High-sensitivity cardiac troponin T in the emergency department : admissions, resource utilization and outcomes

Background Patients presenting with chest pain in the emergency department (ED) may have myocardial infarction (MI) requiring immediate treatment. High-sensitivity cardiac troponin T (hs-cTnT) was recently introduced as a biomarker that aids in determining whether the patient requires hospital admission or can be safely discharged home. The aim of this thesis was to evaluate the implementation of hs-cTnT in the ED, with respect to hospital admission, resource utilization and patient outcomes. Methods and Results Two separate datasets were created by combining administrative information from the ED at Karolinska University Hospital with laboratory data and linking several national health care registers through the National Board of Health and Welfare. The first dataset was used for Studies I and II, while the second dataset was used for Studies III and IV. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Study I: In total, 14,636 patients with chest pain who presented to the EDs at Karolinska University Hospital, Solna and Huddinge, during 2011 and 2012 were included to evaluate whether a first undetectable (<5 ng/L) hs-cTnT level and an electrocardiogram (ECG) without signs of ischaemia could be used to safely rule out MI in the ED. We identified 15 patients with an undetectable hs-cTnT level and non-ischaemic ECG who were diagnosed with MI within 30 days. The negative predictive value for MI using this strategy was 99.8%, and for death 100%. Study II: We included 13,046 patients with chest pain who visited the ED at Karolinska University Hospital, Solna and Huddinge, during 2011 and 2012. We calculated HRs at different hs-cTnT levels for the risk of revisits to the ED, readmissions to hospital and resource utilization in terms of whether the patient was discharged or admitted. In patients with a hs-cTnT level of <5 ng/L who were admitted to the hospital compared with discharged home, we observed a 24% increased risk (adjusted HR 1.24, 95% CI 1.05–1.46) of revisiting the ED within 30 days and a three-fold increased risk of coronary angiography or revascularization during follow-up. Study III: We evaluated trends in admission rates among 15,472 patients with chest pain who presented to the ED at Karolinska University Hospital, Huddinge from 2011 to 2014. Proportions of admitted patients were calculated using each year of the study period (2012, 2013 and 2014) as exposure with year 2011 as reference. We found a 36% relative reduction in hospital admissions. All-cause mortality increased (adjusted HR 1.51, 95% CI 1.18–1.92), but for non-cardiovascular causes only. Coronary angiography significantly increased, but revascularizations remained stable. Study IV: Survival and resource utilization in 31,904 patients with chest pain were compared during the initial 3 years (2011 -2013) when the hs-cTnT assay was implemented to the preceding 2 years (2009-2010) when the conventional troponin (cTnT) assay was in use at Karolinska University Hospital, Solna and Huddinge. Patients who were tested with hs-cTnT had a 15% increase in all-cause mortality (adjusted HR 1.15, 95% CI 1.02–1.29), 13% increase in coronary angiography (adjusted HR 1.13, 95% CI 1.00–1.28) and 18% increase in revascularizations (adjusted HR 1.18, 95% CI 1.01 – 1.37). Conclusions [I] Patients presenting with chest pain, a first undetectable hs-cTnT level and a normal ECG may be safely discharged from the ED because the risk of MI or death is minimal. [II] When patients with chest pain and an undetectable hs-cTnT level are admitted to the hospital instead of discharged home, they have an increased risk of revisits to the ED, recurrent hospital stays, coronary angiography and revascularization. [III] Admissions for chest pain were reduced by 36% during the first 4 years of hscTnT use. All-cause mortality increased, but for non-cardiovascular causes only. [IV] After the introduction of hs-cTnT testing in the ED, an increase in mortality, coronary angiography and revascularizations was observed

Undetectable High-Sensitivity Cardiac Troponin T Level in the Emergency Department and Risk of Myocardial Infarction

ObjectivesThis study sought to evaluate if an undetectable (<5 ng/l) high-sensitivity cardiac troponin T (hs-cTnT) level and an electrocardiogram (ECG) without signs of ischemia can rule out myocardial infarction (MI) in the emergency department (ED).BackgroundChest pain is a common symptom often associated with benign conditions, but may be a sign of MI. Because there is no rapid way to rule out MI, many patients are admitted to the hospital.MethodsAll patients who sought medical attention for chest pain and had at least 1 hs-cTnT analyzed during 2 years at the Karolinska University Hospital, Stockholm, Sweden, were included. We calculated the negative predictive values of an undetectable hs-cTnT and ECG without ischemia for MI and death within 30 days.ResultsWe included 14,636 patients, of whom 8,907 (61%) had an initial hs-cTnT of <5 ng/l; 21% had 5 to 14 ng/l, and 18% had >14 ng/l. During 30-day follow-up, 39 (0.44%) patients with undetectable hs-cTnT had a MI, of whom 15 (0.17%) had no ischemic ECG changes. The negative predictive value for MI within 30 days in patients with undetectable hs-cTnT and no ischemic ECG changes was 99.8% (95% confidence interval [CI]: 99.7 to 99.9). The negative predictive value for death was 100% (95% CI: 99.9 to 100).ConclusionsAll patients with chest pain who have an initial hs-cTnT level of <5 ng/l and no signs of ischemia on an ECG have a minimal risk of MI or death within 30 days, and can be safely discharged directly from the ED

A methylome-wide mQTL analysis reveals associations of methylation sites with GAD1 and HDAC3 SNPs and a general psychiatric risk score

Genome-wide association studies have identified a number of single-nucleotide polymorphisms (SNPs) that are associated with psychiatric diseases. Increasing body of evidence suggests a complex connection of SNPs and the transcriptional and epigenetic regulation of gene expression, which is poorly understood. In the current study, we investigated the interplay between genetic risk variants, shifts in methylation and mRNA levels in whole blood from 223 adolescents distinguished by a risk for developing psychiatric disorders. We analyzed 37 SNPs previously associated with psychiatric diseases in relation to genome-wide DNA methylation levels using linear models, with Bonferroni correction and adjusting for cell-type composition. Associations between DNA methylation, mRNA levels and psychiatric disease risk evaluated by the Development and Well-Being Assessment (DAWBA) score were identified by robust linear models, Pearson's correlations and binary regression models. We detected five SNPs (in HCRTR1, GAD1, HADC3 and FKBP5) that were associated with eight CpG sites, validating five of these SNP-CpG pairs. Three of these CpG sites, that is, cg01089319 (GAD1), cg01089249 (GAD1) and cg24137543 (DIAPH1), manifest in significant gene expression changes and overlap with active regulatory regions in chromatin states of brain tissues. Importantly, methylation levels at cg01089319 were associated with the DAWBA score in the discovery group. These results show how distinct SNPs linked with psychiatric diseases are associated with epigenetic shifts with relevance for gene expression. Our findings give a novel insight on how genetic variants may modulate risks for the development of psychiatric diseases

A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants

The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population-based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES-D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES-D score, occurrence of a major depressive episode (MDE) during follow-up and regular antidepressant treatment during the 6 months preceding follow-up assessment as outcomes. The GRS was associated with MDE occurrence (p =.02) and ln CES-D score (p =.001). The HTR1A rs878567 variant was associated with ln CES-D after adjustment for demographic and clinical variables [p =.02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six-fold higher likelihood of regular AD therapy at follow-up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p =.03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs

A novel diagnostic protocol to identify patients suitable for discharge after a single high-sensitivity troponin

Objective To establish whether a novel accelerated diagnostic protocol (ADP) for suspected acute coronary syndrome (ACS) could successfully identify low-risk patients suitable for discharge after a single high-sensitivity troponin T (hs-cTnT) taken at presentation to the emergency department. We also compared the diagnostic accuracy of this ADP with strategies using initial undetectable hs-cTnT. Methods This prospective observational study evaluated the ability of the Triage Rule-out Using high-Sensitivity Troponin (TRUST) ADP to identify low-risk patients with suspected ACS. The ADP incorporated a single presentation hs-cTnT of <14 ng/L, a non-ischaemic ECG and a modified Goldman risk score. Diagnostic performance of the ADP was compared with the detection limit cut-offs of hs-cTnT (<5 ng/L and <3 ng/L). The primary end point was fatal/non-fatal acute myocardial infarction (AMI) within 30 days. Results 960 participants were recruited, mean age 58.0 years, 80 (8.3%) had an AMI. The TRUST ADP classified 382 (39.8%) as low-risk with a sensitivity for identifying AMI of 98.8% (95% CI 92.5% to 99.9%). hs-cTnT detection limits (<5 ng/L and <3 ng/L) had a sensitivity of 100% (94.3 to 100) and 100% (94.4 to 100), respectively. The TRUST ADP identified more patients suitable for early discharge at 39.8% vs 29.3% (<5 ng/L) and 7.9% (<3 ng/L) (p<0.001) with a lower false-positive rate for AMI detection; specificity 43.3% (95% CI 42.7% to 43.4%) vs 32.0% (95% CI 31.5% to 32.0%) and 8.6% (95% CI 8.1% to 8.6%), respectively. Conclusions The TRUST ADP, which incorporates structured risk-assessment and a single presentation hs-cTnT blood draw, has potential to allow early discharge in 40% of patients with suspected ACS and has greater clinical utility than undetectable hs-cTnT strategies

Baseline high sensitivity cardiac troponin I level below limit of quantitation rules out acute myocardial infarction in the emergency department

The objective of our study was to determine the utility of a baseline high sensitivity cardiac troponin (hs-cTnI) value below the limit of quantitation to rule out acute myocardial infarction (AMI) in patients presenting to the emergency department with any suspicious symptoms of a cardiac etiology. We enrolled subjects presenting to the Emergency Department with symptoms suspicious for AMI. Blood specimens were collected within one hour after a triage electrocardiogram. Cardiac troponin I was measured using the Beckman Coulter Access hs-cTnI assay. The diagnosis of AMI was adjudicated by two cardiologists using the Third Universal Definition of AMI and Roche Diagnostics Troponin T Generation 5 assay with all available clinical data at 30 days after presentation. A total of 567 subjects had all data required for data analyses. AMI was diagnosed in 46 (8.1%) patients. 232 (40.9%) individuals had presentation hs-cTnI results \u3c 4.0 ng/L. None of the patients with baseline hs-cTnI \u3c 4.0 ng/L had an AMI, yielding a negative predictive value of 100.0% and a sensitivity of 100%, and a good prognosis (no AMIs or cardiac-related deaths at 30 days). In this single center emergency department study, a baseline presenting novel hs-cTnI value of \u3c 4.0 ng/L effectively ruled out AMI in 40.9% of all patients presenting to the emergency department and having any symptoms suspicious for AMI. Importantly all patients, not only those with chest pain, and those having symptoms for any duration or those with end-stage renal disease requiring dialysis were included

Feasibility of the Manchester Acute Coronary Syndromes (MACS) decision rule to safely reduce unnecessary hospital admissions: a pilot randomised controlled trial

