Human Medicines Recall Announcements in Saudi Arabia Between 2017 and 2022: An Analysis of Saudi Food and Drug Authority (SFDA) Reports.

PURPOSE: This study aims to explore the characteristics of drug recall announcements issued over six years by the SFDA in Saudi Arabia. Additionally, to examine the patterns of voluntary drug recall requests by pharmaceutical companies (both innovator and generic) in response to product defects. METHODS: A retrospective data analysis was conducted on drug recall announcements issued by the SFDA between 2017 and December 2022. The study included recalls of registered and unregistered drugs posted on the SFDA Drugs Circulars and Withdrawal webpage. Descriptive analysis was performed on relevant variables: recall year, therapeutic class, recall type, pharmaceutical company type, recall reasons and voluntary or involuntary product defect reports. RESULTS: During the study period, a total of 371 products were recalled, with the majority being involuntary recalls (82.4%). About two-thirds of the recalls (66.0%) were related to registered products. The most common reasons for recalls were non-compliance with the manufacturer's specifications (33.2%), contamination (23.7%), and violations (20.5%). A total of 109 pharmaceutical companies were associated with the recalled products, with (85.3%) being generic pharmaceutical companies. The majority of innovator pharmaceutical companies (68.8%) requested voluntary drug recalls of defective products. Innovator pharmaceutical companies requested voluntary recalls more often than generic pharmaceutical companies. CONCLUSION: The study findings highlight the most frequent causes of drug recalls and the patterns of voluntary recall requests by pharmaceutical companies. Non-compliance with manufacturer's specifications was the most common reason for recalls. Significantly, more innovative pharmaceutical companies request voluntary recalls for product defects compared to generic pharmaceutical companies.

Effect of glycerol concentration on levels of toxicants emissions from water-pipe tobacco smoking (WTS).

Glycerol, flavorings and sweeteners constitute approximately 70% of water-pipe tobacco smoking (WTS) mixtures. Tobacco mixture combustion produces smoke toxins (e.g. carbonyl compounds), of which the type and amount are highly dependable on tobacco mixture formula. While glycerol in tobacco mixture contribute to enhanced smoking experience, its' combustion produces toxicants such as acrolein. According to WHO, there are no approved international upper limits regulations on WTS ingredients. This study aims to assess toxicant emission levels corresponding to increasing glycerol concentration in WTS mixtures, which may aid in developing tobacco regulations towards harm reduction.MethodsLaboratory experimental study. Using laboratory water-pipe smoking machine, levels of toxicant emissions in the smoke from WTS mixture samples containing varying glycerol concentrations were measured using High-performance Liquid Chromatography (HPLC). Smoke from 5 consecutive smoking cycles with 35 puffs each (ISO 22486 standard) was led through a trapping system as described in the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) recommended method No. 74 (Determination of selected carbonyls in mainstream cigarette smoke by HPLC). Trapped carbonyls were then analysed by HPLC with a DAD detector.ResultsAcrolein emission is associated with glycerol addition in WTS mixture indicated by lab-made samples throughout all glycerol concentrations (10%, 20%, 40% and 60%), and brand samples with glycerol concentrations 10% to 20%. However, brand samples showed no increase in acrolein emission corresponding to the increase in glycerol concentrations from 20% to 60%.ConclusionThe effect of glycerol addition in waterpipe tobacco on acrolein emission varies between products. Tobacco fillers, additives and contents quality and other factors may affect toxicant emission levels. Therefore, regulatory recommendations towards defining upper limits of content concentrations require further investigations regarding potential confounders in acrolein emissions and health effects of market-available glycerol concentrations in waterpipe tobacco smoking.

Cost-effectiveness of Favipiravir in moderately to severely ill COVID-19 patients in the real-world setting of Saudi arabian pandemic referral hospitals.

