Prospective relationship between duration of untreated psychosis and 13-year clinical outcome: A first-episode psychosis study

Background: The adverse effects of a long duration of untreated psychosis (DUP) have been explored in numerous short-term studies. These studies support the development of early interventions that reduce treatment delay and promote recovery. However, the enduring impact of DUP is largely unknown, partly due to the paucity of prospective long-term studies. Although the DUP-outcome relationship is commonly assumed to be linear, the threshold effect has not been adequately examined. Objective: To explore the relationship between DUP and long-term symptomatic remission. Methods: This was a prospective study of a cohort of 153 first-episode psychosis patients in Hong Kong at the 13-year follow-up. The patients were categorized into short (≤. 30. days), medium (31-180. days) and long (>. 180. days) DUP groups. Results: The long-term outcome was ascertained in 73% of the patients. Nearly half of the patients (47%) fulfilled the criteria for symptomatic remission. The short DUP group experienced a significantly higher remission rate over the course of the illness. The odds of long-term symptomatic remission was significantly reduced in the medium DUP (by 89%) and long DUP (by 85%) groups compared with the short DUP group. Further analysis showed that DUP had a specific impact on negative symptom remission. Conclusion: The findings support the threshold theory that DUP longer than 30. days adversely impacts the long-term outcome. The present study is one of the few studies that confirmed the enduring impact of DUP on long-term outcomes based on well-defined criteria and adequate statistical adjustment. © 2014 Elsevier B.V.link_to_subscribed_fulltex

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo