Prospective Validation of Computed Tomography to Identify Patients at High Risk for Stroke After Transient Ischemic Attack or Minor Stroke.

BACKGROUND: Computed tomography (CT) findings of acute and chronic ischemia are associated with subsequent stroke risk in patients with transient ischemic attack. We sought to validate these associations in a large prospective cohort of patients with transient ischemic attack or minor stroke. METHODS: This prospective cohort study enrolled emergency department patients from 13 hospitals with transient ischemic attack who had CT imaging. Primary outcome was stroke within 90 days. Secondary outcomes were stroke within 2 or 7 days. CT findings were abstracted from radiology reports and classified for the presence of acute ischemia, chronic ischemia, or microangiopathy. Multivariable logistic regression was used to test associations with primary and secondary end points. RESULTS: From 8670 prospectively enrolled patients between May 2010 and May 2017, 8382 had a CT within 24 hours. From this total population, 4547 (54%) patients had evidence of acute ischemia, chronic ischemia, or microangiopathy on CT, of whom 175 had a subsequent stroke within 90 days (3.8% subsequent stroke rate; adjusted odds ratio [aOR], 2.33 [95% CI, 1.62-3.36]). This was in comparison to those with CT imaging without ischemia. Findings associated with an increased risk of stroke at 90 days were isolated acute ischemia (6.0%; aOR, 2.42 [95% CI, 1.03-5.66]), acute ischemia with microangiopathy (10.7%; aOR, 3.34 [95% CI, 1.57-7.14]), chronic ischemia with microangiopathy (5.2%; aOR, 1.83 [95% CI, 1.34-2.50]), and acute ischemia with chronic ischemia and microangiopathy (10.9%; aOR, 3.49 [95% CI, 1.54-7.91]). Acute ischemia with chronic ischemia and microangiopathy were most strongly associated with subsequent stroke within 2 days (aOR, 4.36 [95% CI, 1.31-14.54]) and 7 days (aOR, 4.50 [95% CI, 1.73-11.69]). CONCLUSIONS: In patients with transient ischemic attack or minor stroke, CT evidence of acute ischemia with chronic ischemia or microangiopathy significantly increases the risk of subsequent stroke within 90 days of index visit. The combination of all 3 findings results in the greatest early risk.

Derivation of the Falls Decision Rule to exclude intracranial bleeding without head CT in older adults who have fallen.

BACKGROUND: Ground-level falls are common among older adults and are the most frequent cause of traumatic intracranial bleeding. The aim of this study was to derive a clinical decision rule that safely excludes clinically important intracranial bleeding in older adults who present to the emergency department after a fall, without the need for a computed tomography (CT) scan of the head. METHODS: This prospective cohort study in 11 emergency departments in Canada and the United States enrolled patients aged 65 years or older who presented after falling from standing on level ground, off a chair or toilet seat, or out of bed. We collected data on 17 potential predictor variables. The primary outcome was the diagnosis of clinically important intracranial bleeding within 42 days of the index emergency department visit. An independent adjudication committee, blinded to baseline data, determined the primary outcome. We derived a clinical decision rule using logistic regression. RESULTS: The cohort included 4308 participants, with a median age of 83 years; 2770 (64%) were female, 1119 (26%) took anticoagulant medication and 1567 (36%) took antiplatelet medication. Of the participants, 139 (3.2%) received a diagnosis of clinically important intracranial bleeding. We developed a decision rule indicating that no head CT is required if there is no history of head injury on falling; no amnesia of the fall; no new abnormality on neurologic examination; and the Clinical Frailty Scale score is less than 5. Rule sensitivity was 98.6% (95% confidence interval [CI] 94.9%-99.6%), specificity was 20.3% (95% CI 19.1%-21.5%) and negative predictive value was 99.8% (95% CI 99.2%-99.9%). INTERPRETATION: We derived a Falls Decision Rule, which requires external validation, followed by clinical impact assessment. Trial registration: ClinicalTrials. gov, no. NCT03745755.

Using logistic regression models to investigate the effects of high-sensitivity cardiac troponin T confounders on ruling in acute myocardial infarction.

