Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial- The ABC-Sepsis Trial.

OBJECTIVES: International guidelines recommend IV crystalloid as the primary fluid for sepsis resuscitation, with 5% human albumin solution (HAS) as the second line. However, it is unclear which fluid has superior clinical effectiveness. We conducted a trial to assess the feasibility of delivering a randomized controlled trial comparing balanced crystalloid against 5% HAS as sole early resuscitation fluid in patients with sepsis presenting to hospital. DESIGN: Multicenter, open, parallel-group randomized feasibility trial. SETTING: Emergency departments (EDs) in 15 U.K. National Health Service (NHS) hospitals. PATIENTS: Adult patients with sepsis and a National Early Warning Score 2 greater than or equal to five requiring IV fluids withing one hour of randomization. INTERVENTIONS: IV fluid resuscitation with balanced crystalloid or 5% HAS for the first 6 hours following randomization. MEASUREMENTS AND MAIN RESULTS: Primary feasibility outcomes were recruitment rate and 30-day mortality. We successfully recruited 301 participants over 12 months. Mean ( sd ) age was 69 years (± 16 yr), and 151 (50%) were male. From 1303 participants screened; 502 participants were potentially eligible and 300 randomized to receive trial intervention with greater than 95% of participants receiving the intervention. The median number of participants per site was 19 (range, 1-63). Thirty-day mortality was 17.9% ( n = 53). Thirty-one participants died (21.1%) within 30 days in the 5% HAS arm, compared with 22 participants (14.8%) in the crystalloid arm (adjusted odds ratio, 1.50; 95% CIs, 0.84-2.83). CONCLUSIONS: Our results suggest it is feasible to recruit critically ill patients to a fluid resuscitation trial in U.K. EDs using 5% HAS as a primary resuscitation fluid. There was lower mortality in the balanced crystalloid arm. Given these findings, a definitive trial is likely to be deliverable, but the point estimates suggest such a trial would be unlikely to demonstrate a significant benefit from using 5% HAS as a primary resuscitation fluid in sepsis.

Clinical decision aids and computed tomography coronary angiography in patients with suspected acute coronary syndrome.

BACKGROUND: The HEART score, the T-MACS model and the GRACE score support early decision-making for acute chest pain, which could be complemented by CT coronary angiography (CTCA). However, their performance has not been directly compared. METHODS: In this secondary analysis of a multicentre randomised controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, C-statistics and performance metrics (using the predefined cut-offs) of clinical decision aids and CTCA, alone and then in combination, for the index hospital diagnosis of acute coronary syndrome and for 30-day coronary revascularisation were assessed in those who underwent CTCA and had complete data. RESULTS: Among 699 patients, 358 (51%) had an index hospital diagnosis of acute coronary syndrome, for which the C-statistic was higher for CTCA (0.80), followed by the T-MACS model (0.78), the HEART score (0.74) and the GRACE score (0.60). The negative predictive value was higher for the absence of coronary artery disease on CTCA (0.90) or a T-MACS estimate of <0.05 (0.83) than a HEART score of <4 (0.81) and a GRACE score of <109 (0.55). For 30-day coronary revascularisation, CTCA had the greatest C-statistic (0.80) with a negative predictive value of 0.96 and 0.92 in the absence of coronary artery disease and obstructive coronary artery disease, respectively. The combination of the T-MACS estimates and the CTCA findings was most discriminative for the index hospital diagnosis of acute coronary syndrome (C-statistic, 0.88) and predictive of 30-day coronary revascularisation (C-statistic, 0.85). No patients with a T-MACS estimate of <0.05 and normal coronary arteries had acute coronary syndrome during index hospitalisation or underwent coronary revascularisation within 30 days. CONCLUSIONS: In intermediate-risk patients with suspected acute coronary syndrome, the T-MACS model combined with CTCA improved discrimination of the index hospital diagnosis of acute coronary syndrome and prediction of 30-day coronary revascularisation. TRIAL REGISTRATION NUMBER: NCT02284191.

Cessation of Smoking Trial in the Emergency Department (COSTED): a multicentre randomised controlled trial.

BACKGROUND: Supporting people to quit smoking is one of the most powerful interventions to improve health. The Emergency Department (ED) represents a potentially valuable opportunity to deliver a smoking cessation intervention if it is sufficiently resourced. The objective of this trial was to determine whether an opportunistic ED-based smoking cessation intervention can help people to quit smoking. METHODS: In this multicentre, parallel-group, randomised controlled superiority trial conducted between January and August 2022, adults who smoked daily and attended one of six UK EDs were randomised to intervention (brief advice, e-cigarette starter kit and referral to stop smoking services) or control (written information on stop smoking services). The primary outcome was biochemically validated abstinence at 6 months. RESULTS: An intention-to-treat analysis included 972 of 1443 people screened for inclusion (484 in the intervention group, 488 in the control group). Of 975 participants randomised, 3 were subsequently excluded, 17 withdrew and 287 were lost to follow-up. The 6-month biochemically-verified abstinence rate was 7.2% in the intervention group and 4.1% in the control group (relative risk 1.76; 95% CI 1.03 to 3.01; p=0.038). Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (relative risk 1.80; 95% CI 1.36 to 2.38; p<0.001). No serious adverse events related to taking part in the trial were reported. CONCLUSIONS: An opportunistic smoking cessation intervention comprising brief advice, an e-cigarette starter kit and referral to stop smoking services is effective for sustained smoking abstinence with few reported adverse events. TRIAL REGISTRATION NUMBER: NCT04854616.

Early computed tomography coronary angiography and preventative treatment in patients with suspected acute coronary syndrome: A secondary analysis of the RAPID-CTCA trial.

BACKGROUND: Computed tomography coronary angiography (CTCA) offers detailed assessment of the presence of coronary atherosclerosis and helps guide patient management. We investigated influences of early CTCA on the subsequent use of preventative treatment in patients with suspected acute coronary syndrome. METHODS: In this secondary analysis of a multicenter randomized controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, prescription of aspirin, P2Y12 receptor antagonist, statin, renin-angiotensin system blocker, and beta-blocker therapies from randomization to discharge were compared within then between those randomized to early CTCA or to standard of care only. Effects of CTCA findings on adjustment of these therapies were further examined. RESULTS: In 1,743 patients (874 randomized to early CTCA and 869 to standard of care only), prescription of P2Y12 receptor antagonist, dual antiplatelet, and statin therapies increased more in the early CTCA group (between-group difference: 4.6% [95% confidence interval, 0.3-8.9], 4.5% [95% confidence interval, 0.2-8.7], and 4.3% [95% confidence interval, 0.2-8.5], respectively), whereas prescription of other preventative therapies increased by similar extent in both study groups. Among patients randomized to early CTCA, there were additional increments of preventative treatment in those with obstructive coronary artery disease and higher rates of reductions in antiplatelet and beta-blocker therapies in those with normal coronary arteries. CONCLUSIONS: Prescription patterns of preventative treatment varied during index hospitalization in patients with suspected acute coronary syndrome. Early CTCA facilitated targeted individualization of these therapies based on the extent of coronary artery disease.

The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY.

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, www.guidetopharmacology.org) and its precursor IUPHAR-DB, have captured expert-curated interactions between targets and ligands from selected papers in pharmacology and drug discovery since 2003. This resource continues to be developed in conjunction with the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS). As previously described, our unique model of content selection and quality control is based on 96 target-class subcommittees comprising 512 scientists collaborating with in-house curators. This update describes content expansion, new features and interoperability improvements introduced in the 10 releases since August 2015. Our relationship matrix now describes ∼9000 ligands, ∼15 000 binding constants, ∼6000 papers and ∼1700 human proteins. As an important addition, we also introduce our newly funded project for the Guide to IMMUNOPHARMACOLOGY (GtoImmuPdb, www.guidetoimmunopharmacology.org). This has been 'forked' from the well-established GtoPdb data model and expanded into new types of data related to the immune system and inflammatory processes. This includes new ligands, targets, pathways, cell types and diseases for which we are recruiting new IUPHAR expert committees. Designed as an immunopharmacological gateway, it also has an emphasis on potential therapeutic interventions.

