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Objectives: This study was designed to assess the disproportionality analyses of adverse drug reactions (ADRs) related to hydroxychloroquine and remdesivir and how ADR reporting fluctuated during the COVID-19 pandemic. Methods: A retrospective observational study was conducted utilizing the Food and Drug Administration’s Adverse Event Reporting System (FAERS) data between 2019 and 2021. The study was conducted in two phases. In the first phase, all reports associated with the drugs of interest were evaluated to assess all related adverse drug reactions. In the second phase, specific outcomes of interest (i.e., QT prolongation and renal and hepatic events) were determined to study their association with the drugs of interest. A descriptive analysis was conducted for all adverse reactions related to the drugs being studied. In addition, disproportionality analyses were conducted to compute the reporting odds ratio, the proportional reporting ratio, the information component, and the empirical Bayes geometric mean. All analyses were conducted using RStudio. Results: A total of 9,443 ADR reports related to hydroxychloroquine; 6,160 (71.49) patients were female, and higher percentage of patients of both sexes were over the age of 65 years. QT prolongation (1.48%), pain (1.38%), and arthralgia (1.25%) were most frequently reported ADRs during the COVID-19 pandemic. The association of QT prolongation with use of hydroxychloroquine was statistically significant (ROR 47.28 [95% CI 35.95–62.18]; PRR 42.41 [95% CI 32.25–55.78]; EBGM 16.08; IC 4.95) compared with fluoroquinolone. The outcome was serious medical events in 48.01% of ADR reports; 27.42% required hospitalization and 8.61% resulted in death. Of 6,673 ADR reports related to remdesivir, 3,928 (61.13%) patients were male. During 2020, the top three ADR reports were elevated liver function tests (17.26%), acute kidney injury (5.95%) and death (2.84%). Additionally, 42.71% of ADR reports indicated serious medical events; 19.69% resulted in death and 11.71% indicated hospitalization. The ROR and PRR of hepatic and renal events associated with remdesivir were statistically significant, (4.81 [95% CI 4.46–5.19] and 2.96 [95% CI 2.66–3.29], respectively. Conclusion: Our study showed that several serious ADRs were reported with the use of hydroxychloroquine, which resulted in hospitalization and death. Trends with the use of remdesivir were similar, but to a lesser extent. Therefore, this study showed us that off-label use should be based on thorough evidence-based evaluation.

Introduction: The Saudi health care transformation is taking place through the implementation of many initiatives and programs to serve Saudi Vision 2030, which aims to improve health care services by focusing on digitalization and privatization. This study aimed to evaluate the economic impact of implementing the new digital health transformation initiative (Wasfaty service) on the health care budget using diabetes mellitus as an example. Methods: This study presents a cost analysis evaluation following the implementation of the Wasfaty program during the period between 2017 and 2021. The study compared the pre-Wasfaty period and the Wasfaty period in terms of direct medical costs. Data sources were the Ministry of Health for pre-Wasfaty data and the National Unified Procurement Company, which runs the Wasfaty program, for Wasfaty data. The study focuses on diabetic medications for outpatients. This health economic evaluation used the cost per visit, and sensitivity analyses were conducted utilizing the cost per patient according to the prevalence of diabetes mellitus. Results: After implementing the transformation using the Wasfaty service, the estimated annual mean cost savings per visit were USD 109.18 (SAR 409.43), and the cost savings per patient with a prevalence of 11% were USD 13.89 (SAR 52.1). The saving costs were USD 11,750,600 (SAR 44,064,750) for human resources and USD 97,473,469 (SAR 365,525,508) for pharmacies’ operation costs without including warehouse expenditures. The savings from the clinical decision support system preventing undesirable medication costs were estimated at USD 9,842,720 (SAR 36,910,201), and savings from the prevention of undesirable adverse events were estimated at USD 137,332,615 (SAR 514,997,308) for a 6% prediction. The total healthcare expenditure savings were USD 258,762,981 to 274,972,971 (SAR 970,361,178 ± 1,031,148,640). Conclusions: Implementing the new digitization and privatization initiatives (i.e., the Wasfaty program) as a result of the transformation in the health care sector had led to a significant reduction in health care expenditures and cost savings with respect to clinical and pharmacy services using diabetes mellitus as an example.

