Jason Kendall

NICE guidance. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin

Chest pain is a very common symptom; 20% to 40% of the general population will experience chest pain during their lives,1 and in the UK, up to 1% of visits to a general practitioner are because of chest pain.2 Approximately 700 000 visits (5%) to the emergency department in England and Wales and up to 25% of emergency hospital admissions are because of chest pain.3 There are many causes of chest pain, some of which are benign, while others are potentially life threatening. Importantly, in patients with chest pain caused by an acute coronary syndrome (ACS) or angina, there are effective treatments to improve symptoms and prolong life, emphasising the importance of making timely and accurate diagnoses in patients in whom chest pain may be of cardiac origin. This guideline4 addresses the assessment and diagnosis of patients with recent onset chest pain/discomfort that may be of cardiac origin. Unlike many other National Institute for Health and Clinical Excellence (NICE) clinical guidelines it does not make recommendations for the management of the condition once the diagnosis is made. The NICE unstable angina and NSTEMI clinical guideline5 was published at the same time as the chest pain guideline, and a NICE clinical guideline for the management of angina is currently being prepared.6 The guideline has two separate diagnostic pathways. The first is for patients with acute chest pain who may have an ACS and the second for those with intermittent stable chest pain who may have stable angina. The guideline deals with chest pain of suspected cardiac origin. Thus, for example, the guideline does not apply to patients with pain considered to be caused by recent trauma to the chest. However, many patients presenting with chest pain do not have such clearly apparent alternative explanations and need …

Evaluation of High-Sensitivity Cardiac Troponin I Levels in Patients With Suspected Acute Coronary Syndrome

IMPORTANCE Low concentrations of high-sensitivity cardiac troponin I determined on presentation to the emergency department (ED) have been shown to have an excellent negative predictive value (NPV) for the identification of acute myocardial infarction. The sensitivity, and therefore clinical applicability, of such testing strategies is unknown. OBJECTIVE To determine the diagnostic performance of low concentrations of high-sensitivity cardiac troponin I in patients with suspected cardiac chest pain and an electrocardiogram showing no ischemia as an indicator of acute myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS A pooled analysis of 5 international (Australia, New Zealand, and England) prospective, observational cohort studies with blinded outcome assessment and 30-day follow-up was conducted. A total of 3155 patients presenting with symptoms suggestive of cardiac ischemia were included in the analysis. Eligible patients had a nonischemic electrocardiogram determined and high-sensitivity troponin I measured at presentation. The lower limit of detection (1.2 ng/L) as well as cutoff concentrations rounded to the nearest integer for a high-sensitivity troponin I assay were used in the analysis. Recruitment was undertaken from November 1, 2007, to August 10, 2013. MAIN OUTCOMES AND MEASURES The primary outcome was fatal or nonfatal acute myocardial infarction occurring within 30 days of ED presentation, adjudicated with serial troponin testing. The secondary outcome was the proportion of patients potentially suitable for early discharge at each cutoff concentration. RESULTS Of the 3155 eligible patients, 1771 were male (56.1%), and mean (SD) age was 57.4 (13.3) years. Acute myocardial infarction developed in 291 individuals (9.2%). The 1.2-ng/L limit of detection gave a sensitivity of 99.0% (95% CI, 96.8%-99.7%) and an NPV of 99.5% (95% CI, 98.4%-99.9%). This cutoff level would allow for early discharge of 594 patients (18.8%). All higher rounded cutoff values had sensitivities less than 98.0%. Diagnostic performance of the limit of detection was maintained when patients were stratified by age, sex, risk factors, presence of coronary artery disease, and early presentation. CONCLUSIONS AND RELEVANCE High-sensitivity troponin I concentrations determined at presentation to the ED that were below the limit of detection identified 18.8% of patients potentially suitable for discharge, with a high sensitivity for acute myocardial infarction. Rounded cutoff values above the limit of detection may not have the required sensitivity for clinical implementation.

