We will also derive another model (with aim of 100% sensitivity)

to predict patients who will benefit from cardiac Axitinib purchase monitoring while in the ED. Classification performance As a preliminary validation, we will assess the performance of the tool by comparing the classification of each patient against the occurrence of serious outcome. Inhibitors,research,lifescience,medical This will allow 95% confidence interval (CI) estimation for the sensitivity and specificity of the derived tool. We will perform an internal validation of the scale across 1,000 replications using the bootstrap method [61]. A more robust validation will be carried out later. Resource utilization and physician judgment We will calculate and compare the actual admission rates versus hypothetical Inhibitors,research,lifescience,medical rates if the new tool were implemented. We will calculate the proportion of patients with correct diagnosis made during the ED visit and the proportion of patients who suffer serious outcome outside the

hospital with no specific follow-up arrangements. From the physician prediction probabilities and the model for the new scale, we will calculate and compare the likelihood ratios and area under the receiver operating characteristic (ROC) curves. Sample size 5,000 patients will be enrolled at the six study sites. Since there is no hypothesis being tested, Inhibitors,research,lifescience,medical we determined the sample size based on the number of variables in the final model and the estimation of precision of the sensitivity of the tool to be derived in the study population. Previous studies have identified that there must be at least 10 events per predictor Inhibitors,research,lifescience,medical variable in the final model [62]. For clinical decision tool studies, the specific approach taken (bound on the error of estimation which is the width of the 95% CI estimate) is the standard technique

used in sample size calculation for decision tool studies Inhibitors,research,lifescience,medical [63]. Conservatively assuming the prevalence as 2.5%, we calculated a total sample size of 5,000 patients with 125 patients suffering serious outcomes within 30-days of ED discharge will be needed to derive the tool. Methodological issues We considered the following methodological issues during the planning of this study. Exclusion Anacetrapib of pre-syncope patients There is no standardized definition for the symptom ‘pre-syncope’ and published studies are contradictory with respect to the prognosis of pre-syncope in comparison to syncope [47,64-66]. One study reports that pre-syncope has a benign prognosis, [47] another reports that it is a non-specific symptom with cardiac monitor showing sinus rhythm when captured [65] while two other studies report that the prognosis is the same as syncope [64,66]. The European Society of Cardiology guidelines concluded that the pathophysiology might be different for pre-syncope than syncope [1]. Hence, we elected to exclude pre-syncope patients.