OBJECTIVES: Confounding factors, including sex, age, and renal dysfunction, affect high-sensitivity cardiac troponin T (hs-cTnT) concentrations and the acute myocardial infarction (AMI) diagnosis. This study assessed the effects of these confounders through logistic regression models and evaluated the diagnostic performance of an optimized, integrated prediction model. METHODS: This retrospective study included a primary derivation cohort of 18,022 emergency department (ED) patients at a US medical center and a validation cohort of 890 ED patients at a Canadian medical center. Hs-cTnT was measured with 0/3 h sampling. The primary outcome was index AMI diagnosis. Logistic regression models were optimized to predict AMI using delta hs-cTnT and its confounders as covariates. The diagnostic performance of model cutoffs was compared to that of the hs-cTnT delta thresholds. Serial logistic regressions were carried out to evaluate the relationship between covariates. RESULTS: The area under the curve of the best-fitted model was 0.95. The model achieved a 90.0% diagnostic accuracy in the validation cohort. The optimal model cutoff yielded comparable performance (90.5% accuracy) to the optimal sex-specific delta thresholds (90.3% accuracy), with 95.8% agreement between the two diagnostic methods. Serial logistic regressions revealed that delta hs-cTnT played a more predominant role in AMI prediction than its confounders, among which sex is more predictive of AMI (total effect coefficient 1.04) than age (total effect coefficient 0.05) and eGFR (total effect coefficient -0.008). CONCLUSIONS: The integrated prediction model incorporating confounding factors does not outperform hs-cTnT delta thresholds. Sex-specific hs-cTnT delta thresholds remain to provide the highest diagnostic accuracy.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.

Application of High-Sensitivity Troponin in Suspected Myocardial Infarction.

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).

Sex-Specific Absolute Delta Thresholds for High-Sensitivity Cardiac Troponin T.

BACKGROUND: Sex differences in high-sensitivity cardiac troponin (hs-cTn) concentrations from healthy populations have led to the establishment of sex-specific upper reference limits for hs-cTn assays. This study assessed the performance of sex-specific delta (i.e., changes in concentrations) thresholds for the hs-cTnT assay for ruling in acute myocardial infarction (AMI) in different emergency department (ED) populations. METHODS: This retrospective study consisted of 2 cohorts (Cohort 1 derivation and Cohort 2 validation). Cohort 1 consisted of 18 056 ED patients who had serial hs-cTnT measured using a 0-h/3-h algorithm at a US medical center, with Cohort 2 consisting of 1137 ED patients with 0-h/3-h sampling at a Canadian medical center. The primary outcome was AMI diagnosis with sex-specific deltas derived based on the Youden index and specificity estimates (i.e., ≥90%) in Cohort 1 and validated in Cohort 2. RESULTS: In Cohort 1, 42% of all patients had 0-h hs-cTnT above the sex-specific 99th percentile. Males had higher 0-h hs-cTnT (median 17 ng/L) and absolute deltas (median 2 ng/L) than females (0-h median 11 ng/L, P < 0.0001; deltas median 1 ng/L, P < 0.0001) in non-AMI patients but not in patients with AMI. For ruling in AMI, the sex-specific delta thresholds based on 90% specificity (14 ng/L for males, 11 ng/L for females) performed best and resulted in 91% diagnostic accuracy in both males and females. The sex-specific delta thresholds yielding high specificity estimates were confirmed in the validation data set. CONCLUSIONS: Sex-specific absolute delta thresholds can be used to rule in AMI and are robust across different study populations.

Cardiac Troponin Testing in Patients with COVID-19: A Strategy for Testing and Reporting Results.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged late in 2019 causing COVID-19 (coronavirus disease-2019) may adversely affect the cardiovascular system. Publications from Asia, Europe, and North America have identified cardiac troponin as an important prognostic indicator for patients hospitalized with COVID-19. We recognized from publications within the first 6 months of the pandemic that there has been much uncertainty on the reporting, interpretation, and pathophysiology of an increased cardiac troponin concentration in this setting. CONTENT: The purpose of this mini-review is: a) to review the pathophysiology of SARS-CoV-2 and the cardiovascular system, b) to overview the strengths and weaknesses of selected studies evaluating cardiac troponin in patients with COVID-19, and c) to recommend testing strategies in the acute period, in the convalescence period and in long-term care for patients who have become ill with COVID-19. SUMMARY: This review provides important educational information and identifies gaps in understanding the role of cardiac troponin and COVID-19. Future, properly designed studies will hopefully provide the much-needed evidence on the path forward in testing cardiac troponin in patients with COVID-19.

