搜索结果：Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society

Prostate cancer (PCa) is among the most common malignancies and remains a leading cause of cancer-related mortality in men worldwide. One of the main drivers is the dysregulation of the downstream signalling machinery. The PI3K, AKT, and mTOR signalling pathways play a pivotal role in cellular sustenance, growth, metabolism, and proliferation. In prostate cancer this pathway is generally altered due to the mutation or deletion of the PTEN (phosphatase and tensin homolog) gene and unnecessary activities of some components of PI3K, AKT, or mTOR. Extracellular communication of the androgen receptor (AR) with a wide array of oncogenic signatures is a primary evasion mechanism of cancer therapy and metastasis. This review focuses on the structure and function of the PI3K/AKT/mTOR pathway to better understand its role in prostate tumor biology. Furthermore, current therapeutic strategies that combinatorically target individual components of this pathway, such as allosteric and ATP-competitive AKT inhibitors, isoform-selective PI3K inhibitors, first- and second-generation mTOR inhibitors, are under consideration. The study particularly focuses on the combined use of immunotherapy (checkpoint inhibitors), chemotherapy (docetaxel), and androgen deprivation therapy (ADT), which are designed to break through the resistance-generating mechanisms and increase clinical efficacy. Overall, the findings support the need to conduct comprehensive preclinical and clinical studies on these alternative treatment regimens, and the eventual goal is to develop new treatment options for prostate cancer. The evidence of the pathway-specific therapy approach for the treatment of prostate cancer in recent clinical trials still failed to give a conclusive result. The current discussion also investigates the emerging areas of focus and perfection of combination regimens. The combination of all these developments makes it clear that the PI3K/AKT/mTOR signalling pathway is a key strategic point for developing therapeutics.

Recently, concerns regarding the risk of drug eruption associated with the use of tetracyclines were raised by the United States Food and Drug Administration (U.S. FDA). Therefore, it is necessary to reevaluate this risk. This study aimed to quantify the signal of drug eruption associated with the use of tetracyclines. Also, the signal of drug eruption with the use of two other antimicrobial drugs-macrolides and fluoroquinolones-was investigated for comparison. A pharmacovigilance case/noncase study was conducted using the U.S. FDA Adverse Event Reporting System (FAERS). Reports of drug eruptions using the preferred term were retrieved from the database from 2020-2025 quarter 1. The associations between the risk of drug eruption and the three antibiotic classes were quantified using disproportionality analysis utilizing both Bayesian and traditional statistical analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM) and information component (IC). All three antibiotic classes were significantly associated with the risk of drug eruption. However, compared with fluoroquinolones and macrolides, tetracyclines were more strongly associated with drug eruption. Disproportionality analysis revealed that the ROR for tetracycline was 6.65 (95% confidence interval (CI), 4.00-11.09) in 2020; in 2024, it was 30.75 (95% CI, 24.46-38.67). For macrolides, the RORs were 2.16 (95% CI, 1.20-3.92) and 10.12 (95% CI, 7.16-14.31) in 2020 and 2024, respectively. The RORs for fluoroquinolones were 4.57 (95% CI, 3.20-6.52) in 2020 and 2.27 (95% CI, 1.31-3.92) in 2024. Males were predominant in the tetracycline group (74%), and females were predominant in the macrolide group (56%). Approximately 41% and 40% of patients in the fluoroquinolone and macrolide classes, respectively, were hospitalized. All three antibiotic classes were associated with the signal of drug eruption. The signal of drug eruption occurred across all age groups with all three antibiotics. Also, the signal has affected both males and females across the years studied. However, there is no specific pattern for the signal.

