Chest pain accounts for approximately 6% of Emergency Department (ED) attendances and is the most common reason for emergency hospital admission. For many years, our approach to diagnosis has ...required patients to stay in hospital for at least 6–12 h to undergo serial biomarker testing. As less than one fifth of the patients undergoing investigation actually has an acute coronary syndrome (ACS), there is tremendous potential to reduce unnecessary hospital admissions.
Recent advances in diagnostic technology have improved the efficiency of care pathways. Decision aids such as the Thrombolysis in Myocardial Infarction (TIMI) risk score and the History, Electrocardiogram, Age, Risk factors and Troponin (HEART) score enable rapid ‘rule out’ of ACS within hours of patients arriving in the ED. With high sensitivity cardiac troponin (hs-cTn) assays, approximately one third of patients can have ACS ‘ruled out’ with a single blood test, and up to two thirds could have an acute myocardial infarction ‘ruled out’ with a second sample taken after as little as 1 h.
Building on those recent advances, this paper presents an overview of the principles behind the development of the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid. This clinical prediction model could be used to ‘rule out’ and ‘rule in’ ACS following a single blood test and to calculate the probability of ACS for every patient. The future potential of this approach is then addressed, including practical applications of artificial intelligence, shared decision making, near-patient testing and personalized medicine.
Data from 15 international cohorts of patients with suspected acute MI were used to create and validate a risk-assessment tool integrating high-sensitivity troponin I or T at presentation, the change ...during serial sampling, and the time between samples to estimate the probability of MI on ED presentation and 30-day outcomes.
Study objective We 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. Methods We 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. Results Among 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. Conclusion The hs-cTnT 0-hour/1-hour algorithm performs well for early rule-out and rule-in of acute myocardial infarction.
Objectives This paper sought to evaluate whether high sensitivity troponin (hs-cTnT) can immediately exclude acute myocardial infarction (AMI) at a novel ‘rule out' cut-off. Background Subgroup ...analysis of recent evidence suggests that undetectable hs-cTnT may exclude AMI at presentation. Methods In a cohort study, we prospectively enrolled patients with chest pain, evaluating them with standard troponin T and testing for hs-cTnT (Roche Diagnostics, Basel, Switzerland) at presentation. The primary outcome was a diagnosis of AMI. We also followed up patients for adverse events within 6 months. After subsequent clinical implementation of hs-cTnT, we again evaluated whether initially undetectable hs-cTnT ruled out a subsequent rise. Results Of 703 patients in the cohort study, 130 (18.5%) had AMI, none of whom initially had undetectable hs-cTnT (sensitivity: 100.0%, 95% confidence interval CI: 95.1% to 100.0%, negative predictive value: 100.0%, 95% CI: 98.1% to 100.0%). This strategy would rule out AMI in 27.7% of patients, 2 (1.0%) of whom died or had AMI within 6 months (1 periprocedural AMI, 1 noncardiac death). We evaluated this approach in an additional 915 patients in clinical practice. Only 1 patient (0.6%) with initially undetectable hs-cTnT had subsequent elevation (to 17 ng/l), giving a sensitivity of 99.8% (95% CI: 99.1% to 100.0%) and a negative predictive value of 99.4% (95% CI: 96.6% to 100.0%). Conclusions Undetectable hs-cTnT at presentation has very high negative predictive value, which may be considered to rule out AMI, identifying patients at low risk of adverse events. Pending further validation, this strategy may reduce the need for serial testing and empirical treatment, enabling earlier reassurance for patients and fewer unnecessary evaluations and hospital admissions.
Upper airway angioedema is a rare, unpredictable, and at times life-threatening adverse effect of angiotensin-converting enzyme inhibitors (ACE-Is) with no existing effective pharmacologic treatment. ...Icatibant is a bradykinin B2 receptor antagonist that may be beneficial in patients with ACE-I–induced angioedema.
We aimed to evaluate the efficacy of icatibant in subjects with ACE-I–induced angioedema.
At 31 centers in 4 countries, adults on ACE-Is who presented within 12 hours of the onset of at least moderately severe angioedema were randomized 1:1 to icatibant 30 mg or placebo administered subcutaneously. The primary efficacy end point was time to meeting discharge criteria after study drug administration, based on the severity of airway symptoms assessed hourly by a blinded physician using clinical ratings across 4 domains.
A total of 121 subjects were randomized (icatibant, n = 61; placebo, n = 60); 118 received treatment a median of 7.8 hours from symptom onset. We observed no difference in time to meeting discharge criteria between groups (median, 4.0 hours in each group; P = .63). There also was no difference in time to onset of symptom relief (median, icatibant, 2.0 hours; placebo, 1.6 hours; P = .57) or any other secondary end point. Similar findings were noted in prespecified and post hoc subgroup analyses stratified by symptom severity, time interval to treatment, age, and other clinical covariates. No new safety signals were detected.
Icatibant was no more efficacious than placebo in at least moderately severe ACE-I–induced angioedema of the upper airway.
In order to generate independent performance data regarding accuracy of COVID-19 antigen-based rapid diagnostic tests (Ag-RDTs), prospective diagnostic evaluation studies across multiple sites are ...required to evaluate their performance in different clinical settings. This report describes the clinical evaluation the GENEDIA W COVID-19 Ag Device (Green Cross Medical Science Corp., Chungbuk, Korea) and the ActiveXpress+ COVID-19 Complete Testing Kit (Edinburgh Genetics Ltd, UK), in two testing sites Peru and the United Kingdom.