Purpose: We aimed to evaluate the cost effectiveness of Favipiravir treatment versus standard of care (SC) in moderately to severely ill COVID-19 patients from the Saudi healthcare payer perspective. Methods: We used the patient-level simulation method to simulate a cohort of 415 patients with moderate to severe COVID-19 disease who were admitted to two Saudi COVID-19 referral hospitals: 220 patients on Favipiravir and 195 patients on SC. We estimated the incremental cost-effectiveness ratio (ICER) of Favipiravir versus SC in terms of the probability to be discharged alive from hospital and the mean time in days to discharge one patient alive. The model was performed twice: first, using unweighted, and second, using weighted clinical and economic data. Weighting using the inverse weight probability method was performed to achieve balance in baseline characteristics. Results: In the unweighted model, base case (probabilistic) ICER estimates favored Favipiravir at savings of Saudi Riyal (SAR)1,611,511 (SAR1,998,948) per 1% increase in the probability of being discharged alive. As to mean time to discharging one patient alive, ICERs favored Favipiravir at savings of SAR11,498 (SAR11,125). Similar results were observed in the weighted model with savings using Favipiravir of SAR1,514,893 (SAR2,453,551) per 1% increase in the probability of being discharged alive, and savings of SAR11,989 (SAR11,277) for each day a patient is discharged alive. Conclusion: From the payer perspective, the addition of Favipiravir in moderately to severely ill COVID-19 patients was cost-savings over SC. Favipiravir was associated with a higher probability of discharging patients alive and lower daily spending on hospitalization than SC.

Effect of seaweed (Ecklonia cava extract) on blood glucose and insulin level on prediabetic patients: A double-blind randomized controlled trial.

To investigate the effect of polyphenolic-rich seaweed extract (Ecklonia cava) on postprandial blood glucose (PPBG) and postprandial insulin level (PPIL) as well as investigating any associated side effects related to the study intervention in 20 prediabetic patients in Saudi Arabia. The double-blind, randomized-controlled trial was conducted from November 2020 to April 2021 in Riyadh, in 20 prediabetic patients with no other health complications. Subjects were given 600 mg of seaweed extract in a single dose for acute effect investigation. PPBG and PPIL were measured immediately at intervals of 30, 60, 90, and 120 min following 75 g of carbohydrate consumption, iAUC and peak concentration were calculated accordingly. Insignificant differences were shown for PPBG levels between study groups at intervals of 30 and 60 min (p > .05). However, PPBG results were significantly lower in the intervention group compared to placebo of 90 and 120 min after carbohydrate (75 g) consumption. The mean (SD) of PPBG in the seaweed group at 90 and 120 min was 108.1 (±8.9) and 101.3 (±8.7), respectively, compared to the placebo group at 90 and 120 min with a mean of 122.2 (±16.9) and 112.9 (±12.1), respectively (p value at 90 min = 0.032) and (p value at 120 min = 0.024). iAUC of PPBG shows no significant differences between the study groups (p > .05). There was no significant difference in PPIL between study groups at all study measurements (p > .05). Discomfort symptoms were similar between study groups (p > .05). This study indicated that a single dose of 600 mg of E. cava extract has a lowering effect on postprandial blood glucose with no associated side effects. Further research should investigate the glycemic modulating effects of marine algal extracts in the long-term investigation.

