Prognostic Utility of a Modified HEART Score When Different Troponin Cut-points Are Used

BACKGROUND: Although the recommended cut-point for cardiac troponin (cTn) is the 99th percentile, many institutions use cut-points that are multiples higher than the 99th percentile for diagnosing acute myocardial infarction (AMI). Prior studies have shown that patients with a HEART score (HS) ≤ 3 and normal serial cTn values (modified HS) are at low risk for adverse events. This study aimed to evaluate the prognostic utility of the HS when various cTn cut-points are used. METHODS: This was a sub-study of TRAPID-AMI, a multicenter, international trial evaluating a rapid rule-out AMI study using high sensitivity cTnT (hs-cTnT). 1,282 patients were evaluated for AMI from 12 centers in Europe, United States of America, and Australia from 2011-2013. Blood samples of hs-cTnT were collected at presentation and 2 hours, and each patient had a HS calculated. The US Food and Drug Administration approved 99th percentile for hs-cTnT (19 ng/L) was used. RESULTS: There were 213 (17%) AMIs. Within 30 days, there were an additional 2 AMIs and 8 deaths. The adverse event rates at 30 days (death/AMI) for a HS ≤ 3 and non-elevated hs-cTnT over 2 hours using increasing hs-cTnT cut-points ranged from 0.6% to 5.1%. CONCLUSIONS: Using the recommended 99th percentile cut-point for hs-cTnT, the combination of a HS ≤ 3 with non-elevated hs-cTnT values over 2 hours identifies a low-risk cohort who can be considered for discharge from the emergency department without further testing. The prognostic utility of this strategy is greatly lessened as higher hs-cTnT cut-points are used

Antibody-mediated interferences affecting cardiac troponin assays:recommendations from the IFCC Committee on Clinical Applications of Cardiac Biomarkers

The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results

Protocol for Improving Care by FAster risk-STratification through use of high sensitivity point-of-care troponin in patients presenting with possible acute coronary syndrome in the EmeRgency department (ICare-FASTER):a stepped-wedge cluster randomised quality improvement initiative

Introduction Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The turn-around time from blood draw to posting results in the clinical portal for central laboratory analysers is ~1–2 hours. New generation, high-sensitivity, point-of-care cardiac troponin I (POC-cTnI) assays use whole blood on a bedside (or near bedside) analyser that provides a rapid (8 min) result. This may expedite clinical decision-making and reduce length of stay. Our purpose is to determine if utilisation of a POC-cTnI testing reduces ED length of stay. We also aim to establish an optimised implementation process for the amended clinical pathway.Methods and analysis This quality improvement initiative has a pragmatic multihospital stepped-wedge cross-sectional cluster randomised design. Consecutive patients presenting to the ED with symptoms suggestive of possible AMI and having a cTn test will be included. Clusters (comprising one or two hospitals each) will change from their usual-care pathway to an amended pathway using POC-cTnI—the ‘intervention’. The dates of change will be randomised. Changes occur at 1 month intervals, with a minimum 2 month ‘run-in’ period. The intervention pathway will use a POC-cTnI measurement as an alternate to the laboratory-based cTn measurement. Clinical decision-making steps and logic will otherwise remain unchanged. The POC-cTnI is the Siemens (Erlangen Germany) Atellica VTLi high-sensitivity cTnI assay. The primary outcome is ED length of stay. The safety outcome is cardiac death or AMI within 30 days for patients discharged directly from the ED.Ethics and dissemination Ethics approval has been granted by the New Zealand Southern Health and Disability Ethics Committee, reference 21/STH/9. Results will be published in a peer-reviewed journal. Lay and academic presentations will be made. Māori-specific results will be disseminated to Māori stakeholders.Trial registration number ACTRN12619001189112

Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T

Study objectiveWe aim to prospectively validate the diagnostic accuracy of the recently developed 0-h/1-h algorithm, using high-sensitivity cardiac troponin T (hs-cTnT) for the early rule-out and rule-in of acute myocardial infarction.MethodsWe enrolled patients presenting with suspected acute myocardial infarction and recent (<6 hours) onset of symptoms to the emergency department in a global multicenter diagnostic study. Hs-cTnT (Roche Diagnostics) and sensitive cardiac troponin I (Siemens Healthcare) were measured at presentation and after 1 hour, 2 hours, and 4 to 14 hours in a central laboratory. Patient triage according to the predefined hs-cTnT 0-hour/1-hour algorithm (hs-cTnT below 12 ng/L and Δ1 hour below 3 ng/L to rule out; hs-cTnT at least 52 ng/L or Δ1 hour at least 5 ng/L to rule in; remaining patients to the “observational zone”) was compared against a centrally adjudicated final diagnosis by 2 independent cardiologists (reference standard). The final diagnosis was based on all available information, including coronary angiography and echocardiography results, follow-up data, and serial measurements of sensitive cardiac troponin I, whereas adjudicators remained blinded to hs-cTnT.ResultsAmong 1,282 patients enrolled, acute myocardial infarction was the final diagnosis for 213 (16.6%) patients. Applying the hs-cTnT 0-hour/1-hour algorithm, 813 (63.4%) patients were classified as rule out, 184 (14.4%) were classified as rule in, and 285 (22.2%) were triaged to the observational zone. This resulted in a negative predictive value and sensitivity for acute myocardial infarction of 99.1% (95% confidence interval [CI] 98.2% to 99.7%) and 96.7% (95% CI 93.4% to 98.7%) in the rule-out zone (7 patients with false-negative results), a positive predictive value and specificity for acute myocardial infarction of 77.2% (95% CI 70.4% to 83.0%) and 96.1% (95% CI 94.7% to 97.2%) in the rule-in zone, and a prevalence of acute myocardial infarction of 22.5% in the observational zone.ConclusionThe hs-cTnT 0-hour/1-hour algorithm performs well for early rule-out and rule-in of acute myocardial infarction

A modelling-chain linking climate science and decision-makers for future urban flood management in West Africa

Intensification of the hydrological cycle resulting from climate change in West Africa poses significant risks for the region’s rapidly urbanising cities, but limited research on flood risk has been undertaken at the urban domain scale. Furthermore, conventional climate models are unable to realistically represent the type of intense storms which dominate the West African monsoon. This paper presents a decision-first framing of climate research in co-production of a climate-hydrology-flooding modelling chain, linking scientists working on state-of-the-art regional climate science with decision-makers involved in city planning for future urban flood management in the city of Ouagadougou, Burkina Faso. The realistic convection-permitting model over Africa (CP4A) is applied at the urban scale for the first time and data suggest significant intensification of high-impact weather events and demonstrate the importance of considering the spatio-temporal scales in CP4A. Hydrological modelling and hydraulic modelling indicate increases in peak flows and flood extents in Ouagadougou in response to climate change which will be further exacerbated by future urbanisation. Advances in decision-makers’ capability for using climate information within Ouagadougou were observed, and key recommendations applicable to other regional urban areas are made. This study provides proof of concept that a decision-first modelling-chain provides a methodology for co-producing climate information that can, to some extent, bridge the usability gap between what scientists think is useful and what decision-makers need

Physiological models of body composition and human obesity

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The Anticoagulation of Calf Thrombosis (ACT) project: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Half of all lower limb deep vein thrombi (DVT) in symptomatic ambulatory patients are located in the distal (calf) veins. While proximal disease warrants therapeutic anticoagulation to reduce the associated risks, distal DVT often goes untreated. However, a proportion of untreated distal disease will undoubtedly propagate or embolize. Concern also exists that untreated disease could lead to long-term post thrombotic changes. Currently, it is not possible to predict which distal thrombi will develop such complications. Whether these potential risks outweigh those associated with unrestricted anticoagulation remains unclear. The Anticoagulation of Calf Thrombosis (ACT) trial aims to compare therapeutic anticoagulation against conservative management for patients with acute symptomatic distal deep vein thrombosis.</p> <p>Methods</p> <p>ACT is a pragmatic, open-label, randomized controlled trial. Adult patients diagnosed with acute distal DVT will be allocated to either therapeutic anticoagulation or conservative management. All patients will undergo 3 months of clinical and assessor blinded sonographic follow-up, followed by 2-year final review. The project will commence initially as an external pilot study, recruiting over a 16-month period at a single center to assess feasibility measures and clinical event rates. Primary outcome measures will assess feasibility endpoints. Secondary clinical outcomes will be collected to gather accurate data for the design of a definitive clinical trial and will include: (1) a composite endpoint combining thrombus propagation to the popliteal vein or above, development of symptomatic pulmonary embolism or sudden death attributable to venous thromboembolic disease; (2) the incidence of major and minor bleeding episodes; (3) the incidence of post-thrombotic leg syndrome at 2 years using a validated screening tool; and (4) the incidence of venous thromboembolism (VTE) recurrence at 2 years.</p> <p>Discussion</p> <p>The ACT trial will explore the feasibility of comparing therapeutic anticoagulation to conservative management in acute distal DVT, within a modern cohort. We also aim to provide contemporary data on clot propagation, bleeding rates and long-term outcomes within both groups. These results will inform the conduct of a definitive study if feasibility is established.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN75175695">ISRCTN75175695</a></p

