Cost-Savings Associated with Multi-Disciplinary Team Approach for Reducing Macrovascular and Microvascular Complications in Patients with Type 2 Diabetes: A Predictive Model.

Purpose: This study aims to predict the expected cost savings associated with implementing a multidisciplinary team (MDT) approach to reduce macrovascular and microvascular complications among patients with type 2 diabetes mellitus (T2DM). Methods: This economic evaluation study was conducted in Riyadh First Health Cluster, Saudi Arabia as a predictive model conceptualized by the authors based on models used in previous studies, particularly the CORE Diabetes Model. Our model was designed based on 1) the level of glycemic control among 24,755 T2DM patients served by MDTs; 2) the expected incidence of diabetes-related complications without intervention; 3) the predicted risk reduction of developing diabetes-related complications with MDTs. Costs of complications and cost savings were then calculated and expressed as mean incremental annual cost savings adjusted for a 1% reduction in HbA1c, and a 10 mmHg reduction in systolic blood pressure (SBP). Results: Along with the expected reduction in all diabetes-related complications, the average incremental cost savings per diabetic patient is predicted to be ($38,878) with approximately ($11,108) in the year of complication onset and ($27,770) over the subsequent post-index 10-years. On adjustment of cost savings, the average incremental cost savings are predicted to be ($22,869) for each 1% reduction in HbA1c per diabetic patient and ($27,770) for every 10 mmHg reduction in SBP per diabetic patient. Conclusion: MDT as a model of care is effective in glycemic control among T2DM patients with a predicted significant reduction of all diabetes-related complications and in turn, a predicted significant cost savings.

The effect of penile traction device in men with Peyronie's disease on penile curvature, penile length, and erectile dysfunction: a systematic review and meta-analysis.

Background: Peyronie's disease (PD) results in curvature, pain, and erectile dysfunction (ED). Penile traction devices (PTDs) are a non-invasive treatment option for PD by applying mechanical forces to elicit biochemical responses that reduce curvature and improve penile function. In the present study, we systematically reviewed and analyzed the literature investigating the use of PTD to treat PD. Methods: We have conducted electronic and manual search strategies within the databases and included articles to find relevant studies. A total of Five studies met all the predefined inclusion criteria and were selected for inclusion in the review. Outcomes assessed are penile length, penile curvature, and erectile function (EF). The study population consisted of patients with PD, the intervention was penile traction therapy (PTT), the comparison was matched placebo or follow-up, and the study design was randomized controlled trials (RCTs) or cohort studies. The Cochrane risk of bias assessed the studies' quality for randomized studies and the Newcastle-Ottawa scale (NOS) for non-randomized observational studies. All statistical analyses were performed using R software. Results were considered statistically significant for P<0.05. Results: Only five studies met inclusion and exclusion criteria and were published between 2014 and 2021. The sample sizes range [51-110], totaling 419, with a mean of 83.8 patients-the follow-up with a mean of 6.75 months. This meta-analysis evaluated the efficacy of PTD on curvature degree, penile length, and EF in patients. There is a significant positive effect on the curvature degree (P=0.0373), while there is no significant effect on penile length and EF (P=0.5315 and 0.1010), respectively. They are Indicating low heterogeneity with an estimated total heterogeneity of 0. Overall, the available evidence does not support the efficacy of the intervention for penile length or EF. Conclusions: The current evidence suggests that PTDs can be a safe and effective treatment option for men with PD to reduce penile curvature. However, further research, including more RCTs with extended follow-up periods, is needed to fully understand their efficacy and determine the ideal timing and patient subtypes that would benefit from PTD.

Super pulsed thulium fiber laser outcomes in retrograde intrarenal surgery for ureteral and renal stones: a systematic review and meta-analysis.

BACKGROUND: Laser lithotripsy using a thulium fiber laser (TFL) has become an effective treatment option for small renal stones with low complication rates. TFL has a higher absorption coefficient, smaller fibers, and better pulse rate capability. METHODS: We conducted a systematic review and meta-analysis to evaluate the published evidence regarding TFL's lithotripsy performance in retrograde intrarenal surgery (RIRS), for which we primarily assessed the outcomes of stone-free rate, operation time, and complications. We searched different databases from inception to April 2023. We assessed the methodological quality and risk of bias using the Cochrane Risk of Bias tool for randomized trials and the ROBINS-I tool for non-randomized studies. We used a random-effects model for meta-analysis and assessed heterogeneity using the I2 statistic. RESULTS: Twelve published studies evaluated the efficacy of RIRS using a TFL for treating renal and ureteral stones. The meta-analysis revealed a predicted stone-free rate of 89.37% (95% CI: 83.93% to 93.12%), indicating that, on average, approximately 89.37% of patients achieved a stone-free state after treatment. The substantial heterogeneity among the studies was evident, as shown by a Q-value of 33.1174 and a p-value of 0.0003. The I2 value of 69.80% (95% CI: 25.91% to 92.02%) highlighted the proportion of variability attributed to genuine heterogeneity across the studies. Moreover, the H2 value 3.31 (95% CI: 1.35 to 12.53) indicated significant heterogeneity beyond random chance. The estimated overall effect size (logit-transformed) of 2.1289 was highly statistically significant (z = 8.7648, p < 0.0001) with a confidence interval of 1.6528 to 2.6049. The reported complications varied across studies, encompassing Clavien grade I-II complications in most cases, with a subset experiencing more severe Clavien grade III-V complications. Additionally, other studies noted a range of complications, such as haematuria, fever, transient creatinine elevation, and postoperative issues like bleeding, pain, and sepsis. CONCLUSION: This meta-analysis suggests that RIRS using TFL is an effective and safe treatment option for renal and ureteral stones, with high stone-free and low complication rates. The included studies exhibited a low risk of bias and were of high quality. However, more extensive randomized controlled trials with extended follow-up periods are needed to investigate this technique's efficacy and safety.

Effectiveness of Case Manager Led Multi-Disciplinary Team Approach on Glycemic Control Amongst T2DM Patients in Primary Care in Riyadh: A Retrospective Follow-Up Study.

OBJECTIVES: Our study aims to assess the effectiveness of implementing a case manager-led Multidisciplinary Team approach in the primary healthcare setting on improving glycemic control and reducing cardiovascular risks for T2DM patients over a 6-month period. METHODS: This retrospective record-based follow-up study was carried out on 3060 uncontrolled T2DM patients in primary healthcare centers in Riyadh First Health Cluster over a period of 6 months. The patient records are investigated and analyzed, including demographic characteristics and measurements of Hemoglobin A1c (HbA1c), Low-Density Lipoprotein Cholesterol (LDL-C), total cholesterol, and BP levels at enrollment and after 6 months of Multi-Disciplinary Team follow-up. The changes in the study variables and their correlations to each other are tested using Statistical Package for the Social Sciences software. RESULTS: At enrollment, our patients were characterized by poor glycemic control (HbAIC > 8%). Most of them have high body weight with a mean BMI of (31.2 ± 1.7), and nearly two-thirds are either hypertensive or have dyslipidemia (43.4% and 47.3% respectively). After 6 months of MDT follow-up, there is a significant improvement in glycemic control among 1971 patients (64.4%), with a reduction in the mean level of different outcomes relative to baseline HbA1c (-15%, P < .001), total cholesterol (-9.0%, P < .001), LDL-C (-11.0%, P < .001), systolic BP (-7.7%, P < .001), and diastolic BP (-10.5%, P < .001). The improved glycemic control showed a significant positive correlation with the number of MDT visits but negatively correlated with BMI and the number of comorbidities. In addition, the improvements in secondary outcomes were positively and significantly correlated with such improvements in glycemic control. CONCLUSION: Case-manager-led MDT approach significantly improves glycemic control and significantly improves control over dyslipidemia and hypertension, reducing cardiovascular risks, and unfavorable events among such diabetic patients. We highly recommend developing more MDTs, training case managers, and rigorously evaluating the MDT approach.

Graphene Scaffolds: A Striking Approach to Combat Dermatophytosis.

Exclusive physicochemical and biological properties of carbon allotrope graphene have attracted the peer attention of researchers for the synthesis and development of newer topical remedies including films, scaffolds, microspheres, and hydrogels. Here, graphene nanoplatelets (GN) were embedded into a different ratio of polymeric ERL100/ERS100 solution and fabricated in the form of a scaffold through the electrospinning process. FTIR spectra displayed characteristic similar peaks present both in GN and GN-loaded scaffold owing to the compatibility of GN and polymeric mixture. XRD curve revealed a distinct GN peak at nearly 26° whereas from DSC/TGA thermal stability was observed between polymers and graphene nanoplatelets. FESEM images showed ultrathin architecture of GN-loaded scaffold in a range of 280 ± 90 nm. The fabricated scaffold exhibited hydrophilicity (contact angle 48.8 ± 2.8°) and desirable swelling index (646% in skin pH media) which were desired criteria for the scaffold for topical application. In vitro, antifungal activity was conducted through the broth microdilution method against different virulent dermatophytes i.e., Microsporum gypseum, M. canis, M. fulvum, and Trychophyton rubrum. For in vivo evaluation, T. rubrum inoculum was applied on the dorsal surface of each group of Swiss albino mice, and the degree and intensity of mycelial growth or erythema on skin surfaces was visually investigated. The study depicted complete signs of cure after 14 days of application of G3-loaded scaffold on the infected dorsal site. Hence graphene-loaded scaffold represented a possible alternative for the treatment of topical fungal infections caused by dermatophytes.

Neuroeconomics of decision-making during COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic reveals the decision-making challenges faced by communities, governments, and international organizations, globally. Policymakers are much concerned about protecting the population from the deadly virus while lacking reliable information on the virus and its spread mechanisms and the effectiveness of possible measures and their (direct and indirect) health and socioeconomic costs. This review aims to highlight the various balanced policy decision that would combine the best obtainable scientific evidence characteristically provided by expert opinions and modeling studies. This article's main goal is to summarize the main significant progress in the understanding of neuroeconomics of decision-making and discuss the anatomy of decision making in the light of COVID-19 pandemic.

Optimization of tamoxifen solubility in carbon dioxide supercritical fluid and investigating other molecular targets using advanced artificial intelligence models.

Particle size, shape and morphology can be considered as the most significant functional parameters, their effects on increasing the performance of oral solid dosage formulation are indisputable. Supercritical Carbon dioxide fluid (SCCO2) technology is an effective approach to control the above-mentioned parameters in oral solid dosage formulation. In this study, drug solubility measuring is investigated based on artificial intelligence model using carbon dioxide as a common supercritical solvent, at different pressure and temperature, 120-400 bar, 308-338 K. The results indicate that pressure has a strong effect on drug solubility. In this investigation, Decision Tree (DT), Adaptive Boosted Decision Trees (ADA-DT), and Nu-SVR regression models are used for the first time as a novel model on the available data, which have two inputs, including pressure, X1 = P(bar) and temperature, X2 = T(K). Also, output is Y = solubility. With an R-squared score, DT, ADA-DT, and Nu-SVR showed results of 0.836, 0.921, and 0.813. Also, in terms of MAE, they showed error rates of 4.30E-06, 1.95E-06, and 3.45E-06. Another metric is RMSE, in which DT, ADA-DT, and Nu-SVR showed error rates of 4.96E-06, 2.34E-06, and 5.26E-06, respectively. Due to the analysis outputs, ADA-DT selected as the best and novel model and the find optimal outputs can be shown via vector: (x1 = 309, x2 = 317.39, Y1 = 7.03e-05).

Post-COVID-19 non-traumatic iliopsoas hematoma: A case report.

Background: Critically ill COVID-19 patients have an elevated risk of experiencing hypercoagulable conditions. Currently, many COVID-19 patients have been administered anticoagulation or antiplatelet therapies to lower the risk of systematic thrombosis. Iliopsoas hematoma is a potentially fatal and rare complication of bleeding disorders or anticoagulation therapy which sometimes grows to become clinically significant. The main purpose of this case review is to emphasize the importance of diagnosing iliopsoas hematomas and the possibility of antiplatelet contribution to its development. Case Presentation: We are reporting a rare presentation of non-traumatic iliopsoas hematoma in a non-anticoagulated patient. The patient is a 59-year-old male, with known type-2 diabetes, on oral hypoglycemic medications, 3-weeks post-COVID-19. He had started aspirin 81 mg orally, once daily, to prevent thrombotic events associated with COVID 19 infection, with no anticoagulant use and no other medications. He came in through the ED, presenting with two weeks history of progressive right lower limb weakness in which an iliopsoas hematoma diagnosis was confirmed based on radiological investigation. Conclusion: The possibility of iliopsoas hematoma should be considered in non-anticoagulated patients with no inherited or acquired coagulation disorders presenting with limb weakness. The link between antiplatelet use in a COVID-19 patient and the development of soft tissue bleeding (e.g., iliopsoas hematoma) must be studied further.

Computational simulation and target prediction studies of solubility optimization of decitabine through supercritical solvent.

