IMPORTANCEParkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise.OBJECTIVES To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial. DESIGN, SETTING, AND PARTICIPANTSThe Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control). INTERVENTIONS High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months. MAIN OUTCOMES AND MEASURES Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson's Disease Rating Scale motor score.RESULTS A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P < .001). The mean change in Unified Parkinson's Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, −1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe.CONCLUSIONS AND RELEVANCE High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease.

Physical inactivity, sarcopenia, and frailty are highly prevalent, independent predictors of morbidity and mortality in patients with cirrhosis. Across a range of chronic diseases, exercise training is a key recommendation supported by guidelines and, for some conditions, even by governmental funding of exercise programmes. Consistent with the broader chronic disease literature, the evidence for a benefit of exercise in cirrhosis is promising. Several small trials have reported significant improvements in muscle health (mass, strength, functional capacity), quality of life, fatigue, and reductions in the hepatic venous pressure gradient, without adverse events. With strong emerging evidence surrounding the substantial risks of sarcopenia/frailty and our first-hand experiences with liver pre-transplant exercise programmes, we contend that routine patient care in cirrhosis should include an exercise prescription. Some clinicians may lack the resources and necessary background to translate the existing evidence into a practicable intervention. Our team, comprised of physiotherapists, exercise physiologists, hepatologists, transplant specialists, and knowledge translation experts from six North American centres, has distilled the essential background information, tools, and practices into a set of information ready for immediate implementation into clinics ranging from a family practice setting to specialty cirrhosis clinics. Augmenting the rationale and evidence are supplementary materials including video and downloadable materials for both patients and the physician. Supporting the exercising patient is a section regarding information about nutrition, providing practical tips suitable for all patients with cirrhosis.

Frailty as measured by gait speed is an independent and potentially modifiable risk factor for cirrhosis complications requiring hospitalization. The potential clinical value of frailty measurements to help define such risk merits broader evaluation.

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Frailty with sarcopenia in cirrhosis causes liver transplant wait-list attrition and deaths. Regular physical activity is needed to protect patients with cirrhosis from frailty. We subjectively assess physical performance in selecting patients for transplant listing, but we do not know whether clinical assessments reflect the extent of activity patients actually perform. To investigate this question, 53 wait-listed patients self-assessed their performance of ordinary physical tasks using the Rosow-Breslau survey, and clinicians assessed their physical performance status with the Karnofsky index. We compared these assessments with actual activity measured using an accelerometer/thermal sensing armband worn from 4 to 7 days. We found that their measured activity was among the lowest reported in chronic disease, similar to that of patients with advanced chronic pulmonary disease or renal failure. Their percentages of waking hours spent in sedentary, light, and moderate-vigorous activity were 75.9% ± 18.9%, 18.9% ± 14.3%, and 4.9% ± 6.9%, respectively. Higher mean sedentary and lower mean moderate-vigorous activity was significantly associated with 9 wait-list deaths (P = 0.004). Compared with a range of 7000-13,000 steps/day in healthy adults, patients' mean steps/day were 3164 ± 2842. Both their activity percentage and step data were typical of other severely inactive populations. Neither their Rosow-Breslau scores (mean 2.3 ± 0.8, maximum 3.0) nor their Karnofsky scores (mean 79 ± 12, maximum 100) suggested major impairment or showed a correlation with patients' actual physical performance. In conclusion, physical activity in patients with cirrhosis wait-listed for transplantation is highly sedentary. Self-assessments and provider assessments of physical activity do not reliably indicate actual performance. Whether the gap between assessed and actual performance may be favorably modified by interventions to improve activity and ameliorate frailty merits further study. Liver Transplantation 22 1324-1332 2016 AASLD.