In a pilot study of 10 patients with CFS shown to have abnormal cardiovascular responses to a head-up tilt test, for 6 patients, treatment with midodrine resulted in normalisation of cardiovascular responses at three months, followed by an improvement in fatigue scores 4-8 weeks later [31]. Exploration of the relationship CHIR-99021 clinical trial between autonomic dysfunction and

fatigue, the potential for reversibility of AD with pharmacological intervention, and the impact of this on fatigue and survival in patients with Inhibitors,research,lifescience,medical advanced cancer, are all worthy of further investigation. However, in view of our findings relating to the feasibility of conducting standard clinical tests of autonomic function in a large cohort of patients Inhibitors,research,lifescience,medical with advanced cancer, we recommend that the reliability and validity of novel methods of assessment of autonomic function are investigated further. The findings of Fadul et al suggest that measurement of heart rate variability (HRV) may provide a useful measure of AD in this population, for both research and clinical purposes. Power spectral analysis of heart rate fluctuations,

recorded by continuous Inhibitors,research,lifescience,medical electrocardiogram, provide a simple and non-invasive technique for analysing autonomic function. In their study of men with advanced cancer, Fadul et al found a strong association between the results of the Ewing’s battery and the time domain measure ‘standard deviation of normal to normal beat interval’ (r = 0.44, p = 0.002) [13]. Conclusions Autonomic dysfunction is

highly prevalent in advanced cancer and is associated with severity of fatigue and shorter survival. Research findings in patients with VVS and CFS suggest that correction Inhibitors,research,lifescience,medical of autonomic dysfunction Inhibitors,research,lifescience,medical may result in alleviation of fatigue. Future research on the impact of AD and its treatment in patients with advanced cancer must also address the potential for novel methods of assessment of autonomic function to provide a reliable proxy for the standardised clinical tests; due to frailty, 45% of participants in this study were unable to complete Ewing’s battery of tests emphasising the need to explore alternative methods for evaluation of autonomic function in this population. Competing interests The authors declare that they have no competing interests. Authors’ contributions CS coordinated and designed the study, STK38 collected the data, performed the statistical analysis and drafted the manuscript. RAK conceived of the study, participated in its design and revised the manuscript critically for important intellectual content. BN helped to conduct the data collection and processing and to draft the manuscript. PGL conceived of the study, participated in its design and helped draft the manuscript. All authors read and approved the final manuscript.