Review of the renal endpoints used in cardiovascular safety clinical trials in type 2 diabetes mellitus patients and their importance in primary care

Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2DM). Furthermore, CKD confers a considerable increase in the risk of cardiovascular (CV) morbidity and mortality. In line with the need to improve knowledge in this field, this article aims to describe the renal endpoints used in the different cardiovascular outcome trials (CVOTs). The objective is to better know the renal variables used in the different CVOTs in order to optimize the implementation of advances in the prevention of progressive diabetic kidney disease in patients with T2DM in clinical practice.     

Antithrombotic Management After Transcatheter Aortic Valve Replacement: A Survey of Canadian Physicians

Optimal postprocedural antithrombotic regimen is uncertain after transcatheter aortic valve replacement (TAVR). We developed an online questionnaire on post-TAVR antithrombotic management. After research ethics board approval, we distributed the survey to TAVR implanters across Canada. A total of 24 TAVR implanters from 17 centres responded to the survey for a response rate of 75%. Dual antiplatelet therapy for variable durations was the preferred initial treatment for patients in sinus rhythm after isolated TAVR, TAVR with a recent stent (≤ 1 month), and valve-in-valve procedures (71%, 96%, and 65%, respectively). Most respondents continued patients on acetylsalicylic acid indefinitely after these procedures (100%, 92%, 90%, respectively). In patients with atrial fibrillation, the CHA₂DS₂-VAS_C score was the preferred stroke risk score for 57% of respondents, the CHADS₂ score was the preferred stroke risk score for 22% of respondents, and the CHADS65 score was the preferred stroke risk score for 17% of respondents. To determine the risk of bleeding, the HASBLED score was most often used (52%), but 48% of respondents indicated that they did not use a bleeding risk score. In the presence of atrial fibrillation, antithrombotic therapy choice varied widely. Our survey shows that dual antiplatelet therapy is the most common discharge regimen after TAVR in current practice. However, the choice and duration of antithrombotic regimen vary in patients requiring anticoagulation.     

Follow-up of patients with functional bowel symptoms treated with a low FODMAP diet

AIM: To investigate patient-reported outcomes from, and adherence to, a low FODMAP diet among patients suffering from irritable bowel syndrome and inflammatory bowel disease.METHODS: Consecutive patients with irritable bowel syndrome(IBS) or inflammatory bowel disease(IBD) and co-existing IBS fulfilling the ROME Ⅲ criteria, who previously attended an outpatient clinic for low FODMAP diet(LFD) dietary management and assessment by a gastroenterologist, were invited to participate in a retrospective questionnaire analysis. The questionnaires were sent and returned by regular mail and gathered information on recall of dietarytreatment, efficacy, symptoms, adherence, satisfaction, change in disease course and stool type, and quality of life. Before study enrolment all patients had to sign an informed written consent.RESULTS: One hundred and eighty patients were included, 131(73%) IBS and 49(27%) IBD patients. Median age was 43 years(range: 18-85) and 147(82%) were females. Median follow-up time was 16 mo(range: 2-80). Eighty-six percent reported either partial(54%) or full(32%) efficacy with greatest improvement of bloating(82%) and abdominal pain(71%). The proportion of patients with full efficacy tended to be greater in the IBD group than in the IBS group(42% vs 29%, P = 0.08). There was a significant reduction in patients with a chronic continuous disease course in both the IBS group(25%, P 0.001) and IBD group(23%, P = 0.002) along with a significant increase in patients with a mild indolent disease course of 37%(P 0.001) and 23%(P = 0.002), respectively. The proportion of patients having normal stools increased with 41% in the IBS group(P 0.001) and 66% in the IBD group(P 0.001). One-third of patients adhered to the diet and high adherence was associated with longer duration of dietary course(P 0.001). Satisfaction with dietary management was seen in 83(70%) IBS patients and 24(55%) IBD patients. Eightyfour percent of patients lived on a modified LFD, where some foods rich in FODMAPs were reintroduced, and 16% followed the LFD by the book without deviations. Wheat, dairy products, and onions were the foods most often not reintroduced by patients.CONCLUSION: These data suggest that a diet low in FODMAPs is an efficacious treatment solution in the management of functional bowel symptoms for IBS and IBD patients.     