Factors Contributing to Noncompliance With Diabetic Medications and Lifestyle Modifications in Patients With Type 2 Diabetes Mellitus in the Eastern Province of Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is defined as a chronic medical condition in which the blood glucose level remains high. The risk factors of T2DM are high body mass index due to obesity or being overweight, genetics, and certain medical conditions. Lifestyle modification plays a crucial role in T2DM regulation and prevention, and if it is not controlled well by either lifestyle modification or DM regulatory medications, it may lead to medical complications ranging from mild to life-threatening complications. AIM: The purpose of this study is to find the contributory factors of noncompliance with oral antidiabetic drugs and lifestyle modifications in patients with T2DM in the eastern province of Saudi Arabia. This will help control one of the most widespread comorbidities that might otherwise be a significant burden on patients' health and financial status as well as on the government. METHODOLOGY: A cross-sectional questionnaire study was conducted on T2DM patients in the eastern province of Saudi Arabia through a link distributed on social media, and the contributory factors of noncompliance to diabetes medication and lifestyle modification were evaluated. RESULTS: A total of 426 participants were included in the study. Regarding compliance with DM medications, 199 (46.7%) participants were adherent to their medications, 148 (34.7%) were not adherent to their medication, 42 (9.9%) were sometimes adherent, and 37 (8.7%) were mostly adherent to their medication. Regarding lifestyle modification, the level of adherence to a healthy diet and exercise among T2DM patients in the eastern province was low and unsatisfactory. According to the participants, the most reported factors contributing to noncompliance with DM medications and lifestyle modifications were forgetfulness, lack of knowledge about diabetes and the importance of controlling it, side effects of the medications, and difficulty in following a healthy diet. Regarding the influence of sociodemographic variables on the level of adherence in T2DM patients, factors such as age, marital status, occupation, comorbidities, diagnosis period, and previous complaints of DM complications showed significant associations with compliance with DM medication. CONCLUSION: The findings of this study revealed that the level of adherence to DM medications among T2DM patients in the eastern province was suboptimal. Although free medicines were available with a high level of healthcare access through government primary healthcare centers (PHCCs), poor adherence was observed. This study highlighted that medication adherence might be affected by age, marital status, occupation, chronic diseases, diagnosis period, and previous complaints of DM complications. Regarding lifestyle modification, this study showed that the level of adherence to a healthy diet and exercise among T2DM patients in the eastern province was low and unsatisfactory. Our recommendation is to measure the presence of dietician clinics, patient relationships with their healthcare providers, and their effect on patient compliance with DM medications. Further research is needed to include other factors that could influence adherence, such as patient-healthcare provider communication. Moreover, it is suggested that PHCCs discuss with noncompliant patients the reasons that prevent them from adhering to their medication and lifestyle modifications as part of their care plan.

The effectiveness and safety of direct-acting antivirals for hepatitis C virus treatment: A single-center experience in Saudi Arabia.

Background: The introduction of direct-acting antivirals (DAA) to treat the hepatitis C virus (HCV) overcame many drawbacks of interferon-based therapy. DAA achieved sustained viral response (SVR) rates above 90% and overcame many drawbacks of pegylated interferon regimens.The HCV genotype (GT) distribution varies by geographical area, with GT-4 being most prevalent in the Middle East region, including Saudi Arabia. Yet, the real-world evidence about using DAAs in the Saudi population is limited.Thus, the aim of this study to investigate the effectiveness and safety of DAAs in Saudi patients with HCV infection. Methods: A retrospective cohort study included patients treated with DAAs from 2015 to 2017 at a tertiary care hospital in Riyadh, Saudi Arabia. All patients with HCV treated with either ledipasvir plus sofosbuvir (LDS/SOF) ± ribavarin (RBV) or ombitasvir-paritaprevir-ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± RBV were included. Using a per-protocol analysis, the effectiveness outcome was the end-of-treatment response (EOTr) and Sustained virologic reponce12 weeks after competing the regimen (SVR12). The secondary safety outcome was the adverse event related to the therapy reported by the patients. Results: A total of 97 patients were included; with the majority infected with GT-4 (64 %), followed by GT-1 (18 %), in addition to 8 % having a mixed GT (1 + 4). The EOTr and SVR12 rates were 98 % and 96 %, respectively. SVR12 was 94.4 % within the LDS/SOF ± RBV group and 97.7 % within the OBV/PTV/r ± DSV ± RBV group. Only 4 % had a response failure due to relapse or breakthrough, and all were infected with mixed GT1 + 4. Medications were well tolerated with minimal side effects, including vomiting, nausea, and weakness. Conclusion: DAAs regimens are associated with high rates of SVR12 and are well tolerated with a good safety profile in Saudi HCV-infected patients.

National Survey on Silver Diamine Fluoride (SDF) Awareness, Knowledge, Attitude, and Use among General Dental Practitioners in the Kingdom of Saudi Arabia-An Exploratory Survey.

