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. 2017 Jun 12;7:3309. doi: 10.1038/s41598-017-03110-3

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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A directed acyclic graph to describe the hypotheses: we decomposed the total effect of knee symptomatic osteoarthritis (SxOA) on all-cause mortality into two components: 1) the indirect effect (or mediated effect), i.e., the effect of knee SxOA on all-cause mortality mediated through either a walking disability (knee SxOA → walking disability → death) or Nonsteroidal antiinflammatory drugs (NSAIDs) use (knee SxOA → NSAIDs → death), and 2) the direct effect, i.e., the effect of knee SxOA on all-cause mortality (knee SxOA → death) that was not through either a walking disability or use of NSAIDS. The dotted line between walking disability and NSAIDs indicated that the time sequence was uncertain. CF: confounders.