Intrapleural tissue plasminogen activator and deoxyribonuclease therapy for pleural infection

Pleural infection remains a global health burden associated with significant morbidity. Drainage of the infected pleural fluid is important but can often be hindered by septations and loculations. Intrapleural fibrinolytic therapy alone, to break pleural adhesions, has shown no convincing advantages over placebo in improving clinical outcome. Deoxyribonucleoprotein from degradation of leukocytes contributes significantly to high viscosity of infected pleural fluid. Recombinant deoxyribonuclease (DNase) is effective in reducing pleural fluid viscosity in pre-clinical studies. The combination of tissue plasminogen activator (tPA) and DNase was effective in animal model experiments of empyema. The benefits were established in a randomized clinical trial: those (n=48) treated with tPA/DNase had significantly improved radiological outcomes and reduced need of surgery and duration of hospital stay. A longitudinal observational series of 107 patients further confirmed the effectiveness and safety of tPA/DNase therapy, including its use as ‘rescue therapy’ when patients failed to respond to antibiotics and chest tube drainage. Overall, a short course of intrapleural tPA (10 mg) and DNase (5 mg) therapy provides a cure in over 90% of patients without requiring surgery. The treatment stimulates pleural fluid formation, enhances radiographic clearance and resolution of systemic inflammation. Serious complications are uncommon; pleural bleeding requiring transfusion occurred in ~2% of cases. Pain can occur, especially with the first dose. Treatment is contraindicated in those with significant bleeding diathesis or a bronchopleural fistula. Future research is required to optimize dosing regimens and in refining patient selection.     

The Relationship Between Tobacco and Cannabis Use: A Review

Background: Based on the prevalence and health implications of tobacco and cannabis use, aiming to reduce their use, especially among youth, is a sound objective at both the individual and public health level. A proper understanding of the relationships between tobacco and cannabis use may help to achieve this goal. Objectives: To review the relationships between tobacco and cannabis use. Methods: A selective review of the literature. Results: We present an overview of the motivations for tobacco and cannabis use, and their perceived harmfulness. The article then reviews the gateway theory, reverse gateway theory, route of administration theory, and common liability theory. We describe the link between co-use and dependence symptoms, and the substitution phenomenon between tobacco and cannabis use. Three forms of simultaneous use–mulling, blunt smoking, and chasing–and their impacts are explained. We summarize the impact of tobacco use on cannabis (and vice versa) treatment outcomes, and, finally, review new treatments that simultaneously target tobacco and cannabis dependence. Most of the literature reviewed here relates to substance use among adolescents and young adults. Conclusions: The use of tobacco and cannabis–two of the most widely used substances around the world–are strongly intertwined in several respects. Both health professionals and researchers should have well-informed views on this issue to better evaluate, understand, inform, and provide care to their patients.     

Dispersion of ventricular repolarization: Temporal and spatial

Repolarization heterogeneity(RH) is an intrinsic property of ventricular myocardium and the reason for T-wave formation on electrocardiogram(ECG). Exceeding the physiologically based RH level is associated with appearance of life-threatening ventricular arrhythmias and sudden cardiac death. In this regard, an accurate and comprehensive evaluation of the degree of RH parameters is of importance for assessment of heart state and arrhythmic risk. This review is devoted to comprehensive consideration of RH phenomena in terms of electrophysiological processes underlying RH, cardiac electric field formation during ventricular repolarization, as well as clinical significance of RH and its reflection on ECG parameters. The formation of transmural, apicobasal, left-toright and anterior-posterior gradients of action potential durations and end of repolarization times resulting from the heterogenous distribution of repolarizing ion currents and action potential morphology throughout the heart ventricles, and the different sensitivity of myocardial cells in different ventricular regions to the action of pharmacological agents, temperature, frequency of stimulation, etc., are being discussed. The review is focused on the fact that RH has different aspects – temporal and spatial, global and local; ECG reflection of various RH aspects and their clinical significance are being discussed. Strategies for comprehensive assessment of ventricular RH using different ECG indices reflecting various RH aspects are presented.     

Strawberry extract presents antiplatelet activity by inhibition of inflammatory mediator of atherosclerosis (sP-selectin,sCD40L,RANTES, and IL-1β) and thrombus formation

Cardiovascular disease prevention is of high priority in developed countries. Healthy eating habits including the regular intake of an antithrombotic diet (fruit and vegetables) may contribute to prevention. Platelet function is a critical factor in arterial thrombosis and the effect strawberries have is still unclear. Therefore, the aim of this study was to systematically examine the action of strawberries in preventing platelet activation and thrombus formation. Strawberry extract concentration-dependently (0.1–1?mg/ml) inhibited platelet aggregation induced by ADP and arachidonic acid. At the same concentrations as strawberry inhibits platelet aggregation, it significantly decreased sP-selectin, sCD40L, RANTES, and IL-1β levels. The strawberry may exert significant protective effects on thromboembolic-related disorders by inhibiting platelet aggregation. Also, this suggests that antithrombotic activity may have novel anti-inflammatory effects.