Development and Internal Validation of a Multivariable Prediction Model to Predict Repeat Attendances in the Pediatric Emergency Department: A Retrospective Cohort Study.

OBJECTIVE: Unplanned reattendances to the pediatric emergency department (PED) occur commonly in clinical practice. Multiple factors influence the decision to return to care, and understanding risk factors may allow for better design of clinical services. We developed a clinical prediction model to predict return to the PED within 72 hours from the index visit. METHODS: We retrospectively reviewed all attendances to the PED of Royal Manchester Children's Hospital between 2009 and 2019. Attendances were excluded if they were admitted to hospital, aged older than 16 years or died in the PED. Variables were collected from Electronic Health Records reflecting triage codes. Data were split temporally into a training (80%) set for model development and a test (20%) set for internal validation. We developed the prediction model using LASSO penalized logistic regression. RESULTS: A total of 308,573 attendances were included in the study. There were 14,276 (4.63%) returns within 72 hours of index visit. The final model had an area under the receiver operating characteristic curve of 0.64 (95% confidence interval, 0.63-0.65) on temporal validation. The calibration of the model was good, although with some evidence of miscalibration at the high extremes of the risk distribution. After-visit diagnoses codes reflecting a nonspecific problem ("unwell child") were more common in children who went on to reattend. CONCLUSIONS: We developed and internally validated a clinical prediction model for unplanned reattendance to the PED using routinely collected clinical data, including markers of socioeconomic deprivation. This model allows for easy identification of children at the greatest risk of return to PED.

COVID-19 rapid diagnostics: practice review.

Point-of-care tests for SARS-CoV-2 could enable rapid rule-in and/or rule-out of COVID-19, allowing rapid and accurate patient cohorting and potentially reducing the risk of nosocomial transmission. As COVID-19 begins to circulate with other more common respiratory viruses, there is a need for rapid diagnostics to help clinicians test for multiple potential causative organisms simultaneously.However, the different technologies available have strengths and weaknesses that must be understood to ensure that they are used to the benefit of the patient and healthcare system. Device performance is related to the deployed context, and the diagnostic characteristics may be affected by user experience.This practice review is written by members of the UK's COVID-19 National Diagnostic Research and Evaluation programme. We discuss relative merits and test characteristics of various commercially available technologies. We do not advocate for any given test, and our coverage of commercially supplied tests is not intended to be exhaustive.

Electrocardiographic Diagnosis of Acute Coronary Occlusion Myocardial Infarction in Ventricular Paced Rhythm Using the Modified Sgarbossa Criteria.

STUDY OBJECTIVE: Ventricular paced rhythm is thought to obscure the electrocardiographic diagnosis of acute coronary occlusion myocardial infarction. Our primary aim was to compare the sensitivity of the modified Sgarbossa criteria (MSC) to that of the original Sgarbossa criteria for the diagnosis of occlusion myocardial infarction in patients with ventricular paced rhythm. METHODS: In this retrospective case-control investigation, we studied adult patients with ventricular paced rhythm and symptoms of acute coronary syndrome who presented in an emergency manner to 16 international cardiac referral centers between January 2008 and January 2018. The occlusion myocardial infarction group was defined angiographically as thrombolysis in myocardial infarction grade 0 to 1 flow or angiographic evidence of coronary thrombosis and peak cardiac troponin I ≥10.0 ng/mL or troponin T ≥1.0 ng/mL. There were 2 control groups: the "non-occlusion myocardial infarction-angio" group consisted of patients who underwent coronary angiography for presumed type I myocardial infarction but did not meet the definition of occlusion myocardial infarction; the "no occlusion myocardial infarction" control group consisted of randomly selected emergency department patients without occlusion myocardial infarction. RESULTS: There were 59 occlusion myocardial infarction, 90 non-occlusion myocardial infarction-angio, and 102 no occlusion myocardial infarction subjects (mean age, 72.0 years; 168 [66.9%] men). For the diagnosis of occlusion myocardial infarction, the MSC were more sensitive than the original Sgarbossa criteria (sensitivity 81% [95% confidence interval [CI] 69 to 90] versus 56% [95% CI 42 to 69]). Adding concordant ST-depression in V4 to V6 to the MSC yielded 86% (95% CI 75 to 94) sensitivity. For the no occlusion myocardial infarction control group of ED patients, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 96% (95% CI 90 to 99) versus 97% (95% CI 92 to 99); negative likelihood ratio (LR) 0.19 (95% CI 0.11 to 0.33) versus 0.45 (95% CI 0.34 to 0.65); and positive LR 21 (95% CI 7.9 to 55) versus 19 (95% CI 6.1 to 59). For the non-occlusion myocardial infarction-angio control group, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 84% (95% CI 76 to 91) versus 90% (95% CI 82 to 95); negative LR 0.22 (95% CI 0.13 to 0.38) versus 0.49 (95% CI 0.35 to 0.66); and positive LR 5.2 (95% CI 3.2 to 8.6) versus 5.6 (95% CI 2.9 to 11). CONCLUSION: For the diagnosis of occlusion myocardial infarction in the presence of ventricular paced rhythm, the MSC were more sensitive than the original Sgarbossa criteria; specificity was high for both rules. The MSC may contribute to clinical decisionmaking for patients with ventricular paced rhythm.

Comparison of four decision aids for the early diagnosis of acute coronary syndromes in the emergency department.

OBJECTIVES: To directly compare the diagnostic accuracy of four decision aids (Troponin-only Manchester Acute Coronary Syndromes (T-MACS), History, ECG, Age, Risk factors and Troponin (HEART), Thrombolysis in Myocardial Infarction (TIMI) and Emergency Department Assessment of Chest Pain (EDACS)) used to expedite the early diagnosis of acute coronary syndromes (ACS) in the ED. METHODS: We prospectively included patients who presented to 14 EDs in England (February 2015 to June 2017) with suspected ACS within 12 hours of symptom onset. Data to enable evaluation of the T-MACS, HEART, TIMI and EDACS decision aids (without recalibration) were prospectively collected, blinded to patient outcome. We tested admission blood samples for high-sensitivity cardiac troponin I (hs-cTnI; Siemens ADVIA Centaur). Patients also underwent serial cardiac troponin testing over 3-12 hours. The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI). We also evaluated the incidence of major adverse cardiac events (including death, AMI or coronary revascularisation) at 30 days. Diagnostic accuracy of each decision aid and hs-cTnI alone (using the limit of quantification cut-off, 3 ng/L) was evaluated by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Of 999 included patients, 132 (13.2%) had AMI. C-statistics were 0.96 for T-MACS, 0.78 for HEART and 0.69 for TIMI. The sensitivities of T-MACS, HEART, TIMI, EDACS and hs-cTnI <3 ng/L for AMI were 99.2% (95% CI 95.7% to 100.0%), 91.8% (85.0% to 96.2%), 97.5% (92.9% to 99.5%), 96.2% (92.2% to 99.4%) and 99.2% (95.9% to 100.0%), respectively. The respective strategies would have ruled out 46.5%, 34.9%, 19.4%, 48.3% and 28.8% patients. PPVs for the decision aids that identify 'high-risk' patients were 80.4% (T-MACS), 51.9% (TIMI) and 37.2% (HEART). CONCLUSIONS: In this study, T-MACS could rule out AMI in 46.5% patients with 99.2% sensitivity. EDACS could rule out AMI in 48.3% patients with lower sensitivity, although the difference was not statistically significant. The HEART and TIMI scores had lower diagnostic accuracy.

Diagnostic accuracy of the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid with a point-of-care cardiac troponin assay.

OBJECTIVE: Point-of-care (POC) cardiac troponin (cTn) assays have a rapid turnaround time but are generally less sensitive than laboratory-based assays. Previous research found that the Abbott i-Stat cardiac troponin I (cTnI) assay has good diagnostic accuracy when used with the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid and serial sampling over 3 hours. Accuracy of other assays may differ. We therefore evaluated the diagnostic accuracy of a different POC cTnI assay with serial sampling over 3 hours, both with T-MACS and when used alone. METHODS: In a prospective diagnostic accuracy study at eight EDs in England (July 2015-October 2017), we collected clinical data from consenting adults with suspected ACS at the time of assessment in the ED. Blood samples were drawn on arrival and 3 hours later for POC cTnI (Cardio 3 Triage, Alere). The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI), based on reference standard serial laboratory-based cTn testing. We calculated test characteristics for POC cTnI using the limit of detection (LoD, 0.01 µg/L) and the T-MACS decision aid. RESULTS: Of 347 participants, 59 (14.9%) had AMI. With serial POC cTnI testing over 3 hours, POC cTnI at the LoD cut-off ruled out AMI in 193 (55.6%) patients with 98.1% sensitivity (95% CI 89.9% to 100.0%) and 99.5% negative predictive value (NPV, 95% CI 96.5% to 99.9%). T-MACS ruled out AMI in 117 (33.7%) patients with 98.1% sensitivity (95% CI 89.9% to 100%) and 99.2% NPV (95% CI 94.3% to 99.9%). T-MACS ruled in AMI with 97.9% specificity (95% CI 95.8% to 99.5%) and 83.7% positive predictive value (95% CI 70.6% to 91.7%). CONCLUSIONS: With serial sampling over 3 hours, the Alere Cardio 3 Triage cTnI assay has relatively high NPV for AMI using either the LoD cut-off alone or the T-MACS decision aid. However, wide CIs around the measures of diagnostic accuracy mean that further prospective testing of this strategy is required before clinical implementation. TRIAL REGISTRATION NUMBER: UKCRN 18000.

BET 1: Oseltamivir use for quicker alleviation of symptoms, fewer hospital admissions and lower mortality in adult patients with influenza B.

A short cut review was carried out to establish whether Oseltamivir leads to faster alleviation of symptoms, fewer hospital admissions and lower mortality in adult patients with confirmed influenza B presenting to the Emergency Department. Two studies were directly relevant to the question using the described search methodology on Ovid Medline and Embase. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line: there is no good evidence that oseltamivir results in quicker alleviation of symptoms, fewer hospital admissions or lower mortality in adult patients with influenza B.

Optimising antiplatelet utilisation in the acute care setting: a novel threshold for medical intervention in suspected acute coronary syndromes.

OBJECTIVES: To construct a model to optimise and personalise recommendations for antiplatelet prescription for patients with suspected acute coronary syndrome (ACS). Acknowledging that emergency physicians work with diagnostic uncertainty, we sought to identify the point at which the probability of ACS is sufficiently high that the benefits of antiplatelet treatment outweigh the risks. Second, we evaluated the projected clinical impact of this approach by using a clinical prediction model (Troponin-only Manchester Acute Coronary Syndromes (T-MACS)) to calculate the probability of ACS. METHODS: We conducted three systematic reviews, quantifying the effects of ticagrelor, clopidogrel or aspirin-alone treatment strategies for ACS (November 2017). We extracted data for (a) clinical outcomes and (b) weighted patient preferences (utilities) for each outcome. We then constructed utilitarian models, simulating the probability of clinical outcomes with different treatment strategies. This identified the threshold probability of ACS at which each treatment strategy became superior.We validated this approach in a prospective diagnostic study including patients with suspected ACS that was conducted at two large UK teaching hospitals (St George's Hospital London recruited October 2015 to June 2017 and Manchester Royal Infirmary: February 2015 to August 2017). We calculated the probability of ACS using T-MACS. The diagnosis of ACS was adjudicated based on serial high-sensitivity troponin testing and 30-day follow-up. RESULTS: We constructed three models using data from six studies. Prescribing ticagrelor had greatest overall benefit when the probability of ACS exceeded 8.0%. Below that threshold, aspirin alone yielded greater benefit. The validation study included 660 patients, of which 87 (13.2%) had ACS. Prescription of combined antiplatelet strategy to patients with >8% probability of ACS had greater utility than aspirin alone. CONCLUSION: Treatment with ticagrelor appears to yield greater net benefit for patients when the probability of ACS >8%. The clinical and cost-effectiveness of this 'precision medicine' approach warrants further study.

BET 1: Can the Manchester Acute Coronary Syndromes and Troponin-only Manchester Acute Coronary Syndromes decision aids rule out acute coronary syndromes in the emergency department?

A short-cut review was carried out to establish whether the Manchester Acute Coronary Syndromes (MACS) and Troponin-only MACS (T-MACS) decision aids can safely rule out acute coronary syndromes in patients presenting to the ED with suspected cardiac chest pain. Six studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that both rules have high sensitivity for acute coronary syndromes, including the detection of major adverse cardiac events at 30 days. The original MACS algorithm may have marginally greater sensitivity than T-MACS but has inferior specificity and requires the use of a biomarker assay (for heart-type fatty acid binding protein) that is not currently widely used in practice.

Accuracy of efficient data methods to determine the incidence of hospital-acquired thrombosis and major bleeding in medical and surgical inpatients: a multicentre observational cohort study in four UK hospitals.

OBJECTIVES: We evaluated the accuracy of using routine health service data to identify hospital-acquired thrombosis (HAT) and major bleeding events (MBE) compared with a reference standard of case note review. DESIGN: A multicentre observational cohort study. SETTING: Four acute hospitals in the UK. PARTICIPANTS: A consecutive unselective cohort of general medical and surgical patients requiring hospitalisation for a period of >24 hours during the calendar year 2021. We excluded paediatric, obstetric and critical care patients due to differential risk profiles. INTERVENTIONS: We compared preidentified sources of routinely collected information (using hospital coding data and local contractually mandated thrombosis datasets) to data extracted from case notes using a predesigned workflow methodology. PRIMARY AND SECONDARY OUTCOME MEASURES: We defined HAT as objectively confirmed venous thromboembolism occurring during hospital stay or within 90 days of discharge and MBE as per international consensus. RESULTS: We were able to source all necessary routinely collected outcome data for 87% of 2008 case episodes reviewed. The sensitivity of hospital coding data (International Classification of Diseases 10th Revision, ICD-10) for the diagnosis of HAT and MBE was 62% (95% CI, 54 to 69) and 38% (95% CI, 27 to 50), respectively. Sensitivity improved to 81% (95% CI, 75 to 87) when using local thrombosis data sets. CONCLUSIONS: Using routinely collected data appeared to miss a substantial proportion of outcome events, when compared with case note review. Our study suggests that currently available routine data collection methods in the UK are inadequate to support efficient study designs in venous thromboembolism research. TRIAL REGISTRATION NUMBER: NIHR127454.

Long-term cardiovascular risk prediction in the emergency department: a mixed-methods study protocol.

INTRODUCTION: Cardiovascular disease (CVD) remains one of the leading causes of preventable death in Europe, therefore any opportunity to intervene and improve care should be maximised. Known CVD risk factors are routinely collected in the emergency department (ED), yet they are often not acted on. If the risk factors have prognostic value and a pathway can be created, then this would provide more holistic care for patients and reduce health system inefficiency. METHODS AND ANALYSIS: In this mixed-methods study, we will use quantitative methods to investigate the prognostic characteristics of routinely collected data for long-term CVD outcomes, and qualitative methods to investigate how to use and implement this knowledge. The quantitative arm will use a database of approximately 21 000 chest pain patient episodes with a mean follow-up of 7.3 years. We will use Cox regression to evaluate the prognostic characteristics of routinely collected ED data for long-term CVD outcomes. We will also use a series of semi-structured interviews to co-design a prototype care pathway with stakeholders via thematic analysis. To enable the development of prototypes, themes will be structured into a logic model consisting of situation, inputs, outputs and mechanism. ETHICS AND DISSEMINATION: This work has been approved by Research Ethics Committee (Wales REC7) and the Human Research Authority under reference 19/WA/0312 and 19/WA/0311. It has also been approved by the Confidentiality Advisory Group reference 19/CAG/0209. Dissent recorded in the NHS' opt-out scheme will be applied to the dataset by NHS Digital. This work will be disseminated through peer-review publication, conference presentation and a public dissemination strategy. TRIAL REGISTRATION NUMBER: ISRCTN41008456. PROTOCOL VERSION: V.1.0-7 June 2021.