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ObjectiveWe tested the hypothesis that patients with a potential acute coronary syndrome (ACS) and very low levels of high-sensitivity cardiac troponin I can be efficiently and safely discharged from the emergency department after a single troponin measurement.MethodsThis prospective cohort study recruited 2255 consecutive patients aged ≥18 years presenting to the Emergency Department, Royal Perth Hospital, Western Australia, with chest pain without high-risk features but requiring the exclusion of ACS. Patients were managed using a guideline-recommended pathway or our novel Single Troponin Accelerated Triage (STAT) pathway. The primary outcome was the percentage of patients discharged in ResultsThe study enrolled 1131 patients to the standard cohort and 1124 to the STAT cohort. Thirty-eight per cent of the standard cohort were discharged directly from emergency department compared with 63% of the STAT cohort (pConclusionsAmong low-risk patients with a potential ACS, a pathway which incorporates early discharge based on a single very low level of high-sensitivity cardiac troponin increases the proportion of patients discharged directly from the emergency department, reduces length of stay and is safe.Trial registration numberACTRN12618000797279.

Objective To determine if a combination of the Charlson Comorbidity Index (CCI) and quick-Sequential Organ Failure Assessment (qSOFA) score is superior to qSOFA alone for predicting the outcome of ED patients with suspected infection. Methods A prospective, observational single-centre study recruited consecutive adult patients who underwent blood culture collection in the ED and were admitted to hospital. The primary outcome was 28-day in-hospital mortality, and the secondary outcome a composite of mortality and/or ICU admission ≥72 h duration. The qSOFA and CCI were combined using logistic regression models, and the resulting area under the receiver operating characteristic curve (AUROC) compared to that for qSOFA alone. Results Of 551 patients recruited, 18 (3%) died and 27 (5%) attained the composite outcome. The AUROC for qSOFA/CCI versus qSOFA for the primary outcome is 0.79 versus 0.72 (95% confidence interval 0.71-0.88 vs 0.62-0.82, P = 0.055) and 0.80 versus 0.76 (95% confidence interval 0.73-0.86 vs 0.68-0.84, P = 0.048). Deaths among patients not admitted to ICU (12/495) accounted for most of the overall differences in AUROC. Conclusions This generates the hypothesis that age and comorbid disease status augment the qSOFA score for predicting adverse outcome among patients with suspected infection in the ED. The results may reflect the predominance of these factors in determining suitability for admission to ICU. Reported limitations of qSOFA to detect the risk of adverse outcome may reflect the influence of unmeasured patient factors.

Objectives To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30‐day period at each site, with suspected sepsis and hypotension (systolic blood pressure

OBJECTIVE To investigate the association between timing and volume of intravenous fluids administered to ED patients with suspected infection and all-cause in-hospital mortality. METHODS Retrospective cohort study of ED presentations at four metropolitan hospitals in Sydney, Australia, between October 2018 and May 2019. Patients over 16 years of age with suspected infection who received intravenous fluids within 24 h of presentation were included. RESULTS During the study period, 7533 patients with suspected infection received intravenous fluids. Of these, 1996 (26.5%) and 231 (3.1%) had suspected sepsis and septic shock, respectively. Each 1000 mL increase in intravenous fluids administered was associated with a reduction in risk of in-hospital mortality (adjusted odds ratio [AOR] 0.87, 95% confidence interval [CI] 0.76-0.99). This association was stronger in patients with septic shock (AOR 0.66, 95% CI 0.49-0.89), and those admitted to intensive care unit (ICU) (AOR 0.74, 95% CI 0.56-0.96). Patients with suspected sepsis and septic shock who received a total volume of >3600 mL had lower in-hospital mortality (AOR 0.44, 95% CI 0.22-0.91; AOR 0.16, 95% CI 0.05-0.57) compared to those administered

Objective: To assess whether the initiation of vasopressor infusions via peripheral venous catheters (PVC) compared to central venous catheters (CVC) in ED patients with early septic shock was associated with differences in processes of care and outcomes. Methods: We conducted a post‐hoc analysis of the ARISE trial. We compared participants who had a vasopressor infusion first commenced via a PVC versus a CVC. The primary outcome was 90 day mortality. Results: We studied 937 participants. Of these, 389 (42%) had early vasopressor infusion commenced via a PVC and 548 (58%) via a CVC. Trial participants who received a vasopressor infusion via a PVC were more severely ill, with higher median (interquartile range [IQR]) Acute Physiology And Chronic Health Evaluation (APACHE II) scores (17 [13–23] versus 16 [12–21], P = 0.003), and higher median (IQR) lactate (mmol/L) (3.6 [1.9–5.8] versus 2.5 [1.5–4.5], P

Sepsis is acute organ dysfunction in the setting of infection. An accurate diagnosis is important to guide treatment and disposition. Tissue oxygen saturation (StO2) can be estimated noninvasively by near-infrared spectroscopy (NIRS), and may be an indicator of microcirculatory dysfunction in early sepsis. We aimed to determine the utility of StO2 for sepsis recognition and outcome prediction among patients presenting to the emergency department (ED) with infection.A multicentre, prospective, observational cohort study recruited patients who were being admitted to hospital with infection. StO2 was measured in the ED using a handheld NIRS device, Inspectra 300. Outcomes were sepsis, defined as an increase in sequential organ failure assessment score of at least 2 points within 72 h, and composite in-hospital mortality/ICU admission at least 3 days.A cohort of 323 participants, median age 64 (interquartile range: 47-77) years, was recruited at three Australian hospitals. 143 (44%) fulfilled the criteria for sepsis and 22 (7%) died within 30 days. The mean ± SD StO2 was 74 ± 8% in sepsis and 78 ± 7% in nonsepsis (P 0.0001). StO2 correlated with the peak sequential organ failure assessment score (Spearman's ρ -0.27, P 0.0001). Area under the receiver operating characteristic curve was 0.66 (95% confidence interval: 0.60-0.72) for sepsis and 0.66 (0.58-0.75) for the composite outcome. StO2 less than 75% had an odds ratio of 2.67 (1.45-4.94; P = 0.002), for the composite outcome compared with StO2 at least 75%.NIRS-derived StO2 correlates with organ failure and is associated with outcome in sepsis. However, its ability to differentiate sepsis among ED patients with infection is limited. NIRS cannot be recommended for this purpose.

There is uncertainty about the optimal i.v. fluid volume and timing of vasopressor commencement in the resuscitation of patients with sepsis and hypotension. We aim to study current resuscitation practices in EDs in Australia and New Zealand (the Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis [ARISE FLUIDS] observational study). ARISE FLUIDS is a prospective, multicentre observational study in 71 hospitals in Australia and New Zealand. It will include adult patients presenting to the ED during a 30 day period with suspected sepsis and hypotension (systolic blood pressure This multicentre, observational study will provide insight into current haemodynamic resuscitation practices in patients with sepsis and hypotension as well as estimates of practice variation and patient outcomes. The results will inform the design and feasibility of a multicentre phase III trial of early haemodynamic resuscitation in patients presenting to ED with sepsis and hypotension.

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

IntroductionAccurate triage is an important first step to effectively manage the clinical treatment of severe cases in a pandemic outbreak. In the current COVID-19 global pandemic, there is a lack of reliable clinical tools to assist clinicians to perform accurate triage. Host response biomarkers have recently shown promise in risk stratification of disease progression; however, the role of these biomarkers in predicting disease progression in patients with COVID-19 is unknown. Here, we present a protocol outlining a prospective validation study to evaluate the biomarkers’ performance in predicting clinical outcomes of patients with COVID-19.Methods and analysisThis prospective validation study assesses patients infected with COVID-19, in whom blood samples are prospectively collected. Recruited patients include a range of infection severity from asymptomatic to critically ill patients, recruited from the community, outpatient clinics, emergency departments and hospitals. Study samples consist of peripheral blood samples collected into RNA-preserving (PAXgene/Tempus) tubes on patient presentation or immediately on study enrolment. Real-time PCR (RT-PCR) will be performed on total RNA extracted from collected blood samples using primers specific to host response gene expression biomarkers that have been previously identified in studies of respiratory viral infections. The RT-PCR data will be analysed to assess the diagnostic performance of individual biomarkers in predicting COVID-19-related outcomes, such as viral pneumonia, acute respiratory distress syndrome or bacterial pneumonia. Biomarker performance will be evaluated using sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operating characteristic curve.Ethics and disseminationThis research protocol aims to study the host response gene expression biomarkers in severe respiratory viral infections with a pandemic potential (COVID-19). It has been approved by the local ethics committee with approval number 2020/ETH00886. The results of this project will be disseminated in international peer-reviewed scientific journals.

Collaboration with consumers is an emerging focus for medical researchers worldwide. Public involvement is increasingly encouraged, and in some cases stipulated by funding bodies, in order to secure financial support. While consumer involvement could be viewed as another hurdle in the funding application process, it can add immense value to research outcomes. However, given the diverse and transient nature of our consumer group, how can we develop meaningful public engagement in emergency medicine research?

Background: Persisting post-concussion symptoms (PPCS) is a complex, multifaceted condition in which individuals continue to experience the symptoms of mild traumatic brain injury (mTBI, concussion) beyond the timeframe that it typically takes to recover. Currently, there is no way of knowing which individuals may develop this condition. Method: Patients presenting to a hospital emergency department (ED) within 48 h of sustaining a mTBI underwent neuropsychological assessment and demographic, injury-related information and blood samples were collected. Concentrations of blood-based biomarkers neuron specific enolase, neurofilament protein-light, and glial fibrillary acidic protein were assessed, and a subset of patients also underwent diffusion tensor&ndash, magnetic resonance imaging, both relative to healthy controls. Individuals were classified as having PPCS if they reported a score of 25 or higher on the Rivermead Postconcussion Symptoms Questionnaire at ~28 days post-injury. Univariate exact logistic regression was performed to identify measures that may be predictive of PPCS. Neuroimaging data were examined for differences in fractional anisotropy (FA) and mean diffusivity in regions of interest. Results: Of n = 36 individuals, three (8.33%) were classified as having PPCS. Increased performance on the Repeatable Battery for the Assessment of Neuropsychological Status Update Total Score (OR = 0.81, 95% CI: 0.61&ndash, 0.95, p = 0.004), Immediate Memory (OR = 0.79, 95% CI: 0.56&ndash, 0.94, p = 0.001), and Attention (OR = 0.86, 95% CI: 0.71&ndash, 0.97, p = 0.007) indices, as well as faster completion of the Trails Making Test B (OR = 1.06, 95% CI: 1.00&ndash, 1.12, p = 0.032) at ED presentation were associated with a statistically significant decreased odds of an individual being classified as having PPCS. There was no significant association between blood-based biomarkers and PPCS in this small sample, although glial fibrillary acidic protein (GFAP) was significantly increased in individuals with mTBI relative to healthy controls. Furthermore, relative to healthy age and sex-matched controls (n = 8), individuals with mTBI (n = 14) had higher levels of FA within the left inferior frontal occipital fasciculus (t (18.06) = &minus, 3.01, p = 0.008). Conclusion: Performance on neuropsychological measures may be useful for predicting PPCS, but further investigation is required to elucidate the utility of this and other potential predictors.

To determine if a regimen of restricted fluids and early vasopressor compared to usual care is feasible for initial resuscitation of hypotension due to suspected sepsis. A prospective, randomised, open-label, clinical trial of a restricted fluid resuscitation regimen in the first 6 h among patients in the emergency department (ED) with suspected sepsis and a systolic blood pressure under 100 mmHg, after minimum 1000 ml of IV fluid. Primary outcome was total fluid administered within 6 h post randomisation. There were 99 participants (50 restricted volume and 49 usual care) in the intention-to-treat analysis. Median volume from presentation to 6 h in the restricted volume group was 2387 ml [first to third quartile (Q1–Q3) 1750–2750 ml]; 30 ml/kg (Q1–Q3 32–39 ml/kg) vs. 3000 ml (Q1–Q3 2250–3900 ml); 43 ml/kg (Q1–Q3 35–50 ml/kg) in the usual care group (p

Purpose Endocan, a component of the endothelial glycocalyx (EG), has been linked with respiratory failure in sepsis. This study explored the temporal patterns of three EG biomarkers, including endocan, and their relationships with inflammation and respiratory failure. Materials and methods Plasma endocan, syndecan-1, and hyaluronan concentrations were measured in Emergency Department (ED) patients with sepsis due to pneumonia (n = 44) on ED arrival (T0), 1 h (T1), 3 h (T3) and 12–24 h (T24) later, with change over time tested using mixed regression models. Biomarker associations with inflammatory cytokine concentrations and with respiratory failure on days 1, 2 or 3, need for mechanical ventilation and 30-day mortality were also tested. Results Endocan concentration significantly decreased over time (T0–T24, P = 0.003) whereas both syndecan-1 (T0–T3, P = 0.010; T0–T24, P

Sepsis is characterised by organ dysfunction resulting from infection, with no reliable single objective test and current diagnosis based on clinical features and results of investigations. In the ED, investigations may be conducted to diagnose infection as the cause of the presenting illness, identify the source, distinguish sepsis from uncomplicated infection (i.e. without organ dysfunction) and/ or risk stratification. Appropriate sample collection for microbiological testing remains key for subsequent confirmation of diagnosis and rationalisation of antimicrobials. Routine laboratory investigations such as creatinine, bilirubin, platelet count and lactate are now critical elements in the diagnosis of sepsis and septic shock. With no biomarker sufficiently validated to rule out bacterial infection in the ED, there remains substantial interest in biomarkers representing various pathogenic pathways. New technologies for screening multiple genes and proteins are identifying unique network 'signatures' of clinical interest. Other future directions include rapid detection of bacterial DNA in blood, genes for antibiotic resistance and EMR-based computational biomarkers that collate multiple information sources. Reliable, cost-effective tests, validated in the ED to promptly and accurately identify sepsis, and to guide initial antibiotic choices, are important goals of current research efforts.

Endothelial glycocalyx (EG) shedding may promote organ failure in sepsis. This study describes temporal changes in EG biomarkers from Emergency Department (ED) arrival, and associations with clinical characteristics.This prospective observational study included 23 patients with simple infection, 86 with sepsis and 29 healthy controls. Serum EG biomarkers included syndecan-1, syndecan-4 and hyaluronan. Samples were taken on enrolment in the ED (T0), 1 hour (T1), 3 hours (T3) and 12 to 24 hours (T24) later.Syndecan-1 concentration increased incrementally over time (T0-T24, both patient groups, P.001) whereas hyaluronan concentration peaked at T3 (T0-T3, sepsis group, P.001). Hyaluronan was positively associated with cumulative fluid volumes (P.001) at T0, T1, and T3, independent of illness severity. Both syndecan-1 (OR 1.04, 95% CI 1.01-1.07, P = .017) and hyaluronan (OR 1.83, 95% CI 1.46-2.30, P.001) were associated with organ failure, independent of age and comorbidity. Syndecan-4 concentration was not different between groups or over time.In contrast to previous ICU studies, EG biomarkers increased during the first 24 hours of sepsis treatment and were associated with fluid volumes and organ failure. Further investigation is required to determine if interventions delivered in the ED contribute to EG shedding.

Objective The Sepsis-3 task force recommends the use of the quick Sequential Organ Failure Assessment (qSOFA) score to identify risk for adverse outcomes in patients presenting with suspected infection. Lactate has been shown to predict adverse outcomes in patients with suspected infection. The aim of the study is to investigate the utility of a post hoc lactate threshold (≥2 mmol/L) added qSOFA score (LqSOFA(2) score) to predict primary composite adverse outcomes (mortality and/or ICU stay ≥72 h) in patients presenting to ED with suspected sepsis. Methods Retrospective cohort study was conducted on a merged dataset of suspected or proven sepsis patients presenting to ED across multiple sites in Australia and The Netherlands. Patients are identified as candidates for quality improvement initiatives or research studies at respective sites based on local screening procedures. Data-sharing was performed across sites of demographics, qSOFA, SOFA, lactate thresholds and outcome data for included patients. LqSOFA(2) scores were calculated by adding an extra point to qSOFA score in patients who met lactate thresholds of ≥2 mmol/L. Results In a merged dataset of 12 555 patients where a full qSOFA score and outcome data were available, LqSOFA(2) ≥2 identified more patients with an adverse outcome (sensitivity 65.5%, 95% confidence interval 62.6-68.4) than qSOFA ≥2 (sensitivity 47.6%, 95% confidence interval 44.6- 50.6). The post hoc addition of lactate threshold identified higher proportion of patients at risk of adverse outcomes. Conclusions The lactate ≥2 mmol/L threshold-based LqSOFA(2) score performs better than qSOFA alone in identifying risk of adverse outcomes in ED patients with suspected sepsis.

Sepsis has recently been redefined as acute organ dysfunction due to infection. The ED plays a critical role in identifying patients with sepsis. This is challenging due to the heterogeneity of the syndrome, and the lack of an objective standard diagnostic test. While overall mortality rates from sepsis appear to be falling, there is an increasing burden of morbidity among survivors. This largely reflects the growing proportion of older patients with comorbid illnesses among those treated for sepsis.

OBJECTIVES To determine the priorities for emergency medicine research of patients currently in an ED and to compare their priorities with those of ACEM researchers. METHODS A survey of current patients in the EDs of Royal Perth Hospital and Armadale Health Service. Patients gave their reason for presentation, suggested three important research priorities for emergency medicine and ranked their top 5 choices from a pre-specified list published by the ACEM researchers. Results were analysed using qualitative and quantitative research methods. RESULTS A total of 430 patients completed the survey, of which 218 were men (50.7%), with median age 44 years (interquartile range [IQR] 30-61 years, range 18-92 years). The top 5 priorities suggested by patients were cardiology, trauma, ED processes, mental health and haematology/oncology. The top 5 patient rankings of the ACEM researcher list were resuscitation, trauma, cardiology, infectious diseases and paediatrics. Older age groups tended to rank cardiology high, while trauma and resuscitation were ranked high among all age groups. There was moderate agreement between patients and ACEM researchers (ρ = 0.51, P = 0.03). CONCLUSIONS The top 5 emergency medicine research priorities nominated by patients in ED were cardiology, trauma, ED processes, mental health and haematology/oncology, although many 'system priorities' were identified as well. These priorities were generally consistent with ACEM researchers, but patients also suggested alternative directions for future research.

OBJECTIVE: Vasopressor medications have traditionally been administered via central venous catheters (CVCs), primarily due to concerns of peripheral extravasation of vasoconstrictive medications. Recent studies have suggested that vasopressor administration via peripheral intravenous catheters (PiVCs) may be a feasible and safe alternative. This systematic review evaluates the safety of delivering vasopressor medications via PiVCs. METHODS: We performed a systematic review to assess the frequency of complications associated with the delivery of vasopressors via PiVCs. A literature search for prospective and retrospective studies of vasopressor infusions in adults was performed. We included studies of continuous infusions of vasopressor medications (noradrenaline, adrenaline, metaraminol, phenylephrine, dopamine and vasopressin) delivered via a PiVCs that included at least 20 patients. Data on patient factors, cannulation approach, monitoring protocols, vasopressor dosing and dilutions and adverse events were collected and summarised. RESULTS: Seven studies were identified that fulfilled the inclusion criteria, including 1382 patients. No study fulfilled all of the validity criteria. Noradrenaline was the most commonly administered agent (n = 702 episodes of administration), followed by phenylephrine (n = 546), dopamine (n = 108), metaraminol (n = 74) and vasopressin and adrenaline (

BACKGROUND Multiple cardiac and non-cardiac processes may cause an elevated highly sensitive troponin (hsTn). We postulated that the consumption of a seriously hot vindaloo could cause an increase in hsTn levels in seemingly healthy volunteers. OBJECTIVE To determine whether eating a very hot curry can cause elevated hsTn. METHODS This was a prospective observational cohort study. Participants had blood drawn for hsTn pre-ingestion and at 2 and 4 h post-ingestion of, first, a rather mild butter chicken and, 2 weeks later, a seriously hot lamb vindaloo. We assessed pre-curry tolerance and perception of curry hotness for both curries using the VHOT scale. RESULTS Although no participant had a troponin above the reference range at any point in time, we found dramatic relative increases in troponin in many of our participants. In the vindaloo phase, 8/22 (36%) had a relative change >20%, whereas 5/22 (23%) had a relative change >50% at 4 h. However, these changes were not significantly different to those in the butter chicken phase. Based on biological variability alone, 15/22 (68%) had a relative change of >20%, and 11/22 (50%) had a relative change of >50% between the two sessions (pre-ingestion). CONCLUSIONS Eating a seriously hot vindaloo does not appear to be a risk factor for troponitis, and people may consume vindaloo safely with the knowledge that this is unlikely to result in significant damage to their myocardium. However, clinicians should be aware of the biological variability of hsTn and exercise caution when interpreting apparent changes within the normal range.

This perspective article summarises the experience of conducting a multicentre research project. We describe expected and unexpected hurdles we experienced as well as suggesting possible solutions for researchers embarking on multicentre studies.

Introduction The Surviving Sepsis Campaign guidelines recommend administration of appropriate antibiotics within 1 h in patients with severe sepsis, with two sets of blood cultures taken prior to administration. Objective We evaluated the effect of introducing a Sepsis Early Alert Tool (SEAT) in the ED. Outcomes were antibiotic timing, antibiotic choice and obtaining adequate blood cultures. Methods A retrospective chart review compared consecutive severe sepsis presentations admitted to ICU via the ED during two equivalent 6 month periods before and after SEAT introduction. Results The analyses included 55 patients before and 45 following SEAT introduction. The groups were similar in age, sex, triage category, sepsis source, Acute Physiology and Chronic Health Evaluation III scores and hospital mortality. The percentage receiving antibiotics within 60 min of triage increased from 24% (95% CI 13–37%) to 44% (95% CI 30–60%), P = 0.03. Median time from triage to first antibiotic was 105 (IQR 65–170) min and 85 (IQR 50–140) min before and after SEAT introduction, respectively, P = 0.15. Percentages receiving antibiotics within 60 min of first recognition of severe sepsis were 67% (95% CI 53–79%) and 71% (95% CI 56–84%) before and after SEAT introduction, P = 0.83. The percentage having two sets of blood cultures drawn prior to antibiotic administration increased from 18% (95% CI 9–34%) to 44% (95% CI 27–60%), P = 0.008. Appropriateness of antibiotics was 58% (95% CI 44–71%) and 75% (95% CI 60–87%) before and after SEAT implementation, P = 0.09. Conclusion The introduction of a SEAT in the ED is associated with earlier recognition of severe sepsis and improvements in quality of care.

Hypertonic saline administered during fluid resuscitation may mitigate endothelial glycocalyx (EG) shedding and inflammation. The objective of this pilot randomised controlled trial was to measure the effect of hypertonic saline, compared to isotonic saline, on biomarkers of EG shedding and inflammation in emergency department patients with suspected sepsis.Patients received either 5 mL/kg of 3% saline (hypertonic group, n = 34) or 10 mL/kg of 0.9% saline (isotonic group, n = 31). Change in serum biomarker concentrations of syndecan-1, hyaluronan, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, interleukin-6, -8, -10, interferon-γ, neutrophil gelatinase-associated lipocalin and resistin were compared from baseline (T0) to after fluid (T1), 3 h (T3) and 12-24 h (T24) later, as was serum osmolality, using linear mixed effects models.The hypertonic group had significantly increased mean serum osmolality compared to the isotonic group at T1 (P .001) and T3 (P = .004). Minor differences were found in some biomarker outcomes, including a decreased fold-change in syndecan-1 at T1 (P = .012) and in interleukin-10 at T24 (P = .006) in the isotonic group, compared to the hypertonic group.Although a single bolus of hypertonic saline increased serum osmolality, it did not reduce biomarkers of EG shedding or inflammation, compared to patients that received isotonic saline.ANZCTR.org.au, ACTRN12611001021965, Registered on 23rd September 2011.

To describe the utilization of vasopressors (VP) in patients enrolled in the Australasian Resuscitation In Sepsis Evaluation (ARISE) trial, and to explore the association between time to VP and 90-day mortality.The primary exposure variable was VP use after arrival in the emergency department (ED). Vasoactive agents considered as VP included: norepinephrine, epinephrine, metaraminol, or vasopressin. Time-to-event analysis, multivariable logistic regression, and propensity-matched treatment effects modeling were used to assess the association between time to VP and 90-day mortality.In total 1,102 of 1,588 patients (69%) in ARISE received VP at any point. The median [interquartile range (IQR)] time from ED presentation to commencing VP was 4.4 [2.7, 7.1] h, and 38% did so prior to central venous access. The median [IQR] volume of intravenous (i.v.) fluid administered prior to commencing VP was 3.1 [2.3, 4.3] L. Increasing age and volume of i.v. fluid therapy were associated with a lower likelihood of commencing VP early (within 4 h of ED presentation), while greater illness severity was associated with a higher likelihood, P 0.001, respectively. In those who subsequently died within 90 days, the sub-hazard ratio (95% confidence interval) for commencing VP was 1.4 (1.20, 1.68), P 0.001, adjusted for age, acute physiology and chronic health evaluation II score, study group, inclusion criteria, plasma lactate, i.v. fluid prior to VP, study institution, and site of infection.50% of the ARISE cohort commenced VP within 4.4 h of ED presentation, and many did so prior to central venous access. Earlier initiation of VP was associated with greater crude and adjusted 90-day mortality.

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 – 75 ml/kg (4–6 liters in an 80 kg adult) over 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 (≤2–3 liters)] 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 (NHLBI) Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies—the Crystalloid Liberal Or Vasopressor Early Resuscitation in Sepsis (CLOVERS) trial. The purpose of this manuscript 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.

Background: We have previously identified the upregulation of the innate immune response, neutrophil activation, and apoptosis during anaphylaxis using a microarray approach. This study aimed to validate the differential gene expression and investigate protein concentrations of “hub genes” and upstream regulators during anaphylaxis. Methods: Samples were collected from patients with anaphylaxis on their arrival at the emergency department, and after 1 and 3 h. mRNA levels of 11 genes (interleukin-6 [IL-6], IL-10, oncostatin M [OSM], S100A8, S100A9, matrix metalloproteinase 9 [MMP9], FASL, toll-like receptor 4 [TLR4], MYD88, triggering receptor expressed on myeloid cells 1 [TREM1], and cluster of differentiation 64 [CD64]) were measured in peripheral blood leucocytes using qPCR. Serum protein concentrations were measured by ELISA or cytometric bead array for 6 of these candidates. Results: Of 69 anaphylaxis patients enrolled, 36 (52%) had severe reactions, and 38 (55%) were female. Increases in both mRNA and protein of IL-10, S100A9, MMP9, and TREM1 were observed. OSM, S100A8, TLR4, and CD64 were upregulated and IL-6 protein concentrations were increased during anaphylaxis. Both FASL and soluble Fas ligand decreased during anaphylaxis. Conclusion: These results provide evidence for the involvement of innate immune pathways and myeloid cells during human anaphylaxis, validating previous microarray findings. Elevated S100A8, S100A9, TLR4, and TREM1 expression, and increased S100A9 and soluble TREM1 protein concentrations strongly suggest that neutrophils are activated during acute anaphylaxis.

Although comprehensive guidelines for treatment of sepsis exist, current research continues to refine and revise several aspects of management. Imperatives for rapid administration of broad-spectrum antibiotics for all patients with sepsis may not be supported by contemporary data. Many patients may be better served by a more judicious approach allowing consideration of investigation results and evidence-based guidelines. Conventional fluid therapy has been challenged with early evidence supporting balanced, restricted fluid and early vasopressor use. Albumin, vasopressin and hydrocortisone have each been shown to support blood pressure and reduce catecholamine requirements but without effect on mortality, and as such should be considered for ED patients with septic shock on a case-by-case basis. Measurement of quality care in sepsis should incorporate quality of blood cultures and guideline-appropriateness of antibiotics, as well as timeliness of therapy. Local audit is an essential and effective means to improve practice. Multicentre consolidation of data through agreed minimum sepsis data sets would provide baseline quality data, required for the design and evaluation of interventions.

Background Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified. Methods/design The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support ‘free days’ to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups. Discussion This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium. Trial registration Australia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2137-7) contains supplementary material, which is available to authorized users.

Clinical diagnosis of anaphylaxis is principally based on symptoms and signs. However, particularly for patients with atypical symptoms, laboratory confirmation of anaphylaxis would be useful. This study investigated the utility of mast cell tryptase, an available clinical biomarker, for differentiating anaphylaxis from other causes of critical illness, which can also involve mast cell activation.Tryptase was measured (ImmunoCAP) in serum from patients with anaphylaxis and non-anaphylactic critical illness (controls) at ED arrival, and after 1-2, 3-4 and 12-24 h. Differences in both peak and delta (difference between highest and lowest) tryptase concentrations between groups were investigated using linear regression models, and diagnostic ability was analysed using Receiver Operating Characteristic curve analysis.Peak tryptase was fourfold (95% CI: 2.9, 5.5) higher in anaphylaxis patients (n = 67) than controls (n = 120) (P 0.001). Delta-tryptase was 5.1-fold (95% CI: 2.9, 8.9) higher in anaphylaxis than controls (P 0.001). Optimal test characteristics (sensitivity: 72% [95% CI: 59, 82] and specificity: 72% [95%CI: 63, 80]) were observed when peak tryptase concentrations were11.4 ng/mL and/or delta-tryptase ≥2.0 ng/mL. For hypotensive patients, peak tryptase11.4 ng/mL had improved test characteristics (sensitivity: 85% [95% CI: 65, 96] and specificity: 92% [95% CI: 85, 97]); the use of delta-tryptase reduced test specificity.While peak and delta tryptase concentrations were higher in anaphylaxis than other forms of critical illness, the test lacks sufficient sensitivity and specificity. Therefore, mast cell tryptase values alone cannot be used to establish the diagnosis of anaphylaxis in the ED. In particular, tryptase has limited utility for differentiating anaphylactic from non-anaphylactic shock.

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). 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. 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. 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.

Background Spontaneous pneumothorax can be managed initially by observation, aspiration or chest drain insertion. Aims To determine the clinical features of spontaneous pneumothorax in patients presenting to the emergency department (ED), interventions, outcomes and potential risk factors for poor outcomes after treatment. Methods Retrospective chart review from ED of three major referral and two general hospitals in Australia of presentations with primary spontaneous pneumothorax (PSP) or secondary spontaneous pneumothorax (SSP). Main outcomes were prolonged air leak (>5 days) and pneumothorax recurrence within 1 year. Results We identified 225 people with PSP and 98 with SSP. There were no clinical tension pneumothoraces with hypotension. Hypoxaemia (haemoglobin oxygen saturation measured by pulse oximetry ≤92%) occurred only in SSP and in older patients (age >50 years) with PSP. Drainage was performed in 150 (67%) PSP and 82 (84%) SSP. Prolonged air leak occurred in 16% (95% confidence interval 10–23%) of PSP and 31% (21–42%) of SSP. Independent risk factors for prolonged drainage were non-asthma SSP and pneumothorax size >50%. Complications were recorded in 11% (7.5–16%) of those having drains inserted. Recurrences occurred in 5/91 (5%, 1.8–12%) of those treated without drainage versus 40/232 (17%, 13–23%) of those treated by drainage, of which half occurred in the first month after drainage. Conclusion Pneumothorax drainage is associated with substantial morbidity including prolonged air leak. As PSP appears to be well tolerated in younger people even with large pneumothoraces, conservative treatment in this subgroup may be a viable option to improve patient outcomes, but this needs to be confirmed in a clinical trial.

Background The mechanisms involved in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of neutrophils. These innate immune cells are highly abundant in peripheral blood and can be rapidly activated to trigger both local and systemic inflammation. Objective To investigate neutrophil activation in peripheral blood during acute human anaphylaxis. Methods Patients presenting to the Emergency Department with anaphylaxis underwent blood sampling upon enrolment and at up to three subsequent time points. Traditional anaphylaxis biomarkers, histamine and mast cell tryptase, were measured by ELISA and ImmunoCAP respectively. Plasma myeloperoxidase concentrations were measured by ELISA, serum soluble CD62L concentrations by cytometric bead array, and both compared to healthy controls. Results In 72 patients, 37 (51%) had severe anaphylaxis, 33 (60%) were histamine positive, and 47 (70%) were mast cell tryptase positive. At enrolment, myeloperoxidase concentrations were 2.9- (95% CI: 1.3, 6.5) and 5.0- (95% CI: 2.4, 10.5) fold higher in moderate and severe patients respectively, compared with healthy controls, and remained stable over the first 5 hours following symptom onset. At enrolment, soluble CD62L was 29% (95% CI: 19, 38) and 31% (95% CI: 22, 40) lower in moderate and severe patients respectively, than healthy controls, and was stable over the first 5 hours. There were no associations between myeloperoxidase or soluble CD62L concentrations and either histamine or mast cell tryptase concentrations. Conclusions and Clinical Relevance These results provide compelling evidence for the involvement of neutrophils during acute human anaphylaxis, suggesting they are activated early in the reaction, regardless of mast cell activation. This important finding increases our understanding of the basic mechanisms of anaphylaxis, a necessary precursor to improving treatment and prevention. This article is protected by copyright. All rights reserved.

Objectives To determine whether a booked appointment time improves early outpatient exercise stress testing (EST) guideline adherence in patients discharged from the ED following assessment for possible acute coronary syndrome (ACS). Methods In this pre and post study with a historical control group, patients classified as intermediate risk after negative ECG and serial troponin work-up for possible ACS were referred for EST. The intervention group were given an appointment time for EST at discharge, and the control group were given a referral but asked to book their own appointment. The primary outcome measure was the proportion in each group who attended for EST. Secondary outcomes were time to EST and rates of death, myocardial infarction and coronary revascularisation within 30 days in both groups. In addition, we explored reasons for non-attendance for EST for the intervention group. Results There were 96 participants in the intervention group (mean age 55 ± 3 years) and 121 controls (mean age 62 ± 3 years). Seventy-two (75%) of the intervention group attended for EST compared with 38 (31%) of the control group, P < 0.001 after adjustment for differences in baseline variables. A poor understanding of the rationale for EST was a significant factor in patient non-attendance. Conclusion Pre-booked appointment times for EST improve timely attendance among patients discharged from the ED with intermediate-risk ACS. Compliance might improve further with patient education.

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.

OBJECTIVE: To compare two methods of risk stratification for suspected acute coronary syndrome (ACS) in the ED. METHODS: A prospective observational multicentre study was undertaken of patients undergoing evaluation in the ED for possible ACS. We compared the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand (NHF/CSANZ) guideline and the Thrombolysis in Myocardial Infarction (TIMI) risk score for differentiating high- and low-risk patients. Composite outcome was all cause death, myocardial infarction or coronary revascularisation within 30 days. RESULTS: Of 1758 enrolments, 223 (13%) reached the study outcome. Area under the receiver operator characteristic (ROC) curve was 0.79 (95% CI 0.76-0.81) for the NHF/CSANZ group and 0.71 (0.68-0.75) for TIMI score based on initial troponin result (P

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.

The Predisposition Insult Response and Organ failure (PIRO) scoring system has been developed for use in the emergency department (ED) to risk stratify sepsis cases, but has not been well studied among high-risk patients with severe sepsis and septic shock. The PIRO score was compared with the Sequential Organ Failure Assessment (SOFA) and Mortality in ED Sepsis (MEDS) scores to predict mortality in ED patients with features suggesting severe sepsis or septic shock in the ED.This was an analysis of sepsis patients enrolled in a prospective observational ED study of patients presenting with evidence of shock, hypoxemia, or other organ failure. PIRO, MEDS, and SOFA scores were calculated from ED data. Analysis compared areas under the receiver operator characteristic (ROC) curves for 30-day mortality.Of 240 enrolled patients, final diagnoses were septic shock in 128 (53%), severe sepsis without shock in 70 (29%), and infection with no organ dysfunction in 42 (18%). Forty-eight (20%) patients died within 30 days of presentation. Area under the ROC curve (AUC) for mortality was 0.86 (95% confidence interval [CI] = 0.80 to 0.92) for PIRO, 0.81 (95% CI = 0.74 to 0.88) for MEDS, and 0.78 (95% CI = 0.71 to 0.87) for SOFA scores. Pairwise comparisons of the AUC were as follows: PIRO versus SOFA, p = 0.01; PIRO versus MEDS, p = 0.064; and MEDS versus SOFA; p = 0.37. Mortality increased with increasing PIRO scores: PIRO5, 0%; PIRO 5 to 9, 5%; PIRO 10 to 14, 5%; PIRO 15 to 19, 37%; and PIRO ≥ 20, 80% (p0.001). The MEDS score also showed increasing mortality with higher scores: MEDS5, 0%; MEDS 5 to 7, 12%; MEDS 8 to 11, 15%; MEDS 12 to 14, 48%; and MEDS15, 65% (p0.001).The PIRO model, taking into account comorbidities and septic source as well as physiologic status, performed better than the SOFA score and similarly to the MEDS score for predicting mortality in ED patients with severe sepsis and septic shock. These findings have implications for identifying and managing high-risk patients and for the design of clinical trials in sepsis.

Simon Brown and Stephen Macdonald argue that patients with stroke should not be given thrombolysis outside clinical trials, but Graeme Hankey says the benefits are clear in carefully selected patients

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 (StO 2 ), which may be an indirect measure of the adequacy of the microcirculation. StO 2 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 StO 2 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 StO 2 as a resuscitation target.

AimThe 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.MethodsA 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.ResultsOf 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, pConclusionsmTIMI 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.

To determine whether a booked appointment time improves early outpatient exercise stress testing (EST) guideline adherence in patients discharged from the ED following assessment for possible acute coronary syndrome (ACS).In this pre and post study with a historical control group, patients classified as intermediate risk after negative ECG and serial troponin work-up for possible ACS were referred for EST. The intervention group were given an appointment time for EST at discharge, and the control group were given a referral but asked to book their own appointment. The primary outcome measure was the proportion in each group who attended for EST. Secondary outcomes were time to EST and rates of death, myocardial infarction and coronary revascularisation within 30 days in both groups. In addition, we explored reasons for non-attendance for EST for the intervention group.There were 96 participants in the intervention group (mean age 55 ± 3 years) and 121 controls (mean age 62 ± 3 years). Seventy-two (75%) of the intervention group attended for EST compared with 38 (31%) of the control group, P0.001 after adjustment for differences in baseline variables. A poor understanding of the rationale for EST was a significant factor in patient non-attendance.Pre-booked appointment times for EST improve timely attendance among patients discharged from the ED with intermediate-risk ACS. Compliance might improve further with patient education.

Background Acute Decompensated Cardiac Failure (ADCF) is frequently associated with deterioration in renal function. Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We aimed to determine if NGAL measured at admission predicts in-hospital acute kidney injury (AKI) in ADCF. Methods A prospective observational study measured NGAL and B-natriuretic peptide (BNP) from patients with ADCF presenting to two tertiary hospitals. Patients received standard care and were followed up daily as inpatients. ADCF was defined by PRIDE score ≥ 6 and AKI by RIFLE criteria. Results One hundred and two patients (median age 80, IQR 69-84 years, 52% male) were enrolled. AKI developed in 22 (25%) of 90 for whom outcome data was available. Seven patients died. NGAL was significantly elevated in those who developed AKI versus those who did not (median 130 ng/ml vs 69 ng/ml, p = 0.002). NGAL was also higher in those who died (median 136 ng/ml vs 68 ng/ml, p = 0.005). AKI was significantly associated with risk of death (5/22 (23%) vs 1/68 (1.5%), p = 0.001), but not length of hospital stay. NGAL significantly correlated with admission eGFR but not BNP. For prediction of AKI, NGAL > 89 ng/ml had sensitivity of 68% and specificity of 70% with area under the receiver operator characteristic (ROC) curve of 0.71 (0.58-0.84). After adjustment for baseline renal function, the odds ratio (OR) for AKI was 3.73 (1.26-11.01) if admission NGAL > 89 ng/ml. Conclusions Elevated NGAL at admission is associated with in-hospital AKI and mortality in patients with ADCF. However, it has only moderate diagnostic accuracy in this setting.