Nasopharyngeal swabs collected from 456 symptomatic patients at primary points of care in Lima, Peru and 610 symptomatic participants at a COVID-19 Drive-Through testing site in Liverpool, England were analyzed by Ag-RDT and compared to RT-PCR. Analytical evaluation of both Ag-RDTs was assessed using serial dilutions of direct culture supernatant of a clinical SARS-CoV-2 isolate from the B.1.1.7 lineage.
For GENEDIA brand, the values of overall sensitivity and specificity were 60.4% 95% CI 52.4-67.9%, and 99.2% 95% CI 97.6-99.7% respectively; and for Active Xpress+ the overall values of sensitivity and specificity were 66.2% 95% CI 54.0-76.5%, and 99.6% 95% CI 97.9-99.9% respectively. The analytical limit of detection was determined at 5.0 x 102 pfu/ml what equals to approximately 1.0 x 104 gcn/ml for both Ag-RDTs. The UK cohort had lower median Ct values compared to that of Peru during both evaluations. When split by Ct, both Ag-RDTs had optimum sensitivities at Ct<20 (in Peru; 95% 95% CI 76.4-99.1% and 100.0% 95% CI 74.1-100.0% and in the UK; 59.2% 95% CI 44.2-73.0% and 100.0% 95% CI 15.8-100.0%, for the GENDIA and the ActiveXpress+, respectively).
Whilst the overall clinical sensitivity of the Genedia did not meet WHO minimum performance requirements for rapid immunoassays in either cohort, the ActiveXpress+ did so for the small UK cohort. This study illustrates comparative performance of Ag-RDTs across two global settings and considers the different approaches in evaluation methods.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Aims
We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1h-algorithms and to derive and externally validate alternative cut-offs specific ...to older patients.
Methods and results
We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age <55 years (young), ≥55 to <70 years (middle-age), ≥70 years (old). Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% 95% confidence interval (95% CI) 94.9–100 in young, 99.3% (95% CI 96.0–99.9) in middle-age, and 99.3% (95% CI 97.5–99.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8–97.9) in young, 96.1% (95% CI 94.5–97.2) in middle-age, and 92.7% (95% CI 90.7–94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P < 0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P < 0.01), reduced overall efficacy for hs-cTnT (P < 0.01), while maintaining efficacy for hs-cTnI. Findings were confirmed in two validation cohorts (n = 2767).
Conclusion
While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnI.
Clinical Trial Registration
https://clinicaltrials.gov/ct2/show/NCT00470587, number NCT00470587 and NCT02355457 (BACC).
IntroductionTraumatic brain injury (TBI) is a major global health burden that results in disability and loss of health. Identifying those patients who require specialist neuroscience care can be ...challenging due to the low accuracy of existing prehospital trauma triage tools. Despite the widespread use of decision aids to ‘rule out’ TBI in hospitals, they are not widely used in the prehospital environment. We aim to provide a snapshot of current prehospital practices in the UK, and to explore facilitators and challenges that may be encountered when adopting new tools for decision support.Methods and analysisA mixed-methods study will be conducted using a convergent design approach. In the first phase, we will conduct a national survey of current practice in which every participating ambulance service in the UK will receive an online questionnaire, and only one response is required. In the second phase, semistructured interviews will be conducted to explore the perceptions of ambulance service personnel regarding the implementation of new triage methods that may enhance triage decisions. The survey questions and the interview topic guide were piloted and externally reviewed. Quantitative data will be summarised using descriptive statistics; qualitative data will be analysed thematically.Ethics and disseminationThis study has been approved by the Health Research Authority (REC reference 22/HRA/2035). Our findings may inform the design of future care pathways and research as well as identify challenges and opportunities for future development of prehospital triage tools for patients with suspected TBI. Our findings will be published in peer-reviewed journals, relevant national and international conferences, and will be included in a PhD thesis.
The 1-hour (h) algorithm triages patients presenting with suspected acute myocardial infarction (AMI) to the emergency department (ED) towards "rule-out," "rule-in," or "observation," depending on ...baseline and 1-h levels of high-sensitivity cardiac troponin (hs-cTn). The economic consequences of applying the accelerated 1-h algorithm are unknown.
We performed a post-hoc economic analysis in a large, diagnostic, multicenter study of hs-cTnT using central adjudication of the final diagnosis by two independent cardiologists. Length of stay (LoS), resource utilization (RU), and predicted diagnostic accuracy of the 1-h algorithm compared to standard of care (SoC) in the ED were estimated. The ED LoS, RU, and accuracy of the 1-h algorithm was compared to that achieved by the SoC at ED discharge. Expert opinion was sought to characterize clinical implementation of the 1-h algorithm, which required blood draws at ED presentation and 1h, after which "rule-in" patients were transferred for coronary angiography, "rule-out" patients underwent outpatient stress testing, and "observation" patients received SoC. Unit costs were for the United Kingdom, Switzerland, and Germany. The sensitivity and specificity for the 1-h algorithm were 87% and 96%, respectively, compared to 69% and 98% for SoC. The mean ED LoS for the 1-h algorithm was 4.3h-it was 6.5h for SoC, which is a reduction of 33%. The 1-h algorithm was associated with reductions in RU, driven largely by the shorter LoS in the ED for patients with a diagnosis other than AMI. The estimated total costs per patient were £2,480 for the 1-h algorithm compared to £4,561 for SoC, a reduction of up to 46%.
The analysis shows that the use of 1-h algorithm is associated with reduction in overall AMI diagnostic costs, provided it is carefully implemented in clinical practice. These results need to be prospectively validated in the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