Pharmaceutical calculations are a core competency in pharmacy education and are essential for patient safety and effective clinical care. In the context of pharmacy education, diverse delivery and assessment strategies exist, and there are ongoing modifications to the pharmacy education landscape. This study explored the perceptions, confidence levels, and educational experiences of senior PharmD students regarding their pharmaceutical calculation skills and perceived preparedness for clinical practice. A qualitatively driven mixed-methods design was employed. A structured, anonymous survey comprising Likert-scale and open-ended questions was distributed to all fifth-year PharmD students at KSU (N = 141). A total of 141 complete responses were analyzed using descriptive statistics, the Chi-square test, and the Mann-Whitney U test for quantitative data, as well as thematic analysis for qualitative responses. The results revealed that most students (76.9%) reported positive experience with pharmaceutical calculations, and 79% indicated that extra academic support was available. The mode confidence rating was 5 (very confident), with a median of 4, suggesting a generally high self-reported perceived confidence. No statistically significant gender differences were observed in terms of confidence or experience. Students predominantly relied on digital tools (e.g., ChatGPT, YouTube, Excel) rather than traditional academic resources, and the majority expressed a desire for more real-world applications and practice-based learning. In summary, while students reported high perceived confidence in their pharmaceutical calculation abilities, many expressed uncertainties about their real-world relevance. These findings highlight the importance of practice-based, context-driven instruction, and the thoughtful integration of digital learning tools to enhance students' perceived relevance and engagement with pharmaceutical calculations.

Adalimumab is a monoclonal antibody approved for managing inflammatory bowel disease (IBD) and other autoimmune conditions. Biosimilars can offer a more affordable alternative to reference biologics and improve access to treatments. Despite their advantages, there are still concerns regarding physicians' adoption of biosimilar products. This study aimed to compare the clearance of originator adalimumab with its biosimilar products in patients with inflammatory bowel disease and other autoimmune diseases. This multicenter retrospective study was conducted across seven hospitals in Saudi Arabia and Qatar. The study population included adult patients who received adalimumab and underwent routine therapeutic drug monitoring. Population pharmacokinetic analysis was performed using Monolix software, and the empirical Bayesian estimate of clearance was determined for individual patients. Stepwise linear regression was then conducted to assess the effects of product type and other covariates on adalimumab clearance. This study included a total of 99 patients. Patients received various adalimumab products, including the reference biologic (Humira, 70.7%) and biosimilars (Amgevita, 16.2%; Hyrimoz, 13.1%). The average estimated clearance was 0.018 ± 0.012 L/hr. The only significant covariates in the multivariable regression were age and the presence/absence of antibodies. There was no significant difference in clearance between the originator and biosimilar products. Our study compared the clearance of adalimumab originator and its biosimilars in patients with inflammatory bowel disease and other autoimmune disorders. No significant differences in clearance were observed, suggesting comparable clearance. The adoption of biosimilars in clinical practice could improve patient access to biologic therapies while substantially reducing healthcare costs.

There is a need for assessing the impact of current drug availability regulations across the various stages of the pharmaceutical supply chain and among different stakeholders involved. This mixed methods survey assessed the impact of pharmaceutical availability regulations across the drug supply chain in Saudi Arabia. This research utilized a cross-sectional study design involving a survey conducted at a single point in time to collect data from key stakeholders across the various stages of the pharmaceutical supply chain. Various metrics, such as availability ratings, accessibility issues, and stakeholder perspectives on regulatory effectiveness were examined. Mixed methods analysis combined survey statistics with qualitative insights. The data source for this study comprised an online survey targeting key stakeholders involved along the pharmaceutical supply chain (n = 27), including drug manufacturers (n = 10), distributors (n = 4), and healthcare settings, such as hospitals (n = 9) and pharmacies (n = 4). The data were collected in September 2023. Manufacturers (mean availability rating of 3.8) and distributors (mean availability rating of 3.5) viewed regulations to be more effective versus hospital/pharmacies (mean availability rating of 3.3) citing lack of harmonization and transparency as key efficiency deterrents. Centralized inventory monitoring and unified availability benchmarks were strongly advocated as enhancements alongside improved communication flows. Ultimately, a collaborative, yet guided approach is imperative for balancing industrial priorities and access imperatives to attain synchrony across the pharmaceutical value chain in order to augment both health and economic outcomes.

The Kingdom of Saudi Arabia has been making significant progress as part of its Vision 2030 to diversify its economy and reduce dependence on fossil fuels. Key components of this transformation include the development of a robust research and development (R&D) ecosystem and biotechnology-based industry. The Kingdom has recently formed the Research, Development and Innovation Authority (RDIA) to regulate and fund research with Health and Wellness being among its top priorities, and the Saudi National Institute of Health (SNIH) to support translational health research and clinical trials. In addition, the country has launched its National Biotechnology Strategy with a bold goal of becoming a biotechnology hub in the region by 2030 and globally by 2040. Toxicology research is central to these transformations. Historically, it has served as a cornerstone to biomedical and healthcare R&D. Today, with advancements in materials science and the integration of multiple technologies (e.g., biotechnology, nanotechnology, artificial intelligence, etc.) across the different industry sectors, it has become more critical than ever to assess safety early in the development process. In this editorial, we discuss the essence of toxicology research in realizing the country's ambitious goals of Vision 2030 and beyond, particularly in the development of the healthcare and biomedical R&D sectors and advancing a biotechnology-based industry. We first provide an overview of the current state of toxicology research and discuss its critical role in advancing the goals of Vision 2030. Finally, we discuss future directions for harnessing toxicology research towards achieving the country's ambitious goals.

In the community pharmacy sector the concept of service quality is important. Pharmacists working in these settings provide useful services that go beyond merely dispensing medications. This study aimed to translate the short Perceived Service Quality Scale (PSQS-SF) to Arabic and to use this scale to assess the determinants of service quality of community pharmacies in relation to competitively priced high quality service and loyalty intention. A pre-validated short Perceived Service Quality Scale (pSQS-A-SF) was translated from English to Arabic, validated and approved by the original authors. The scale consisted of six questions assessing pharmacy service quality, two questions evaluating the perception of price competitiveness, and three questions measuring loyalty intentions. All of the items were rated on a 5-point Likert scale. Community pharmacy users have been approached to answer the survey and descriptive statistics were reported. The pSQS-SF was successfully translated and culturally adapted to Arabic context (pSQS-A-SF) with minor modifications. A total of 207 respondents completed the survey. Perceived service quality was rated highly across most items, whereas perceptions of price competitiveness were lower. In confirmatory factor analysis, the measurement model showed improved fit after minor modification (deletion of one service-quality item), with acceptable factor loadings and composite reliability, although average variance extracted was marginal. Service quality was strongly correlated with loyalty intentions. In the structural model, higher perceived service quality predicted greater patronage loyalty (β=0.26, p=0.023) and prescription loyalty (β=0.41, p=0.002), while price competitiveness did not significantly predict loyalty outcomes; private health insurance showed a small positive association with patronage loyalty (β=0.156, p=0.022). The Arabic version of the perceived service quality short-form demonstrates preliminary evidence of construct validity and reliability and can support evaluation of patient experience in Saudi community pharmacies. Perceived service quality-rather than price competitiveness-was linked with self-reported patronage loyalty in this sample. Further research should strengthen validation (including discriminant validity and broader sampling) and assess performance across settings and subgroups.

Sterile Injectable Products (SIPs) represent a critical class of pharmaceuticals that frequently face shortages and ultimately compromise patient care. Disruptions within the pharmaceutical supply chain are significant factors contributing to these shortages. This study aimed to investigate the causes and impacts of SIPs shortages in Saudi Arabia, with the central hypothesis that pharmaceutical supply chain disruptions are the primary drivers of these shortages and that they negatively affect patient outcomes. A cross-sectional questionnaire was administered to two key stakeholder groups: supply chain management (SCM) personnel and healthcare professionals (HCPs). A total of 350 responses were collected and statistically analyzed. Our findings demonstrate a strong consensus among SCM respondents, with 73% agreeing that supply chain disruptions significantly affect SIPs availability. Poor demand forecasting and limited sourcing capabilities were identified as the primary contributing factors. From the perspective of HCPs, over 65% indicated that SIP shortages adversely impacted patient care, resulting in treatment delays, extended hospital stays, and increased healthcare costs. Additionally, many respondents reported that staff time is often wasted in the search for alternative therapies, which may also be of short supply. Interestingly, more than 70% of respondents from both groups expressed robust support for the adoption of advanced technologies such as artificial intelligence (AI) and machine learning (ML) to enhance forecasting and inventory management. Taken together, these findings underscore the urgent need for integrated strategies including proactive forecasting, sustainable inventory management, expanded local manufacturing, and AI-driven tools to strengthen the resilience of the SIP supply chain in Saudi Arabia and beyond.