Analytical assessment of ortho clinical diagnostics high-sensitivity cardiac troponin I assay.

OBJECTIVES: To analytically evaluate Ortho Clinical Diagnostics VITROS high-sensitivity cardiac troponin I (hs-cTnI) assay in specific matrices with comparison to other hs-cTn assays. METHODS: The limit of detection (LoD), imprecision, interference and stability testing for both serum and lithium heparin (Li-Hep) plasma for the VITROS hs-cTnI assay was determined. We performed Passing-Bablok regression analyses between sample types for the VITROS hs-cTnI assay and compared them to the Abbott ARCHITECT, Beckman Access and the Siemens ADVIA Centaur hs-cTnI assays. We also performed Receiver-operating characteristic curve analyses with the area under the curve (AUC) determined in an emergency department (ED)-study population (n=131) for myocardial infarction (MI). RESULTS: The VITROS hs-cTnI LoD was 0.73 ng/L (serum) and 1.4 ng/L (Li-Hep). Stability up to five freeze-thaws was observed for the Ortho hs-cTnI assay, with the analyte stability at room temperature in serum superior to Li-Hep with gross hemolysis also affecting Li-Hep plasma hs-cTnI results. Comparison of Li-Hep to serum concentrations (n=202), yielded proportionally lower concentrations in plasma with the VITROS hs-cTnI assay (slope=0.85; 95% confidence interval [CI]:0.83-0.88). In serum, the VITROS hs-cTnI concentrations were proportionally lower compared to other hs-cTnI assays, with similar slopes observed between assays in samples frozen <-70 °C for 17 years (ED-study) or in 2020. In the ED-study, the VITROS hs-cTnI assay had an AUC of 0.974 (95%CI:0.929-0.994) for MI, similar to the AUCs of other hs-cTn assays. CONCLUSIONS: Lack of standardization of hs-cTnI assays across manufacturers is evident. The VITROS hs-cTnI assay yields lower concentrations compared to other hs-cTnI assays. Important differences exist between Li-Hep plasma and serum, with evidence of stability and excellent clinical performance comparable to other hs-cTn assays.

Sensitivity and specificity of self-reported psychiatric diagnoses amongst patients treated for opioid use disorder.

BACKGROUND: Patients with opioid use disorder (OUD) frequently present with comorbid psychiatric illnesses which have significant implications for their treatment outcomes. Notably, these are often identified by self-report. Our study examined the sensitivity and specificity of self-reported psychiatric diagnoses against a structured diagnostic interview in a cohort of patients receiving outpatient pharmacological treatment for OUD. METHODS: Using cross-sectional data from adults receiving outpatient opioid agonist treatment for OUD in clinics across Ontario, Canada, we compared participants' self-reported psychiatric diagnoses with those identified by the Mini Neuropsychiatric Interview (MINI) Version 6.0 administered at the time of study entry. Sensitivity and specificity were calculated for self-report of psychiatric diagnoses. RESULTS: Amongst a sample of 683 participants, 24% (n = 162) reported having a comorbid psychiatric disorder. Only 104 of these 162 individuals (64%) reporting a comorbidity met criteria for a psychiatric disorder as per the MINI; meanwhile, 304 (75%) participants who self-reported no psychiatric comorbidity were in fact identified to meet MINI criteria for a psychiatric disorder. The sensitivity and specificity for any self-reported psychiatric diagnoses were 25.5% (95% CI 21.3, 30.0) and 78.9% (95% CI 73.6, 83.6), respectively. CONCLUSIONS: Our findings raise questions about the utility of self-reported psychiatric comorbidity in patients with OUD, particularly in the context of low sensitivity of self-reported diagnoses. Several factors may contribute to this including remittance and relapse of some psychiatric illnesses, underdiagnosis, and the challenge of differentiating psychiatric and substance-induced disorders. These findings highlight that other methods should be considered in order to identify comorbid psychiatric disorders in patients with OUD.

Factors associated with opioid overdose during medication-assisted treatment: How can we identify individuals at risk?