Background Observational studies suggest that the Manchester Acute Coronary Syndromes (MACS) decision rule can effectively rule out' and rule in' acute coronary syndromes (ACS) following a single blood test. In a pilot randomised controlled trial, we aimed to determine whether a large trial is feasible. Methods Patients presenting to two EDs with suspected cardiac chest pain were randomised to receive care guided by the MACS decision rule (intervention group) or standard care (controls). The primary efficacy outcome was a successful discharge from the ED, defined as a decision to discharge within 4 hours of arrival providing that the patient did not have a missed acute myocardial infarction (AMI) or develop a major adverse cardiac event (MACE: death, AMI or coronary revascularisation) within 30 days. Feasibility outcomes included recruitment and attrition rates. Results In total, 138 patients were included between October 2013 and October 2014, of whom 131 (95%) were randomised (66 to intervention and 65 controls). Nine (7%) patients had prevalent AMI and six (5%) had incident MACE within 30 days. All 131 patients completed 30-day follow-up and were included in the final analysis with no missing data for the primary analyses. Compared with standard care, a significantly greater proportion of patients whose care was guided by the MACS rule were successfully discharged within 4 hours (26% vs 8%, adjusted OR 5.45, 95% CI 1.73 to 17.11, p=0.004). No patients in either group who were discharged within 4 hours had a diagnosis of AMI or incident MACE within 30 days (0.0%, 95% CI 0% to 20.0% in the intervention group). Conclusions In this pilot trial, use of the MACS rule led to a significant increase in safe discharges from the ED but a larger, fully powered trial remains necessary. Our findings seem to support the feasibility of that trial. Trial registration number ISRCTN 86818215. Research Ethics Committee reference 13/NW/0081. UKCRN registration ID 14334

Factors affecting airport route development activity and performance

Airports have become increasingly active in route development as a means of attracting, growing and retaining air services. However, little is known about the different levels of route development activity at airports, or the extent to which route development activity affects performance. Based on the findings of a survey of 124 airports worldwide, this study finds that larger airports are significantly more active than smaller airports. It also finds that private airports are more active than public airports, and that airports in Europe are more active than airports in other world regions, although differences according to ownership and location are not significant. Route development activity has a significant positive effect on performance. Factors associated with the airport business environment (market turbulence, competitive intensity, market growth and airport constraints) were not found to have a significant moderating effect on the relationship between route development activity and performance. However, two factors were found to have a significant direct effect on performance; market growth has a significant positive effect while airport constraints have a significant negative effect

Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid: single biomarker re-derivation and external validation in three cohorts.

BACKGROUND: The original Manchester Acute Coronary Syndromes model (MACS) 'rules in' and 'rules out' acute coronary syndromes (ACS) using high sensitivity cardiac troponin T (hs-cTnT) and heart-type fatty acid binding protein (H-FABP) measured at admission. The latter is not always available. We aimed to refine and validate MACS as Troponin-only Manchester Acute Coronary Syndromes (T-MACS), cutting down the biomarkers to just hs-cTnT. METHODS: We present secondary analyses from four prospective diagnostic cohort studies including patients presenting to the ED with suspected ACS. Data were collected and hs-cTnT measured on arrival. The primary outcome was ACS, defined as prevalent acute myocardial infarction (AMI) or incident death, AMI or coronary revascularisation within 30 days. T-MACS was built in one cohort (derivation set) and validated in three external cohorts (validation set). RESULTS: At the 'rule out' threshold, in the derivation set (n=703), T-MACS had 99.3% (95% CI 97.3% to 99.9%) negative predictive value (NPV) and 98.7% (95.3%-99.8%) sensitivity for ACS, 'ruling out' 37.7% patients (specificity 47.6%, positive predictive value (PPV) 34.0%). In the validation set (n=1459), T-MACS had 99.3% (98.3%-99.8%) NPV and 98.1% (95.2%-99.5%) sensitivity, 'ruling out' 40.4% (n=590) patients (specificity 47.0%, PPV 23.9%). T-MACS would 'rule in' 10.1% and 4.7% patients in the respective sets, of which 100.0% and 91.3% had ACS. C-statistics for the original and refined rules were similar (T-MACS 0.91 vs MACS 0.90 on validation). CONCLUSIONS: T-MACS could 'rule out' ACS in 40% of patients, while 'ruling in' 5% at highest risk using a single hs-cTnT measurement on arrival. As a clinical decision aid, T-MACS could therefore help to conserve healthcare resources