Computational analysis of drug solubility was carried out using machine learning approach. The solubility of Decitabine as model drug in supercritical CO2 was studied as function of pressure and temperature to assess the feasibility of that for production of nanomedicine to enhance the solubility. The data was collected for solubility optimization of Decitabine at the temperature 308-338 K, and pressure 120-400 bar used as the inputs to the machine learning models. A dataset of 32 data points and two inputs (P and T) have been applied to optimize the solubility. The only output is Y = solubility, which is Decitabine mole fraction solubility in the solvent. The developed models are three models including Kernel Ridge Regression (KRR), Decision tree Regression (DTR), and Gaussian process (GPR), which are used for the first time as a novel model. These models are optimized using their hyper-parameters tuning and then assessed using standard metrics, which shows R2-score, KRR, DTR, and GPR equal to 0.806, 0.891, and 0.998. Also, the MAE metric shows 1.08E-04, 7.40E-05, and 9.73E-06 error rates in the same order. The other metric is MAPE, in which the KRR error rate is 4.64E-01, DTR shows an error rate equal to 1.63E-01, and GPR as the best mode illustrates 5.06E-02. Finally, analysis using the best model (GPR) reveals that increasing both inputs results in an increase in the solubility of Decitabine. The optimal values are (P = 400, T = 3.38E + 02, Y = 1.07E-03).

Application of CO2 Supercritical Fluid to Optimize the Solubility of Oxaprozin: Development of Novel Machine Learning Predictive Models.

Over the last years, extensive motivation has emerged towards the application of supercritical carbon dioxide (SCCO2) for particle engineering. SCCO2 has great potential for application as a green and eco-friendly technique to reach small crystalline particles with narrow particle size distribution. In this paper, an artificial intelligence (AI) method has been used as an efficient and versatile tool to predict and consequently optimize the solubility of oxaprozin in SCCO2 systems. Three learning methods, including multi-layer perceptron (MLP), Kriging or Gaussian process regression (GPR), and k-nearest neighbors (KNN) are selected to make models on the tiny dataset. The dataset includes 32 data points with two input parameters (temperature and pressure) and one output (solubility). The optimized models were tested with standard metrics. MLP, GPR, and KNN have error rates of 2.079 × 10-8, 2.173 × 10-9, and 1.372 × 10-8, respectively, using MSE metrics. Additionally, in terms of R-squared, they have scores of 0.868, 0.997, and 0.999, respectively. The optimal inputs are the same as the maximum possible values and are paired with a solubility of 1.26 × 10-3 as an output.

Amphotericin B-PEG Conjugates of ZnO Nanoparticles: Enhancement Antifungal Activity with Minimal Toxicity.

Amphotericin B (AMB) is commonly used to treat life-threatening systemic fungal infections. AMB formulations that are more efficient and less nephrotoxic are currently unmet needs. In the current study, new ZnO-PEGylated AMB (ZnO-AMB-PEG) nanoparticles (NPs) were synthesized and their antifungal effects on the Candida spp. were investigated. The size and zeta potential values of AMB-PEG and ZnO-AMB-PEG NPs were 216.2 ± 26.9 to 662.3 ± 24.7 nm and -11.8 ± 2.02 to -14.2 ± 0.94 mV, respectively. The FTIR, XRD, and EDX spectra indicated that the PEG-enclosed AMB was capped by ZnO, and SEM images revealed the ZnO distribution on the surface NPs. In comparison to ZnO-AMB NPs and free AMB against C.albicans and C.neoformans, ZnO-AMB-PEG NPs significantly reduced the MIC and MFC. After a week of single and multiple dosage, the toxicity was investigated utilizing in vitro blood hemolysis, in vivo nephrotoxicity, and hepatic functions. ZnO-AMB-PEG significantly lowered WBC count and hematocrit concentrations when compared to AMB and ZnO-AMB. RBC count and hemoglobulin content, on the other hand, were unaltered. ZnO-AMB-PEG considerably lowered creatinine and blood urea nitrogen (BUN) levels when compared to AMB and ZnO-AMB. The difference in liver function indicators was determined to be minor by all formulae. These findings imply that ZnO-AMB-PEG could be utilized in the clinic with little nephrotoxicity, although more research is needed to determine the formulation's in vivo efficacy.

Development and optimization of oral nanoemulsion of rutin for enhancing its dissolution rate, permeability, and oral bioavailability.