Diagnostic yield of an ambulatory patch monitor in patients with unexplained syncope after initial evaluation in the emergency department: the PATCH-ED study.

OBJECTIVES: Diagnosing underlying arrhythmia in ED syncope patients remains problematic. This study investigates diagnostic yield, event prevalence, patient satisfaction and compliance, and influence on resource utilisation of an ambulatory patch monitor in unexplained ED syncope patients. METHODS: Prospective pilot study conducted in a single tertiary ED in Scotland between 17 November 2015 and 16 June 2017 with a historical unmatched comparator group. Patients 16 years or over presenting within 6 hours of unexplained syncope were fitted in the ED with an ambulatory patch ECG recorder (Zio XT monitor), which continuously records a single-lead ECG for up to 14 days. Patients with an obvious underlying cause were excluded. An unmatched historical group of 603 syncope patients with no obvious diagnosis in ED, recruited to a prior cohort study (2007-2008), were used as a comparator. Primary endpoint was symptomatic significant arrhythmia at 90-day follow-up. RESULTS: During the prospective study period, 86 patients were recruited. 90-day diagnostic yield for symptomatic significant arrhythmia was 10.5% (95% CI 4.0 to 16.9; 9 of 86) versus 2.0% (95% CI 0.9 to 3.1; 12 of 603) in the comparator group. 24 patients (27.9%) had a significant arrhythmia (five serious); 26 patients (30.2%) had serious outcomes (major adverse cardiac event and/or death). Blinded patch report review suggested the patch would significantly reduce requirement for standard outpatient ambulatory ECG monitoring. 56 of 76 returned patches had a diagnostic finding within±45 s of a triggered/diary event (73.7% diagnostic utility; 95% CI 63.7 to 83.6); 34 of 56 (61%) for sinus rhythm or ectopic beats only. CONCLUSIONS: Routine, early ambulatory ECG monitoring in ED patients with unexplained syncope is probably warranted. A large-scale trial comparing this approach to standard care with cost-effectiveness and safety analysis is now required. TRIAL REGISTRATION: NCT02683174.

High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study.

BACKGROUND: Suspected acute coronary syndrome is the commonest reason for emergency admission to hospital and is a large burden on health-care resources. Strategies to identify low-risk patients suitable for immediate discharge would have major benefits. METHODS: We did a prospective cohort study of 6304 consecutively enrolled patients with suspected acute coronary syndrome presenting to four secondary and tertiary care hospitals in Scotland. We measured plasma troponin concentrations at presentation using a high-sensitivity cardiac troponin I assay. In derivation and validation cohorts, we evaluated the negative predictive value of a range of troponin concentrations for the primary outcome of index myocardial infarction, or subsequent myocardial infarction or cardiac death at 30 days. This trial is registered with ClinicalTrials.gov (number NCT01852123). FINDINGS: 782 (16%) of 4870 patients in the derivation cohort had index myocardial infarction, with a further 32 (1%) re-presenting with myocardial infarction and 75 (2%) cardiac deaths at 30 days. In patients without myocardial infarction at presentation, troponin concentrations were less than 5 ng/L in 2311 (61%) of 3799 patients, with a negative predictive value of 99·6% (95% CI 99·3-99·8) for the primary outcome. The negative predictive value was consistent across groups stratified by age, sex, risk factors, and previous cardiovascular disease. In two independent validation cohorts, troponin concentrations were less than 5 ng/L in 594 (56%) of 1061 patients, with an overall negative predictive value of 99·4% (98·8-99·9). At 1 year, these patients had a lower risk of myocardial infarction and cardiac death than did those with a troponin concentration of 5 ng/L or more (0·6% vs 3·3%; adjusted hazard ratio 0·41, 95% CI 0·21-0·80; p<0·0001). INTERPRETATION: Low plasma troponin concentrations identify two-thirds of patients at very low risk of cardiac events who could be discharged from hospital. Implementation of this approach could substantially reduce hospital admissions and have major benefits for both patients and health-care providers. FUNDING: British Heart Foundation and Chief Scientist Office (Scotland).

Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital.

UNLABELLED: Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in the Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated the potential of a panel of novel biomarkers (with enhanced liver expression or linked to the mechanisms of toxicity) to identify patients with acetaminophen-induced acute liver injury (ALI) at first presentation to the hospital when currently used markers are within the normal range. In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction). Receiver operator characteristic curve analysis and positive/negative predictive values were used to compare sensitivity to report liver injury versus alanine transaminase (ALT) and International Normalized Ratio (INR). In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR. In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose. CONCLUSION: Elevations in plasma miR-122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range. The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies.

Risk scores and coronary artery disease in patients with suspected acute coronary syndrome and intermediate cardiac troponin concentrations.

BACKGROUND: Guidelines recommend the use of risk scores to select patients for further investigation after myocardial infarction has been ruled out but their utility to identify those with coronary artery disease is uncertain. METHODS: In a prospective cohort study, patients with intermediate high-sensitivity cardiac troponin I concentrations (5 ng/L to sex-specific 99th percentile) in whom myocardial infarction was ruled out were enrolled and underwent coronary CT angiography (CCTA) after hospital discharge. History, ECG, Age, Risk factors, Troponin (HEART), Emergency Department Assessment of Chest Pain Score (EDACS), Global Registry of Acute Coronary Event (GRACE), Thrombolysis In Myocardial Infarction (TIMI), Systematic COronary Risk Evaluation 2 and Pooled Cohort Equation risk scores were calculated and the odds ratio (OR) and diagnostic performance for obstructive coronary artery disease were determined using established thresholds. RESULTS: Of 167 patients enrolled (64±12 years, 28% female), 29.9% (50/167) had obstructive coronary artery disease. The odds of having obstructive disease were increased for all scores with the lowest and highest increase observed for an EDACS score ≥16 (OR 2.2 (1.1-4.6)) and a TIMI risk score ≥1 (OR 12.9 (3.0-56.0)), respectively. The positive predictive value (PPV) was low for all scores but was highest for a GRACE score >88 identifying 39% as high risk with a PPV of 41.9% (30.4-54.2%). The negative predictive value (NPV) varied from 77.3% to 95.2% but was highest for a TIMI score of 0 identifying 26% as low risk with an NPV of 95.2% (87.2-100%). CONCLUSIONS: In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been excluded, clinical risk scores can help identify patients with and without coronary artery disease, although the performance of established risk thresholds is suboptimal for utilisation in clinical practice. TRIAL REGISTRATION NUMBER: NCT04549805.

Troponin in acute chest pain to risk stratify and guide effective use of computed tomography coronary angiography (TARGET-CTCA): a randomised controlled trial.

BACKGROUND: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. METHODS: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. DISCUSSION: This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03952351. Registered on May 16, 2019.

FAIR in action - a flexible framework to guide FAIRification.

The COVID-19 pandemic has highlighted the need for FAIR (Findable, Accessible, Interoperable, and Reusable) data more than any other scientific challenge to date. We developed a flexible, multi-level, domain-agnostic FAIRification framework, providing practical guidance to improve the FAIRness for both existing and future clinical and molecular datasets. We validated the framework in collaboration with several major public-private partnership projects, demonstrating and delivering improvements across all aspects of FAIR and across a variety of datasets and their contexts. We therefore managed to establish the reproducibility and far-reaching applicability of our approach to FAIRification tasks.

The FAIR Cookbook - the essential resource for and by FAIR doers.

