Evidence Level Methodology1++: High-quality meta-analyses, systematic reviews of randomized controlled trials (RCTs), or RCTs with low risk of bias. 1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias. 1-: Meta-analyses, systematic reviews of RCTs or RCTs with a high risk of bias. 2++: High-quality systematic reviews of case-control or cohort studies; High-quality case control or cohort studies with very low risk of confounding bias and a high probability that the relationship is causal. 2+: Well-conducted case-control or cohort studies with low risk of confounding bias or chance and a moderate probability that the relationship is causal; Well-conducted basic science with low risk of bias. 2-: Case-control or cohort studies with a high risk of confounding bias or chance and significant risk that the relationship is not causal. 3: Non-analytic studies (for example case reports, case series). 4: Expert opinion.