Rutin-loaded nanoemulsion (NE-RU) formulation is the core research work in this report. Labrafil® M 1944 CS was used as the oil phase, Tween 80 as the surfactant, and Transcutol P as the co-surfactant in the preparation of nanoemulsion. By utilizing a three-level central composite design (CCD), the composition was optimized. The optimized formulation showed a droplet size of 98.53 ± 3.22 nm, zeta potential -46.70 ± 4.78 mV, and drug loading 92.34 ± 3.87%. The results of dissolution, permeability, and oral bioavailability showed about 25.55 folds, 1.98 folds, and 33.68 folds, respectively, in the case of NE-RU as compared to its naïve form. The response of fresh and aged NE was non-significantly different in terms of particle size, zeta potential, and drug loading, indicating that the formulation was stable. The successful development of NE-RU with an improved bioavailability profile suggested that this formulation might be used to examine the pharmacodynamics of oxidative stress-related metabolic disorders.

Preparation and Characterization of a Novel Mucoadhesive Carvedilol Nanosponge: A Promising Platform for Buccal Anti-Hypertensive Delivery.

Carvedilol (CRV) is a non-selective third generation beta-blocker used to treat hypertension, congestive heart failure and angina pectoris. Oral administration of CRV showed poor bioavailability (25%), which might be ascribed to its extensive first-pass metabolism. Buccal delivery is known to boost drugs bioavailability. The aim of this study is to investigate the efficacy of bilosomes-based mucoadhesive carvedilol nanosponge for enhancing the oral bioavailability of CRV. The bilosomes were prepared, optimized and characterized for particle size, surface morphology, encapsulation efficiency and ex-vivo permeation studies. Then, the optimized formula was incorporated into a carboxymethyl cellulose/hydroxypropyl cellulose (CMC/HPC) composite mixture to obtain buccal nanosponge enriched with CRV bilosomes. The optimized bilosome formula (BLS9), showing minimum vesicle size, maximum entrapment, and highest cumulative in vitro release, exhibited a spherical shape with 217.2 nm in diameter, 87.13% entrapment efficiency, and sustained drug release for up to 24 h. In addition, ex-vivo drug permeation across sheep buccal mucosa revealed enhanced drug permeation with bilosomal formulations, compared to aqueous drug suspension. Consecutively, BLS9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain bilosomal nanosponge to enhance CRV buccal delivery. Morphological analysis of the prepared nanosponge revealed improved swelling with a porosity of 67.58%. The in vivo assessment of rats indicated that CRV-loaded nanosponge efficiently enhanced systolic/diastolic blood pressure, decreased elevated oxidative stress, improved lipid profile and exhibited a potent cardio-protective effect. Collectively, bilosomal nanosponge might represent a plausible nanovehicle for buccal delivery of CRV for effective management of hypertension.

Optimization and Characterization of Cuscuta reflexa Extract Loaded Phytosomes by the Box-Behnken Design to Improve the Oral Bioavailability.

The purpose of this study is to determine whether the complexing hydroalcoholic extract of Cuscuta reflexa (HECR) with phosphatidyl choline increases its bioavailability. As a result, a novel phytosomal delivery system for the HECR-soya lecithin complex was developed (HECR-phytosome). The HECR-phytosome complex was synthesized and characterized as phytovesicles. The formulation was prepared using a variable concentration of soya lecithin (1:1-1:3 percent w/v), a temperature range of (45-65°C), and sonication time (4-8 min). Optimization of HECR-loaded phytosomal formulations was performed using Design Expert software. A three-factor, three-level Box-Behnken design was used to optimize this HECR delivery system, as dependent variables, vesicular size and entrapment efficiency were evaluated using a Box Behnken factorial design. Further characterization of the optimized formulation included vesicle size, PDI, zeta potential, entrapment efficiency, FTIR, DSC, TEM, and in vitro release. Vesicle sizes ranged from 173.5±6.17 nm to 215.9±6.53 nm, and response rates for entrapment efficiency ranged from 52.9±1.65 to 77.2±1.1%. The uniform structure and spherical shape were demonstrated by transmission electron microscopy. Among the drug release kinetic models, the formulation followed the Higuchi model (R2 = 0.9978), releasing 96.3±3.7% of the polyphenol and flavonoids phytoconstituents from HECR-loaded phytosomes in 12 hours, compared to 49.3±2.5% in the plain extract. In addition, the optimized formulation passes the stability test. Therefore, the results demonstrated that phytosomal nanocarriers have the potential to increase the bioavailability of Cuscuta reflexa extract.