The notion that data should be Findable, Accessible, Interoperable and Reusable, according to the FAIR Principles, has become a global norm for good data stewardship and a prerequisite for reproducibility. Nowadays, FAIR guides data policy actions and professional practices in the public and private sectors. Despite such global endorsements, however, the FAIR Principles are aspirational, remaining elusive at best, and intimidating at worst. To address the lack of practical guidance, and help with capability gaps, we developed the FAIR Cookbook, an open, online resource of hands-on recipes for "FAIR doers" in the Life Sciences. Created by researchers and data managers professionals in academia, (bio)pharmaceutical companies and information service industries, the FAIR Cookbook covers the key steps in a FAIRification journey, the levels and indicators of FAIRness, the maturity model, the technologies, the tools and the standards available, as well as the skills required, and the challenges to achieve and improve data FAIRness. Part of the ELIXIR ecosystem, and recommended by funders, the FAIR Cookbook is open to contributions of new recipes.

Early computed tomography coronary angiography in adults presenting with suspected acute coronary syndrome: the RAPID-CTCA RCT.

BACKGROUND: Acute coronary syndrome is a common medical emergency. The optimal strategy to investigate patients who are at intermediate risk of acute coronary syndrome has not been fully determined. OBJECTIVE: To investigate the role of early computed tomography coronary angiography in the investigation and treatment of adults presenting with suspected acute coronary syndrome. DESIGN: A prospective, multicentre, open, parallel-group randomised controlled trial with blinded end-point adjudication. SETTING: Thirty-seven hospitals in the UK. PARTICIPANTS: Adults (aged ≥ 18 years) presenting to the emergency department, acute medicine services or cardiology department with suspected or provisionally diagnosed acute coronary syndrome and at least one of the following: (1) a prior history of coronary artery disease, (2) a cardiac troponin level > 99th centile and (3) an abnormal 12-lead electrocardiogram. INTERVENTIONS: Early computed tomography coronary angiography in addition to standard care was compared with standard care alone. Participants were followed up for 1 year. MAIN OUTCOME MEASURE: One-year all-cause death or subsequent type 1 (spontaneous) or type 4b (stent thrombosis) myocardial infarction, measured as the time to such event adjudicated by two cardiologists blinded to the computerised tomography coronary angiography ( CTCA ) arm. Cost-effectiveness was estimated as the lifetime incremental cost per quality-adjusted life-year gained. RESULTS: Between 23 March 2015 and 27 June 2019, 1748 participants [mean age 62 years (standard deviation 13 years), 64% male, mean Global Registry Of Acute Coronary Events score 115 (standard deviation 35)] were randomised to receive early computed tomography coronary angiography (n = 877) or standard care alone (n = 871). The primary end point occurred in 51 (5.8%) participants randomised to receive computed tomography coronary angiography and 53 (6.1%) participants randomised to receive standard care (adjusted hazard ratio 0.91, 95% confidence interval 0.62 to 1.35; p = 0.65). Computed tomography coronary angiography was associated with a reduced use of invasive coronary angiography (adjusted hazard ratio 0.81, 95% confidence interval 0.72 to 0.92; p = 0.001) but no change in coronary revascularisation (adjusted hazard ratio 1.03, 95% confidence interval 0.87 to 1.21; p = 0.76), acute coronary syndrome therapies (adjusted odds ratio 1.06, 95% confidence interval 0.85 to 1.32; p = 0.63) or preventative therapies on discharge (adjusted odds ratio 1.07, 95% confidence interval 0.87 to 1.32; p = 0.52). Early computed tomography coronary angiography was associated with longer hospitalisations (median increase 0.21 days, 95% confidence interval 0.05 to 0.40 days) and higher mean total health-care costs over 1 year (£561 more per patient) than standard care. LIMITATIONS: The principal limitation of the trial was the slower than anticipated recruitment, leading to a revised sample size, and the requirement to compromise and accept a larger relative effect size estimate for the trial intervention. FUTURE WORK: The potential role of computed tomography coronary angiography in selected patients with a low probability of obstructive coronary artery disease (intermediate or mildly elevated level of troponin) or who have limited access to invasive cardiac catheterisation facilities needs further prospective evaluation. CONCLUSIONS: In patients with suspected or provisionally diagnosed acute coronary syndrome, computed tomography coronary angiography did not alter overall coronary therapeutic interventions or 1-year clinical outcomes, but it did increase the length of hospital stay and health-care costs. These findings do not support the routine use of early computed tomography coronary angiography in intermediate-risk patients with acute chest pain. TRIAL REGISTRATION: This trial is registered as ISRCTN19102565 and Clinical Trials NCT02284191. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 37. See the NIHR Journals Library website for further project information.

