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

A review of the role of emerging environmental contaminants in the development of breast cancer in women

The incidence of breast cancer is on a rise worldwide; it is a disease having a complex etiology. Besides genetics, environmental and other lifestyle factors play a role in the development of the disease. There has been a keen interest in studying associations between breast cancer and exposures to emerging environmental chemicals, which mimic estrogens or influence estrogen levels and signaling in the human body. The common consequence of an endocrine disrupting chemical exposure is that it may have an impact on breast cancer etiology by stimulating formation as well as progression of breast cancer. Exposures to selected emerging environmental contaminants such as alkylphenols (APs), bisphenol A (BPA), parabens, perfluoroalkyl substances (PFASs), phthalates, polybrominated diphenyl ethers (PBDEs), synthetic musks and triclosan, and their probable role in breast cancer development are reviewed. Studies evaluated include the experimental in vitro and in vivo studies as well as human population based studies. In vitro and in vivo evidences indicate that a number of emerging environmental contaminants may play a role in the initiation and/or progression of breast cancer. Although exposures have been assessed in some human populations, breast and other cancer risks associated with these exposures are largely unknown. Efforts should be focussed on the evaluation of these environmental exposures in human populations and their interactions with each other and other genetic and lifestyle risk factors