Journey of Alpinia galanga from kitchen spice to nutraceutical to folk medicine to nanomedicine.

ETHANOPHARMACOLOGICAL IMPORTANCE: Alpinia galanga (L.) Willd (AG), belonging to Zingiberaceae family is used as a spice and condiment in various culinary preparations of Indonesia, Thailand and Malaysia. It has been also used as a key ingredient in various traditional systems of medicine for the treatment of throat infection, asthma, urinary ailments, inflammation and rheumatism amongst other conditions. AG is widely used as a functional food and included in various preparations to obtain its nutraceutical and pharmacological benefits of its phytoconstituents such as phenyl propanoids, flavonoids and terpenoids. Over the past decades, several researchers have carried out systematic investigation on various parts of AG. Numerous studies on AG rhizomes have shown positive pharmacological effects such as anti-inflammatory, anticancer, antipsoriasis, antiallergic, neuroprotective and thermogenesis. Till date, no comprehensive review summarizing the exploitation of AG into nanomedicine has been published. AIM OF THE REVIEW: This comprehensive review aims to briefly discuss cultivation methods, propagation techniques, extraction processes for AG. The ethnopharmacological uses and pharmacological activities of AG extracts and its isolates are discussed in detail which may contribute well in further development of novel drug delivery system (NDDS) i.e. future nanomedicine. MATERIALS AND METHODS: Information about AG was collected using search engine tools such as Google, Google Scholar, PubMed, Google Patent, Web of Science and bibliographic databases of previously published peer-reviewed review articles and research works were explored. The obtained data sets were sequentially arranged for better understanding of AG's potential. RESULTS: More advanced genetic engineering techniques have been utilized in cultivation and propagation of AG for obtaining better yield. Extraction, isolation and characterization techniques have reported numerous phytoconstituents which are chemically phenolic compounds (phenyl propanoids, flavonoids, chalcones, lignans) and terpenes. Ethnopharmacological uses and pharmacological activity of AG are explored in numerous ailments, their mechanism of action and its further potential to explore into novel drug delivery system are also highlighted. CONCLUSIONS: The review highlights the importance of plant tissue culture in increasing the production of AG plantlets and rhizomes. It was understood from the review that AG and its phytoconstituents possess numerous pharmacological activities and have been explored for the treatment of cancer, microbial infection, gastrointestinal disorders, neuroprotective effects, obesity and skin disorders. However, the use of AG as alternative medicine is limited owing to poor solubility of its bioactive components and their instability. To overcome these challenges, novel drug delivery systems (NDDS) have been utilized and found good success in overcoming its aforementioned challenges. Furthermore, efforts are required towards development of scalable, non-toxic and stable NDDS of AG and/or its bioactives.

Formulation of Chitosan-Coated Brigatinib Nanospanlastics: Optimization, Characterization, Stability Assessment and In-Vitro Cytotoxicity Activity against H-1975 Cell Lines.

The purpose of the current study was to develop Brigatinib (BGT)-loaded nanospanlastics (BGT-loaded NSPs) (S1-S13) containing Span 60 with different edge activators (Tween 80 and Pluronic F127) and optimized based on the vesicle size, zeta potential (ZP), and percent entrapment efficiency (%EE) using Design-Expert® software. The optimum formula was recommended with desirability of 0.819 and composed of Span-60:Tween 80 at a ratio of 4:1 and 10 min as a sonication time (S13). It showed predicted EE% (81.58%), vesicle size (386.55 nm), and ZP (-29.51 mv). The optimized nanospanlastics (S13) was further coated with chitosan and further evaluated for Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro release, Transmission Electron Microscopy (TEM), stability and in-vitro cytotoxicity studies against H-1975 lung cancer cell lines. The DSC and XRD revealed complete encapsulation of the drug. TEM imagery revealed spherical nanovesicles with a smooth surface. Also, the coated formula showed high stability for three months in two different conditions. Moreover, it resulted in improved and sustained drug release than free BGT suspension and exhibited Higuchi kinetic release mechanism. The cytotoxic activity of BGT-loaded SPs (S13) was enhanced three times in comparison to free the BGT drug against the H-1975 cell lines. Overall, these results confirmed that BGT-loaded SPs could be a promising nanocarrier to improve the anticancer efficacy of BGT.