BACKGROUND: Due to the loss of tolerance to opioids during medication-assisted treatment (MAT), this period may represent a time of heightened risk for overdose. Identifying factors associated with increased risk of overdose during treatment is therefore paramount to improving outcomes. We aimed to determine the prevalence of opioid overdoses in patients receiving MAT. Additionally, we explored factors associated with opioid overdose during MAT and the association between length of time enrolled in MAT and overdose. METHODS: Data were collected prospectively from 2360 participants receiving outpatient MAT in Ontario, Canada. Participants were divided into three groups by overdose status: no history of overdose, any lifetime history of overdose, and emergency department visit for opioid overdose in the last year. We used a multivariate multinomial regression model to assess demographic and clinical factors associated with overdose status. RESULTS: Twenty-four percent of participants reported a lifetime history of overdose (n = 562), and 8% reported an emergency department (ED) visit for opioid overdose in the last year (n = 179). Individuals with a recent ED visit for opioid overdose were in treatment for shorter duration (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.87, 0.97, p = 0.001). Individuals with a lifetime or recent history of overdose were more likely to be younger in age (OR 0.93, 95% CI 0.89, 0.98, p = 0.007 and OR 0.84, 95% CI 0.77, 0.92, p < 0.001, respectively), report more physical symptoms (OR 1.02, 95% CI 1.01, 1.03, p = 0.005 and OR 1.03, 95% CI 1.01, 1.05, p = 0.005, respectively), and had higher rates of non-prescription benzodiazepine use (OR 1.87, 95% CI 1.32, 2.66, p < 0.001 and OR 2.34, 95% CI 1.43, 3.81, p = 0.001, respectively) compared to individuals with no history of overdose. CONCLUSIONS: A considerable number of patients enrolled in MAT have experienced overdose. Our study highlights that there are identifiable factors associated with a patient's overdose status that may represent areas for intervention. In particular, longer duration in MAT is associated with a decreased risk of overdose.

The association between cannabis use and outcome in pharmacological treatment for opioid use disorder.

BACKGROUND: With the ongoing opioid crisis and policy changes regarding legalization of cannabis occurring around the world, it is necessary to consider cannabis use in the context of opioid use disorder (OUD) and its treatment. We aimed to examine (1) past-month cannabis use in patients with OUD, (2) self-reported cannabis-related side effects and craving, and (3) the association between specific characteristics of cannabis use and opioid use during treatment in cannabis users. METHODS: Participants receiving pharmacological treatment for OUD (n = 2315) were recruited from community-based addiction treatment clinics in Ontario, Canada, and provided information on past-month cannabis use (self-report). Participants were followed for 3 months with routine urine drug screens in order to assess opioid use during treatment. We used logistic regression analysis to explore (1) the association between any cannabis use and opioid use during treatment, and (2) amongst cannabis-users, specific cannabis use characteristics associated with opioid use. Qualitative methods were used to examine responses to the question: "What effect does marijuana have on your treatment?". RESULTS: Past-month cannabis use was reported by 51% of participants (n = 1178). Any cannabis use compared to non-use was not associated with opioid use (OR = 1.03, 95% CI 0.87-1.23, p = 0.703). Amongst cannabis users, nearly 70% reported daily use, and half reported experiencing cannabis-related side effects, with the most common side effects being slower thought process (26.2%) and lack of motivation (17.3%). For cannabis users, daily cannabis use was associated with lower odds of opioid use, when compared  with occasional use (OR = 0.61, 95% CI 0.47-0.79, p < 0.001) as was older age of onset of cannabis use (OR = 0.97, 95% CI 0.94, 0.99, p = 0.032), and reporting cannabis-related side effects (OR = 0.67, 95% CI 0.51, 0.85, p = 0.001). Altogether, 75% of cannabis users perceived no impact of cannabis on their OUD treatment. CONCLUSION: Past-month cannabis use was not associated with more or less opioid use during treatment. For patients who use cannabis, we identified specific characteristics of cannabis use associated with differential outcomes. Further examination of characteristics and patterns of cannabis use is warranted and may inform more tailored assessments and treatment recommendations.

Examining the association between paramedic transport to the emergency department and hospital admission: a population-based cohort study.

