Review article: Biomarkers of clinical outcomes in advanced chronic kidney disease

Chronic kidney disease (CKD) is a complex condition, where the decrease in kidney function is accompanied by numerous metabolic changes affecting virtually all the organ systems of the human body. Many of the biomarkers characteristic of the individually affected organ systems have been associated with adverse outcomes including higher mortality in advanced CKD, whereas in persons without CKD these biomarkers may have no bearing on survival. It is believed that the high mortality seen in CKD is a result of several abnormalities conspiring to induce or aggravate a heightened degree of cardiovascular morbidity and predisposition to wasting syndrome. Not all the biomarkers may, however, be causally responsible for the adverse outcomes associated with them. We review various biomarkers of protein-energy wasting, inflammation, oxidative stress, potassium disarrays, acid-base disorders, bone and mineral disorders, glycemic status, and anemia. Although all of these biomarkers have shown associations with worsened outcomes in CKD, markers of protein-energy wasting, especially serum albumin, remain the strongest predictor of survival in CKD patients, especially those undergoing maintenance dialysis treatment. We also review the putative pathophysiologic mechanisms behind these associations, and present potential therapeutic interventions that could result in remedies to improve poor clinical outcomes in CKD, pending the results of current and future controlled trials.     

A review of drug prevention system development in Romania and its impact on youth drug consumption trends, 1995–2005

Issues. A tremendous growth occurred in the reported drug use and abuse in Romania from 1995 to 1999. Lack of concern by government and little policy attention contributed to the surprising delay of drug policy and drug prevention system development. General public stigmatize drug users and drug consumption is considered a matter of personal fault and responsibility. There is some but not sufficient research and evaluation on drug use, abuse problem. Approach. Drug use, abuse and prevention are discussed from research‐based, user‐focused and prevention system development perspectives. Prevalence and trends of drug use, abuse in the past decade (1995–2005) are summarized. Prevention issues are discussed based on research data from adolescents, parents and teachers. The Romanian primary drug prevention system has been evaluated based on our experiences in drug use prevention activities carried out in schools and recreational environments. Key Findings. Public and scientific perspectives on drug consumption in Romania, between 1995 and 1999, were dominated by an idealistic, non‐realistic perception. Since 1995, drug use among adolescents increased almost four times in less than 4 years. The first law against drug traffic and consumption was issued only in 2000. Now primary drug prevention strategies are in action, but in general they are lacking standard evaluation procedures. Implications/Conclusion. Conclusions are drafted for new perspectives in prevention activities. More long‐term, user‐focused, demand‐centred prevention activities should be carried out in more and more diversified settings and evaluation should be thoroughly considered.[Dégi CL. A review of drug prevention system development in Romania and its impact on youth drug consumption trends, 1995–2005. Drug Alcohol Rev 2009;28:419–425]     

Suppression of Erythromycin-induced Early Afterdepolarizations and Torsade de Pointes Ventricular Tachycardia by Mexiletine

Erythromycin is a selective I_Kr-blocking, action potential duration (APD)-prolonging drug, which may induce early afterdepolarizations (EADs) and torsade de pointes ventricular tachycardia. The successful termination of an erythromycin-induced clinical torsades de pointes by the authors with mexiletine prompted them to investigate in vitro whether erythromycin is able to induce EADs in Purkinje fibers and, if so, whether EADs are suppressible or not by mexiletine. Electrically stimulated canine Purkinje fibers (n=9) were superfused with erythromycin (200 mg/l) and action potentials were recorded by an intracellular microelectrode technique. Erythromycin induced a pronounced prolongation of APD and the appearance of EADs in all Purkinje preparations (9/9). After the addition of mexiletine (10 mM), a marked shortening of APD and the disappearance of EADs (7/9) were observed. Mexiletine, an inhibitor of the tetrodotoxin-sensitive window Na+-current, may prevent IKr-blocking drug-induced torsade de pointes ventricular tachycardia by abolishing APD prolongation and EADs.     

Autoimmune skin and connective tissue diseases and risk of venous thromboembolism: a population‐based case‐control study

Summary. Background: Systemic inflammation is associated with vessel wall damage, upregulation of procoagulants, downregulation of anticoagulants, and suppression of fibrinolysis. Autoimmune diseases may therefore increase the risk of venous thromboembolism (VTE). Objectives: To examine whether autoimmune skin and connective tissue diseases are associated with increased VTE risk. Methods: We conducted this population‐based case–control study in northern Denmark, using administrative databases. From 1999 to 2009, we identified 14 721 VTE cases and 147 210 birth year‐matched, sex‐matched and county‐matched population controls. The date of diagnosis/matching was considered to be the index date for cases and controls. For all study subjects, we identified hospital diagnoses of autoimmune skin or connective tissue diseases between 1977 and the index date. We used conditional logistic regression with adjustment for VTE risk factors to calculate odds ratios and 95% confidence intervals (CIs) for patients with vs. without autoimmune disease. Given the risk‐set sampling design, odds ratios estimate incidence rate ratios (IRRs). Results: Autoimmune skin disease was not associated with VTE (IRR 1.0; 95% CI 0.9–1.2). Patients with connective tissue disease had an increased VTE risk within 90 days (IRR 2.3; 95% CI 1.5–3.7) and 91–365 days (IRR 2.0; 95% CI 1.5–2.8) after diagnosis, but not thereafter (IRR 1.1; 95% CI 1.0–1.2). Among connective tissue diseases, the greatest overall risk increases were found for juvenile rheumatoid arthritis (IRR 3.0; 95% CI 1.4–6.4) and systemic lupus erythematosus (IRR 2.8; 95% CI 1.7–4.7). Conclusions: Autoimmune connective tissue disease was associated with an increased risk of VTE within 1 year after diagnosis, whereas skin diseases were not.