Clinical Outcomes of Aspirin and Clopidogrel among Patients with Chronic Obstructive Lung Disease: Insights from a Meta-Analysis.

(1) Background: Aspirin and clopidogrel have been found helpful in improving clinical outcomes among patients with chronic obstructive lung disease (COPD). However, the evidence on the efficacy of aspirin and/or clopidogrel on clinical outcomes has not been synthesized and summarized in the prior reviews. Hence, we undertook a meta-analysis of the research studies examining the effect of aspirin and/or clopidogrel on varying clinical outcomes among COPD patients; (2) Methods: Using key search terms, we searched databases, including MEDLINE, CINAHL, Google Scholar, and EMBASE to find observational studies and RCTs. Our search was limited to research written in English. We used a random effect model to calculate the 95% confidence intervals and pooled hazard ratio; (3) Results: We included 12 eligible research studies (33,8008 patients) in the current meta-analysis. Among COPD patients, the hazard of all-cause mortality among users of aspirin or clopidogrel was 17% lower (HR: 0.83; 95% CIs (0.70, 0.97; I2 = 73%, X2: 33.34) compared to non-users of anticoagulants (aspirin or clopidogrel). The hazard of dyspnea among users of aspirin or clopidogrel was 3% lower (HR: 0.97; 95% CIs (0.27, 3.49; I2 = 93%, X2: 42.15) compared to non-users of anticoagulants (aspirin or clopidogrel). There was no statistically significant effect of aspirin on other clinical outcomes such as myocardial infarction (HR: 2.04; 95% CIs (0.02, 257.33) and major bleeding (HR: 1.93; 95% CIs (0.07, 1002.33). The funnel plot and Egger's regression test did not show any evidence of publication bias; (4) Conclusions: Overall, we found a positive and beneficial effect of aspirin and/or clopidogrel in reducing all-cause mortality among COPD patients. However, there is uncertainty of evidence for other clinical outcomes such as exacerbation of dyspnea, myocardial infarction, and major bleeding. A limited number of studies examining other clinical outcomes warrant conducting more robust epidemiological studies to assess the efficacy and safety of aspirin and clopidogrel on other clinical outcomes among COPD patients.

Clinical Outcomes of Anticoagulant Therapy in COVID-19 Patients with Pre-Existing Cardiovascular Diseases: A Systematic Review.

The COVID-19 infection caused by SARS-CoV-2 is a healthcare crisis that has led to unparalleled disruption and has impacted healthcare services, leading to significant morbidity and mortality in the worldwide population. Insufficient data on the management of COVID-19 complications such as hypercoagulability and the controversy about the benefits of anticoagulant therapy are major challenges encountered by clinicians, especially for patients with pre-existing cardiovascular diseases (CVD), and are still debatable. Therefore, we endeavored to conduct a systematic review to assess the clinical outcomes of prior anticoagulant therapy in patients with COVID-19 having pre-existing CVD. Electronic searches of the PubMed database and EBSCO Information Services were carried out, and all relevant articles were employed. Seven articles with data from 21,989 subjects were included. Despite the promised clinical outcomes of anticoagulant therapy, the results of the current systematic review indicated insignificant improvements in the reduction of mortality rate or ICU admission among patients with COVID-19 having pre-existing CVD. Furthermore, direct oral anticoagulant (DOAC) were favored over vitamin K antagonists (VKAs) due to better action and less side effects. In conclusion, the findings are controversial as we did not statistically analyze the results. The data showed inconsistent information with no clear effect of anticoagulant use before patient hospitalization or decreasing COVID-19 severity, particularly in those with CVD. Further studies including randomized controlled trials are required to describe the best course as well as optimal dose of anticoagulant use in the treatment of patients with COVID-19, particularly those with comorbidities such as CVD.

The Influence of Active Learning on the Development of Learner Capabilities in the College of Applied Medical Sciences: Mixed-Methods Study.