BACKGROUND: Increasing hospitalization rates present unique challenges to manage limited inpatient bed capacity and services. Transport by paramedics to the emergency department (ED) may influence hospital admission decisions independent of patient need/acuity, though this relationship has not been established. We examined whether mode of transportation to the ED was independently associated with hospital admission. METHODS: We conducted a retrospective cohort study using the National Ambulatory Care Reporting System (NACRS) from April 1, 2015 to March 31, 2020 in Ontario, Canada. We included all adult patients (≥18 years) who received a triage score in the ED and presented via paramedic transport or self-referral (walk-in). Multivariable binary logistic regression was used to determine the association of mode of transportation between hospital admission, after adjusting for important patient and visit characteristics. RESULTS: During the study period, 21,764,640 ED visits were eligible for study inclusion. Approximately one-fifth (18.5%) of all ED visits were transported by paramedics. All-cause hospital admission incidence was greater when transported by paramedics (35.0% vs. 7.5%) and with each decreasing Canadian Triage and Acuity Scale level. Paramedic transport was independently associated with hospital admission (OR = 3.76; 95%CI = 3.74-3.77), in addition to higher medical acuity, older age, male sex, greater than two comorbidities, treatment in an urban setting and discharge diagnoses specific to the circulatory or digestive systems. CONCLUSIONS: Transport by paramedics to an ED was independently associated with hospital admission as the disposition outcome, when compared against self-referred visits. Our findings highlight patient and visit characteristics associated with hospital admission, and can be used to inform proactive healthcare strategizing for in-patient bed management.

Sample matrix and high-sensitivity cardiac troponin I assays.

Background Manufacturers of high-sensitivity cardiac troponin (hs-cTn) assays have restricted use of what sample types or matrices are acceptable to use for measurement. Our goal was to evaluate the comparability of the Siemens ADVIA Centaur hs-cTnI assay across different matrices and under different storage conditions. Methods Three different QC-plasma matrices were evaluated for imprecision <10 ng/L. Passing-Bablok regression and difference plots were determined for cTnI concentrations spanning the reference interval (limit of quantification to male 99th-percentile: 2.5 ng/L to <60 ng/L) between serum and lithium heparin plasma, lithium heparin and EDTA plasma and between the Siemens and Abbott hs-cTnI assays. Stability at room temperature (RT) and 2-8 °C was also assessed across the three matrices. Results Over 16-weeks the SDs were ≤1.0 ng/L for QCs ranging from 5.0 to 8.3 ng/L. Across the reference interval there was excellent agreement between lithium heparin plasma and serum for the Siemens hs-cTnI assay (slope=0.98/intercept=-0.1), however, cTnI concentrations were proportionally lower in EDTA as compared to lithium heparin plasma (slope=0.90, 95% CI: 0.88-0.92). In lithium heparin plasma the Siemens hs-cTnI concentrations were higher than the Abbott hs-cTnI concentrations (slope=1.26/intercept=-0.2). Stability of cTnI in lithium heparin plasma as compared in serum and EDTA plasma appeared more labile, with decreases ≥20% in concentrations evident as early as 1-day in storage at RT. Conclusions There is excellent agreement in concentrations between lithium heparin plasma and serum with the Siemens ADVIA Centaur hs-cTnI assay; however, cTnI concentrations in EDTA plasma are lower. Reference intervals and clinical studies in EDTA plasma for the Centaur hs-cTnI assay are required before clinical use.

Quality of reporting in abstracts of RCTs published in emergency medicine journals: a systematic survey of the literature suggests we can do better.

OBJECTIVE: We investigated the association between the publication of the Consolidated Standards of Reporting Trials extension for abstracts (CONSORT-EA) and other variables of interest on the quality of reporting of abstracts of randomised controlled trials (RCTs) published in emergency medicine (EM) journals. METHODS: We performed a survey of the literature, comparing the quality of reporting before (2005-2007) with after (2014-2015) the publication of the dedicated CONSORT-EA in 2008. The quality of reporting was measured as the sum of items of the CONSORT-EA checklist reported in each abstract, ranging from 0 to 15. The main explanatory variable was the period of publication: pre-CONSORT-EA versus post-CONSORT-EA public. Other explanatory variables were journal's endorsement of the CONSORT statement, number of centres participating in the study, study's sample size, type of intervention, significance of results, source of funding and study setting. We analysed the data using generalised estimation equations, performing a univariate and a multivariable analysis. RESULTS: We retrieved 844 articles, and randomly selected 60 per period for review, after stratifying for journal. The mean (SD) number of items reported was 6.4 (1.9) in the period before and 6.9 (1.8) in the period after the publication of the CONSORT-EA, with an adjusted mean difference (aMD) of 0.47 (95% CI -0.13 to 1.06). Abstracts of trials of pharmacological interventions had a significantly larger mean number of reported items than those of trials of non-pharmacological interventions (aMD 1.59; 95% CI 0.94 to 2.24). CONCLUSIONS: The quality of reporting in abstracts of RCTs published in EM journals is low and was not significantly impacted by the publication of a dedicated CONSORT-EA.

Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia.

To conduct a systematic review of the literature reporting efficacy and safety of recombinant factor VIIa (rFVIIa) for the treatment of bleeding in acquired haemophilia and, if data permitted, undertake a meta-analysis of the current evidence. MEDLINE®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for all studies on rFVIIa treatment in acquired haemophilia. Heterogeneity of included studies was measured using the inconsistency index (I2). Of the 2353 publications screened, 290 potentially relevant references were identified: 12 studies published in 32 publications met inclusion criteria. In total, 1244 patients and 1714 bleeds were included (671 patients received rFVIIa treatment for 1063 bleeds). In seven of 12 studies, the initial dose of Recombinant FVIIa was 90 ± 10 µg/kg. Recombinant FVIIa was used as first-line therapy in the majority of cases. Median number of doses administered ranged from 10 to 28. Between 68 and 74% of bleeds were spontaneous, whereas 4-50% were traumatic. Thirty-nine to 90% of bleeds were severe. Haemostatic effectiveness was > 90% in 5/6 studies for both patient and bleed level. Recombinant FVIIa had a favourable safety profile with low risk of general adverse events and thromboembolic-associated events. The heterogeneity of the studies and data precluded a meta-analysis. Recombinant FVIIa demonstrated effectiveness for the treatment of bleeds and had a good safety profile. It is apparent from these data that there is a need for more standardised measures of clinical effectiveness in acquired haemophilia to enable comparison and pooling of results in the future.

Correction to: Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia.

The article Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia, written by Andreas Tiede and Andrew Worster, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 26 May 2018 without open access.

Clinical chemistry score versus high-sensitivity cardiac troponin I and T tests alone to identify patients at low or high risk for myocardial infarction or death at presentation to the emergency department.

BACKGROUND: Testing for high-sensitivity cardiac troponin (hs-cTn) may assist triage and clinical decision-making in patients presenting to the emergency department with symptoms of acute coronary syndrome; however, this could result in the misclassification of risk because of analytical variation or laboratory error. We sought to evaluate a new laboratory-based risk-stratification tool that incorporates tests for hs-cTn, glucose level and estimated glomerular filtration rate to identify patients at risk of myocardial infarction or death when presenting to the emergency department. METHODS: We constructed the clinical chemistry score (CCS) (range 0-5 points) and validated it as a predictor of 30-day myocardial infarction (MI) or death using data from 4 cohort studies involving patients who presented to the emergency department with symptoms suggestive of acute coronary syndrome. We calculated diagnostic parameters for the CCS score separately using high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: For the combined cohorts (n = 4245), 17.1% of participants had an MI or died within 30 days. A CCS score of 0 points best identified low-risk participants: the hs-cTnI CCS had a sensitivity of 100% (95% confidence interval [CI] 99.5%-100%), with 8.9% (95% CI 8.1%-9.8%) of the population classified as being at low risk of MI or death within 30 days; the hs-cTnT CCS had a sensitivity of 99.9% (95% CI 99.2%-100%), with 10.5% (95% CI 9.6%-11.4%) of the population classified as being at low risk. The CCS had better sensitivity than hs-cTn alone (hs-cTnI < 5 ng/L: 96.6%, 95% CI 95.0%-97.8%; hs-cTnT < 6 ng/L: 98.2%, 95% CI 97.0%-99.0%). A CCS score of 5 points best identified patients at high risk (hs-cTnI CCS: specificity 96.6%, 95% CI 96.0%-97.2%; 11.2% [95% CI 10.3%-12.2%] of the population classified as being at high risk; hs-cTnT CCS: specificity 94.0%, 95% CI 93.1%-94.7%; 13.1% [95% CI 12.1%-14.1%] of the population classified as being at high risk) compared with using the overall 99th percentiles for the hs-cTn assays (specificity of hs-cTnI 93.2%, 95% CI 92.3-94.0; specificity of hs-cTnT 73.8%, 95% CI 72.3-75.2). INTERPRETATION: The CCS score at the chosen cut-offs was more sensitive and specific than hs-cTn alone for risk stratification of patients presenting to the emergency department with suspected acute coronary syndrome. Study registration: ClinicalTrials.gov, nos. NCT01994577; NCT02355457.