Silver diamine fluoride (SDF) has been accepted as an appropriate alternative for caries management. However, knowledge and utilization of SDF among dentists vary considerably. The authors in the present study aimed to assess the awareness, knowledge, attitudes, and use of SDF among general dentists (GD) in Saudi Arabia and to correlate the differences based on the different regions and experience levels of the dentists. In this regard, a cross-sectional web-based questionnaire was conducted, and a response was received from 311 GDs from different parts of the country. Information regarding demographic data, knowledge, attitudes, use, and barriers to SDF in dentists' professional lives were elicited. The mean age of the participants (55.3%) was between 25-35 years. Most (92.45%) of the dentists were aware of the material and (61%) agreed that SDF could arrest carious lesions. More than half of the dentists agreed/strongly agreed that SDF was a good treatment alternative for restorations in children with behavioral issues (63.1%), medically fragile patients (53.7%), patients with severe anxiety (64.5%), patients who underwent radiation or chemotherapy (47.3%), and patients needing general anesthesia for dental treatment (74%). Comparative evaluation using ANOVA revealed regional differences based on knowledge, attitudes, and use. Tukey HSD further highlighted that the practitioners in the western region are more knowledgeable regarding its benefits and utilize it more frequently in their practice compared to other regions. On the other hand, the experience level of the GDs did not have any impact on their knowledge, attitudes, and use of SDF.

The value of social media use in improving nursing students' engagement: A systematic review.

AIM: This systematic review was undertaken to investigate the impact of social media use in relation to student engagement in nursing education. BACKGROUND: The availability of social media has transformed global connectivity within education systems. Social media has been used in various educational contexts. The widespread use of social media has prompted a demand for a better understanding of how it might be used in nursing education. While research has previously explored the positive effects of using social media on a range of learning outcomes in nursing education, studies have not specifically focused on how these positive features have an impact on students' engagement as a vital component of successful learning. DESIGN: This review uses the Joanna Briggs Institute approach to conducting systematic reviews and follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting a systematic review. METHODS: Following predefined inclusion criteria, a search of electronic databases was performed using a three-step strategy to identify relevant studies. The following databases were searched: Cumulative Index of Nursing and Allied Health Literature (CINAHL), Education Resources Information Centre (ERIC), MEDLINE and PubMed. A further manual search was performed to identify potentially relevant articles. The included studies were assessed for methodological quality by all reviewers using the Mixed Methods Appraisal Tool. NVivo software was used for organising data and developing themes. RESULTS: Data from sixteen studies with different designs were extracted and thematically synthesised. The synthesised findings yielded five themes: 1) interaction and communication; 2) managing stress; 3) positive online community; 4) time spent; and 5) digital literacy and e-professionalism. CONCLUSIONS: This review reveals that using social media to support nursing students' learning has positive benefits in terms of promoting several aspects of their engagement, such as rapid interaction and communication. Further empirical studies, however, should aim to measure social media's effects on nursing students' engagement with their courses and their academic attainment.

Using Phages to Reduce Salmonella Prevalence in Chicken Meat: A Systematic Review.

Salmonellosis is an infection that significantly impacts chicken and humans who consume it; it is a burden on public health and a contributor to commercial losses in the chicken industry worldwide. To tackle chicken meat-related bacterial infections, significant quantities of antibiotics alongside several infection prevention measures are used worldwide. However, chemical additives, such as organic acids, and chlorine-based interventions all have different limitations. These include feed refusal due to a change of taste, and incompatibility between organic acids and other inoculated preservative agents such as antimicrobial agents. Phages are host-specific viruses that interact with bacteria in a specific manner. Therefore, they possess unique biological and therapeutic features that can be used to reduce bacterial contamination, leading to improved food safety and quality. This systematic review examines the current evidence regarding the effectiveness of various phages on Salmonella colonization in chicken meat. This review summarizes findings from 17 studies that were conducted in vitro with similar experimental conditions (temperature and incubation parameters) to test the efficacy of isolated and commercially available phages on chicken raw meat samples. The current evidence suggests that most of the in vitro studies that used phages as a biocontrol to eradicate Salmonella contamination in chicken meat were successful. This indicates that phages constitute a promising solution worldwide for tackling foodborne bacteria, including Salmonella.

Association of lncRNA LINC01173 Expression with Vitamin-D and Vitamin B12 Level Among Type 2 Diabetes Patients.

Background: Type 2 diabetes mellitus (T2DM) has risen to become the world's most serious public health problem in recent years, and the role of long noncoding RNAs (lncRNAs) in the onset and progression of T2DM, as well as special attention to vitamins, has gotten a lot of attention recently. Methods: The aim of the study was to analyze lncRNA LINC01173 expression along with assessment of vitamin-D and B12 among the T2DM cases. Quantitative RT-PCR was used to analyze the expression of lncRNA LINC01173. Vitamin-D and B12 were analyzed by chemiluminescence-based assay. Results: The present study observed that the T2DM cases had 6.67-fold increased lncRNA LINC01173 expression compared to healthy controls. Expression of lncRNA LINC01173 was found to be associated with hypertension (p=0.03), wound healing (p=0.04), and blurred vision (p<0.0001). It was observed that the T2DM cases with vitamin-D deficiency had a significant association with fasting glucose level (p=0.01) and HbA1C level (p=0.01) among the T2DM cases. The association of lncRNA LINC01173 with vitamin-D was analyzed and it was observed that the vitamin-D deficient cases had higher lncRNA LINC01173 expression compared to insufficient T2DM cases (p=0.01) and sufficient T2DM cases (p=0.0006). It was also observed that the T2DM cases with smoking had a 8.33-fold lncRNA LINC01173 expression while non-smokers had a 5.43-fold lncRNA LINC01173 expression (p<0.0001). Conclusion: The study concluded that the increased lncRNA LINC01173 expression was observed to be linked with alteration in vitamin-D level and smoking habit. Altered expression of lncRNA LINC01173 expression was linked with fasting glucose and HbA1C alteration. Collectively, lncRNA LINC01173 expression, vitamin-D alteration, as well as smoking habit may cause the disease severity and increase the pathogenesis of disease.

New Therapeutic Options for Type 2 Diabetes Mellitus and Their Impact Against Ischemic Heart Disease.

Type 2 diabetes mellitus (T2DM) greatly increases risk for cardiovascular disease, including ischemic heart disease and myocardial infarction. With the completion of several cardiovascular outcomes trials (CVOTs) for new glucose-lowering therapies, including the sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists, we now have strong evidence alluding to the cardioprotective nature of these agents in people with T2DM. These agents have frequently been observed to reduce rates for 3-point major adverse cardiovascular events, which encompass death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Herein we will provide an overview on whether reductions in nonfatal myocardial infarction and ischemic heart disease status are a key component of the improved cardiovascular outcomes in people with T2DM treated with either SGLT2 inhibitors or GLP-1R agonists. Observations from preclinical studies will be compared to their clinical counterparts, while being further interrogated to define potential mechanisms that may account for SGLT2 inhibitor or GLP-1R agonist-induced cardioprotection against ischemic heart disease. A better understanding of the role these agents have in impacting the progression of ischemic heart disease in individuals with T2DM will have a substantial impact in our management of this patient population.

Clinical Importance of FNDC-5 and Selectin-E mRNA Expression Among Type 2 Diabetics with and without Obesity.

Background: Type 2 diabetes mellitus (T2DM) is growing illnesses associated with metabolic dysregulation such as obesity affecting a large population become leading causes of death worldwide. Fibronectin type III domain-containing protein 5 (FNDC-5) and selectin-E were suggested to have effects on metabolism and diabetes, therefore present study aimed to evaluate the clinical importance of FNDC-5 and selectin-E among the T2DM patients with and without obesity. Methods: Study included cohort of 200 T2DM patients with and without obesity. We evaluated FNDC-5, selectin-E mRNA expression as well as vitamin-D, and vitamin-B12 levels in among the T2DM patients with and without obesity. Results: Study observed significant difference in biochemical parameters included in study. T2DM patients with obesity had significantly higher fasting blood glucose levels (p<0.0001) and HbA1c (glycated hemoglobin) (p<0.0001) compared to those T2DM patients without obesity. T2DM patients with obesity also had higher systolic blood pressure (p=0.001), LDL (low density lipoprotein) (p=0.02), TG (triglycerides) (p=0.02) and cholesterol (p=0.01) compared to T2DM patients without obesity. The mRNA expression of FNDC-5 (p<0.0001) was lower in T2DM patients with obesity compared to T2DM patients without obesity. It was observed that the T2DM patients with vitamin-D deficiency had significantly lower FNDC-5 mRNA expression (p=0.03) when compared with those with sufficient vitamin-D level. T2DM patients with clinically normal vitamin-B12 level expressed 0.60 fold FNDC-5 mRNA expression while B12 deficient T2DM patients had 0.28 fold FNDC-5 mRNA expression (p=0.005). No as such significant association was was observed with selectin-E. A negative correlation of FNDC-5 mRNA expression with Post prandial glucose (mg/dl) (p=0.04) and TG (mg/dl) (p=0.02) was observed. Conclusion: FNDC-5 down regulation was observed with T2DM with obesity, vitamin-D and vitamin-B12 deficiency suggesting obesity, vitamin-D and vitamin-B12 deficiency could be the factor for FNDC-5 down-regulation leading to worseness or progression of disease. We suggest that FNDC-5 down-regulation could be used as an indicator for T2DM worseness and development of other associated complications.

