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Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation. Elevated suPAR levels are associated with adverse clinical outcomes, but a small subset of patients with low suPAR also experience poor outcomes. Therefore, we aimed to characterize patients presenting to the emergency department with low suPAR (<3 ng/mL) who died within 90 days after discharge in a registry‐based study. Compared to patients with low suPAR who survived (n = 15 122), those who died within 90 days (n = 87) had higher age (75.4 years), higher medication use (7.0; 71.3% with polypharmacy) and more blood tests outside reference intervals (5.0) (including C‐reactive protein, neutrophils and albumin), and the most common diagnoses were chronic pulmonary disease (27.6%), cerebrovascular disease (18.4%) and dementia (11.5%). Patients with low suPAR were more morbid than what was reflected by suPAR alone. Future studies must determine which factors that contribute the most to potential algorithms when stratifying patients based on their risk of adverse clinical outcomes. These data indicate that inclusion of medication data could be relevant. [ABSTRACT FROM AUTHOR]

Aims: To investigate whether the association between levels of medication use (including polypharmacy and potentially inappropriate medications [PIMs]) and health outcomes such as readmission and mortality is dependent on baseline soluble urokinase plasminogen activator receptor (suPAR). Methods: This registry‐based cohort study included medical patients admitted to the emergency department at Copenhagen University Hospital Hvidovre, Denmark. Patients were grouped according to their admission suPAR levels: low (0–3 ng/mL), intermediate (3–6 ng/mL), or high (>6 ng/mL). Hyper‐polypharmacy was defined as ≥10 prescribed medications. PIMs were identified based on the EU(7)‐PIM list, and data on admissions and mortality were obtained from national registries. Risk of 90‐day readmission and mortality was assessed by Cox regression analysis adjusted for sex, age and Charlson comorbidity index. Results were reported as hazard ratios within 90 days of index discharge. Results: In total, 26 291 patients (median age 57.3 y; 52.7% female) were included. Risk of 90‐day readmission and mortality increased significantly for patients with higher suPAR or higher number of medications. Among patients with low suPAR, patients with ≥10 prescribed medications had a hazard ratio of 2.41 (95% confidence interval = 2.09–2.78) for 90‐day readmission and 8.46 (95% confidence interval = 2.53–28.28) for 90‐day mortality compared to patients with 0 medications. Patients with high suPAR generally had high risk of readmission and mortality, and the impact of medication use was less pronounced in this group. Similar, but weaker, association patterns were observed between suPAR and PIMs. Conclusion: The association between levels of medication use and health outcomes is dependent on baseline suPAR. [ABSTRACT FROM AUTHOR]

Background Increasing acute admissions in Emergency Departments (EDs) negatively affect quality of care, safety and flow. Thus, the Danish Health Authorities recommend the presence of experienced physicians in the ED. In 2016, consultant-led triage and continuous presence of consultants were introduced at a larger ED in Copenhagen, Denmark. This study investigated whether the employment of consultants in a Danish ED affected the quality of care for acutely admitted medical patients in terms of length of admission, readmission and mortality, as well as socioeconomic equality in quality of care delivery. Methods Admission data were collected during two 7-month periods, one prior to and one after the organizational intervention, with 9869 adult medical patients admitted for up to 48 h in the ED. Linear regression and Cox proportional hazards regression analyses adjusted for age, sex, comorbidities, level of education and employment status were applied. Results Following the employment of consultants, an overall 11% increase in index-admissions was observed, and 90% of patients were discharged by a consultant with a reduced mean length of admission by 1.4 h (95% CI: 1.0–1.9). No change was found in in-hospital mortality, readmission or mortality within 90 days after discharge. No change in distribution of quality indicators across patients' socioeconomic status was found. Conclusions Consultants in the ED was found to reduce length of hospitalization without a negative effect on the quality of care for ED-admitted medical patients in general or patients with lower socioeconomic status. [ABSTRACT FROM AUTHOR]

Soluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate of 60% for the variation in suPAR and performed a genome-wide association meta-analysis on suPAR levels measured in Iceland (N = 35,559) and in Denmark (N = 12,177). We identified 13 independently genome-wide significant sequence variants associated with suPAR across 11 distinct loci. Associated variants were found in and around genes encoding uPAR (PLAUR), its ligand uPA (PLAU), the kidney-disease-associated gene PLA2R1 as well as genes with relations to glycosylation, glycoprotein biosynthesis, and the immune response. These findings provide new insight into the causes of variation in suPAR plasma levels, which may clarify suPAR's potential role in associated diseases, as well as the underlying mechanisms that give suPAR its prognostic value as a unique marker of chronic inflammation. Dowsett and colleagues used a genome-wide association approach to investigate the genetic influence on soluble urokinase-type plasminogen activator receptor presence in the plasma of humans. Their findings indicate a 60% heritability factor in British twins, and using a wide sample of Northern European genome samples they identify eleven genetic loci associated with an increase or decrease of this chronic inflammation marker. [ABSTRACT FROM AUTHOR]

Background: To understand and measure the association between chronic inflammation, aging, and age-related diseases, broadly applicable standard biomarkers of systemic chronic inflammation are needed. We tested whether elevated blood levels of the emerging chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR) were associated with accelerated aging, lower functional capacity, and cognitive decline.Methods: We used data from the Dunedin Study, a population-representative 1972-1973 New Zealand birth cohort (n = 1037) that has observed participants to age 45 years. Plasma suPAR levels were analyzed at ages 38 and 45 years. We performed regression analyses adjusted for sex, smoking, C-reactive protein, and current health conditions.Results: Of 997 still-living participants, 875 (88%) had plasma suPAR measured at age 45. Elevated suPAR was associated with accelerated pace of biological aging across multiple organ systems, older facial appearance, and with structural signs of older brain age. Moreover, participants with higher suPAR levels had greater decline in physical function and cognitive function from childhood to adulthood compared to those with lower suPAR levels. Finally, improvements in health habits between ages 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years.Conclusions: Our findings provide initial support for the utility of suPAR in studying the role of chronic inflammation in accelerated aging and functional decline. [ABSTRACT FROM AUTHOR]

Background: Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft‐reported inflammatory biomarker C‐reactive protein (CRP). Methods: Prospective study of a population‐representative 1972–1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhood experiences (ACEs), low IQ, and poor self‐control. Main adult outcomes were adulthood inflammation measured as suPAR and high‐sensitivity CRP (hsCRP). Results: Participants with available plasma samples at age 38 were included (N = 837, 50.5% male). suPAR (mean 2.40 ng/ml; SD 0.91) was positively correlated with hsCRP (r 0.15, p < .001). After controlling for sex, body mass index (BMI), and smoking, children who experienced more ACEs, lower IQ, or had poorer self‐control showed elevated adult suPAR. When the five childhood risks were aggregated into a Cumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk was associated with higher suPAR (b 0.10; SE 0.03; p = .002). Cumulative Childhood Risk predicted elevated suPAR, after controlling for hsCRP (b 0.18; SE 0.03; p < .001). Conclusions: Exposure to more childhood risk factors was associated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhood risk to adult inflammatory burden. [ABSTRACT FROM AUTHOR]

Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic low-grade inflammation and a potent predictor of cardiovascular events. We hypothesized that plasma suPAR levels would predict new-onset atrial fibrillation (AF) in a large cohort of consecutively admitted acute medical patients during long-term follow-up. In 14,764 acutely ad-mitted patients without prior or current AF, median suPAR measured upon admission was 2.7 ng/ml (interquartile range (IQR) 1.9-4.0). During a median follow-up of 392 days (IQR 218-577), 349 patients (2.4%) were diagnosed with incident AF. suPAR levels at admission significantly predicted subsequent incident AF (HR per doubling of suPAR: 1.21, 95% CI 1.05-1.41, adjusted for age and sex). After further adjustment for Charlson score, plasma C-reactive protein (CRP), plasma creatinine and blood hemoglobinlevels, the result remained essentially unaltered (HR per doubling of suPAR: 1.20, 95% CI: 1.01-1.42). In multivariate ROC curve analysis, combining age, sex, Charlson score, CRP, creatinine, and hemoglobin (AUC 0.77, 95% CI 0.75-0.79), the addition of suPAR did not improve the prediction of incident AF (AUC 0.77, 95% CI 0.75-0.79, P=0.89). Plasma suPAR is independently associated with subsequent new-onset AF in a population of recently hospitalized patients, but the addition of suPAR to baseline risk markers appears not to improve the prediction of AF. [ABSTRACT FROM AUTHOR]