Use of the prognostic biomarker suPAR in the emergency department improves risk stratification but has no effect on mortality:a cluster-randomized clinical trial (TRIAGE III)

Abstract Background Risk stratification of patients in the emergency department can be strengthened using prognostic biomarkers, but the impact on patient prognosis is unknown. The aim of the TRIAGE III trial was to investigate whether the introduction of the prognostic and nonspecific biomarker: soluble urokinase plasminogen activator receptor (suPAR) for risk stratification in the emergency department reduces mortality in acutely admitted patients. Methods The TRIAGE III trial was a cluster-randomized interventional trial conducted at emergency departments in the Capitol Region of Denmark. Eligible hospitals were required to have an emergency department with an intake of acute medical and surgical patients and no previous access to suPAR measurement. Three emergency departments were randomized; one withdrew shortly after the trial began. The inclusion period was from January through June of 2016 consisting of twelve cluster-periods of 3-weeks alternating between intervention and control and a subsequent follow-up of ten months. Patients were allocated to the intervention if they arrived in interventional periods, where suPAR measurement was routinely analysed at arrival. In the control periods suPAR measurement was not performed. The main outcome was all-cause mortality 10 months after arrival of the last patient in the inclusion period. Secondary outcomes included 30-day mortality. Results The trial enrolled a consecutive cohort of 16,801 acutely admitted patients; all were included in the analyses. The intervention group consisted of 6 cluster periods with 8900 patients and the control group consisted of 6 cluster periods with 7901 patients. After a median follow-up of 362 days, death occurred in 1241 patients (13.9%) in the intervention group and in 1126 patients (14.3%) in the control group. The weighted Cox model found a hazard ratio of 0.97 (95% confidence interval, 0.89 to 1.07; p = 0.57). Analysis of all subgroups and of 30-day all-cause mortality showed similar results. Conclusions The TRIAGE III trial found no effect of introducing the nonspecific and prognostic biomarker suPAR in emergency departments on short- or long-term all-cause mortality among acutely admitted patients. Further research is required to evaluate how prognostic biomarkers can be implemented in routine clinical practice. Trial registration clinicaltrials.gov, NCT02643459. Registered 31 December 2015

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards Bedside

The retinal vascular system is the only part of the human body available for direct, in vivo inspection. Noninvasive retinal markers are important to identity patients in risk of sight-threatening diabetic retinopathy. Studies have correlated structural features like retinal vascular caliber and fractals with micro- and macrovascular dysfunction in diabetes. Likewise, the retinal metabolism can be evaluated by retinal oximetry, and higher retinal venular oxygen saturation has been demonstrated in patients with diabetic retinopathy. So far, most studies have been cross-sectional, but these can only disclose associations and are not able to separate cause from effect or to establish the predictive value of retinal vascular dysfunction with respect to long-term complications. Likewise, retinal markers have not been investigated as markers of treatment outcome in patients with proliferative diabetic retinopathy and diabetic macular edema. The Department of Ophthalmology at Odense University Hospital, Denmark, has a strong tradition of studying the retinal microvasculature in diabetic retinopathy. In the present paper, we demonstrate the importance of the retinal vasculature not only as predictors of long-term microvasculopathy but also as markers of treatment outcome in sight-threatening diabetic retinopathy in well-established population-based cohorts of patients with diabetes

The formation and design of the TRIAGE study--baseline data on 6005 consecutive patients admitted to hospital from the emergency department

BACKGROUND: Patient crowding in emergency departments (ED) is a common challenge and associated with worsened outcome for the patients. Previous studies on biomarkers in the ED setting has focused on identification of high risk patients, and and the ability to use biomarkers to identify low-risk patients has only been sparsely examined. The broader aims of the TRIAGE study are to develop methods to identify low-risk patients appropriate for early ED discharge by combining information from a wide range of new inflammatory biomarkers and vital signs, the present baseline article aims to describe the formation of the TRIAGE database and characteristize the included patients. METHODS: We included consecutive patients ≥ 17 years admitted to hospital after triage staging in the ED. Blood samples for a biobank were collected and plasma stored in a freezer (−80 °C). Triage was done by a trained nurse using the Danish Emergency Proces Triage (DEPT) which categorizes patients as green (not urgent), yellow (urgent), orange (emergent) or red (rescusitation). Presenting complaints, admission diagnoses, comorbidities, length of stay, and ‘events’ during admission (any of 20 predefined definitive treatments that necessitates in-hospital care), vital signs and routine laboratory tests taken in the ED were aslo included in the database. RESULTS: Between September 5(th) 2013 and December 6(th) 2013, 6005 patients were included in the database and the biobank (94.1 % of all admissions). Of these, 1978 (32.9 %) were categorized as green, 2386 (39.7 %) yellow, 1616 (26.9 %) orange and 25 (0.4 %) red. Median age was 62 years (IQR 46–76), 49.8 % were male and median length of stay was 1 day (IQR 0–4). No events were found in 2658 (44.2 %) and 158 (2.6 %) were admitted to intensive or intermediate-intensive care unit and 219 (3.6 %) died within 30 days. A higher triage acuity level was associated with numerous events, including acute surgery, endovascular intervention, i.v. treatment, cardiac arrest, stroke, admission to intensive care, hospital transfer, and mortality within 30 days (p < 0.001). CONCLUSION: The TRIAGE database has been completed and includes data and blood samples from 6005 unselected consecutive hospitalized patients. More than 40 % experienced no events and were therefore potentially unnecessary hospital admissions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13049-015-0184-1) contains supplementary material, which is available to authorized users