Colistin has served as a last-resort agent against multidrug-resistant Gram-negative bacilli (MDR-GNB). However, the emergence of resistance has substantially eroded its therapeutic value, particularly among hospitalized patients. Evidence regarding the clinical outcomes of colistin-resistant infections in Saudi Arabia, however, remains scarce. This study aimed at assessing the clinical characteristics and outcomes of colistin-resistant bacterial infections among hospitalized patients in the Qassim region. We conducted a single-center retrospective observational study at King Fahad Specialist Hospital, Qassim, Saudi Arabia, reviewing the records of hospitalized patients with colistin-resistant infections between 2019 to 2023. Demographic, clinical, microbiological, therapeutic, and outcome data were retrieved from both electronic and paper health records. Eighty-five patients (mean age, 65.8 years; 60% male) with eighty-five colistin-resistant isolates were identified. Enterobacterales predominated (85.9%), followed by Pseudomonas aeruginosa (9.4%) and Acinetobacter baumannii (4.7%). All isolates showed extensive colistin resistance (100% in Acinetobacter and Pseudomonas, 82.8% in Enterobacterales), acknowledging the small number of non-Enterobacterales isolates. Limited sensitivity to cephalosporins and carbapenems, underscoring the therapeutic challenge of MDR-GNB. Meropenem (39.7%) and tigecycline (15.1%) were the most frequently prescribed agents, whereas combination therapy was employed in 16.6% of cases. The overall in-hospital mortality was 54.1% (95% CI: 43.0-65.0), with substantially higher mortality among patients admitted to the ICU (70.8%, 95% CI: 55.9-83.0) compared with those managed in non-ICU settings (32.4%, 95% CI: 18.0-49.8). After adjustment for clinical indicators, ICU admission was independently associated with increased mortality. Colistin-resistant Gram-negative infections hospitalized patients were characterized by severely limited therapeutic options, substantial reliance on carbapenems and tigecycline, and high observed mortality. These observations underscore the need for strengthened antimicrobial stewardship, improved availability of rapid diagnostic tools, and expanded access to newer therapeutic agents. In the absence of such measures, the burden of colistin resistance is likely to persist in hospital settings, including patients requiring intensive care.

Cervical cancer is one of the major and serious risks to women. Salidroside, a natural compound, shows promise in treating cervical cancer. However, its specific molecular mechanisms remain unclear and require further investigation. This study aimed to elucidate the pharmacological activity of salidroside and its underlying molecular mechanisms in cervical cancer, employing network pharmacology, molecular docking, and experimental approaches. Genes associated with cervical cancer were gathered from The Cancer Genome Atlas Program (TCGA), Gene Expression Omnibus (GEO) databases, and network pharmacology. Furthermore, we integrated the drug targets with the disease targets pertinent to cervical cancer, subsequently conducting analyses utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) to explain the pharmacological pathways through which salidroside operates in the milieu of cervical cancer. Survival analysis was performed to screen the core therapeutic targets of salidroside. Salidroside constituents and hub genes binding affinity were assessed by molecular docking studies. In vitro experiments, including Cell Counting Kit-8 (CCK-8) assays, flow cytometry, and western blotting, were performed to further validate the computational findings. Study findings revealed that salidroside inhibited the cervical cancer cell progression, reduced viability, and induced apoptosis.Ten target genes related to salidroside's anti-cancer effects have been identified. Survival analysis revealed that MMP1 and MMP3 exhibited the highest binding capability among all the target genes. Molecular docking indicated that the salidroside's active entities showed a strong binding tendency with the MMP1 and MMP3 genes. Western blot analysis revealed that it significantly reduced the expression of MMP-1 and MMP-3. In Vitro studies suggested that suppressing MMP1 and MMP3 genes might be responsible for salidroside's anticancer effects.