Evaluation of miRNA-143 and miRNA-145 Expression and Their Association with Vitamin-D Status Among Obese and Non-Obese Type-2 Diabetic Patients.

Objective: Growing epidemics of type-2 diabetes mellitus (T2DM) and obesity have become a serious health concern. Since miRNAs and vitamin levels affect the development and progression of numerous pathogenic diseases, including diabetes, the present study aimed to evaluate miRNA-143 and miRNA-145 expression and vitamin-D status among obese and non-obese T2DM patients. Methods: The study included 100 clinically confirmed newly diagnosed obese and non-obese T2DM cases and 100 healthy subjects. Total RNA was extracted from collected blood samples and 100 ng of RNA was used for cDNA synthesis, then TaqMan assay was performed to evaluate the miRNA-143 and miRNA-145 relative expression. Results: T2DM cases with hypertension (4.08 fold, p=0.01; 5.36 fold, p=0.009), fatigue (5.07 fold, p=0.04; 5.32 fold, p=0.03) and blurred vision (5.15 fold, p=0.01) showed higher miRNA-143 and miRNA-145 relative expression compared with their counterparts, respectively. A positive correlation was observed between miRNA-143 and miRNA-145 expression and decreased vitamin-D status in T2DM had significant association with impaired blood glucose fasting (p=0.001) and HDL level (p<0.0001). Obese T2DM cases showed higher miRNA-143 and miRNA-145 expression compared with their counterparts. Vitamin-D deficient T2DM cases had higher miRNA-143 and miRNA-145 expression (5.69 fold, 5.91 fold) compared with insufficient (4.27 fold, p=0.03; 4.61 fold, p=0.03) and sufficient (4.08 fold, p=0.002; 4.29 fold, p=0.003). ROC curve for miRNA-143 and miRNA-145 between obese T2DM vs non-obese T2DM cases, at best possible cutoff value of 4.39 fold, 4.0 fold showed increased miRNA-143 and miRNA-145 expression, the sensitivity and specificity were 85%, 88% and 61%, 53% respectively (AUC=0.83, p<0.0001; AUC=0.81, p<0.0001). Conclusion: Higher miRNA-143 and miRNA-145 expression could be a predictive indicator for obese T2DM cases, decreased status of vitamin-D was also significantly associated with impaired fasting blood sugar and HDL level, therefore it is important to evaluate the vitamin-D status among T2DM cases for better clinical outcome during the intervention.

Severity of COVID-19 infection in ACEI/ARB users in specialty hospitals: A retrospective cohort study.

BACKGROUND: The uncertainty about COVID-19 outcomes in angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. This study aimed to determine the effect of ACEI/ARB use in patients with severe COVID-19. METHODS: This retrospective cohort study was done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with a confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted multivariate logistic regression and sensitivity analyses using propensity score matching (PSM) and Inverse propensity score weighting (IPSW) for high-risk patient subsets. RESULTS: Compared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR = 8.25, 95%CI = 3.32-20.53); a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88-15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR = 4.77,95%CI = 2.15-10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR = 5.40,95%CI = 2.0-14.54]. These results were confirmed in the PSM and IPSW analyses. CONCLUSION: In general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care.

Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis.