The study aimed to develop cisplatin-loaded PEGylated chitosan nanoparticles. The optimal batch of cisplatin-loaded PEGylated chitosan nanoparticles had a + 49.9 mV zeta potential, PDI of 0.347, and % PDI of 58.9. Nanoparticle zeta size was 741.4 z. d.nm, the size in diameter was 866.7 ± 470.5 nm, and nanoparticle conductivity in colloidal solution was 0.739 mS/cm. Differential scanning calorimetry (DSC) revealed that cisplatin-loaded PEGylated chitosan nanoparticles had sharp endothermic peaks at temperatures at 168.6 °C. The thermogravimetric analysis (TGA) showed the weight loss of cisplatin-loaded PEGylated chitosan nanoparticles, which was observed as 95% at 262.76 °C. XRD investigation on cisplatin-loaded PEGylated chitosan nanoparticles exhibited distinct peaks at 2θ as 9.7°, 20.4°, 22.1°, 25.3°, 36.1°, 38.1°, 39.5°, 44.3°, and 64.5°, confirming crystalline structure. The 1H NMR analysis showed the fingerprint region of cisplatin-loaded PEGylated chitosan nanoparticles as 0.85, 1.73, and 1.00 ppm in the proton dimension and de-shielded proton peaks appeared at 3.57, 3.58, 3.58, 3.59, 3.65, 3.67, 3,67, 3,67, 3.70, 3.71, 3.77, 3.78 and 4.71 ppm. The 13C NMR spectrum showed specified peaks at 63.18, 69.20, and 70.77 ppm. The FT-IR spectra of cisplatin loaded PEGylated nanoparticles show the existence of many fingerprint regions at 3186.52, 2931.68, 1453.19, 1333.98, 1253.71, 1085.19, 1019.60, 969.98, 929.53, 888.80, 706.13, and 623.67 cm−1. The drug release kinetics of cisplatin loaded PEGylated chitosan nanoparticles showed zero order kinetics with 48% of drug release linearity fashion which has R2 value of 0.9778. Studies on the MCF-7 ATCC human breast cancer cell line in vitro revealed that the IC50 value 82.08 µg /mL. Injectable nanoparticles had good physicochemical and cytotoxic properties. This method is novel since the application of the PEGylation processes leads to an increased solubility of chitosan nanoparticles at near neutral pH.

Statins have been reported to have potential anti-proliferative effects through an unknown mechanism. This study aims to investigate the anti-proliferative activities of five statins, including simvastatin, rosuvastatin, fluvastatin, atorvastatin, and pravastatin, against five different cancer cell lines; cervical epithelial carcinoma DoTc2 4510, malignant melanoma A-375, muscle Ewing's sarcoma A-673, hepatocellular carcinoma HUH-7, as well as breast cancer cells MCF-7. At 100 µM, simvastatin and atorvastatin significantly inhibited 70% of cellular proliferation. At the same concentration, rosuvastatin and fluvastatin showed about 50% of inhibition only in A-375 and A-673 cancer cells in a time- and dose-dependent manner. Of all the statin drugs used, pravastatin had the least inhibitory effect on all the cancer cell lines. Western Blot analysis showed a decrease in mTOR level, and the expression of p53 tumour suppression and BCL-2 proteins was relatively elevated compared to the untreated cells. Simvastatin and atorvastatin may inhibit cellular proliferation via BCL-2/p53, Bax/Bak, and PI3K/Akt/mTOR signalling pathways. This is the first research to evaluate the anti-cancer effects of simvastatin, rosuvastatin, fluvastatin, atorvastatin, and pravastatin against five different cell lines from distinct origins and provided a relevant comparison of their efficacies for their anti-proliferative activity.

Background: Ruboxistaurin (RBX) used to treat retinopathy in diabetic patients which caused by microvascular damage and leakage which contributes to visual loss. There are no published studies on the use of liquid chromatography-tandem mass spectrometry for development and validation of a simple, sensitive, and accurate method for measuring RBX in rat plasma. Method: Chromatographic separation of RBX was achieved using ultra-performance liquid chromatography. Multiple-reaction monitoring quantification used RBX [M + H] + ion at m/z 469.18 and daughter ions at m/z 84, 58.12, and 98.10. Atorvastatin was used as internal standard (IS), has a single daughter ion, and was identified using m/z 559.6 → 249.9. Validation of the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for RBX in rat plasma for linearity (greater than0.997) was carried out at 25–1000 ng/mL. Results: In rat plasma, the accuracy was within 3.4%, and the intra- and inter-day precision was within 11.8%. Stability, recovery, and matrix effect were all within acceptable limits. The drug retention time (0.85 ± 0.03 min) was remarkably short. Conclusion: The method developed in the current study is suitable to quantify RBX in plasma or bulk doses.

This observational descriptive study that was carried out with the objective of exploring the contribution of the local pharmaceutical industry to the Saudi drug security. Using a drug formulary provided from the Saudi Food and Drug Authority, containing all registered pharmaceutical products available in Saudi Arabia, we extracted information about drug class, drug type, country and place of manufacturing, shelf-life and price. Results showed that the majority of drugs in the market are manufactured in Europe (43.86%), followed by Saudi Arabia (22.55%), China and India (20.47%), Americas (10.24%), and other nations (2.61%). Most of the manufactured drugs were prescription drugs (90.62%). In this work, the local pharmaceutical industry with the highest percentage of contribution to local drug security was Pharmaceutical Solution Industries (PSI), representing the 5% of the items available in the Saudi market. The second highest percentage was 4% by TABUK Pharmaceutical Manufacturing CO., followed by SPIMACO (3%), JAMJOOM pharmaceutical company (2%), Riyadh pharma (2%), and Jazeera pharmaceutical industries (2%). In addition, results from this study provide information about the most essential pharmaceutical products that needs to be nationally manufactured or increased in production in order to rise the contribution of local pharmaceutical industries in Saudi drug security. Unfortunately, the small contribution of the Saudi pharmaceutical industry in local drug security increases the burden on the Kingdom's annual budget due to the over-reliance on international pharmaceuticals.