WHY DID WE DO THE RESEARCH?: Chest pain is a common medical emergency. It is important to decide if the cause is a heart attack. The two tests that are often used are a heart recording (electrocardiogram) and a blood test (troponin levels). If both are normal, the cause of chest pain is unlikely to be a heart attack and the patient is often discharged home. If either test is positive or if the patient has had previous heart problems, then the patient may require further investigation. We wanted to test whether or not adding a heart scan called a computerised tomography coronary angiogram improved patients' care. HOW DID WE DO THE RESEARCH?: We carried out a randomised trial in which half of the patients attending hospital with chest pain had a computerised tomography coronary angiography scan as part of their assessment and half of the patients did not. In total, 1749 patients were recruited and followed up for 1 year. BRINGING IT ALL TOGETHER: The use of an additional early computerised tomography coronary angiography scan for chest pain patients of medium risk produced only small improvements in patient care.

Presentation cardiac troponin and early computed tomography coronary angiography in patients with suspected acute coronary syndrome: a pre-specified secondary analysis of the RAPID-CTCA trial.

AIMS: To evaluate the potential associations between presentation cardiac troponin and the clinical impact of early computed tomography coronary angiography (CTCA) in intermediate-risk patients with suspected acute coronary syndrome. METHODS AND RESULTS: In a large multicentre randomized controlled trial of patients with intermediate-risk chest pain due to suspected acute coronary syndrome, early CTCA had no effect on the primary outcome-death or subsequent Type 1 or 4b myocardial infarction-but reduced the rate of invasive coronary angiography. In this pre-specified secondary analysis, cardiovascular testing and clinical outcomes were compared between those with or without cardiac troponin elevation at presentation. Of 1748 patients, 1004 (57%) had an elevated cardiac troponin concentration and 744 (43%) had a normal concentration. Patients with cardiac troponin elevation had a higher Global Registry of Acute Coronary Events score (132 vs. 91; P < 0.001) and were more likely to have obstructive coronary artery disease (59 vs. 33%; P < 0.001), non-invasive (72 vs. 52%; P < 0.001) and invasive (72 vs. 38%; P < 0.001) testing, coronary revascularization (47 vs. 15%; P < 0.001), and the primary outcome (8 vs. 3%; P = 0.007) at 1 year. However, there was no evidence that presentation cardiac troponin was associated with the relative effects of early CTCA on rates of non-invasive (Pinteraction = 0.33) and invasive (Pinteraction = 0.99) testing, coronary revascularization (Pinteraction = 0.57), or the primary outcome (Pinteraction = 0.41). CONCLUSION: Presentation cardiac troponin had no demonstrable associations between the effects of early CTCA on reductions in non-invasive and invasive testing, or the lack of effect on coronary revascularization or the primary outcome in intermediate-risk patients with suspected acute coronary syndrome.

One-year prognosis after syncope and the failure of the ROSE decision instrument to predict one-year adverse events.

STUDY OBJECTIVE: We investigate the incidence of adverse events at 1 year in the cohort of emergency department (ED) syncope patients enrolled in the original Risk Stratification of Syncope in the Emergency Department (ROSE) study, the time to adverse event, and the test performance of the ROSE decision instrument to detect events at 1 year. METHODS: This report details the 1-year follow-up of adult syncope patients presenting to the ED who were enrolled into the ROSE study, a single-center, prospective, observational cohort study. The primary endpoint was the combination of serious outcome and all-cause death at 1 year. Serious outcome encompassed acute myocardial infarction, life-threatening arrhythmia, need for pacemaker/implantable defibrillator, pulmonary embolus, cerebrovascular accident, intracranial or subarachnoid hemorrhage, and interventional procedure or hemorrhage requiring blood transfusion. Secondary endpoints were all-cause death and cardiovascular serious outcome at 1 year. RESULTS: One thousand forty-three patients were available for analysis; 162 patients (15.5%) had a primary outcome. Twenty-eight (17%) of these were within 24 hours, 56 (35%) were within 1 week, and 78 (48%) were within 1 month. The remaining 84 (52%) outcomes occurred between months 2 and 12. At 1 year, 71 (6.8%) patients had died and 76 (7.3%) had a cardiovascular serious outcome. The sensitivity and specificity of the ROSE decision instrument for 1-year serious outcome and all-cause death were, respectively, 71.6% (95% confidence interval [CI] 63.9% to 78.3%) and 71.1% (95% CI 67.9% to 74.0%); for 1-year all-cause death, 76.1% (95% CI 64.2% to 85.1%) and 67.4% (95% CI 64.3% to 70.3%); and for 1-year cardiovascular serious outcome, 75.0% (95% CI 63.5% to 83.9%) and 67.5% (95% CI 64.5% to 70.5%). CONCLUSION: The proportion of patients with serious outcome and all-cause death 1 year after syncope is similar to that reported in recent international syncope studies. We have defined the proportion of patients with cardiovascular serious outcome at 1 year and have shown that most events occurred in the first month, with decreased frequency of events observed after that time especially marked for cardiovascular serious outcome. More than 50% of the outcomes observed, however, occurred after the first month. The ROSE decision instrument does not perform well at predicting 1-year outcome of ED syncope patients.

Critical care in the emergency department: acute respiratory failure.

Acute respiratory failure (ARF) is a frequent emergency department (ED) presentation. The definition and common causes of ARF are discussed in this article and ED management of the condition is discussed, using an illustrative case report. The paper considers the role of B-type natriuretic peptide in diagnosis and non-invasive ventilation (NIV) in treatment. Intensive care unit admission denial is common in ARF, although the evidence base is lacking. Finally, the decision-making process is described when a patient with ARF fails to improve with NIV.

A semantic sensor web for environmental decision support applications.

Sensing devices are increasingly being deployed to monitor the physical world around us. One class of application for which sensor data is pertinent is environmental decision support systems, e.g., flood emergency response. For these applications, the sensor readings need to be put in context by integrating them with other sources of data about the surrounding environment. Traditional systems for predicting and detecting floods rely on methods that need significant human resources. In this paper we describe a semantic sensor web architecture for integrating multiple heterogeneous datasets, including live and historic sensor data, databases, and map layers. The architecture provides mechanisms for discovering datasets, defining integrated views over them, continuously receiving data in real-time, and visualising on screen and interacting with the data. Our approach makes extensive use of web service standards for querying and accessing data, and semantic technologies to discover and integrate datasets. We demonstrate the use of our semantic sensor web architecture in the context of a flood response planning web application that uses data from sensor networks monitoring the sea-state around the coast of England.

Early computed tomography coronary angiography in patients with suspected acute coronary syndrome: randomised controlled trial.

