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Therapeutic strategies such as hit hard and early and treat-to-target, especially with TNF- inhibitors, can modulate the course of the disease enormously, as they have been shown to lead to drug-free remission, lower disease activity, and higher functional status, which ultimately leads to an improvement in patients quality of life [64,65,66]

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In the following discussion of the determinants of bilirubin neurotoxicity, it becomes clear that the importance of each factor must vary with the clinical circumstances (see Table 26.3 )

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Magnesium supports glutathione synthetase activity