Objective: The objectives of this study were to explore the wastage of narcotics and controlled medications and, their financial impact in a tertiary care setting over a one-year period. Methodology: The study period was of one year, i.e., October 2020 – September 2021. The venue of study was a tertiary care hospital. The narcotic medications included Fentanyl, Tramadol, Morphine, and Meperidine. The controlled medications included Midazolam, Phenobarbital, Diazepam, Ketamine and Lorazepam. The annual consumption and wastage of the narcotic and controlled medications were documented using data report generated by narcotics and controlled medication in-charge pharmacist through the hospital’s online system. Data was reported using average, minimum and maximum values. Quantities of wastage is expressed in terms of ampoules. Costs per ampoule were calculated and expressed in both Saudi Riyal (SAR) and United States Dollar (USD). The study was approved by an ethics committee. Results: The annual wastage of narcotics was 3.19 % while the same for controlled medications was 21.3 %. An annual wastage of 3.81 % was reported for narcotics and controlled medications combined. The total wastage cost of narcotics and controlled medications was 15,443.1 SAR that was equivalent to USD 4085.5. Fentanyl 500mcg formulations had the highest consumption, i.e., 28,580 ampoules followed by Morphine 10 mg formulations, i.e., 27,122 ampoules. The highest ampoule wastage was observed for Morphine 10 mg formulations, i.e., 1956 ampoules. The highest % wastage was observed for Midazolam formulations, i.e., 29.3 %. Conclusion: The overall wastage was less than 5% of the total consumption, however, midazolam was observed to have the highest wastage. Shifting to prefilled syringes supplied by pharmacies, making protocols, and safely pooling costly drugs could result in significant savings.

The pathogenesis of diabetic nephropathy (DN) involves cellular activation of oxidative stress and inflammation. Eriodictyol is a citrus-derived flavonoid with multiple pharmacological and protective effects in various conditions. The protective role of Eriodictyol against diabetes and diabetic nephropathy is less investigated. The current research aimed to explore the role of eriodictyol in protecting against DN prompted by streptozotocin in male rats and investigate some possible mechanisms of action. Diabetes was brought about in rats by an i.p injection of a lone dose (65 mg/kg). Five groups of rats were included (n = 8 each) as control (non-diabetic), eriodictyol (20 mg/kg, orally), STZ-diabetic, STZ + eriodictyol (20 mg/kg, orally), and STZ + eriodictyol (20 mg/kg, orally) + ML385 (30 µg/kg, i.p.). Kidney histology and the levels of some markers of kidney function, renal oxidative stress, and renal inflammation were analyzed in all groups of rats. Treatment with eriodictyol prevented the damage in the renal glomeruli and tubules and reduced renal immune cell infiltration in STZ-treated animals. It also spiked urinary creatinine excretion and reduced urine volume and urinary levels of albumin, monocyte chemoattractant protein 1 (MCP-1), urinary kidney injury molecule-1 (KIM-1), and nephrin in these diabetic rats. In addition, eriodictyol stimulated the nuclear protein accumulation of Nrf2 and boosted the expression of superoxide dismutase (SOD), glutathione (GSH), heme oxygenase-1 (HO-1), and catalase (CAT) in the diabetic rat kidneys. In concomitance, it reduced the nuclear levels of NF-κB and levels of interleukine-6 (IL-6), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) and attenuated the reduction in renal ATP levels and the increase in the mitochondria transition pore opening (mtTPT). However, the administration of eriodictyol did not affect rats’ body weights and fasting glucose and insulin levels but significantly reduced serum levels of cholesterol, triglycerides, LDL-c, and oxidized LDL-c (ox-LDL-c). In conclusion, eriodictyol prevents STZ-induced nephropathy by a hypolipidemic effect and concomitant antioxidant and anti-inflammatory effects mediated by activating Nrf2/NF-κB/antioxidant axis.

Pulmonary fibrosis (PF) is the last phase of interstitial lung diseases (ILDs), which are a collection of pulmonary illnesses marked by parenchymal remodeling and scarring. Treatment can only halt the functional decline of the lung, raising the necessity of identifying the basic processes implicated in lung fibrogenesis. The Interferon lambda-3 (IFNL3) gene variant, rs12979860, was determined to be related to an elevated risk of fibrosis in different organs, but the mechanism through which it mediates fibrogenesis is not clear. In the current research, we aim to figure out some of the mechanistic pathways by which IFN-λ3 mediates ILDs. 100 healthy controls and 74 ILD patients were genotyped for IFNL3 rs12979860. Then the mRNA expression of IFNL3 and some other proinflammatory mediators was examined according to genotype in the peripheral blood mononuclear cells (PBMCs) of ILDs patients. The IFNL3 rs12979860 genotype distribution of healthy individuals and ILDs patients was shown to be in Hardy-Weinberg equilibrium (HWE) with a minor allele frequency (MAF) of 0.293 and 0.326, respectively. Furthermore, the CC genotype was demonstrated to be linked to enhanced IFNL3 expression. Also, the CC genotype was linked to an increase in the mRNA expression of TLR4 (P = 0.03) and the inflammatory cytokines IL-1β and TNF-α (P = 0.01 and 0.04, respectively) and had no effect on the NF-kB level (P = 0.3). From these results, we can deduce that IFN-λ3 may mediate tissue fibrosis via increasing the expression of IFN-λ3 itself and other proinflammatory mediators. This stimulates a self-sustaining loop mechanism which includes a reciprocal production of IFN-λ3, TLR4, IL-1β, and TNF-α leading to persistent inflammation and fibrosis.