Malaria remains a significant public health challenge in regions where it is endemic. Pregnant women and young children are particularly vulnerable to the disease. Effective and timely diagnostic methods are crucial for reducing severe health outcomes. These methods help prevent deaths and lessen the widespread clinical and epidemiological burden on at-risk populations. However, traditional methods involved in the process of malaria parasite detections such as microscopic examination of blood smear by medical trained technicians is known to be time consuming, purely subjective and highly prone to errors. Therefore, Artificial Intelligence (AI) based OD (Object Detection) model like YOLO are preferred for overcoming these issues faced by traditional approaches as YOLO is known to be more rapid and precise by predicting bounding boxes and class probabilities than other models. However, existing YOLO model face challenges such as higher localization error, struggle with small objects and better accuracy of the model. Therefore, proposed research work focuses on employing YOLOv3 model with modified MobileNetv2 in backbone structure for classifying Plasmodium vivax (P. vivax) cells with the aim of improving the performance and speed of the model for detecting objects as MobileNetv2 is known for its faster processing and reduced resource consumption. However, accuracy is still measured as one of the key downsides for detecting and classifying the classes of thin blood smear, therefore modified MobileNetv2 is used, where proposed TCL (Transformed Convolution Layer) is employed at bottleneck layer, where weights are calculated based on different classes of image features thereby making the process more effective for classifying the infected and uninfected malaria cells of thin blood smear images effective. Besides, the performance of the proposed model is evaluated by implementing different metrics where the findings obtained are accuracy value of 1.00, precision value of 0.98, recall of 0.98, F1 score of 0.97 and mean average precision (mAP) value of 0.90. The major contribution of the study focuses on providing a better diagnostic approach for medical professionals in order to obtain improved results.

Practically, all patients treated with Minoxidil (MXD) reported experiencing hypertrichosis, even though the original intended usage of the drug was the treatment of hypertension. This limitation supports the potential of repurposing MXD as a topical agent for the treatment of hair loss. Accordingly, the outset of the current study was to exploit the cutaneous influence of MXD and limit the drawbacks of conventional available dosage forms. This could be achieved via developing a nanocarrier, mainly; nanoemulsion (NE) for transdermal delivery of MXD. Therefore, several NEs were prepared containing MXD and optimized according to their particle size and in vitro release study using Response Surface Methodology. The optimized formulation was examined for its organoleptic properties, pH, viscosity, and drug content. Moreover, Morphology, kinetic study was investigated a long with the stability testing upon keeping in two distinct settings: room temperature and refrigerator for 12 months. Eventually, the in vivo hair growth rate was monitored and documented for 28 days in pretreated mice. The developed MXD-NEs were developed and optimized using Box Behnken Design software to obtain the most desired formula. The optimized MXD-NE demonstrated a nanosize (83.1 nm) and performs a successful in vitro release (75.6%) over a period of 6 h. Additionally, it showed ideal physical properties with pH (5.9), viscosity (26.7 cP), and drug content (99.4%). The droplets in the formula seemed to be spherical. The formula was stable when preserved for 12 months at both applied conditions. Finally, the formula demonstrated significant faster rate of hair growth that mostly owed to the value of nanocarrier in delivering drug into follicular hairs.

The optimal management strategy for hypertriglyceridemia-induced acute pancreatitis (HTGAP) remains uncertain, despite widespread use of treatment modalities including insulin therapy, heparin infusion, and plasmapheresis. Current evidence supporting the effectiveness and safety of these interventions is limited, leading to ongoing debate about their role in HTGAP treatment. This study aimed to synthesize the available evidence on the efficacy and safety of various management strategies for HTGAP. Following PRISMA guidelines for systematic reviews, we conducted a comprehensive search of the following electronic databases from their inception until October 2024: PubMed, EMBASE, Science Direct, Cochrane library, ProQuest, and Scopus. Studies were included if they were human-based quantitative study design involving a comparison group. The quality assessment tools applied were Jadad scale and CASP tool. Fourteen eligible studies were included in this review were the majority of which were cohort studies (n = 12) with (n = 10) followed a retrospective observational study design. Plasmapheresis significantly reduced triglyceride levels in six studies, while hemofiltration showed similar effectiveness in two studies. Plasmapheresis also demonstrated a statistically significant reduction in length of hospital stay across four studies. The majority of the studies (n = 12) reported no statistically significant effect on mortality. Safety reporting was notably limited, with only four studies documenting treatment-related adverse events. Plasmapheresis and hemofiltration show potential benefits in HTGAP management, but definitive conclusions regarding efficacy and safety remain challenging due to heterogeneous data and limited high-quality studies. Further robust research is needed to establish a well-informed consensus on optimal treatment strategies.