Cost-effectiveness of presentation versus delayed troponin testing for acute myocardial infarction

Objectives To estimate the cost-effectiveness of delayed troponin testing for myocardial infarction compared with troponin testing at presentation. Design Decision analysis modelling of cost-effectiveness using secondary data sources. Setting Acute hospitals in the UK. Population Patients attending hospital with suspected myocardial infarction but a normal or non-diagnostic ECG and no major comorbidities requiring admission. Interventions Delayed troponin testing (10 h after symptom onset) compared with standard and high-sensitivity troponin testing at presentation and no testing. Sensitivity analysis evaluated high-sensitivity troponin testing 3 h after initial assessment. Main outcome measures The incremental cost per quality-adjusted life year (QALY) gained by each strategy, compared with the next most effective alternative, and the probability of each strategy being cost-effective at varying willingness-to-pay per QALY gained. Results In all scenarios tested, presentation high-sensitivity troponin testing was the most effective strategy with an incremental cost-effectiveness ratio below the £20 000/QALY threshold. 10 h troponin testing was only likely to be cost-effective if a discharge decision could be made as soon as a negative result was available and the £30 000/QALY threshold was used, or if a lower sensitivity estimate for presentation high-sensitivity troponin was assumed. Sensitivity analysis showed that including high-sensitivity troponin testing at presentation and 3 h in the analysis makes this the most cost-effective strategy. Conclusions Delayed troponin testing is unlikely to be cost-effective compared with high-sensitivity troponin testing at presentation in most scenarios. Current NICE chest pain guidelines do not promote cost-effective care.

A novel multipatient intranasal diamorphine spray for use in acute pain in children: pharmacovigilance data from an observational study

Objectives To establish the safety of an intranasal diamorphine (IND) spray in children. Design An open-label, single-dose pharmacovigilance trial. Setting Emergency departments in eight UK hospitals. Participants Children aged 2–16 years with a fracture or other trauma. Outcome measures Adverse events (AE) specifically related to nasal irritation, respiratory and central nervous system depression. Results 226 patients received 0.1 mg/kg IND. No serious or severe AEs occurred. The incidence of treatment-emergent AEs (TEAEs) was 26.5% (95% CI 20.9% to 32.8%), 93% being mild. 89% were related to treatment, all being known effects of the drug or route of administration except for three events in two patients. 20.4% (95% CI 15.3% to 26.2%) patients reported nasal irritation, all mild except one moderate and one ‘unknown’ severity. No respiratory depression was reported. Three AEs related to reduced Glasgow Coma Score (GCS) occurred, all mild. Conclusions There were no safety concerns raised during the conduct of the study. In addition to expected side effects, IND can cause mild nasal irritation in a proportion of patients. European Union Drug Regulating Authorities Clinical Trial No 2009-014982-16.

Interhospital variation in the RATPAC trial (Randomised Assessment of Treatment Using Panel Assay of Cardiac Markers)

Background The RATPAC trial showed that using a point-of-care panel of CK-MB(mass), myoglobin and troponin at baseline and 90 min increased the proportion of patients successfully discharged home, leading to reduced median length of initial hospital stay. However, it did not change mean hospital stay and may have increased mean costs per patient. The aim of this study was to explore variation in outcome and costs between participating hospitals. Methods RATPAC was a pragmatic multicentre randomised controlled trial (N=2243) and economic analysis comparing diagnostic assessment using the panel to standard care for patients with acute chest pain due to suspected myocardial infarction at six hospitals. The difference in the proportion of patients successfully discharged (primary outcome) and mean costs per patient between the participating hospitals was compared. Results Point-of-care assessment led to a higher proportion of successful discharges in four hospitals, a lower proportion in one and was equivocal in another. The OR (95% CI) for the primary outcome varied from 0.12 (0.01 to 1.03) to 11.07 (6.23 to 19.66) with significant heterogeneity between the centres (p<0.001). The mean cost per patient for the intervention group ranged from being £214.49 less than the control group (−132.56 to 657.10) to £646.57 more expensive (73.12 to 1612.71), with weak evidence of heterogeneity between the centres (p=0.0803). Conclusion The effect of point-of-care panel assessment on successful discharge and costs per patient varied markedly between hospitals and may depend on local protocols, staff practices and available facilities.