The growing concerns and cases of COVID-19 with the appearance of novel variants i.e., BA.2.75. BA.5 and XBB have prompted demand for more effective treatment options that could overcome the risk of immune evasion. For this purpose, discovering novel small molecules to inhibit druggable proteins such as PLpro required for viral pathogenesis, replication, survival, and spread is the best choice. Compounds from the Dark chemical matter (DCM) database is consistently active in various screening tests and offer intriguing possibilities for finding drugs that are extremely selective or active against uncommon targets. Considering the essential role of PLpro, the current study uses DCMdatabase for the identification of potential hits using in silico virtual molecular screening and simulation approaches to inhibit the current and emerging variants of SARS-CoV-2. Our results revealed the 10 best compounds with docking scores between −7.99 to −7.03 kcal/mol better than the control drug (GRL0617) among which DC 5977–0726, DC 6623–2024, DC C879-0379 and DC D135-0154 were observed as the best hits. Structural-dynamics properties such as dynamic stability, protein packing, and residue flexibility demonstrated the pharmacologically favorable properties of these top hits in contrast to GRL0617. The hydrogen bonding half-life revealed that Asp164, Arg166, Tyr264, and Tyr268 have major contributions to the hydrogen bonding during the simulation. However, some of the important hydrogen bonds were missing in the control drug (GRL0617). Finally, the total binding free energy was reported to be −34.41 kcal/mol for GRL0617 (control), −41.03 kcal/mol for the DC5977-0726-PLpro, for the DC6623-2024-Plpro complex the TBE was −48.87 kcal/mol, for the for DCC879-0379-Plpro complex the TBE was −45.66 kcal/mol while for the DCD135-0154-PLpro complex the TBE was calculated to be −40.09 kcal/mol respectively, which shows the stronger potency of these compounds against PLpro and further in in vivo and in vitro test are required for the possible usage as potential drug against SARS-CoV-2.

Parkinson's disease (PD) is the gradual and selective degradation of dopamine-releasing neurons in substantia nigra pars compacta (SNpc) and results in postural instability, stiffness, bradykinesia, and resting tremor. The goal of this research was to see how hibiscetin action on PD in rotenone-treated rats. Rats were administered orally with hibiscetin (10 mg/kg) after 1 h rotenone (0.5 mg/kg, s.c.). This therapy regimen was followed on a daily basis for 28 days.Rats were tested for catalepsy and akinesia on day 29 after the last dosage of rotenone. Biochemical parameters were performed to measure reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), nitrite, neuroinflammatory cytokines, and neurotransmitter and their metabolite levels such as dopamine (DA), norepinephrine (NE), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). Rotenone-induced akinesia and catatonia in rats decreased endogenous antioxidant (GSH, CAT, and SOD) levels, increased MDA and nitrite levels, and changed neurotransmitter and metabolite levels. Hibiscetin effectively reduced rotenone-induced akinesia and catatonia, improved endogenous antioxidant (GSH, CAT and SOD) levels, and reduced oxidative and nitrative stress in the treated rats. Moreover, hibiscetin restored altered neurotransmitters and their metabolites to normal levels in rotenone-treated rats. The study results showed that hibiscetin has anti-Parkinson's activity against rotenone-induced PD in rats.

Background: Vaccine adverse event reporting system (VAERS) was established in the United States (U.S.) as an early warning system with a main purpose of collecting post-marketing Adverse events following immunizations (AEFIs) reports to monitor the vaccine safety and to mitigate the risks from vaccines. During the coronavirus diseases 2019 (COVID-19) pandemic, VAERS got more attention as its important role in monitoring the safety of the vaccines. The aim of this study was to investigate VAERS patterns, reported AEFI, vaccines, and impact of different pandemics since its inception. Methods: This was an observational study using VARES data from 2/7/1990 to 12/11/2021. Patterns of reports over years were first described, followed by a comparison of reports statistics per year. Furthermore, a comparison of incidents (death, ER visits, etc.) statistics over years, in addition to statistics of each vaccine were calculated. Moreover, each incident's statistics for each vaccine were calculated and top vaccines were reported. All analyses were conducted using R (Version 1.4.1717) and Excel for Microsoft 365. Results: There were 1,396,280 domestic and 346,210 non-domestic reports during 1990–2021, including 228 vaccines. For both domestic and non-domestic reports, year of 2021 had the highest reporting rate (48.52 % and 70.33 %), in addition a notable change in AEFIs patterns were recorded during 1991, 1998, 2000, 2006, 2009, 2011, and 2017. AEFIs were as follow: deaths (1.00 % and 4.08 %), ER or doctor visits (13.37 % and 2.27 %), hospitalizations (5.84 % and 27.78 %), lethal threat (1.42 % and 4.38 %), and disabilities (1.4 % and 7.96 %). Pyrexia was the top reported symptom during the past 31 years, except for 2021 where headache was the top one. COVID-19 vaccines namely Moderna, Pfizer-Biontech, and Janssen were the top 3 reported vaccines with headache, pyrexia, and fatigue as the top associated AEFIs. Followed by Zoster, Seasonal Influenza, Pneumococcal, and Human papillomavirus vaccines. Conclusions: The large data available in VARES make it a useful tool for detecting and monitoring vaccine AEFIs. However, its usability relies on understating the limitations of this surveillance system, the impact of governmental regulations, availability of vaccines, and public health recommendations on the reporting rate.