A novel class of antidiabetic drugs known as sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) prevents the renal proximal tubules from reabsorbing glucose. While a recent study showed that SGLT2-Is may be able to slow the proliferation of cancer cells that express SGLT2, limited evidence exists regarding their effects on renal cell carcinoma (RCC). Here, we examine the ability of the SGLT2-I canagliflozin (Cana) to prevent experimentally induced kidney carcinogenesis in male rats. A total of twenty-four rats were divided into four groups, six in each: negative control, DEN/TAA control; rats (60-70 g) were fed a choline-deficient diet (CDD) for 4 weeks, then rats were subjected to four doses of 50 mg/kg diethyl nitrosamine (DEN) over 8 weeks followed by thioacetamide 100 mg/kg (TAA) intraperitoneal injections twice weekly for 15 weeks, treated groups: rats were given canagliflozin (10 and 20 mg/kg b.wt.) orally starting from the 24th week of the experiment till the end of the 29th week. The obtained findings showed that treatment with canagliflozin reduced renal oxidative stress and toxicity indicator levels and considerably reinforced renal antioxidant capacity. The histological changes further supported the biochemical findings. In addition, canagliflozin therapy activated AMPK and inhibited Nrf2, NLRP3 and IL-6/STAT3 pro-inflammatory pathway. Immunohistochemistry exhibited upregulation of pro-apoptotic protein caspase-3 and downregulation of PCNA expression in Cana-treated groups. Conclusion: the results showed that canagliflozin has anti-carcinogenic efficacy against renal carcinogenesis via activating AMPK and suppressing NLRP3/IL-6/STAT3 signaling pathways.

The rise of multidrug-resistant bacteria now poses significant challenges, rendering many conventional medicines ineffective and necessitating the search for new antimicrobial agents. Polyacetylenes, both natural and synthetic, possess diverse biological activities, with their remarkable antibacterial potential being particularly significant. This review offers an in-depth evaluation of the therapeutic roles of polyacetylenes as antibacterial, antibiofilm, and anti-quorum-sensing agents, summarizing the tested compounds, their natural sources, the assays employed, and the bacterial strains investigated. It also provides an overview of their biosynthesis, distribution, and pharmacokinetic properties, along with a comprehensive analysis of their chemical classification and 13C-NMR data. Despite decades of research on polyacetylenes, no previous review has systematically integrated their antibacterial mechanisms, biofilm-inhibitory effects, quorum-sensing disruption, and structure-activity relationships (SAR). Our analysis revealed that antibacterial and antibiofilm activities are highly dependent on chain length, conjugation, and specific functional substituents, with halogenation, carbonyl and cinnamate incorporation, and stereochemical configuration significantly modulating potency beyond the previously assumed requirement for hydroxylation. This work fills that gap by compiling information on about 90 polyacetylenes that were reported between 1947 and January 2025. It draws attention to their dual antibacterial mechanism, involving disruption of membrane and downregulation of key QS-related genes, leading to attenuated virulence, suppressed biofilm formation, and marked decrease in bacterial burden. In conclusion, polyacetylenes represent promising antibacterial, antibiofilm, and anti-quorum-sensing candidates, offering valuable scaffolds for developing new therapies against multidrug-resistant infections.

This cross-sectional study examines the use of complementary and alternative medicine (CAM) among patients with multiple sclerosis (MS) in Riyadh. A survey was conducted among 151 multiple sclerosis patients enrolled at the neurology clinics of two hospitals in Riyadh (KSUMC and KFMC). The study indicated that a significant majority of respondents (60.93%) used complementary and alternative medicine, demonstrating a pronounced preference for religious-spiritual modalities, including Islamic ruqyah and cupping therapy, in addition to other practices such as massage, oils, dietary supplements, honey, and herbal remedies. The findings underscore the importance of symptom alleviation, optimism about a cure or a delay in disease progression, and social sources of support (from family, healthcare professionals, and the media) in driving decisions to use CAM. The results showed an association between educational level, marital status, and CAM use. Additionally, many patients did not disclose their CAM use to their physicians or pharmacists, either because they perceived it as insignificant or because they did not receive sufficient prompting to disclose it. This highlights the need for more proactive, non‑judgmental communication from healthcare practitioners about CAM, as well as targeted training to improve patients' understanding of potential interactions between CAM and conventional treatments.