FebriDx point-of-care test in patients with suspected COVID-19: a pooled diagnostic accuracy study

Background: Point-of-care (POC) tests for COVID-19 could relieve pressure on isolation resource, support infection prevention and control, and help commence more timely and appropriate treatment. We aimed to undertake a systematic review and pooled diagnostic test accuracy study of available individual patient data (IPD) to evaluate the diagnostic accuracy of a commercial POC test (FebriDx) in patients with suspected COVID-19.Methods: A literature search was performed on the 1st of October 2020 to identify studies reporting diagnostic accuracy statistics of the FebriDx POC test versus real time reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Studies were screened for risk of bias. IPD were sought from studies meeting the inclusion and exclusion criteria. Logistic regression was performed to investigate the study effect on the outcome of the RT-PCR test result in order to determine whether it was appropriate to pool results. Diagnostic accuracy statistics were calculated with 95% confidence intervals (CIs).Results: 15 studies were screened, and we included two published studies with 527 hospitalised patients. 523 patients had valid FebriDx results for Myxovirus resistance protein A (MxA), an antiviral host response protein. The FebriDx test produced a pooled sensitivity of 0.920 (95% CI: 0.875-0.950) and specificity of 0.862 (0.819-0.896) compared with RT-PCR, where there was an estimated true COVID-19 prevalence of 0.405 (0.364-0.448) and overall FebriDx test yield was 99.2%. Patients were tested at a median of 4 days [interquartile range: 2:9] after symptom onset. No differences were found in a sub-group analysis of time tested since the onset of symptoms.Conclusions: Based on a large sample of patients from two studies during the first wave of the SARS-CoV-2 pandemic, the FebriDx POC test had reasonable diagnostic accuracy in a hospital setting with high COVID-19 prevalence, out of influenza season. More research is required to determine how FebriDx would perform in other healthcare settings with higher or lower COVID-19 prevalence, different patient populations, or when other respiratory infections are in circulation

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Examining the signs and symptoms experienced by individuals with suspected acute coronary syndrome in the Asia-pacific region: A prospective observational study

Study objective: This study examines whether symptoms reported by patients presenting with possible acute coronary syndrome vary across different ethnic backgrounds. We also assess the predictive value of individual symptoms according to ethnic background. Methods: The study used prospectively collected data on adult patients presenting with suspected acute coronary syndrome to 12 emergency departments in the Asia-Pacific region. Trained research nurses collected data on ethnicity, type of pain, and associated symptoms, using a customized case report form. The primary endpoint was acute coronary syndrome within 30 days of presentation, as adjudicated by cardiologists using standardized guidelines. Logistic regression analyses assessed the relationship between ethnicity and symptom type and the predictive value of symptom type for acute coronary syndrome. Results: Acute coronary syndrome was diagnosed in 358 (19.2%) of the 1,868 patients recruited. In comparison with white patients, Chinese patients were less likely to report atypical pain (odds ratio [OR]=0.26; 95% confidence interval [CI] 0.2 to 0.34), exertional pain (OR=0.41; 95% CI 0.32 to 0.53), pleuritic pain (OR=0.26; 95% CI 0.19 to 0.35), pain on palpation (OR=0.31; 95% CI 0.2 to 0.49), nausea (OR=0.52; 95% CI 0.42 to 0.67), diaphoresis (OR=0.41; 95% CI 0.33 to 0.51), and shortness of breath (OR=0.59; 95% CI 0.48 to 0.73). The comparison of white with other ethnic groups yielded similar results. The predictive value of symptoms was similarly poor across different ethnic groups, with the notable exception of India, where typical pain was predictive of acute coronary syndrome (OR 8.82; 95% CI 2.19 to 35.48). Conclusion: There are cross-cultural differences in symptoms reported by patients with suspected acute coronary syndrome. Such differences are not likely to be clinically relevant because the majority of symptoms display limited diagnostic value for acute coronary syndrome. Copyrigh