂ receptors. It is used to treat gastrointestinal disturbances and has antipsychotic effects depending on the dose given. Sulpiride is subject to P-glycoprotein efflux, resulting in limited bioavailability and erratic absorption. Hence, the aim of this study was to generate a glycerosomal in situ gel of sulpiride for intranasal administration, specifically targeting children with schizophrenia who may have difficulty swallowing traditional solid medications, for enhancing its bioavailability. This study aimed to demonstrate the efficacy of intranasal administration of glycerin-encapsulated lipid-nanovesicles (glycerosomes) mixed with in situ gels for prolonged release of anti-psychotic medication. A Box–Behnken design was utilized to create sulpiride-loaded glycerosomes (Sul-GMs), with the lipid amount (A), glycerin concentration (B), and sonication time (C) acting as independent variables. Their impact on the entrapment efficiency, EE% (Y₁), and in vitro drug release (Y₂) were evaluated. The sulpiride EE% showed an increase when the glycerin concentration was raised to 25% v/v. Nevertheless, when the glycerin concentration was raised to 40% v/v, there was a notable decrease in the EE%. The optimized glycerosome was added to pH triggered carbopol 974P in situ gel formulations including HPMC K15M with different concentrations. The in situ gel formulation (G3) comprising 0.6% carbopol 974P and 0.6% hydroxypropyl methyl cellulose-K15M (HPMC K15M) demonstrated suitable pH, viscosity, desired gel strength, spreadability, and mucoadhesive strength. Consequently, it was selected for in vitro study, ex vivo permeation investigation, and in vivo evaluations. The glycerosomal in situ gel exhibited favorable ex vivo permeability of SU when applied to the nasal mucosa. The pharmacokinetic investigation revealed that the optimized Sul-loaded glycerosomal in situ gel exhibited a significant fourfold and twofold enhancement in systemic bioavailability compared to both the control gel and the commercially available formulation. Finally, the intranasal administration of Sul-loaded glycerosomal in situ gel is a promising alternative to oral treatment for pediatric patients with psychosis.

The present study explored the effectiveness of bile-salt-based nano-vesicular carriers (bilosomes) for delivering anti-psychotic medication, Sulpiride (Su), via the skin. A response surface methodology (RSM), using a 3³ Box–Behnken design (BBD) in particular, was employed to develop and optimize drug-loaded bilosomal vesicles. The optimized bilosomes were assessed based on their vesicle size, entrapment efficiency (% EE), and the amount of Sulpiride released. The Sulpiride-loaded bilosomal gel was generated by incorporating the optimized Su-BLs into a hydroxypropyl methylcellulose polymer. The obtained gel was examined for its physical properties, ex vivo permeability, and in vivo pharmacokinetic performance. The optimum Su-BLs exhibited a vesicle size of 211.26 ± 10.84 nm, an encapsulation efficiency of 80.08 ± 1.88% and a drug loading capacity of 26.69 ± 0.63%. Furthermore, the use of bilosomal vesicles effectively prolonged the release of Su over a period of twelve hours. In addition, the bilosomal gel loaded with Su exhibited a three-fold increase in the rate at which Su transferred through the skin, in comparison to oral-free Sulpiride. The relative bioavailability of Su-BL gel was almost four times as high as that of the plain Su suspension and approximately two times as high as that of the Su gel. Overall, bilosomes could potentially serve as an effective technique for delivering drugs through the skin, specifically enhancing the anti-psychotic effects of Sulpiride by increasing its ability to penetrate the skin and its systemic bioavailability, with few adverse effects.