Background: Stress and anxiety are relatively common, particularly in females and college students. Stress can impact students’ overall performance and their physical and mental health. The COVID-19 pandemic has affected all aspects of life and is associated with high levels of psychological distress. It has considerably affected the education sector, not only locally but worldwide, forcing a shift in the education system from on-site to virtual learning. This cross-sectional study was undertaken to evaluate the prevalence of anxiety and stress regarding virtual learning among health sciences college students in the Kingdom of Saudi Arabia (KSA) after introducing blended virtual classes and exams and in-person laboratory training. The study was carried six months after the COVID-19 outbreak. Methodology: Participants were recruited by convenient sampling and snowballing strategies. Our study was conducted between November 18 and December 6, 2020. Questionnaires were employed; they included the General Anxiety Disorder-7 (GAD-7) scale and focused on the participants’ attitudes toward virtual learning. The present research was validated by a pilot study, followed by implementing some amendments. Results: A total of 418 health sciences college students, aged 18–27 (M = 20.88, SD = 1.97), participated in the study. Our analysis indicated that more than half the sample (51.44%) reported a risk of moderate to severe GAD. Anxiety was recognized more frequently in women (72.09%) than in men (27.91%). Interestingly, our Χ2 analysis revealed an association between marital status and anxiety, with a higher risk of GAD found in single people (compared with married). In addition, we found that the risk of anxiety increased in junior students (1st-3rd year) compared to senior students (4th-6th year). Conclusion: Our study highlights the need to establish gender-based tailored mental health support systems that provide preventive measures. The study findings also recommend that institutions develop programs and platforms that safely support students to interact and seek guidance, particularly those at higher risk of stress, such as females and first-year students. Overall, our study underlines the need to pursue an understanding of the complicated nature of anxiety disorders..

Background: Identifying, preventing, and resolving medical problems are some of the most central functions of clinical pharmacy (CP) and pharmaceutical care (PC) practitioners. Usually, the practitioners and researchers find a challenging to link the problem and the appropriate intervention to be included in the care plan. A comprehensive, well-structured, validated, simple use and standardized tool, which fulfill these requirements in daily clinical practice, are currently rare. Purpose: To design and validate a comprehensive medical problem-oriented plan (MPOP) classification system in addition to assessment and care plan tools for use in practicing, researching, and teaching CP and PC. Materials and methods: The methodology was composed of five steps: literature searching and classification of the problems; developing the assessment of treatments and care plan templates; implementing the tutorial; validation; completion and evaluation of the final version. Results: The classification system (MPOP tool) is an open hierarchical structure, where higher levels are broadly defined, consisting of 5 main categories, and lower levels become more specific. In the MPOP tool's final version, a total of 24 major subcategories were distributed to the major five categories as 4 (Indication), 5 (Effectiveness), 7 (Safety), 3 (Patient), and 5 (Miscellaneous). Different minor subcategories (subcategory 2, n = 62) and 95 plans (interventions) were determined. Each of the subcategories and plans includes a notes section that represents a specific detail. There was strong agreement on using the MPOP tool between the two authors (κ = 1.000, p

Amla (Phyllanthus emblica) has long been used in traditional folk medicine to prevent and cure a variety of inflammatory diseases. In this study, the antioxidant activity (DPPH scavenging and reducing power), anti-inflammatory activity (RBC Membrane Stabilization and 15-LOX inhibition), and anticoagulation activity (Serin protease inhibition and Prothrombin Time assays) of the methanolic extract of amla were conducted. Amla exhibited a substantial amount of phenolic content (TPC: 663.53 mg GAE/g) and flavonoid content (TFC: 418.89 mg GAE/g). A strong DPPH scavenging effect was observed with an IC50 of 311.31 µg/ml as compared to standard ascorbic acid with an IC50 of 130.53 µg/ml. In reducing power assay, the EC50 value of the extract was found to be 196.20 µg/ml compared to standard ascorbic acid (EC50 = 33.83 µg/ml). The IC50 value of the RBC membrane stabilization and 15-LOX assays was observed as 101.08 µg/ml (IC50 of 58.62 µg/ml for standard aspirin) and 195.98 µg/ml (IC50 of 19.62 µg/ml for standard quercetin), respectively. The extract also strongly inhibited serine protease (trypsin) activity with an IC50 of 505.81 µg/ml (IC50 of 295.44 µg/ml for standard quercetin). The blood coagulation time (PTT) was found to be 11.91 min for amla extract and 24.11 min for standard Warfarin. Thus, the findings of an in vitro study revealed that the methanolic extract of amla contains significant antioxidant, anti-inflammatory, and anticoagulation activity. Furthermore, in silico docking and simulation of reported phytochemicals of amla with human 15-LOXA and 15-LOXB were carried out to validate the anti-inflammatory activity of amla. In this analysis, epicatechin and catechin showed greater molecular interaction and were considerably stable throughout the 100 ns simulation with 15-lipoxygenase A (15-LOXA) and 15-lipoxygenase B (15-LOXB) respectively.