OBJECTIVES: To establish if the use of early computed tomography (CT) coronary angiography improves one year clinical outcomes in patients presenting to the emergency department with acute chest pain and at intermediate risk of acute coronary syndrome and subsequent clinical events. DESIGN: Randomised controlled trial. SETTING: 37 hospitals in the UK. PARTICIPANTS: Adults with suspected or a provisional diagnosis of acute coronary syndrome and one or more of previous coronary heart disease, raised levels of cardiac troponin, or abnormal electrocardiogram. INTERVENTIONS: Early CT coronary angiography and standard of care compared with standard of care only. MAIN OUTCOME MEASURES: Primary endpoint was all cause death or subsequent type 1 or 4b myocardial infarction at one year. RESULTS: Between 23 March 2015 and 27 June 2019, 1748 participants (mean age 62 years (standard deviation 13), 64% men, mean global registry of acute coronary events (GRACE) score 115 (standard deviation 35)) were randomised to receive early CT coronary angiography (n=877) or standard of care only (n=871). Median time from randomisation to CT coronary angiography was 4.2 (interquartile range 1.6-21.6) hours. The primary endpoint occurred in 51 (5.8%) participants randomised to CT coronary angiography and 53 (6.1%) participants who received standard of care only (adjusted hazard ratio 0.91 (95% confidence interval 0.62 to 1.35), P=0.65). Invasive coronary angiography was performed in 474 (54.0%) participants randomised to CT coronary angiography and 530 (60.8%) participants who received standard of care only (adjusted hazard ratio 0.81 (0.72 to 0.92), P=0.001). There were no overall differences in coronary revascularisation, use of drug treatment for acute coronary syndrome, or subsequent preventive treatments between the two groups. Early CT coronary angiography was associated with a slightly longer time in hospital (median increase 0.21 (95% confidence interval 0.05 to 0.40) days from a median hospital stay of 2.0 to 2.2 days). CONCLUSIONS: In intermediate risk patients with acute chest pain and suspected acute coronary syndrome, early CT coronary angiography did not alter overall coronary therapeutic interventions or one year clinical outcomes, but reduced rates of invasive angiography while modestly increasing length of hospital stay. These findings do not support the routine use of early CT coronary angiography in intermediate risk patients with acute chest pain and suspected acute coronary syndrome. TRIAL REGISTRATION: ISRCTN19102565, NCT02284191.

Troponin-Guided Coronary Computed Tomographic Angiography After Exclusion of Myocardial Infarction.

BACKGROUND: Patients with suspected acute coronary syndrome in whom myocardial infarction has been excluded are at risk of future adverse cardiac events. OBJECTIVES: This study evaluated the usefulness of high-sensitivity cardiac troponin I (hs-cTnI) to select patients for further investigation after myocardial infarction has been excluded. METHODS: This is a prospective cohort study of patients presenting to the emergency department with suspected acute coronary syndrome and hs-cTnI concentrations below the sex-specific 99th percentile. Patients were recruited in a 2:1 fashion, stratified by peak hs-cTnI concentration above and below the risk stratification threshold of 5 ng/L. All patients underwent coronary computed tomography angiography (CCTA) after hospital discharge. RESULTS: Overall, 250 patients were recruited (61.4 ± 12.2 years 31% women) in whom 62.4% (156 of 250 patients) had coronary artery disease (CAD). Patients with intermediate hs-cTnI concentrations (between 5 ng/L and the sex-specific 99th percentile) were more likely to have CAD than those with hs-cTnI concentrations <5 ng/L (71.9% [120 of 167 patients] vs 43.4% [36 of 83 patients]; odds ratio: 3.33; 95% CI: 1.92-5.78). Conversely, there was no association between anginal symptoms and CAD (63.2% [67 of 106 patients] vs 61.8% [89 of 144 patients]; odds ratio: 0.92; 95% CI: 0.48-1.76). Most patients with CAD did not have a previous diagnosis (53.2%; 83 of 156 patients) and were not on antiplatelet and statin therapies (63.5%; 99 of 156 patients) before they underwent CCTA. CONCLUSIONS: In patients who had myocardial infarction excluded, CAD was 3× more likely in those with intermediate hs-cTnI concentrations compared with low hs-cTnI concentrations. In such patients, CCTA could help to identify those with occult CAD and to target preventative treatments, thereby improving clinical outcomes.