Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure

Background & Aims Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. Methods Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). Results There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. Conclusions These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. Impact and implications This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. Clinical trial number NCT03065699

Real-Time Associations Between Engaging in Leisure and Daily Health and Well-Being

BackgroundEngagement in leisure has a wide range of beneficial health effects. Yet, this evidence is derived from between-person methods that do not examine the momentary within-person processes theorized to explain leisure's benefits.PurposeThis study examined momentary relationships between leisure and health and well-being in daily life.MethodsA community sample (n = 115) completed ecological momentary assessments six times a day for three consecutive days. At each measurement, participants indicated if they were engaging in leisure and reported on their mood, interest/boredom, and stress levels. Next, participants collected a saliva sample for cortisol analyses. Heart rate was assessed throughout the study.ResultsMultilevel models revealed that participants had more positive and less negative mood, more interest, less stress, and lower heart rate when engaging in leisure than when not.ConclusionsResults suggest multiple mechanisms explaining leisure's effectiveness, which can inform leisure-based interventions to improve health and well-being

Social, Human and Positive Psychological Capital in the Labour Market Re-integration of People Deported to the Dominican Republic

More than six million people have been deported from the United States since 1996. The Dominican Republic is one of the top ten countries to which deportees are sent. Most scholarship on deportation focuses on the challenges deportees face post-deportation. There is also a long history of scholarship on how migrants draw from social, human and financial capital to integrate into host societies. This article thus asks what forms of capital are useful for deportees’ re-integration and focuses on the forms of capital deportees draw from to survive in the aftermath of deportation. An analysis of 60 in-depth interviews with Dominican deportees reveals how deportees’ combination of limited human capital, fractured social capital and positive psychological capital assists in their re-integration. Results also show that access to employment is not only an important step in social and economic integration, but that it also helps deportees to achieve emotional stability