Background: On March 11th, 2020, The World Health Organization (WHO) declared that the COVID-19 is a pandemic due to its worldwide spread. The COVID-19 pandemic has extended its impact to Saudi Arabia. By mid-February 2021, The Kingdom of Saudi Arabia has reported more than 373,000 COVID-19 cases impacting different population categories (i.e., male, female, different age groups, comorbidities status). The objective of this nationwide study was to describe and explore the characteristics of hospitalized patients diagnosed with COVID-19 in Saudi Arabia. Methods: This study was an observational epidemiological study based on collected clinical data from ten health institutions across all regions in Saudi Arabia. The study was conducted during the period from March 2nd, 2020, to January 31st, 2021. The data were collected included demographics, medical information, medications, and laboratory and diagnostic. More detailed information on usually missing factors such as smoking status, comorbidities, length of hospital stay were also collected. Both descriptive and inferential analyses were conducted using the statistical analysis software “SAS®” version 9.4. Results: During the study period, 5286 patients were included in this study. Of these, (79.15%) were male. Of all 5286 patients, quite a high number of the studied population 2010 (38.02%) were smokers. The majority of the patients 3436 (65%) were reported to have comorbidities, with hypertension being the most common disease 1725 (32.6%), followed by diabetes 1641(31.04%). A high proportion of the patients, 2220 patients (41.99%), were admitted to the intensive care unit; of these, (33.52%) were on mechanical ventilation. Most patients received anticoagulant prophylaxis medications (n = 4414, 83.5%). All patients were given more than one antibiotic prophylaxis. Overall, the median hospital stay was 5.5 days, and the median length in the intensive care unit was 4.26 days. Around (89.14%) of patients were discharged from the hospital, and (10.8%) died. Conclusion: In this real-world study utilizing a large sample size, this study provides confirmatory results on the COVID-19 patients characteristics that are similar to other populations. Healthcare professionals need to give COVID-19 patients with specific characteristics including smoking, diabetes mellitus and cardiac disease more care to avoid losing these patients.

Background: This review aimed to conduct an indirect comparison using a Bayesian network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of delafloxacin versus other single antibiotic regimens for the empiric treatment of Acute Bacterial Skin and Skin Structure Infections. Method: A systematic search with no start date restrictions was conducted. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs. Results: Of the 577 studies initially identified, nine RCTs were included in the review. The network meta-analysis showed that ceftaroline, ceftobiprole, delafloxacin and tigecycline had similar efficacy in the indirect comparisons [Ceftaroline Odds Ratio (OR) = 1.2, 95% Crl = 0.46–3.6), ceftobiprole (OR = 1.3, 95% Crl = 0.34–3.0) and tigecycline (OR = 0.96, 95% Crl = 0.30–2.9)]. However, the ranking plot for the intention to treat (ITT) population showed that delafloxacin had a probability of 80.8% to be ranked first followed by ceftobiprole (13.1%). The analysis of the overall adverse events showed that ceftaroline (OR = 0.88, 95% Crl = 0.65–1.2), ceftobiprole (OR = 1.1, 95% Crl = 0.69–2.0), delafloxacin (OR = 0.88, 95% Crl = 0.57–1.3) and tigecycline (OR = 1.4, 95% Crl = 0.88–2.2) had similar safety profiles. Conclusion: Delafloxacin did not show any statistically significant differences when compared to ceftaroline, ceftobiprole, and tigecycline in terms of efficacy and safety. However, the surface under the cumulative ranking curve (SUCRA) probability ranked delafloxacin as the first option for the ITT population.

Introduction: Since December 2020, three COVID-19 vaccines have been authorized in the United States (U.S.) and were proceeded by large immunization programs. The aim of this study was to characterize the U.S. post-marketing safety (PMS) profiles of these vaccines with an in-depth analysis of mortality data. Methods: This was a retrospective database analysis study. Details of the U.S. PMS reports (15 December 2020 to 19 March 2021) of the three vaccines (Pfizer-BioNTech, Moderna, and Janssen Ad26.COV2.S) were retrieved from the U.S. Vaccine Adverse Event Reporting System (VAERS). A descriptive analysis was conducted to characterize the reported adverse events (AEs). A comparative (Pfizer-BioNTech vs. Moderna) analysis of mortality was conducted. The mean count ratio of death between the two vaccines was estimated using a negative binomial regression model adjusting for the measured confounders. Results: A total of 44,451 AE reports were retrieved (corresponding to 0.05% of the U.S. population who received at least one dose). The most commonly reported AEs were injection site reactions (30.4% of the reports), pain (reported in 26.7% of the reports), and headache (18.6% of the reports). Serious AEs were reported in only 14.6% of the reports with 4,108 hospitalizations. The total number of deaths was 1,919 with a mean count ratio of Moderna (n = 997) vs. Pfizer-BioNTech (n = 899) of 1.07 (95% confidence interval 0.86 to 1.33). Conclusions: The vast majority of PMS AEs in the U.S. were non-serious, and the number of serious AEs is very low given the total number of vaccinated U.S. population.

