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Section 1833(g)(5)(E) of the Act states that CMS shall identify and conduct targeted medical review using factors that may include the following: (1) The therapy provider has had a high claims denial percentage for therapy services under this part or is less compliant with applicable requirements under this title

The resultant oxidative stress induces macromolecular oxidation of proteins, lipids and DNA/RNA, leading to lipid peroxidation of biomembranes, denaturation of intracellular proteins and enzymes and DNA damage

Similarly, the use of valproic acid at high doses used by patients can have noteworthy effects on the gut microbiota, altering the biosynthesis of fatty acid by different microorganisms [270]