Assessment of the 2016 National Institute for Health and Care Excellence high-sensitivity troponin rule-out strategy

Objective We aimed to evaluate the limit of detection of high-sensitivity troponin (hs-cTn) and Thrombolysis In Myocardial Infarction (TIMI) score combination rule-out strategy suggested within the 2016 National Institute for Health and Care Excellence (NICE) Chest Pain of Recent Onset guidelines and establish the optimal TIMI score threshold for clinical use. Methods A pooled analysis of adult patients presenting to the emergency department with chest pain and a non-ischaemic ECG, recruited into six prospective studies, from Australia, New Zealand and the UK. We evaluated the sensitivity of TIMI score thresholds from 0 to 2 alongside hs-cTnT or hs-cTnI for the primary outcome of major adverse cardiac events within 30 days. Results Data were available for 3159 patients for hs-cTnT and 4532 for hs-cTnI, of these 376 (11.9%) and 445 (9.8%) had major adverse cardiac events, respectively. Using a TIMI score of 0, the sensitivity for the primary outcome was 99.5% (95% CI 98.1% to 99.9%) alongside hs-cTnT and 98.9% (97.4% to 99.6%)%) alongside hs-cTnI, identifying 17.9% and 21.0% of patients as low risk, respectively. For a TIMI score ≤1 sensitivity was 98.9% (97.3% to 99.7%)%) alongside hs-cTnT and 98.4% (96.8% to 99.4%)%) alongside hs-cTnI, identifying 28.1% and 35.7% as low risk, respectively. For TIMI≤2, meta-sensitivity was <98% with either assay. Conclusions Our findings support the rule-out strategy suggested by NICE. The TIMI score threshold suggested for clinical use is 0. The proportion of patients identified as low risk (18%–21%) and suitable for early discharge using this threshold may be sufficient to encourage change of practice. Trial registration numbers ADAPT observational study/IMPACT intervention trial ACTRN12611001069943. ADAPT-ADP randomised controlled trial ACTRN12610000766011. EDACS-ADP randomised controlled trial ACTRN12613000745741. TRUST observational study ISRCTN no. 21109279.

Reducing delay to stroke thrombolysis—lessons learnt from the Stroke 90 Project

Background The Stroke 90 Project was implemented to reduce delays to stroke thrombolysis and involved 7 hospitals and 2 ambulance services in the Avon, Gloucester, Wiltshire and Somerset regional network. Interventions included a direct to CT (DtoCT) protocol for paramedics to transport patients directly to the CT scanner. Coincidentally, there were severe winter pressures on all participating emergency departments during this period. Methods Comparison of data from 2 groups across all 7 hospitals: preintervention (n=136) and postintervention patients (n=215) thrombolysed from August 2012 to January 2013. The χ2 test, t tests, multiple and linear regression were used for analysis. Results Ambulance transport times were 56.8 min for preintervention versus 57.5 min for postintervention patients (p=0.78). 11.7% of preintervention patients received thrombolysis within 90 min of call for help versus 23.7% of postintervention cases (p=0.0135). 44% of postintervention patients entered the DtoCT pathway and achieved a mean reduction in door to CT time of 17 min (95% CI 11.5 to 21.5; p<0.0001) and a 19 min reduction in door to needle time (95% CI 10.8 to 26.8; p<0.0001). CT to needle times were 43.8 min preintervention and 42.1 min postintervention (p=0.57). Conclusions The DtoCT pathway was successful in reducing delays to thrombolysis and should be implemented routinely. The call to door and CT to needle times were not improved by our interventions and further work is required to streamline these. Factors beyond the control of most hospitals may play a role in delaying treatment, but local changes can be implemented to mitigate this.