Melanoma is an aggressive skin cancer with a high rate of metastasis to other organs. Recent studies specified the overexpression of V-domain Ig suppressor of T-cell activation (VISTA) and Aryl Hydrocarbon Receptor (AHR) in melanoma. Metformin shows anti-tumor activities in several cancer types. However, the mechanism is unclear. This study aims to investigate the inhibitory effect of metformin on VISTA via AHR in melanoma cells (CHL-1, B16) and animal models. VISTA and AHR levels were assessed by qPCR, Western blot, immunofluorescence microscope, flow cytometry, and immunohistochemistry. Here, metformin significantly decreased VISTA and AHR levels in vitro and in vivo. Furthermore, metformin inhibited all AHR-regulated genes. VISTA levels were dramatically inhibited by AHR modulations using shRNA and αNF, confirming the central role of AHR in VISTA. Finally, melanoma cells were xenografted in C57BL/6 and nude mice. Metformin significantly reduced the tumor volume and growth rate. Likewise, VISTA and AHR-regulated protein levels were suppressed in both models. These findings demonstrate for the first time that VISTA is suppressed by metformin and identified a new regulatory mechanism through AHR. The data suggest that metformin could be a new potential therapeutic strategy to treat melanoma patients combined with targeted immune checkpoint inhibitors.

Research studies have indicated that the comorbidity burden of mood disorders and obesity is reasonably high. Insulin signaling has been shown to modulate multiple physiological functions in the brain, indicating its association with neuropsychiatric diseases, including mood disorders. Leptin is a hormone responsible for regulating body weight and insulin homeostasis. Previous studies on db/db mice (a mouse model that carries a spontaneous genetic mutation in leptin receptor Leprdb) have shown that they exhibit inflammation as well as neurobehavioral traits associated with mood. Therefore, targeting inflammatory pathways such as TNF-α may be an effective strategy in the treatment of obesity-linked mood disorders. The objective of this study was to investigate the effect of long-term administration of etanercept (a TNF-α blocker) on anxiety and depressive-like behaviors in db/db mice. This was performed using light/dark box, forced swim, and open field tests with lean littermate wild type (WT) mice serving as a control group. Using flow cytometry in peripheral blood, we further examined the molecular effects of etanercept on NF-κB p65, TNF-α, IL-17A, and TLR-4 expressing CD4+, CD8+, and CD14+ cells in the peripheral blood. Our data show that peripheral administration of etanercept decreased these cells in db/db mice. Furthermore, our results indicated that peripheral administration of etanercept reduced anxiety and depressive-like behaviors. Therefore, targeting TNF-α signaling might be an effective strategy for modulating obesity-associated depression and anxiety.

Introduction: Health outcomes and policies is a growing areas that is needed in the healthcare culture. This study aimed to examine the availability, extent and type of teaching curricula (pharmacoeconomics, pharmacoepidemiology, pharmacovigilance, patient safety) in Arab countries. Methods: A retrospective observational study was conducted during the period of November 2019 to January 2020. The collection strategy was performed by listing of pharmacy colleges in each country and then reviewing the institutions’ websites that met the inclusion criteria. Five criteria were utilized to assess the availability of these courses: full-time mandatory, full-time elective, partial mandatory, partial elective, and not offered. Results: One hundred ninety-one academic institutions were screened during the study period. Of those, 151 (79.1%) institutions were included in the study and their curricular descriptions were retrieved from their electronic websites. Pharmacoeconomics was the most taught subject among the four subjects. It was offered in 89/151 of the colleges among Arab countries. Among these 89 colleges that offered pharmacoeconomics, 74/89 offered it as a mandatory. While, Pharmacoepidemiology was offered in 51 colleges, with 44/51 offering the subject as a mandatory, and 6 out of those 44 list it as a full-time mandatory, while 38 out of those 44 offer it as a partially mandatory. Only 22 of the colleges offered pharmacovigilance, with 14/22 offering the subject as a mandatory. Finally, there was only one institution that offers the subject of patient safety. Moreover, most of the four courses investigated are only taught in the final two years of study. Conclusions: The study found a clear shortcoming in the teaching pharmaceutical outcomes. More efforts are needed by academic institutions to adopt and teach these subjects to ensure they meet the work needs and advanced pharmacy practice transformation.

The impact of different sociodemographic and clinical characteristics on the COVID-19-related morbidity and mortality rates have been studied extensively around the world; however, there is a dearth of data on the impact of different clinical and sociodemographic variables on the COVID-19-related outcomes in Saudi Arabia. This study aimed to identify those at high risk of worse clinical outcomes, such as hospitalization and longer length of stay (LOS) among young and middle-aged adults (18 to 55 years). In this questionnaire-based cross-sectional study, 706 patients with real-time polymerase chain reaction (RT-PCR) confirmed COVID-19 infection were interviewed. Patients’ demographic characteristics, dietary habits, medical history, and lifestyle choices were collected through phone interviews. Patients with chronic health conditions, such as diabetes and hypertension, reported a higher rate of hospitalization, ICU admission, oxygen-support needs, and a longer period of recovery and LOS. Multiple logistic regression showed that diabetes, hypertension, and pulmonary disease (e.g., asthma and chronic obstructive pulmonary disease (COPD)) were associated with a higher risk of hospitalization and longer LOS. Multiple logistic regression showed that symptoms of breathlessness, loss of smell and/or taste, diarrhea, and cough were associated with a longer recovery period. Similarly, breathlessness, vomiting, and diarrhea were associated with higher rates of hospitalization. The findings of this study confirm the similarity of the factors associated with worse clinical outcomes across the world. Future studies should use more robust designs to investigate the impact of different therapies on the COVID-19-related morbidity and mortality in Saudi Arabia.