Background: The learning process and the development of learning capabilities depend heavily on students' active participation in their education. However, no study from the Gulf region has previously evaluated the effects of active participation in the capability development of students studying in the College of Applied Medical Sciences (COAMS). Objectives: The study's objectives were twofold: to assess the undergraduate students' active participation in the development of their abilities at COAMS, and then to evaluate the teachers' viewpoints on how active participation affects the general capabilities of COAMS students were examined. Methods: This mixed-methods study employed an explanatory sequential design with quantitative (survey) data collected before qualitative data (face-to-face interviews). All final year students and faculty members from four programs were included. Eligible students were invited to complete the self-administered "Student Engagement Questionnaire (SEQ)" along with a questionnaire eliciting demographic information between January and April 2022. We further conducted open-ended ethnographic interviews with 12 faculty members. The programs and their effects on the students" abilities were assessed using ANOVA. The contribution of categorical variables to student active engagement was analysed using the Chi-square test. The responses from faculty members were analyzed thematically. Responses from the faculty members were analyzed using a thematic approach. Results: Total of 145 eligible students (100%) completed the questionnaires. With regard to most of the questions regarding active engagement in the development of abilities, students expressed a high level of satisfaction. Therefore, modifying the curriculum to include critical thinking that addresses community issues, providing real-world experience, collaborative learning, and peer learning would improve students' cognitive, learning, and skills while also improving engagement. Conclusion: This study provides first-hand information on the effects of active participation in the development of capabilities. It suggests that these effects are related to the interactions between students and teachers as well as the learning environment, which are essential for improving academic performance.

Translation and cross-cultural validation of the non-invasive prenatal testing questionnaire in Arabic.

OBJECTIVES: To translate and cross-culturally adapt a Swedish questionnaire to Arabic to assess the awareness of pregnant women in Saudi Arabia regarding the availability of an accurate and safe prenatal screening procedure. METHODS: The study was conducted at the Obstetrics and Gynecology Clinic, King Abdulaziz Medical City, Riyadh, Saudi Arabia between December 2018 to April 2019. The non-invasive prenatal testing (NIPT) questionnaire, translated and validated in Arabic. Cronbach's alpha reliability testing was carried out to validate the Arabic version of the questionnaire. The sample size was 100 pregnant women, at any gestational period, from 20 to 44 years old. This is a prospective cross-sectional. RESULTS: An Arabic translated, and culturally validated questionnaire related to the attitudes, knowledge, and self-perceived probability of delivering a child with chromosomal abnormality.  Conclusion: We translated and validated the NIPT questionnaire to assess the attitude and awareness of pregnant women regarding the availability of the NIPT.

The hypocoagulant effect of Crataegus aronia in rats entails vitamin K-dependent and vitamin K-independent effects.

This study investigated the effect of the aqueous extract of Crataegus aronia on blood coagulation in rats. Rats (200 ± 10 g,) were divided into two groups (6 rats/each) of control or C. aronia-treated rats which treated with the vehicle or the extract (200 mg/kg) for 21 days. With normal liver structure, serum levels of ALT, AST and É£-GT, platelet count, and plasma levels of vWF, values of PT and aPTT were significantly increased in C. aronia-treated rats. Also, it lowered serum levels of vitamin K (VK) and plasma activities of FII, FV, FVII, FVIII, FIX, FX, and FXI and downregulated hepatic levels of the VK-dependent factors (FII, FVII, FIX, and FX). In addition, C. aronia reduced fecal levels of triglycerides and cholesterol and serum levels triglycerides, cholesterol, LDL-c, and vLDL-c. In conclusion, with the hypocoagulant effect of C. aronia activity involves VK-dependent and non-vitamin K-dependent factors. PRACTICAL APPLICATIONS: In this study, we are reporting for the first time an in vivo hypocoagulant effect of C. aronia in rats. Such effect involved both VK-dependent and independent factors. However, the decrease in the activity and expression of VK-dependent factors was associated with reduced fecal levels of TGs and CHOL and serum levels of TGs, CHOL, LDL-c, and vLDL-c. These data suggest a possible impairment in the VK absorption, transport, or hepatic uptake. These data encourage further pharmacological, translational, and clinical studies to isolate the active ingredients to investigate them at the human level.

The burden of leukemia in the Kingdom of Saudi Arabia: 15 years period (1999-2013).

BACKGROUND: Leukemia is a malignant neoplasm that arises from hematopoietic cells. The number of leukemia cases has dramatically increased from 297,000 to 437, 033 cases worldwide. As result, the the Saudi Cancer Registry ramked leukemia as the 5th type of cancer cases among both genders in Saudi Arabia. Data on the trend and incidence of leukemnia in Saudi Arabia is lacking. This study aims to report the trend and incidence of leukemia in Saudi Arabia using available data from the Saudi Cancer Registry (SCR), as a population-based cancer registry in the country over a period of 15 years (1999-2013). METHODS: Data of registered leukemia cases between years 1999-2013 were retrieved from the Saudi Council of Health, Saudi Cancer Registry. Data were coded using the International Classification of Diseases for Oncology (ICD-O). Main and essential variables were retrieved such as age, sex, years of incidence, residency, and histopathological type of leukemia. RESULTS: A total of 8712 cases of leukemia were analyzed in this study, 57.2% were males and 42.8% were females. Around 33.6% of cases were from the central region of Saudi Arabia. The most diagnosed type of leukemia was the Precursor B-cell lymphoblastic leukemia (18.7%), followed by Precursor cell lymphoblastic leukemia, NOS (17.3%) with equal percentage of reported cases between males and females in these subsets. CONCLUSION: Ove a period of 15 years, the trend of leukemia showed the likelihood of increase in rate particularly in males with highest incidence reported from the central region of Saudi Arabia which needs more investigation. Resources for diagnosis and treatment should be planned with more orientation toward the accurate diagnosis of leukemia to minimize the number of "none specific diagnosis".

Chronic testosterone administration improves cardiac contractility and has a beneficial effect on the haemostatic system by enhancing fibrinolytic activity and inducing hypocoagulation in healthy rats.

This study investigated the effects of chronic supraphysiological dose of testosterone propionate administration cardiovascular function in rats from the perspective of haemostatic function including platelet functions, coagulation, and fibrinolysis. Testosterone significantly enhanced cardiac contractility by enhancing LVSP (10%), dp/dtmax (36.7%), dp/dtmin (14.6%) without altering heart rate, diastolic function, and serum lipid profile. While it has no effect on platelets count, thromboxane B2 levels, and platelet aggregation, testosterone significantly enhanced bleeding time and increased circulatory and thoracic aorta mRNA and protein levels of tPA (46.5%, 58.2%, and 74.3%, respectively) and significantly decreased those of PAI-1 (29.3%, 26.4%, and 32.8%, respectively). While there were no significant changes in PT and aPTT, mRNA and protein levels of prothrombin and factor VII were downregulated in the livers of the testosterone-treated rats (57.7% and 64.9%, respectively). Overall, chronic testosterone administration in rats may act as a cardio-protective agent by modulating haemostasis in rats.

Administration of testosterone improves the prothrombotic and antifibrinolytic parameters associated with its deficiency in an orchidectiomized rat model.

This study investigated the effect of testosterone deficiency and replacement on platelets function and aggregation, coagulation, and fibrinolysis in young adult healthy male rats. Rats were classified into three groups (n = 6/group) of either "a sham-operated+ vehicle," "an orchidectomized (ORX)+ vehicle," and "an ORX+testosterone propionate (0.5 mg/kg, 3X/week, S.C)." All treatments were carried out for 12 weeks. Our results showed that ORX rats had induced platelets aggregation and coagulation and inhibited fibrinolysis. ORX-induced rats had increased ratios of adenosine diphosphate-induced aggregation, shorter bleeding time, clotting time, prothrombin time, and activated partial thromboplastin time and their sera showed increased levels of thromboxane B2 and fibrinogen levels. Concomitantly, their plasma showed increased TPA-1 and decreased tissue plasminogen activator (tPA) levels. At molecular levels, the aorta of ORX-induced rats showed increased aortic mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), protein levels of von Willebrand Factor (vWF) and decreased mRNA and protein levels of tPA, and their liver showed increased protein levels of prothrombin and factor VII. Testosterone post-therapy to ORX-induced rats significantly reversed all these hematological and molecular changes. In conclusion, independent of any other risk factors, testosterone deficiency induces platelets aggregation and hypercoagulation and inhibits fibrinolysis, effects that can be reversed by testosterone therapy.