Vancomycin (VAN) is a first-line agent for methicillin-resistant Staphylococcus aureus (MRSA) infections, but it poses nephrotoxicity risks. While VAN-fosfomycin (FOS) combination shows synergistic efficacy and lower mutant prevention concentrations, its renoprotective effects compared to VAN alone remain unclear. This study aims to directly compare renal function parameters and acute kidney injury incidence between VAN monotherapy and VAN + FOS combination therapy. After propensity score matching of the initial 156 patients, 76 individuals were included in the final analysis; 38 were assigned to the vancomycin monotherapy group and 38 in the VAN + FOS combination group. Renal function parameters were recorded at 48 h and 72 h post-treatment, and the incidence of acute kidney injury (AKI) was compared between the two groups. Univariate analyses were performed to identify baseline factors associated with AKI. The VAN + FOS group had a significantly lower incidence of AKI compared to the VAN-alone group (5.26% vs. 21.05%, P = 0.04). Due to the limited number of AKI cases, multivariate adjustment was not possible. Univariate analysis revealed significant associations between AKI incidence and FOS combination therapy, age, and vancomycin trough concentration (P = 0.04, P = 0.00, and P = 0.02, respectively). These findings warrant validation in larger, prospective studies. Fosfomycin adjunct therapy was associated with a lower incidence of vancomycin-induced AKI. However, these associations should be interpreted cautiously and require validation in larger cohorts.

Cardiac rhabdomyomas (CRHM) are the most common primary cardiac tumors in neonates and are closely linked to tuberous sclerosis complex (TSC). While many tumors regress spontaneously, large or strategically located lesions may require intervention. Everolimus, an mTOR inhibitor, has shown efficacy in managing TSC-associated tumors, though its use in neonatal CRHM remains largely supported by case reports. We report a term male neonate diagnosed with multiple CRHMs and found to have a heterozygous variant of uncertain significance in the TSC2 gene. The tumor size and location led to early initiation of oral everolimus at 0.06 mg/kg twice daily. Therapeutic drug monitoring revealed supratherapeutic levels during the first week, requiring stepwise dose reduction. Over five weeks of treatment, serial echocardiograms demonstrated marked regression of all tumor masses without adverse effects. A clinical pharmacist supervised the extemporaneous preparation, dose adjustment, and caregiver education to ensure treatment accuracy and safety. This case highlights the role of early, closely monitored everolimus therapy as a safe, non-surgical alternative for managing neonatal CRHM. To our knowledge, this is the first reported case from Saudi Arabia describing early everolimus treatment for neonatal CRHM and highlighting the critical role of the clinical pharmacist in individualized dosing, therapeutic monitoring, and caregiver education.

This study aimed to develop and evaluate orally disintegrating tablets (ODTs) and sublingual tablets (SLTs) containing Bisoprolol fumarate (BF) to enhance the onset of action and provided rapid relief of these cardiovascular diseases. For ODTs, experimental design was used to evaluate the effect of different independent factors on dissolution efficiency (DE%), disintegration time (DT), and hardness. Two independent variables, namely superdisintegrant concentration (crospovidone; CPV; X1) and taste masking agent concentration (Eudragit E100; X2) were selected to study their impact on the attributes of the BF ODTs. For SLTs, super disintegrant concentration (X1) and mixing time (X2) were selected to study their impact on SLTs attributes, as in the case of ODTs. The optimized ODTs formula (based on 8.3% CPV and 3.7% Eudragit) showed DE% of 85%, disintegration time (DT) of 39.3 s, and hardness of 2.55 Kp. Moreover, the optimized SLTs formula (based on 9.26% CPV and 16.2 min mixing time) showed DE% of 92%, DT was 35 s and hardness was 3.6 Kp. The optimized formula was compressed into an ODT and SLTs and studied according to USP criteria. All tablet examinations (Friability, Hardness, Disintegration Time, Drug Content, and Weight Variation) were within the accepted values and showed a high stability after six months of storage under accelerated conditions. The obtained results of the current study verified the efficacious formulation of BF as ODTs and SLTs to improve the onset of action and convalesce patient compliance in managing hypertension and arrhythmia.