Univariate analysis Univariate analysis will be performed to determine the strength of association between the predictor variables and serious outcomes. We will choose the appropriate univariate technique based on the type of data: chi square test with continuity correction for nominal variables; unpaired, two tailed t-test for continuous

variables, using pooled or separate variance estimate Inhibitors,research,lifescience,medical as appropriate; and, the Mann–Whitney U test for ordinal variables. For continuous variables we will assess for the most discriminative cut point to include in multivariate analysis. Multivariate analysis Variables that are reliable (kappa ≥0.6) and strongly Epacadostat chemical structure associated with serious outcomes (p-value <0.2) will be selected for

multivariate analysis by logistic regression using Statistical Analysis System (SAS) software or using recursive partitioning. We will use multivariate analysis to identify the risk factors for serious outcomes within 30 days of ED discharge and to derive a clinical decision tool. When building the model, for Inhibitors,research,lifescience,medical missing predictor variables, we plan to either impute Inhibitors,research,lifescience,medical by multiple imputations or assume as normal if it is in young patients with obvious vasovagal syncope [58]. We will evaluate interaction among predictor variables using Mantel-Haenszel and logistic model procedures. We will consider appropriate combining of variables and use composite variables for incorporation (e.g. bifascicular block). We will assess Inhibitors,research,lifescience,medical for multicolinearity in the model, a statistical phenomenon in which two or more predictor variables are highly correlated. We will also assess for lack of fit

by Hosmer-Lemeshow goodness-of-fit test and for overfitting in the model by Akaike information criterion [59,60]. If difficulties arise in developing a clinical decision tool with acceptable diagnostic test characteristics, we will explore the option of building models Inhibitors,research,lifescience,medical with separation of serious events: before and after the 7-day mark; detection of serious underlying conditions (serious structural heart disease, aortic dissection, pulmonary embolism, severe pulmonary hypertension, subarachnoid hemorrhage or significant hemorrhage) versus prediction of serious events (arrhythmia or death); separation of cardiac versus non-cardiac events; and excluding patients with procedural interventions performed without evidence of underlying Casein kinase 1 serious condition (e.g. pacemaker insertion without evidence of bradyarrhythmia). If there is considerable variation in the ED length of stay among the study patients, we will also explore the option of the primary outcome as occurrence of serious outcome 6 hours after ED arrival. The majority of syncope patients are assigned a Canadian Triage and Acuity Scale (CTAS) 3. As a result, in most Canadian provinces it is expected that a disposition decision is made within six hours of arrival. Hence, we will choose a 6 hour cut off point if needed.