Antiplatelets and profibrinolytic activity of Citrullus colocynthis in control and high-fat diet-induced obese rats: mechanisms of action.

The current study aimed to investigate the effect of Citrullus colocynthis (C. colocynthis) hydro-alcoholic extract on blood haemostasis in control and high-fat diet (HFD) induced obese rats. In control rats, the extract significantly enhanced bleeding time and plasma levels of tPA and significantly decreased plasma levels PAI-1 and serum levels of thromboxane B2 leading to inhibition of platelets aggregation. In HFD induced obese rats, similar effects were seen and the extract was also able to reverse HFD induced increases in fibrinogen and VWF. Searching for the mechanism, C. colocynthis acts by (1) inhibiting of food intake, (2) inhibiting the activity of pancreatic lipase, (3) decreasing levels of TNF-α and IL-6 and (4) decreasing circulatory levels of the prothrombotic adipokine, leptin and enhanced circulatory levels of the antithrombic adipokines and adiopnectin. In conclusion, C. colocynthis has antiplatelets and profibrinolytic activity in both control and HFD induced obese rats.

TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook.

Background & Objective: Thioredoxin-interacting protein (TXNIP) also known as thioredoxin binding protein-2 is a ubiquitously expressed protein that interacts and negatively regulates expression and function of Thioredoxin (TXN). Over the last few years, TXNIP has attracted considerable attention due to its wide-ranging functions impacting several aspects of energy metabolism. TXNIP acts as an important regulator of glucose and lipid metabolism through pleiotropic actions including regulation of ß-cell function, hepatic glucose production, peripheral glucose uptake, adipogenesis, and substrate utilization. Overexpression of TXNIP in animal models has been shown to induce apoptosis of pancreatic ß-cells, reduce insulin sensitivity in peripheral tissues like skeletal muscle and adipose, and decrease energy expenditure. On the contrary, TXNIP deficient animals are protected from diet induced insulin resistance and type 2 diabetes. SUMMARY: Consequently, targeting TXNIP is thought to offer novel therapeutic opportunity and TXNIP inhibitors have the potential to become a powerful therapeutic tool for the treatment of diabetes mellitus. Here we summarize the current state of our understanding of TXNIP biology, highlight its role in metabolic regulation and raise critical questions that could help future research to exploit TXNIP as a therapeutic target.

The tyrosine kinase inhibitor, nilotinib potentiates a prothrombotic state.

Tyrosine kinase inhibitors (TKI) such as imatinib, nilotinib and dasatinib are now established as highly effective frontline therapies for chronic myeloid leukaemia (CML). Disease control is achieved in the majority of patients and survival is excellent such that recent focus has been on toxicities of these agents. Cumulative data have reported an excess of serious vascular complications, including arterial thrombosis and peripheral arterial occlusive disease, in patients receiving nilotinib in comparison with other TKIs, with resultant interest in delineating the pathophysiology and implications for rationale cardiovascular risk modification. To address this issue, we studied the effects of imatinib, nilotinib and dasatinib on platelet function and thrombus formation in human and mouse models using in vitro, ex vivo and in vivo approaches. In vitro studies demonstrated that dasatinib and imatinib but not nilotinib inhibited ADP, CRP, and collagen-induced platelet aggregation and moreover, that nilotinib potentiated PAR-1-mediated alpha granule release. Pretreatment of wild-type C57BL/6 mice with nilotinib but not imatinib or dasatinib, significantly increased thrombus growth and stability, on type I collagen under ex vivo arterial flow conditions and increased thrombus growth and stability following FeCl3-induced vascular injury of mesenteric arterioles and carotid artery injury in vivo. Whole blood from nilotinib-treated CML patients, demonstrated increased platelet adhesion ex vivo under flow, increased plasma soluble P- and E-selectin, sICAM-1, sVCAM-1, TNF-alpha, IL-6 levels and endogenous thrombin potential (ETP) levels in vivo, despite being on daily low-dose aspirin. These results demonstrate that nilotinib can potentiate platelet and endothelial activation and platelet thrombus formation ex vivo and in vivo.