A minimum of one test achieving 30 mmHg for 12 s was required for inclusion. Heart rate response was taken as the ratio of the maximum R-R interval shortly after the manoeuvre to the minimum R-R interval during the procedure. Sympathetic test 1. Active stand The change in BP was measured as the difference between the baseline BP whilst supine and the lowest BP after standing. Results for the valsalva

manoeuvre were graded as ACY-1215 in vivo normal or abnormal, and all other tests as normal, borderline or abnormal using Inhibitors,research,lifescience,medical the values recommended by Ewing et al [17]. Overall autonomic function was described using Ewing’s classification system: • Normal: all tests normal or one borderline • Early dysfunction: one of the three HR tests abnormal or two borderline • Definite dysfunction: two Inhibitors,research,lifescience,medical or more HR tests abnormal • Severe dysfunction: two or more HR tests abnormal plus one BP test abnormal or both borderline • Atypical pattern: any other combination of abnormal tests [17]. Severity of tiredness, nausea, loss of appetite and shortness of breath were measured using the Edmonton Symptom Assessment Scale; an 11 point

numerical rating scale from 0-10, whereby larger numbers represent increased symptom severity [21]. Information regarding survival of study participants was obtained from an electronic palliative care patient administration database system, used by Our Lady’s Inhibitors,research,lifescience,medical Hospice & Care Services and the hospitals within its catchment area. Survival in days was measured from the day of assessment. The analysis of survival times was conducted on Sept 24, 2011. BMI was calculated from participants’ height and weight as measured on the day of assessment, and weight loss by subtracting current weight from reported weight prior Inhibitors,research,lifescience,medical to cancer diagnosis. Walking speed was measured using the timed ‘Up and Go’ (TUAG) whereby the participant is asked to rise from a seated position, walk Inhibitors,research,lifescience,medical to a marked spot three metres away, turn around and return to their seat.

The participant is instructed to walk at their normal pace and may use any gait aid normally used. Timing is started when the participant is instructed to ‘go’ and stopped when they are seated in the chair again [22]. Grip strength was measured 3 times in each hand using a hydraulic hand dynamometer (Jamar, Samons Preston Rolyan, Bolingbrook, IL). The result used 17-DMAG (Alvespimycin) HCl was the best result of the six measurements. Statistical methods Demographic details and clinical variables were summarised using descriptive statistics. Comparisons of groups of categorical variables were conducted using the Chi-squared test, of normally distributed continuous variables using the 2-sample t-test and of non-parametric variables using the Mann-Whitney U test. Variables shown to be associated with AD in univariate analyses, with p < 0.1, were entered into logistic regression models, using forwards and backwards stepwise variable entry. Only variables that were significant at p < 0.