INTRODUCTION: Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients. METHODS: This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients ≥18 years) admitted April-August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg twice daily loading dose, followed by 800 mg or 600 mg twice daily) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan-Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis. RESULTS: Overall, median time to discharge was 10 days (95%CI = 9-10) in the favipiravir arm versus 15 days (95%CI = 14-16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI = 1.56-2.46). Progression to mechanical ventilation was slower with favipiravir (HRadj = 0.10, 95%CI = 0.04-0.29). There was no significant effect on mortality (HRadj = 1.56, 95%CI = 0.73-3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HRadj = 2.80, 95%CI = 0.99-7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings. CONCLUSION: Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum.

The GLP-1 Receptor Agonist Liraglutide Increases Myocardial Glucose Oxidation Rates via Indirect Mechanisms and Mitigates Experimental Diabetic Cardiomyopathy.

BACKGROUND: Type 2 diabetes (T2D) increases risk for cardiovascular disease. Of interest, liraglutide, a therapy for T2D that activates the glucagon-like peptide-1 receptor to augment insulin secretion, reduces cardiovascular-related death in people with T2D, though it remains unknown how liraglutide produces these actions. Notably, the glucagon-like peptide-1 receptor is not expressed in ventricular cardiac myocytes, making it likely that ventricular myocardium-independent actions are involved. We hypothesized that augmented insulin secretion may explain how liraglutide indirectly mediates cardioprotection, which thereby increases myocardial glucose oxidation. METHODS: C57BL/6J male mice were fed either a low-fat diet (lean) or were subjected to experimental T2D and treated with either saline or liraglutide 3× over a 24-hour period. Mice were subsequently euthanized and had their hearts perfused in the working mode to assess energy metabolism. A separate cohort of mice with T2D were treated with either vehicle control or liraglutide for 2 weeks for the assessment of cardiac function via ultrasound echocardiography. RESULTS: Treatment of lean mice with liraglutide increased myocardial glucose oxidation without affecting glycolysis. Conversely, direct treatment of the isolated working heart with liraglutide had no effect on glucose oxidation. These findings were recapitulated in mice with T2D and associated with increased circulating insulin levels. Furthermore, liraglutide treatment alleviated diastolic dysfunction in mice with T2D, which was associated with enhanced pyruvate dehydrogenase activity, the rate-limiting enzyme of glucose oxidation. CONCLUSIONS: Our data demonstrate that liraglutide augments myocardial glucose oxidation via indirect mechanisms, which may contribute to how liraglutide improves cardiovascular outcomes in people with T2D.

Pimozide Alleviates Hyperglycemia in Diet-Induced Obesity by Inhibiting Skeletal Muscle Ketone Oxidation.

Perturbations in carbohydrate, lipid, and protein metabolism contribute to obesity-induced type 2 diabetes (T2D), though whether alterations in ketone body metabolism influence T2D pathology is unknown. We report here that activity of the rate-limiting enzyme for ketone body oxidation, succinyl-CoA:3-ketoacid-CoA transferase (SCOT/Oxct1), is increased in muscles of obese mice. We also found that the diphenylbutylpiperidine pimozide, which is approved to suppress tics in individuals with Tourette syndrome, is a SCOT antagonist. Pimozide treatment reversed obesity-induced hyperglycemia in mice, which was phenocopied in mice with muscle-specific Oxct1/SCOT deficiency. These actions were dependent on pyruvate dehydrogenase (PDH/Pdha1) activity, the rate-limiting enzyme of glucose oxidation, as pimozide failed to alleviate hyperglycemia in obese mice with a muscle-specific Pdha1/PDH deficiency. This work defines a fundamental contribution of enhanced ketone body oxidation to the pathology of obesity-induced T2D, while suggesting pharmacological SCOT inhibition as a new class of anti-diabetes therapy.

Oral Health-related Quality of Life and Oral Hygiene Practice of Adults with Fixed Dental Prostheses in Riyadh, Saudi Arabia.