Assessment of the European Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute Myocardial Infarction.

BACKGROUND: The new European Society of Cardiology guidelines to rule-in and rule-out acute myocardial infarction (AMI) in the emergency department include a rapid assessment algorithm based on high-sensitivity cardiac troponin and sampling at 0 and 1 hour. Emergency department physicians require high sensitivity to confidently rule-out AMI, whereas cardiologists aim to minimize false-positive results. METHODS: High-sensitivity troponin I and T assays were used to measure troponin concentrations in patients presenting with chest-pain symptoms and being investigated for possible acute coronary syndrome at hospitals in New Zealand, Australia, and Canada. AMI outcomes were independently adjudicated by at least 2 physicians. The European Society of Cardiology algorithm performance with each assay was assessed by the sensitivity and proportion with AMI ruled out and the positive predictive value and proportion ruled-in. RESULTS: There were 2222 patients with serial high-sensitivity troponin T and high-sensitivity troponin I measurements. The high-sensitivity troponin T algorithm ruled out 1425 (64.1%) with a sensitivity of 97.1% (95% confidence interval [CI], 94.0%-98.8%) and ruled-in 292 (13.1%) with a positive predictive value of 63.4% (95% CI, 57.5%-68.9%).The high-sensitivity troponin I algorithm ruled out 1205 (54.2%) with a sensitivity of 98.8% (95% CI, 96.4%-99.7%)) and ruled-in 310 (14.0%) with a positive predictive value of 68.1% (95% CI, 62.6%-73.2%). CONCLUSIONS: The sensitivity of the European Society of Cardiology rapid assessment 0-/1-hour algorithm to rule-out AMI with high-sensitivity troponin may be insufficient for some emergency department physicians to confidently send patients home. These algorithms may prove useful to identify patients requiring expedited management. However, the positive predictive value was modest for both algorithms.

Simulation Models of Misclassification Error for Single Thresholds of High-Sensitivity Cardiac Troponin I Due to Assay Bias and Imprecision.

BACKGROUND: Clinical outcome studies for cardiac troponins (cTn) are expensive and difficult to design owing to variation in patients, in the assays, and in the incidence of different types of myocardial infarction (MI). To overcome these difficulties, simulation models were used to estimate the rate of misclassification error for MI and risk prediction resulting from assay bias and imprecision. METHODS: Finite mixture analysis of Abbott high-sensitivity cTnI (hs-cTnI) results at time 0 h in patients presenting early with acute coronary syndrome (ACS) symptoms to the emergency department (ED) [n = 145, Reducing the Time Interval for Identifying New Guideline (RING) study] allowed derivation of a simulation data set (n = 10000). hs-cTnI concentrations were modified by addition of bias or imprecision error. The percentage of all 10000 modified hs-cTnI results that were misclassified for MI at thresholds of 2, 5, 26.2, and 52 ng/L was determined by Monte Carlo simulation. Analyses were replicated with an all-comer emergency department (ED) population (n = 1137) ROMI (Optimum Troponin Cutoffs for ACS in the ED) study. RESULTS: In the RING study, simulation at 26.2-ng/L (99th percentile) and 52-ng/L thresholds were affected by both bias ±2 ng/L and imprecision (10%-20%) and had misclassification rates of 0.4% to 0.6%. Simulations at the 2-ng/L and 5-ng/L thresholds were only affected by bias. Misclassification rates at bias of ±1 ng/L were 10% for the 2-ng/L threshold, and 5% for the 5-ng/L threshold. CONCLUSIONS: Simulation models predicted that hs-cTnI results are seldom misclassified (<1% of patients) when interpretative thresholds are near or exceed the overall 99th percentile. However, simulation models also predicted that low hs-cTnI results, as recommended in guidelines, are prone to misclassification of 5%-10% of patients.