Memory, one of the most vital aspects of the human brain, is necessary for the effective survival of an individual. ‘Memory’ can be defined in various ways but in an overall view, memory is the retention of the information that the brain grasps. Different factors are responsible for the disbalance in the brain’s hippocampus region and the acetylcholine level, which masters the memory and cognitive functions. Plants are a source of pharmacologically potent drug molecules of high efficacy. Recently herbal medicine has evolved rapidly, gaining great acceptance worldwide due to their natural origin and fewer side effects. In this review, the authors have discussed the mechanisms and pharmacological action of herbal bioactive compounds to boost memory. Moreover, this review presents an update of different herbs and natural products that could act as memory enhancers and how they can be potentially utilized in the near future for the treatment of severe brain disorders. In addition, the authors also discuss the differences in biological activity of the same herb and emphasize the requirement for a higher standardization in cultivation methods and plant processing. The demand for further studies evaluating the interactions of herbal drugs is mentioned.

Background: The coronavirus disease 2019 (COVID-19) pandemic has affected many countries negatively, particularly in terms of their health care and financial systems. Numerous countries have attempted to employ precautions to address this pandemic. This study was aimed at exploring and assessing the early precautionary actions taken by 175 countries on six continents to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: An observational study utilizing available public data was conducted on the basis of data collected from December 31, 2019 until the end of April 2020 and then compared with data in January 2021. Several data were extracted, including information related to the date of the first reported case of SARS-CoV-2, total confirmed cases, total active cases and more. In addition, seven validated indicators were used to assess the countries’ preparedness and precautionary actions. Results: A total of 175 countries were included in the study. The total COVID-19 infection rate increased exponentially and rapidly in North America and Europe from March to April. The application of precautions (indicators) varied between countries. School closures, quarantines and curfews were the most-applied indicators among all countries. As for the relationship between the indicators and their effects on the infection rate, Italy and Spain were the top countries in Europe and adopted all the indicators. Nevertheless, they faced high infection rates: 239,639 and 205,463 COVID-19 cases in Spain and Italy, respectively. Conclusion: The precautionary actions might have played a role in limiting the spread of COVID-19 in several countries. However, many countries might not benefit from applying these indicators.

Background: Emergencies and disasters are major threats to health care systems. Coronavirus Disease 2019 (COVID-19) is at the center of a recent emergency situation that requires increased attention from health care professionals, including pharmacists. This study was aimed at providing an overview of pharmacists’ roles in disasters and formulating a definition of expected roles and tasks through which they can perform these roles properly. Methods: A systematic review was conducted utilizing a literature search performed on the Medline, EMBASE and PubMed databases. The last search occurred on 14 July 2020. Data were extracted and recorded on a data extraction sheet by the reviewers, then categorized using the prevention, preparedness, response, and recovery (PPRR) model. Study quality was evaluated using the Critical Appraisal Skills Program (CASP) checklist. Results: Fifteen articles addressing pharmacists’ roles in disasters were included. Of these, three addressed pharmacists’ roles during the COVID-19 pandemic. Pharmacists’ roles in the prevention of emergencies, including COVID-19, are focused on chronic disease medication supply and education. Regarding pharmacists’ preparedness to perform their roles in disasters, they were more focused on health policy and population health planning, especially regarding the COVID-19 pandemic. Direct patient care continues to support patients through medication availability, and pharmacists’ clinical roles are examples of their response to disasters. In addition, pharmacists have an important role in disaster recovery that involves several activities, such as restocking emergency kits and reestablishing normal stock. Studies were generally of a reasonable quality. However, some limitations were noted among studies, and higher quality studies that contribute to existing knowledge are needed. Conclusion: Health care systems’ utilization of pharmacists’ new roles can result in a well-prepared disaster response, as observed during the COVID-19 pandemic. Pharmacists’ engagement in decision-making processes and adequate demonstration of pharmacists’ nontraditional roles in the literature can facilitate the health care community’s acceptance of such roles.

Late in 2019, several cases of infection with a new strain of coronavirus were reported in China. This new strain was later officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the World Health Organization (WHO). This new virus (SARS-CoV2-) mainly affects the respiratory system and causes coronavirus disease 2019 (COVID-19). The first case of COVID-19 was reported to the WHO on December 31st, 2019, and the virus has spread dramatically in many countries worldwide. On March 11th, 2020, the WHO declared that COVID-19 had affected most of the world, and many deaths were linked to COVID-19. Unfortunately, there is no available treatment for COVID-19, and there is no available vaccine against SARS-CoV-2. Thus, preventive methods are the only way to limit the spread of the virus. Preventive actions have been taken by many countries, such as travel bans, closing borders and working from home. Saudi Arabia was one of the countries that took very early precautionary actions in the belief that these actions are the best way to fight the virus. Therefore, we present the actions that were taken by the Kingdom of Saudi Arabia to fight the new viral pandemic.