OBJECTIVES: Missing teeth are routinely replaced with fixed dental prostheses (FDPs); thus, knowing the patient's oral health-related quality of life (OHRQoL) after placement of FDP and factors affecting their quality of life in addition to their oral hygiene practices is important. This study aimed to measure OHRQoL with FDPs and oral hygiene practices of adults in Riyadh, Saudi Arabia. MATERIALS AND METHODS: A survey was distributed in hard and soft copy forms. Target subjects were adults older than 18 years with FDP and living in Riyadh. The questionnaire contained four domains: demographic data, medical history, characteristics of the prostheses and oral hygiene practices, and Oral Health Impact Profile (OHIP)-14 questionnaire, which measures OHRQoL. RESULTS: The study included 528 subjects. More than half of the participants (56.6%) had poor OHRQoL, which was associated with female gender, full-time employment, and low income. The presence of toothache, periodontal diseases, oral abscess, and broken teeth were all associated with poor OHRQoL. Participants with diabetes were also found to have poor OHRQoL. As for oral hygiene practices, 47% of subjects did not receive oral hygiene instructions after the placement of their FDP. It was also found that 53.4% of the study population brush only once daily. CONCLUSION: Many factors can have an influence on OHRQoL. Both dentist and patient awareness regarding postoperative oral hygiene instructions should be increased to ensure the durability of the prosthodontic appliances and improve patients' OHRQoL.

Saudi teachers' confidence and attitude about their role in anaphylaxis management.

BACKGROUND AND AIMS: Anaphylaxis is a common emergency and life-threatening hypersensitivity reaction defined as a rapid generalized allergic reaction. Prior international studies have shown that school personnel is often not familiar with the signs of hypersensitivity or with appropriate management strategies that should be initiated at school for children with an anaphylactic reaction. Moreover, no studies have evaluated the awareness of anaphylaxis by school teachers in Saudi Arabia. The aim of this study was to determine teachers' knowledge, attitudes, and practices toward anaphylaxis in Al-Qassim, Saudi Arabia. METHODS: This was a cross-sectional study conducted at a public school in Al-Qassim, Saudi Arabia via a validated fourteen items questionnaire aimed to survey teacher knowledge, attitudes, and practices toward anaphylaxis. The questionnaires were disseminated using a multistage random sampling technique to Saudi national's teachers from different regions in Al-Qassim. RESULTS: Most teachers had a low level of knowledge (85.3%) of anaphylaxis and positive attitudes (72.9%), and the level of practice was reported as low (48.9%) to moderate (47.5%). The most common sources of information regarding anaphylaxis were the internet and social media. When considering significant factors associated with knowledge, attitudes, and practices (KAP), we found that sex, years of experience in teaching and witnessing students suffering from anaphylaxis were all positively associated with KAP. CONCLUSION: The overall knowledge and practices of teachers regarding anaphylactic reactions were poor, although teachers' attitudes toward learning this information were positive. Thus, teachers need further education regarding the management of allergic reaction.

The antianginal ranolazine mitigates obesity-induced nonalcoholic fatty liver disease and increases hepatic pyruvate dehydrogenase activity.

Obese individuals are often at risk for nonalcoholic fatty liver disease (NAFLD), insulin resistance, type 2 diabetes (T2D), and cardiovascular diseases such as angina, thereby requiring combination therapies for their comorbidities. Ranolazine is a second-line antianginal agent that also improves glycemia, and our aim was to determine whether ranolazine modifies the progression of obesity-induced NAFLD. Twelve-week-old C57BL/6J male mice were fed a low-fat or high-fat diet for 10 weeks and then treated for 30 days with either vehicle control or ranolazine (50 mg/kg via daily s.c. injection). Glycemia was monitored via glucose/pyruvate/insulin tolerance testing, whereas in vivo metabolism was assessed via indirect calorimetry. Hepatic triacylglycerol content was quantified via the Bligh and Dyer method. Consistent with previous reports, ranolazine treatment reversed obesity-induced glucose intolerance, which was associated with reduced body weight and hepatic steatosis, as well as increased hepatic pyruvate dehydrogenase (PDH) activity. Ranolazine's actions on hepatic PDH activity may be directly mediated, as ranolazine treatment reduced PDH phosphorylation (indicative of increased PDH activity) in HepG2 cells. Therefore, in addition to mitigating angina, ranolazine also reverses NAFLD, which may contribute to its documented glucose-lowering actions, situating ranolazine as an ideal antianginal therapy for obese patients comorbid for NAFLD and T2D.