Assessing the impact of different heparin dosing regimens for cardiopulmonary bypass on anticoagulation: the HepDOSE pilot study.

PURPOSE: It has been suggested that a larger heparin dose during cardiopulmonary bypass (CPB) is associated with reduced perioperative coagulopathy and thromboembolic complications. We investigated the effect of different heparin doses during routine elective cardiac surgery. Our primary outcomes include blood loss and transfusion and secondary outcomes investigate the effects on coagulation biomarkers. METHODS: In this prospective pilot trial, we allocated 60 patients undergoing cardiac surgery on CPB in a single tertiary cardiac centre into three groups to receive an initial dose of 300, 400, or 500 units (U) per kilogram of intravenous heparin prior to the commencement of CPB. Blood was sampled after induction of anesthesia, at 30 and 60 min of CPB, and three minutes after heparin reversal with protamine. Samples were analyzed for fibrinopeptide A (FPA), fibrinopeptide B (FPB), D-dimer, and thrombin-antithrombin (TAT) complexes. Postoperative blood loss and transfusion was measured for the first 24-hr period after surgery. RESULTS: The total mean (95% CI) administered heparin dose in the 300 U·kg-1, 400 U·kg-1, and 500 U·kg-1 groups were 39,975 (36,528 to 43,421) U, 43,195 (36,940 to 49,449) U and 47,900 (44,807 to 50,992) U, respectively. There were no statistically significant differences in FPA, FPB or D-dimer levels at the measured time intervals. There was a trend towards lower TAT levels while on CPB with greater heparin dosing, which was statistically significant after the administration of protamine. The clinical significance appears to be negligible, as there is no difference in overall blood loss and amount of packed red blood cell transfusion or other blood product transfusion. CONCLUSION: This pilot study indicates that, while larger heparin dosing for routine cardiac surgery results in subtle biochemical changes in coagulation, there is no demonstrable benefit in postoperative blood loss or transfusion requirements.

RéSUMé: OBJECTIF: Il a été suggéré qu'une dose plus élevée d'héparine pendant la circulation extracorporelle (CEC) serait associée à une réduction de la coagulopathie périopératoire et des complications thromboemboliques. Nous avons étudié l'effet de différentes doses d'héparine au cours d'une chirurgie cardiaque non urgente de routine. Nos critères d'évaluation principaux comprenaient la perte de sang et la transfusion, et les critères d'évaluation secondaires exploraient les effets sur les biomarqueurs de la coagulation. MéTHODE: Dans cette étude pilote prospective, nous avons réparti 60 patient·es bénéficiant d'une chirurgie cardiaque sous CEC dans un seul centre cardiaque tertiaire en trois groupes à recevoir une dose initiale de 300, 400 ou 500 unités (U) par kilogramme d'héparine intraveineuse avant le début de la CEC. Le sang a été prélevé après l'induction de l'anesthésie, à 30 et 60 minutes de CEC, et trois minutes après la neutralisation de l'héparine avec la protamine. Les échantillons ont été analysés pour les complexes fibrinopeptide A (FPA), fibrinopeptide B (FPB), D-dimère et thrombine-antithrombine (TAT). La perte de sang postopératoire et la transfusion ont été mesurées pendant la première période de 24 heures après la chirurgie. RéSULTATS: La dose moyenne totale (IC 95 %) d'héparine administrée dans les 300 U·kg−1, 400 U·kg−1, et 500 U·kg−1 était de 39 975 (36 528 à 43 421) U, 43 195 (36 940 à 49 449) U et 47 900 (44 807 à 50 992) U, respectivement. Il n'y avait aucune différence statistiquement significative dans les taux de FPA, FPB ou D-dimères aux intervalles de temps mesurés. Une tendance à des niveaux de TAT plus bas pendant la CEC a été observée avec une dose d'héparine plus élevée, ce qui était statistiquement significatif après l'administration de protamine. La signification clinique semble négligeable, car il n'y a pas de différence dans la perte de sang globale et la quantité de transfusion de concentrés globulaires ou d'autres produits sanguins. CONCLUSION: Cette étude pilote indique que, bien qu'une dose plus importante d'héparine pour la chirurgie cardiaque de routine entraîne des changements biochimiques subtils dans la coagulation, il n'y a aucun avantage démontrable en matière de saignement postopératoire ou de besoins transfusionnels.

Pathway and Network Analyses Identify Growth Factor Signaling and MMP9 as Potential Mediators of Mitochondrial Dysfunction in Severe COVID-19.

Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction.

Small nucleolar RNA networks are up-regulated during human anaphylaxis.

BACKGROUND: Anaphylaxis is a severe, potentially life-threatening allergic reaction driven primarily by the activation of mast cells. We still fail to understand factors underlying reaction severity. Furthermore, there is currently no reliable diagnostic test to confirm anaphylaxis in the emergency department (ED). OBJECTIVE: This study sought to explore gene expression changes associated with anaphylaxis severity in peripheral blood leucocytes and evaluate biomarker potential. METHODS: Microarray analysis (total RNA) was performed using peripheral blood samples from ED patients with moderate (n = 6) or severe (n = 12) anaphylaxis and sepsis (n = 20) at presentation (T0) and one hour later (T1). Results were compared between groups and healthy controls (n = 10 and n = 11 matched to anaphylaxis and sepsis patients, respectively). Changes in gene expression were determined using R programming language, and pathway analysis applied to explore biological processes and pathways associated with genes. Differentially expressed genes were validated in an independent cohort of anaphylaxis (n = 30) and sepsis (n = 20) patients, and healthy controls (n = 10), using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: Significant up-regulation of small nucleolar RNAs (snoRNAs) was demonstrated in anaphylaxis compared to sepsis patients in the microarray cohort, at T0 and T1. qRT-PCR analysis of the validation cohort showed five genes: SNORD61, SNORD8, SNORD69, SNORD119 and HIST1H1D to be significantly up-regulated (adjusted p < 0.05) in severe anaphylaxis compared to sepsis. Seven genes (SNORD61, SNORD8, SCARNA21, SNORD69, SNORD110, SNORD119 and SNORD59A) were significantly up-regulated (adjusted p < 0.05) in severe anaphylaxis compared to healthy controls. CONCLUSION: This study demonstrates for the first time the unique involvement of snoRNAs in the pathogenesis of anaphylaxis and suggests they are not a general feature of systemic inflammation. Further investigation of snoRNA expression in anaphylaxis could provide insights into disease pathogenesis. CLINICAL RELEVANCE: SnoRNAs are up-regulated during acute anaphylaxis in humans and could potentially be used as biomarkers of severe anaphylaxis.

Evaluation of Point-of-Care ACT Coagulometers and Anti-Xa Activity During Cardiopulmonary Bypass.

OBJECTIVE: The activated clotting time (ACT) is used worldwide to confirm safe heparin anticoagulation for cardiopulmonary bypass. For the present study, the performances of 2 commonly used ACT devices were compared with each other and with anti-Xa levels throughout the surgical procedure in order to understand whether they can be used interchangeably. DESIGN: Prospective study. SETTING: Tertiary care center. PARTICIPANTS: The study comprised 33 elective adult cardiac surgical patients. INTERVENTIONS: Blood samples were taken at standard times throughout the surgery (after induction, after heparin bolus, 4 samples at 30-minute intervals during cardiopulmonary bypass, after protamine), and ACTs and anti-Xa levels were analyzed. Data were compared using receiver operating characteristics and LOESS regression. MEASUREMENTS AND MAIN RESULTS: The correlation between anti-Xa levels and the Hemochron ACT (Instrumentation Laboratory, Bedford, MA) was acceptable (r = 0.82, 95% confidence interval [CI] 0.757-0.868; p < 0.0001), as was the correlation between anti-Xa levels and the i-STAT (Abbott Point of Care, Abbott Park, IL) (r = 0.81, 95% CI 0.738-0.858; p < 0.0001). The correlation between the 2 ACT methods was poorer (r = 0.77, 95% CI 0.707-0.828; p < 0.0001) than their correlation to anti-Xa levels. When compared with anti-Xa levels, the sensitivity and specificity were mediocre for both devices, although the i-STAT performed better than the Hemochron ACT. The Hemochron ACT read higher values than the i-STAT ACT throughout the course of the surgery. CONCLUSION: The correlation between the Hemochron ACT and i-STAT ACT is moderate, and they have different sensitivity and specificity when compared with anti-Xa levels. This suggests that ACT devices should not be used interchangeably, but cut-off values for safe anticoagulation during cardiopulmonary bypass should be determined for each type of device, particularly when switching supplier.

A diagnostic solution for haemostasis laboratories for patients taking direct oral anticoagulants using DOAC-Remove.

This study describes the use of a simple charcoal product (DOAC-RemoveTM ) to allow haemostasis assays on patients taking direct oral anticoagulants (DOAC). In the proposed algorithm, patients taking DOAC are screened using the dilute thrombin time (dTT) and anti-Xa assay. If either are positive then DOAC-Remove is utilised. In a validation, DOAC-Remove did not interfere with coagulation testing in normal plasma or in patients on DOAC with a known lupus anticoagulant (LA). Of 1566 routine patient samples tested, 125 (8%) had evidence of anti-Xa activity (>0·1 iu/ml) or prolonged dTT suggestive of either a direct/indirect Xa inhibitor or direct thrombin inhibitor. All of these 125 patients had a prolonged dilute Russell viper venom time (dRVVT) screening test and 106 had a LA detected by dRVVT after phospholipid correction. After DOAC-Remove, 91 patients (73%) had a negative dRVVT screen. After further investigation only 9 (7%) had a positive LA. DOAC-Remove prevented 5% of patients having a LA inappropriately detected. DOAC did not significantly affect the LA activated partial thromboplastin time (aPTT) ratio, protein S antigen or protein C activity. DOAC cause low intrinsic factor assays, high prothrombin time/aPTT and high activated protein C sensitivity ratio, which DOAC-Remove reversed (P < 0·05). Despite recommendations, haemostasis testing for patients on DOAC continues; this algorithm aids diagnostic accuracy. Further validation and research are warranted.

Twice upon a time: Examining the effect socio-economic status has on the experience of dyslexia in the United Kingdom.

From the mid-1990s, there have been a number of campaigns aimed at raising awareness of dyslexia and social inclusion. In conjunction with these campaigns, educational and employment policies have been implemented that advocate inclusive and workplace adjustments for people with dyslexia. This study aims to explore the intersectional relationship between dyslexia and socio-economic status. The findings analyse adult perceptions of education and employment, which have been shaped by 23 years of social policies promoting anti-discriminatory practice. The study applies a quantitative approach, which collected data from a national survey conducted from 2015 to 2017. The sample consists of 442 adult participants who reported having dyslexia. The social model of disability has been applied in this study to interpret the data findings from a disability studies perspective. The article suggests that socio-economic status significantly affects issues of diagnosis, educational, and employment experiences. The findings illustrate an intersectional relationship between socio-economic status and disability inequalities, which have an effect on the experiences of people with dyslexia in adulthood.

Clinical bleeding and thrombin generation in admissions to critical care with prolonged prothrombin time: an exploratory study.

BACKGROUND: Prolongation of prothrombin time (PT) is often recorded in critical illness, but has limited ability to predict risk of bleeding. This exploratory study was aimed at assessing a role for thrombin generation (TG) to predict bleeding. STUDY DESIGN AND METHODS: TG was measured by calibrated automated thrombography in admissions to intensive care with prolonged PT. Bleeding events were recorded up to Day 5 after enrollment and correlated with results of PT ratio (PTR) and variables of TG. RESULTS: A total of 306 patients were recruited. A total of 101 bleeding events developed in 46 patients during the period of observation. Many patients with prolonged PT had endogenous thrombin potential (ETP), which was within the normal range (120/251 patients, 47.8%) or even elevated (8%). Although some patients had a reduction in ETP or peak thrombin, these were present over a wide range of PTR. There was no suggestion by receiver operating characteristic analysis that variables of conventional TG were sensitive at predicting bleeding. No bleeding events were documented in patients defined as ETP high, despite elevated PTR. CONCLUSION: Future studies need to explore a role for alternatives tests of coagulation in critical illness. Development of TG assays is required to positively identify more patients at increased bleeding risk or to exclude a larger number at low risk and how this relates to subgroups, such as patients with liver disease, and the need for prophylactic plasma transfusion.

Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial.

Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.

Resistin and NGAL are associated with inflammatory response, endothelial activation and clinical outcomes in sepsis.

OBJECTIVE AND DESIGN: Resistin and neutrophil gelatinase-associated lipocalin (NGAL) are upregulated in circulating leucocytes in sepsis, but the significance of this is uncertain. We evaluated associations between Resistin and NGAL with endothelial cell activation and clinical outcomes in a prospective observational study in the Emergency Department (ED). METHODS: Serum levels of Resistin, NGAL, inflammatory cytokines (IL-6, IL-10) and soluble endothelial adhesion molecules (VCAM-1, ICAM-1) were measured at defined time points up to 24 h. Patterns and relationships between markers were investigated using linear mixed regression models. Predictive values for clinical outcomes for markers at enrollment were assessed by logistic regression and receiver operator characteristic (ROC) curves. RESULTS: 186 participants (89 septic-shock, 69 sepsis, 28 uncomplicated infection) were compared with 29 healthy controls. Median Resistin and NGAL were higher in uncomplicated infection compared to controls, and in septic shock compared to non-shock sepsis. Resistin and NGAL correlated with IL-6 and IL-10, with VCAM-1 and ICAM-1, and with organ failure. Resistin and NGAL were associated with septic shock but had limited predictive utility for mortality. CONCLUSION: Resistin and NGAL correlate with expression of endothelial cell adhesion molecules in sepsis. Further evaluation of the role of Resistin and NGAL in sepsis pathogenesis is warranted.