Patterns of Otorhinolaryngological Manifestations of Covid-19: A Longitudinal Questionnaire-Based Prospective Study in a Tertiary Hospital in Saudi Arabia.

OBJECTIVE: Many studied investigated the manifestations of COVID-19, yet few described the pattern and severity of otolaryngological symptoms. We aim to describe the picture of COVID-19-associated otorhinolaryngological manifestations and recovery to explore individualized treatment, onward referral, and complications prevention. DESIGN: Prospective longitudinal questionnaire-based study. SETTING: The online questionnaire was filled 3 times through a remote interview over a period of 1 month from June 2020 to July 2020. PARTICIPANTS: Patients with confirmed COVID-19 by RT-PCR who were clinically stable. MAIN OUTCOME MEASURES: Date of diagnosis, sociodemographic data, and the presence of predictive factors, such as nasal and paranasal disease, anosmia and dysgeusia. Validated tools were used, such as Sino-nasal Outcome Test (SNOT-22), smell test (medical academy screening tool), Voice Handicap Index (VHI), and Reflux Symptoms Index (RSI). RESULT: The questionnaire was sent to 363 patients and the response rate was 70.80% (n = 257). The mean age was 34.58 years (SD = 11.22) and the rate of male participants was 60.7%. The most common otorhinolaryngological symptoms at the time of enrollment was fever (48.6%), whilst the commonest severe symptom was cough (57%). After 1 month, only 11 participants had persistent severe symptoms, especially sleep and psychological symptoms (73%), and the majority were female (63.6%). All of them had at least 1 comorbidity. There was a significant difference between the mean age of participants with severe symptoms (mean = 27.45, SD = 8.39) and without severe symptoms (mean = 34.90, SD = 2.53, t(255) = 2.17, P = .031). CONCLUSION: COVID-19 has a wide-ranged spectrum of presentations, with otorhinolaryngological symptoms being the commonest and most serious. Studying these symptoms is vital to advance management options.

Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial.

OBJECTIVE: To evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo. METHODS: In this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality. RESULTS: Two hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32-44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6-12 days) in the favipiravir group and 8 days (IQR: 6-12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571-1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4-11 days) in the favipiravir group and 7 days (IQR: 5-10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events. CONCLUSION: In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.

Differences in Clinical Nature and Outcome Among Young Patients Suffering from an Acute Coronary Syndrome.

PURPOSE: Acute coronary syndrome (ACS) is a life-threatening cardiac disease identified by acute, regional reductions in coronary blood flow, resulting in myocardial ischemia, or infarction, and manifesting as discomfort in the chest area, neck, or arms. Frequently, ACS is provoked by an atherosclerotic plaque; therefore, coronary atherosclerosis is converted into a chronic disease to an acute medical emergency. The purpose of this study was to explore the differences among these variables in patients less than 45 years of age suffering from this major health problem compared to older adults admitted with an ACS diagnosis, and to adopt an optimized temporary management. PATIENTS AND METHODS: A retrospective chart review study was conducted on a total of 652 ACS patients admitted at King Fahad Hospital of the University (KFHU) between 2015 and 2020. The patients' medical records were utilized for obtaining demographic data, presenting symptoms, risk factors, and clinical outcomes. RESULTS: Overall, 652 patients were enrolled. Of these, 109 patients (16.7%) were under 45, with a mean age of 38 ± 7. Younger patients showed a higher rate of palpitation (23.9% versus. 13.6%; P = 0.019). A positive smoking history and a family history of CAD were seen more often in younger patients (42.2% vs 27.3%, P < 0.001; 22.9% vs 9.4%, P < 0.001, respectively). Older patients had greater renal impairment with higher creatinine (median = 1.10 mg/dl (range, 0.3-13.0) vs 1.0 (0.3-19.0; p = 0. 001), BUN (median = 16.0 (mange, 0.9-141.0) vs 12.0 (0.9-49.0); P < 0.001)). Younger patients had higher levels of LDL and total cholesterol (median 138c. 115; p < 0.001) and cholesterol (median 209 vs 178.5; p < 0.001). Hospital mortality was 0.9% in younger patients versus 7.4% in older patients (P = 0.004). CONCLUSION: Palpitations, smoking, family history, higher LDL levels, and total cholesterol levels were more prevalent in adults younger than 45 years old with ACS. Impaired renal function, hypertension, and diabetes were more in older patients with ACS.