Low Concentrations of High-Sensitivity Troponin T at Presentation to the Emergency Department

To the Editor: Several issues around rule-out strategies utilizing low concentrations of high-sensitivity cardiac troponin assays taken at presentation to the Emergency Department (ED)1 remain unexplored. First, large-scale analyses investigating cutoff concentrations for high-sensitivity cardiac troponin I (hs-cTnI; Abbott Architect) <99th percentile, have failed to investigate outcomes that incorporate the full spectrum of clinically relevant acute coronary syndromes, namely emergency revascularization (1, 2). Second, whether these strategies work with the high-sensitivity cardiac troponin T (hs-cTnT; Roche Elecsys) assay is underexplored. Finally, the impact of laboratory rounding (i.e., rounding the reported value up or down to the next whole integer depending on the exact post–decimal point value—e.g., 4.5 ng/L to 5 ng/L) upon diagnostic performance at low cutoff concentrations, and how this effects the proportion of patients potentially eligible for early discharge, remains unknown. In this post hoc analysis of a prospectively recruited cohort we aimed to establish the diagnostic performance of a single hs-cTnT result taken at ED presentation in patients with a nonischemic electrocardiogram (ECG), using the limit of detection (LoD) and additional cutoff concentrations <99th percentile, and also the impact of laboratory rounding. The methods and results of the primary analysis have been published previously, including reporting of diagnostic accuracy at the LoD …

Thrombolysis for acute ischaemic stroke: a new challenge for emergency medicine.

Introduction: Acute ischaemic stroke (AIS) is a leading cause of death and disability within the United Kingdom. Despite evidence of the benefit of thrombolysis for appropriately selected patients with AIS, this intervention remains markedly underutilised in this country when compared with other developed countries. The delivery of thrombolysis for AIS has become a political, as well as a clinical, priority in the United Kingdom. Discussion: Research has shown that, althongh thrombolysis for AIS is associated with increased shout-term mortality, this is offset by a signficant benefit in terms of reduced long-term death and disability. Recent observational data have shown that it can be safely and effectively delivered in the ”normal„ clinical setting (ie, a non-research environment). Furthermore, thrombolysis for AIS is supported by the Royal College of Physicians and the National Insititute for Health and Clinical Excellence. Emergency physicians are trained to receive and assess patients with possible stroke. The emergency department (ED) is an ideal location in which to perform these clinical duties and to communicate and coordinate the necessary tasks required for the delivery of thrombolysis. All of the skills and resources are already available within the ED, with the exception of a single training requirement: certification in the National Institute for Health Stroke Scale scoring system, which can be acquired following limited Internet-based traning. Results: Emergency physicians should be integrally involved in the development of protocols for the delivery of thrombolysis to patients with AIS. This will require communication and collaboration locally with stroke physicians and radiologists, a process that should be facilitated by the newly emerging Stroke Networks.

Evaluation of a Telephone Advice System for Remote Intravenous Thrombolysis in Ischemic Stroke: Data From a United Kingdom Network

Background and Purpose— There is limited evidence for remote stroke thrombolysis using telephone consultation and teleradiology. Results from a UK network using this treatment model are presented. Methods— Retrospective study of consecutive patients thrombolysed in 5 hospitals, with well organized stroke services, between 2012 and 2013. Remote thrombolysis was compared with thrombolysis delivered in person for symptomatic intracerebral hemorrhage, death within 7 days, and 90-day modified Rankin scores. Results— Of 586 patients, 220 (37.5%) were thrombolysed remotely. The 2 groups were well matched (median age 77 years, NIHSS 12). Remote thrombolysis increased treatment time by 22 minutes. Outcomes were no different in the 2 groups (remote versus standard): symptomatic intracerebral hemorrhage (3.6% versus 4.6%), death within 7 days (6.4% versus 7.1%), modified Rankin score <2 (46.0% versus 46.1%), and modified Rankin score 6 (15% versus 17.5%) at 90 days. Conclusion— Telephone advice and teleradiology, within an organized system of care, can be an effective method of delivery of intravenous thrombolysis.