Ten TAK-632 Techniques Defined
25 Heterogeneity between trials was assessed using the standard Q-test statistic (testing the hypothesis of homogeneity), and we present the I2 value, which can be interpreted as the percentage of total variation across the studies due to heterogeneity.26 Methodological quality and risk of bias assessment The methodological quality of the cohort studies was assessed using a published check list.27 Two of the authors (MH and MWC) assessed this individually and judged each criterion to be ��Adequately described��, ��Unclear��, or ��Inadequately described���Ccorresponding to ��low risk of bias��, ��unclear risk of bias��, and ��high risk of bias��, respectively. Disagreement was resolved by discussion. If an included study was authored IWR-1 supplier by one or more of the current authors, a third reviewer (HL) was asked to perform a quality assessment. One quality assessment item was omitted (��Was a dose�Cresponse relationship between exposure and outcome demonstrated?��) because this item relates to the findings of the study and not the methodological quality, and assessment of dose�Cresponse Ipatasertib mouse forms part of the Bradford Hill criteria for causation (see below). The overall extent of risk of bias and methodological quality within each study was assessed using the GRADE approach to evaluate study limitations.28 Evaluation of evidence for causality Based on the Bradford Hill considerations on causality,21 a causation score was developed and used to systematically evaluate the evidence of a causal link between knee joint loading during walking and structural progression of knee OA. A similar score has previously been derived from the Bradford Hill considerations to assess the causal relationship between dietary factors and coronary heart disease.23 The following criteria were used in the review of the cohort studies and given a score of 1 (criterion satisfied) or 0 (criterion not satisfied): Strength of association: Associations quantified as a pooled OR ��5.0, with lower 95% CI above 2.0; the expected direction was defined as ��strong association.�� ��Moderate association�� is defined as any statistically significant pooled OR (pTAK-632 requires replication in other studies. Consistency is defined as ��75% of associations being strong or moderate. Temporality: Refers to temporal relationship of association between exposure and outcome; exposure has to precede outcome. It is difficult to ensure temporal correctness because study participants are assumed to walk daily and are, therefore, exposed to knee joint loading throughout observation periods. We retained this criterion because temporality is necessary to infer causation; absence of temporal relationship between exposure and outcome precludes a causal link.
