Risk assessment models for potential use in the emergency department have lower predictive ability in older patients compared to the middle-aged for short-term mortality - a retrospective cohort study

Table S1. Comparison of Baseline characteristics of the TRIAGE II study and TRIAGE III study. Patients above 40 years were included in the current study Table S2. Comparison of AUCs of individual predictors in discriminating short-term mortality of ED patients, grouped according to age: 40–69 years (middle-aged), and 70+ years (older). Figure S1. Area under the Curve (AUC) for Receiver operating characteristics for all-cause mortality within 7 days for acutely admitted patients. Comparison of patients aged 40-69 (Middle-aged, blue colour), and patients aged 70+ (Older, red colour). The graph presents four different approaches of risk assessment of patients acutely presenting at the emergency department. Two different triage algorithms; Adaptive Process Triage (ADAPT) and Copenhagen Triage Algorithm (CTA), a predictive model using four vital signs (heart rate, arterial oxygen saturation, respiratory rate and systolic blood pressure), and a predictive model using levels of seven routine biomarkers (albumin, creatinine, c-reactive protein, haemoglobin, leucocytes, potassium, sodium). (DOCX 241 kb

Atherosclerosis Imaging with 18F-Sodium Fluoride PET

The evidence on atherosclerosis imaging with 18F-sodium-fluoride (NaF) positron emission tomography (PET) is hotly debated because of the different patient characteristics, methodology, vascular beds, etc. in reported studies. This review is a continuation of a previous review on this topic, which covered the period 2010–2018. The purpose was to examine whether some of the most important questions that the previous review had left open had been elucidated by the most recent literature. Using principles of a systematic review, we ended analyzing 25 articles dealing with the carotids, coronary arteries, aorta, femoral, intracranial, renal, and penile arteries. The knowledge thus far can be summarized as follows: by targeting active arterial microcalcification, NaF uptake is considered a marker of early stage atherosclerosis, is age-dependent, and consistently associated with cardiovascular risk. Longitudinal studies on NaF uptake, conducted in the abdominal aorta only, showed unchanged uptake in postmenopausal women for nearly four years and varying uptake in prostate cancer patients over 1.5 years, despite constant or increasing calcium volume detected by computed tomography (CT). Thus, uncertainty remains about the transition from active arterial wall calcification marked by increased NaF uptake to less active or consolidated calcification detected by CT. The question of whether early-phase atherosclerosis and calcification can be modified remains also unanswered due to lack of intervention studies

Social isolation, loneliness, and inflammation: a multi-cohort investigation in early and mid-adulthood

Social isolation and loneliness have been associated with poor health and increased risk for mortality, and inflammation might explain this link. We used data from the Danish TRIAGE Study of acutely admitted medical patients (N=6,144, mean age 60 years), and from two population-representative birth cohorts: the New Zealand Dunedin Longitudinal Study (N=881, age 45) and the UK Environmental Risk (E-Risk) Longitudinal Twin Study (N=1448, age 18), to investigate associations of social isolation with three markers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer inflammation marker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. In the TRIAGE Study, socially isolated patients (those living alone) had significantly higher median levels of suPAR (but not CRP or IL-6) compared with patients not living by themselves. Social isolation prospectively measured in childhood was longitudinally associated with higher CRP, IL-6, and suPAR levels in adulthood (at age 45 in the Dunedin Study and age 18 in the E-Risk Study), but only suPAR remained associated after controlling for covariates. Dunedin Study participants who reported loneliness at age 38 or age 45 had elevated suPAR at age 45. In contrast, E-Risk Study participants reporting loneliness at age 18 did not show any elevated markers of inflammation. In conclusion, social isolation in childhood was robustly associated with increased inflammation in adulthood, both in medical patients and in the general population. It was associated in particular with systemic chronic inflammation, evident from the consistently stronger associations with suPAR than other inflammation biomarkers

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

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants’ PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges