Showing papers by "Steve Goodacre published in 2006"

Measurement of the clinical and cost-effectiveness of non-invasive diagnostic testing strategies for deep vein thrombosis.

Abstract: Objectives: To estimate the diagnostic accuracy of non-invasive tests for proximal deep vein thrombosis (DVT) and isolated calf DVT, in patients with clinically suspected DVT or high-risk asymptomatic patients, and identify factors associated with variation in diagnostic performance. Also to identify practical diagnostic algorithms for DVT, and estimate the diagnostic accuracy, clinical effectiveness and cost-effectiveness of each. Data sources: Electronic databases (to April 2004). A postal survey of hospitals in the UK. Review methods: Selected studies were assessed against validated criteria. A postal survey of hospitals in the UK was undertaken to describe current practice and availability of tests, and identify additional diagnostic algorithms. Pooled estimates of sensitivity, specificity and likelihood ratios were obtained for each test using random effects meta-analysis. The effect of study-level covariates was explored using random effects metaregression. A decision-analytic model was used to combine estimates from the meta-analysis and estimate the diagnostic performance of each algorithm in a theoretical population of outpatients with suspected DVT. The net benefit of using each algorithm was estimated from a health service perspective, using cost–utility analysis, assuming thresholds of willingness to pay of £20,000 and £30,000 per quality-adjusted lifeyear (QALY). The model was analysed probabilistically and cost-effectiveness acceptability curves were generated to reflect uncertainty in estimated costeffectiveness. Results: Individual clinical features are of limited diagnostic value, with most likelihood ratios being close to 1. Wells clinical probability score stratifies proximal, but not distal, DVT into high-, intermediate- and low-risk categories. Unstructured clinical assessment by experienced clinicians may have similar performance to Wells score. In patients with clinically suspected DVT, D-dimer has 91% sensitivity and 55% specificity for DVT, although performance varies substantially between assays and populations. D-dimer specificity is dependent on pretest clinical probability, being higher in patients with a low clinical probability of DVT. Plethysmography and rheography techniques have modest sensitivity for proximal DVT, poor sensitivity for distal DVT, and modest specificity. Ultrasound has 94% sensitivity for proximal DVT, 64% sensitivity for distal DVT and 94% specificity. Computed tomography scanning has 95% sensitivity for all DVT (proximal and distal combined) and 97% specificity. Magnetic resonance imaging has 92% sensitivity for all DVT and 95% specificity. The diagnostic performance of all tests is worse in asymptomatic patients. The most costeffective algorithm discharged patients with a low Wells score and negative D-dimer without further testing, and then used plethysmography alongside ultrasound, with venography in selected cases, to diagnose the remaining patients. However, the cost-effectiveness of this algorithm was dependent on assumptions of test independence being met and the ability to provide plethysmography at relatively low cost. Availability of plethysmography and venography is currently limited at most UK hospitals, so implementation would involve considerable reorganisation of services. Two algorithms were identified that offered high net benefit and would be feasible in most hospitals without substantial reorganisation of services. Both involved using a combination of Wells score, D-dimer and above-knee ultrasound. For thresholds of willingness to pay of £10,000 or £20,000 per QALY the optimal strategy involved discharging patients with a low or intermediate Wells score and negative D-dimer, ultrasound for those with a high score or positive D-dimer, and repeat scanning for those with positive D-dimer and a high Wells score, but negative initial scan. For thresholds of £30,000 or more a similar strategy, but involving repeat ultrasound for all those with a negative initial scan, was optimal. Conclusions: Diagnostic algorithms based on a combination of Wells score, D-dimer and ultrasound (with repeat if negative) are feasible at most UK hospitals and are among the most cost-effective. Use of repeat scanning depends on the threshold for willingness to pay for health gain. Further diagnostic testing for patients with a low Wells score and negative D-dimer is unlikely to represent a cost-effective use of resources. Recommendations for research include the evaluation of the costs and outcomes of using the optimal diagnostic algorithms in routine practice, the development and evaluation of algorithms appropriate for specific groups of patients with suspected DVT, such as intravenous drug abusers, pregnant patients and those with previous DVT, the evaluation of the role of plethysmography: interaction with other diagnostic tests, outcome of low-risk patients with negative plethysmography and measurement of the costs of providing plethysmography, and methodological research into the incorporation of meta-analytic data into decision-analytic modelling.

Prediction of mortality among emergency medical admissions

Abstract: Background: The Rapid Acute Physiology Score (RAPS) and Rapid Emergency Medicine Score (REMS) are risk adjustment methods for emergency medical admissions developed for use in audit, research, and clinical practice. Each predicts in hospital mortality using four (RAPS) or six (REMS) variables that can be easily recorded at presentation. We aimed to evaluate the predictive value of REMS, RAPS, and their constituent variables. Methods: Age, heart rate, respiratory rate, blood pressure, Glasgow Coma Score (GCS) and oxygen saturation were recorded for 5583 patients who were transported by emergency ambulance, admitted to hospital and then followed up to determine in hospital mortality. The discriminant power of each variable, RAPS, and REMS were compared using the area under the receiver operator characteristic curve (AROCC). Multivariate analysis was used to identify which variables were independent predictors of mortality. Results: REMS (AROCC 0.74; 95% CI 0.70 to 0.78) was superior to RAPS (AROCC 0.64; 95% CI 0.59 to 0.69) as a predictor of in hospital mortality. Although all the variables, except blood pressure, were associated with mortality, multivariate analysis showed that only age (odds ratio 1.74, p Conclusion: REMS is a better predictor of mortality in emergency medical admissions than RAPS. Age, GCS, and oxygen saturation appear to be the most useful predictor variables. Inclusion of other variables in risk adjustment scores, particularly blood pressure, may reduce their value.

Utility of admission cardiac troponin and “Ischemia Modified Albumin” measurements for rapid evaluation and rule out of suspected acute myocardial infarction in the emergency department

Abstract: Objective: To assess if the combination of cardiac troponin (cTn) and Ischemia Modified Albumin (IMA) can be used for early exclusion of acute myocardial infarction (AMI). Methods: Prospective consecutive admissions to the emergency department (ED) with undifferentiated chest pain were assessed clinically and by electrocardiography. A total of 539 patients (335 men, 204 women; median age 51.9 years) considered at low risk of AMI had blood drawn on admission. If the first sample was less than 12 hours from onset of chest pain, a second sample was drawn two hours later, at least six hours from onset of chest pain. Creatine kinase MB isoenzyme (CKMB) mass was measured on the first sample and CKMB mass and cTnT on the second sample. An aliquot from the first available sample was frozen and subsequently analysed for IMA. If cTnT had not been measured on the original sample cTnI was measured (n = 189). Results: Complete data were available for 538/539 patients. IMA or cTn was elevated in the admission sample of all patients with a final diagnosis of AMI (n = 37) with IMA alone elevated in 2/37, cTn alone in 19/37, and both in 16/37. In 173/501 patients in whom AMI was excluded both tests were negative. In the non-AMI group 22 patients had elevation of both IMA and cTn in the initial sample, suggesting ischaemic disease. Conclusion: Admission measurement of cardiac troponin plus IMA can be used for early classification of patients presenting to the ED to assist in patient triage.

How should we diagnose suspected deep-vein thrombosis?

Abstract: Background: Many different approaches are used to diagnose suspected deep-vein thrombosis (DVT), but there has been little formal comparison of strategies. Aim: To identify the most cost-effective strategy for the UK National Health Service (NHS). Design: Systematic review, meta-analysis and cost-effectiveness analysis. Methods: We identified 18 strategies and estimated the diagnostic performance of constituent tests by systematic review and meta-analysis. Outcomes of testing and treatment were estimated from published data or by an expert panel. Costs were estimated from NHS reference costs and published data. We built a decision-analysis model to estimate, for each strategy, the overall accuracy, costs, and outcomes (valued as quality-adjusted life-years, QALYs), compared to a 'no testing, no treatment' alternative. Probabilistic analysis estimated the net benefit of each strategy at varying thresholds for willingness to pay for health gain. Results: At the thresholds for willingness to pay recommended by the National Institute for Clinical Excellence (£20 000–£30 000 per QALY), the optimal strategy was to discharge patients with a low or intermediate Wells score and negative D-dimer, limiting ultrasound to those with a high score or positive D-dimer. Strategies using radiological testing for all patients were only cost-effective at £40 000 per QALY or more. Discussion: The optimal strategy for DVT diagnosis is to use ultrasound selectively in patients with a high clinical risk or positive D-dimer. Radiological testing for all patients does not appear to be a cost-effective use of health service resources.

Evaluating and implementing new services

Abstract: Evidence based health care should apply to the way that services are delivered as much as it does to treatments

Comparison of biomarker strategies for rapid rule out of myocardial infarction in the emergency department using ACC/ESC diagnostic criteria

Abstract: Objective Creatine kinase MB isoenzyme (CK-MB) mass and rate of change of CK-MB have been proposed as superior to cardiac troponin measurement for very early exclusion of acute myocardial infarction (AMI). All three markers were examined prospectively in patients presenting to the Emergency Department (ED) for rule out of AMI. Methods Consecutive admissions to the ED with undifferentiated chest pain were initially assessed clinically and by electrocardiography. A total of 786 patients (490 male, median age 52.5 years) considered at low risk of AMI had blood drawn on admission. If the first sample was less than 12 h from onset of chest pain, a second sample was then drawn at least 2 h later and at least 6 h from onset of chest pain. CK-MB mass was measured on the first sample and CK-MB mass and cardiac troponin T (cTnT) were measured on the second sample. Measurement of cTnT was using an Elecsys 2010 with the third generation assay (Roche Diagnostics, Lewes, UK). Assay coefficient of variation (CV) was 5.8% and 5.7% at 0.47 and 11.5 microg/L, respectively, with measuring range 0.01-25.0 microg/L; analytical sensitivity of 0.01 microg/L and functional sensitivity of 0.03 microg/L. CK-MB (mass) was measured by electrochemiluminesence using an Elecsys 2010 (Roche Diagnostics). The assay CV was 4.0% at 5.89 microg/L and 4.1% at 60.5 microg/L, with a detection limit of 0.1 microg/L and an upper measuring limit of 500 microg/L. Myocardial infarction was diagnosed if either sample had a CK-MB of more than 5 microg/L, if there was a change in CK-MB (DeltaCK-MB) of more than 1.5 microg/L or if the cTnT was more than 0.05 microg/L. When AMI was excluded, patients proceeded to stress electrocardiography and reattended 72 h from presentation for follow up phlebotomy for cTnT measurement. A final diagnosis of AMI was made according to American College of Cardiology/ European Society of Cardiology criteria using a cut-off of 0.05 microg/L cTnT in any of the samples. Diagnostic efficiency was compared by receiver operator characteristic (ROC) curve analysis with comparison of area under the curve (AUC) for four strategies: admission CK-MB measurement; 6-h post-pain CK-MB measurement; DeltaCK-MB; and 6-h post-pain cTnT measurement. Results On admission the AUC for CK-MB was 0.830 (95% confidence interval [CI] 0.757-0.904). At 6 h post pain the respective values were: CK-MB 0.939 (95% CI 0.889-0.988); DeltaCK-MB 0.948 (95% CI 0.906-0.990); and cTnT 0.989 (95% CI 0.966-1.0). Conclusion cTnT at 6 h has high diagnostic sensitivity for AMI and is superior to CK-MB mass and DeltaCK-MB even using a low cut-off value.

How do clinical features help identify paediatric patients with fractures following blunt wrist trauma

Abstract: Objective: Wrist injuries are a common presentation to the emergency department (ED). There are no validated decision rules to help clinicians evaluate paediatric wrist trauma. This study aimed to identify which clinical features are diagnostically useful in deciding the need for a wrist radiograph, and then to develop a clinical decision rule. Methods: This prospective cohort study was carried out in the ED of Sheffield Children’s Hospital. Eligible patients were recruited if presenting within 72 hours following blunt wrist trauma. A standardised data collection form was completed for all patients. The outcome measure was the presence or absence of a fracture. Univariate analysis was performed with the χ 2 test. Associated variables (p Results: In total, 227 patients were recruited and 106 children were diagnosed with fractures (47%). Of 10 clinical features analysed, six were found by univariate analysis to be associated with a fracture. CART analysis identified the presence of radial tenderness, focal swelling, or an abnormal supination/pronation as the best discriminatory features. Cross fold validation of this decision rule had a sensitivity of 99.1% (95% confidence interval 94.8% to 100%) and a specificity of 24.0% (17.2% to 32.3%). The radiography rate would be 87%. Conclusions: Radial tenderness, focal swelling, and abnormal supination/pronation are associated with wrist fractures in children. The clinical decision rule derived from these features had a high sensitivity, but low specificity, and would not substantially alter our current radiography rate. The potential for a clinical decision rule for paediatric wrist trauma appears limited.

Meta‐analysis of plethysmography and rheography in the diagnosis of deep vein thrombosis

Abstract: Background: Plethysmography and rheography techniques have been widely studied as diagnostic tests for deep vein thrombosis (DVT). This study aimed to systematically review the accuracy of these tests for diagnosing clinically suspected DVT. Methods: The following databases were searched: Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews , Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club (1966 to 2004), and citation lists of retrieved articles. Studies that compared plethysmography or rheography to a reference standard of ultrasound or contrast venography were selected. Standardised data were extracted and study quality determined against validated criteria. Data were analysed by random effects meta-analysis and meta-regression. Results: The meta-analysis included 78 studies, reporting 82 patient cohorts. Sensitivity and specificity (95% CI) were: 75% (73% to 77%) and 90% (89% to 91%) for impedance plethysmography, 83% (81% to 85%) and 81% (79% to 82%) for strain-gauge plethysmography, 85% (79% to 90%) and 91% (81% to 95%) for air plethysmography, 91% (87% to 94%) and 71% (66% to 75%) for light-reflex rheography, and 86% (83% to 89%) and 93% (91% to 95%) for phleborheography. Meta-regression was limited by poor reporting of studies. There was some evidence that diagnostic performance depended on the proportion of males in the cohort and reporting of study setting. Conclusions: Although plethysmography and rheography techniques add diagnostic value, they have inadequate diagnostic performance to act as a stand-alone test in DVT diagnosis. Evaluation of their role in combination with other tests, or standardised clinical assessment, is required.

Safe discharge: an irrational, unhelpful and unachievable concept

Abstract: Emergency doctors often decide whether to advise hospital admission or discharge by assessing whether a decision to discharge home is considered safe. This implies that hospital admission may be recommended on the basis of exceeding an arbitrarily defined risk of adverse outcome, rather than weighing the potential benefits, risks and costs of hospital admission. This approach is likely to lead to irrational decision making, unnecessary hospitalisation and unrealistic expectations regarding risk. Instead of using the concept of a safe discharge, we should take a more rational approach to decision making, weighing the benefits, risks and costs of hospitalisation against a default option of discharge home. Hospital admission should be recommended only if the expected benefits outweigh the risks and can be accrued at an acceptable cost. Guidelines should be developed using this approach and used to promote and support rational decision making.