Near-infrared spectroscopy in the assessment of suspected sepsis in the emergency department.

BACKGROUND AND AIMS: The conventional approach to sepsis resuscitation involves early interventions targeting global oxygenation and macro-haemodynamic variables such as central venous and systemic arterial pressures. There is increasing recognition of the importance of microcirculatory changes in shock states, including sepsis, and the relationship of these to outcome. Near-infrared spectroscopy (NIRS) is a recently developed non-invasive technology that measures tissue oxygen saturations (StO2), which may be an indirect measure of the adequacy of the microcirculation. StO2 measurements, therefore, have the potential to identify patients who are at risk of progressing to organ dysfunction and could be used to guide resuscitation. This article reviews the current state of knowledge of NIRS in the setting of sepsis, examining its application, validity and prognostic value. METHODS: A search of the relevant literature was performed using Medline, Embase and Cochrane databases, and a qualitative analysis was undertaken. RESULTS: A limited number of observational studies, mostly conducted among patients with severe sepsis, have shown that NIRS may correlate with severity of illness but demonstrate a variable relationship between StO2 and outcome. CONCLUSIONS: Outstanding questions still remain as to whether NIRS can help to risk-stratify patients with suspected sepsis in the emergency department and the utility of StO2 as a resuscitation target.

Randomized controlled trial of intravenous antivenom versus placebo for latrodectism: the second Redback Antivenom Evaluation (RAVE-II) study.

STUDY OBJECTIVE: Latrodectism is the most important spider envenomation syndrome worldwide. There remains considerable controversy over antivenom treatment. We aimed to investigate whether antivenom resulted in resolution of pain and systemic effects in patients with latrodectism who received standardized analgesia. METHODS: In a multicenter randomized placebo-controlled trial of redback spider antivenom for latrodectism, 224 patients (>7 years) with a redback spider bite and severe pain, with or without systemic effects, were randomized to receive normal saline solution (placebo) or antivenom after receiving standardized analgesia. The primary outcome was a clinically significant reduction in pain 2 hours after trial medication compared with baseline. A second primary outcome for the subgroup with systemic features of envenomation was resolution of systemic features at 2 hours. Secondary outcomes were improved pain at 4 and 24 hours, resolution of systemic features at 4 hours, administration of opioid analgesics or unblinded antivenom after 2 hours, and adverse reactions. RESULTS: Two hours after treatment, 26 of 112 patients (23%) from the placebo arm had a clinically significant improvement in pain versus 38 of 112 (34%) from the antivenom arm (difference in favor of antivenom 10.7%; 95% confidence interval -1.1% to 22.6%; P=.10). Systemic effects resolved after 2 hours in 9 of 41 patients (22%) in the placebo arm and 9 of 35 (26%) in the antivenom arm (difference 3.8%; 95% confidence interval -15% to 23%; P=.79). There was no significant difference in any secondary outcome between antivenom and placebo. Acute systemic hypersensitivity reactions occurred in 4 of 112 patients (3.6%) receiving antivenom. CONCLUSION: The addition of antivenom to standardized analgesia in patients with latrodectism did not significantly improve pain or systemic effects.

Modified TIMI risk score cannot be used to identify low-risk chest pain in the emergency department: a multicentre validation study.

AIM: The Thrombolysis in Myocardial Infarction (TIMI) risk score (range 0-7), used for emergency department (ED) risk stratification of patients with suspected acute coronary syndrome (ACS), underestimates risk associated with ECG changes or cardiac troponin elevation. A modified TIMI score (mTIMI, range 0-10), which gives increased weighting to these variables, has been proposed. We aimed to evaluate the performance of the mTIMI score in ED patients with suspected ACS. METHODS: A multicentre prospective observational study enrolled patients undergoing assessment for possible ACS. TIMI and mTIMI scores were calculated. The study outcome was a composite of all-cause death, myocardial infarction or coronary revascularisation within 30 days. RESULTS: Of the 1666 patients, 219 (13%) reached the study outcome. Area under the receiver operating characteristic curve for the composite outcome was 0.80 (0.76 to 0.83) for the mTIMI score compared with 0.71 (0.67 to 0.74) for the standard TIMI score, p<0.001, but there was no significant difference for death or revascularisation outcomes. Sensitivity and specificity for the composite outcome were 0.96 (0.92 to 0.98) and 0.23 (0.20 to 0.26), respectively, at score 0 for TIMI and mTIMI. At score <2, sensitivity and specificity were 0.82 (0.77 to 0.87) and 0.53 (0.51 to 0.56) for mTIMI, and 0.74 (0.68 to 0.79) and 0.54 (0.51 to 0.56) for standard TIMI, respectively. CONCLUSIONS: mTIMI score performs better than standard TIMI score for ED risk stratification of chest pain, but neither is sufficiently sensitive at scores >0 to allow safe and early discharge without further investigation or follow-up. Observed differences in performance may be due to incorporation bias.

Association between intravenous fluid administration and endothelial glycocalyx shedding in humans: a systematic review.

INTRODUCTION: Several studies have demonstrated associations between greater rate/volume of intravenous (IV) fluid administration and poorer clinical outcomes. One postulated mechanism for harm from exogenous fluids is shedding of the endothelial glycocalyx (EG). METHODS: A systematic review using relevant search terms was performed using Medline, EMBASE and Cochrane databases from inception to October 2023. Included studies involved humans where the exposure was rate or volume of IV fluid administration and the outcome was EG shedding. The protocol was prospectively registered on PROSPERO: CRD42021275133. RESULTS: The search yielded 450 articles, with 20 articles encompassing 1960 participants included in the review. Eight studies were randomized controlled clinical trials. Half of studies examined patients with sepsis and critical illness; the remainder examined perioperative patients or healthy subjects. Almost all reported blood measurements of soluble EG components; one study used in vivo video-microscopy to estimate EG thickness. Four of 10 sepsis studies, and 9 of 11 non-sepsis studies, found a positive relationship between IV fluid rate/volume and measures of EG shedding. CONCLUSIONS: A trend toward an association between IV fluid rate/volume and EG shedding was found in studies of stable patients, but was not consistently observed among studies of septic and critically ill patients.

Critical Illness Outside the Intensive Care Unit: Research Challenges in Emergency and Prehospital Settings.

Patients with acute critical illness require prompt interventions, yet high-quality evidence supporting many investigations and treatments is lacking. Clinical research in this setting is challenging due to the need for immediate treatment and the inability of patients to provide informed consent. Attempts to obtain consent from surrogate decision-makers can be intrusive and lead to unacceptable delays to treatment. These problems may be overcome by pragmatic approaches to study design and the use of supervised waivers of consent, which is ethical and appropriate in situations where there is high risk of poor outcome and a paucity of proven effective treatment.

A snapshot on a journey from frustration to readiness-A qualitative pre-implementation exploration of readiness for technology adoption in Public Health Protection in Ireland.

In an era of emergent infectious disease, the timely and efficient management of disease outbreaks is critical to public health protection. Integrated technologies for case and incident management (CIM) collect real-time health intelligence for decision making in Public Health. In Ireland, a Public Health reform program is preparing for implementation of a health information system for health protection. Project implementers seek to document and understand the readiness and willingness of future users to adopt the new system, prior to system procurement and implementation. Qualitative key informant interviews were conducted (n = 8) with Public Health personnel from a single regional department of Public Health representing medical, nursing, disease surveillance and administrative roles, at managerial and staff levels. A qualitative thematic analysis was performed. Participants were frustrated by weaknesses in the current practice of CIM and were ready and willing to adopt a digital CIM system if it met their needs. However, they were frustrated by lack of clear timelines. We identified 7 enablers and 3 barriers to readiness and willingness to adopt a CIM system. 'Newness of the workforce' was the main enabler of readiness and willingness, while 'lack of knowledge and familiarity with system' was the main barrier to readiness and willingness. Experiences during the COVID-19 pandemic gave a clear understanding of the problems and need for a digital CIM system and the reform program facilitated a culture of change, readying the workforce for the new health information system. New members of the Public Health departments are a likely ready and eager cohort for adoption of a modern, 'fit for purpose' CIM system and the execution of implementation will likely determine how ready and willing the wider network of departments will be to adopt a national CIMS.

Taipan snake venom time has high sensitivity for lupus anticoagulants in non-anticoagulated, triple positive antiphospholipid syndrome patients.

INTRODUCTION: Dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) are the mainstay assays in lupus anticoagulant (LA) detection yet they have limitations, particularly in relation to interferences and specificity. The recently validated Taipan snake venom time (TSVT) screening with ecarin time (ET) confirmatory assays overcome many of those limitations due to the innate specificity engendered from direct prothrombin activation, and insensitivity to the effects of vitamin K antagonists (VKA). The present study aimed to further evidence diagnostic utility of TSVT/ET by performing them in samples from 116 nonanticoagulated patients with established triple-positive antiphospholipid syndrome (APS). METHODS: Samples were identified in three expert centres who performed dRVVT, APTT and solid phase antiphospholipid antibody assays with reagents from a variety of manufacturers. All samples additionally received TSVT/ET analysis using standardised reagents. RESULTS: Ninety seven of 116 (83.6%) were dRVVT- and APTT-positive, 85/97 (87.6%) of which were TSVT/ET-positive, 9/116 (7.8%) were dRVVT-positive only, 6 of which were TSVT/ET-positive, and 10/116 (8.6%) were APTT-positive only, 5 of which were TSVT/ET-positive. 96/116 TSVT/ET-positivity returned a high sensitivity for LA of 82.8%. Low coefficients of determination revealed weak relationships between LA potency and anticardiolipin and anti-ß2-glycoprotein I antibody titres for all three LA assays. CONCLUSIONS: TSVT/ET has high sensitivity for the clinically significant LA found in triple positive APS patients. TSVT/ET can establish multiple LA assay positivity in nonanticoagulated patients negative for one of dRVVT or APTT, and is the only assay pairing insensitive to VKAs, the recommended anticoagulation for APS.

Serial multiple biomarkers in the assessment of suspected acute coronary syndrome: multiple infarct markers in chest pain (MIMIC) study.

OBJECTIVE: To evaluate the accuracy of a 2-h serial multiple biomarker (SMB) protocol for exclusion of myocardial infarction (MI) in the Emergency Department. METHODS: A prospective, multicentre, observational study enrolled patients undergoing evaluation for possible MI. Blood samples at presentation and 2 h later were analysed for myoglobin, creatinine kinase-MB, troponin-I and B-natriuretic peptide. Thrombolysis in Myocardial Infarction (TIMI) score and National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand (NHF/CSANZ) guideline for acute coronary syndrome were used to determine clinical risk. Primary outcome was MI diagnosed at index presentation. Secondary outcome was composite of all-cause mortality, MI and previously unplanned coronary revascularisation within 30 days. RESULTS: 1758 patients were recruited. 168 (11%) of 1501 with data sufficient for analysis had MI, and 223 (14%) of 1620 had a secondary outcome. SMB sensitivity and specificity were 0.90 (95% CI 0.84 to 0.94) and 0.41 (95% CI 0.39 to 0.44) for MI. For 30-day outcome, SMB sensitivity and specificity were 0.84 (95% CI 0.78 to 0.88) and 0.41 (95% CI 0.39 to 0.44), compared with standard 8-12 h troponin sensitivity and specificity of 0.79 (95% CI 0.73 to 0.84) and 0.96 (95% CI 0.95 to 0.97). Combined with risk scores, SMB had sensitivity and specificity for MI of 0.99 (0.96 to 1.00) and 0.11 (95% CI 0.09 to 0.12) for TIMI score 0, compared with 0.98 (95% CI 0.94 to 0.99) and 0.31 (95% CI 0.29 to 0.34) for NHF/CSANZ low/intermediate risk groups. CONCLUSIONS: SMB alone is not sufficiently sensitive to exclude MI. Combined with risk scoring, SMB appears to identify patients at lower risk. This requires prospective validation.

ACEM adding its voice to the Voice hits the wrong note.

ACEM has endorsed the proposal for an Aboriginal Voice to Parliament in Australia as a means of delivering its objectives to provide culturally safe care in EDs and to improve health outcomes for Aboriginal and Torres Strait Islander people. Unfortunately the Voice proposal has become a politically conentious issue. There is currently insufficient detail about how the Voice would operate and whether it will achieve the outcomes its proponents intend. This article argues that the claims in the ACEM statement are speculative rather than based on facts. In addition, by taking a position on this complex and controversial political matter ACEM is operating beyond its remit and risks distracting attention from its core mission.