Chronotropic Incompetence During Exercise Testing as a Marker of Autonomic Dysfunction in Individuals with Early Parkinson's Disease.

BACKGROUND: An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early stages of PD. OBJECTIVE: To investigate the relationship between chronotropic incompetence, orthostatic blood pressure change (supine - standing), and exercise performance (maximal oxygen consumption, VO2peak) in individuals with early PD within 5 years of diagnosis not on dopaminergic medications. METHODS: We performed secondary analyses of heart rate and blood pressure data from the Study in Parkinson's Disease of Exercise (SPARX). RESULTS: 128 individuals were enrolled into SPARX (63.7±9.3 years; 57.0% male, 0.4 years since diagnosis [median]). 103 individuals were not taking chronotropic medications, of which 90 had a normal maximal heart rate response to exercise testing (155.3±14.0 bpm; PDnon-chrono) and 13 showed evidence of chronotropic incompetence (121.3±11.3 bpm; PDchrono, p < 0.05). PDchrono had decreased VO2peak compared to PDnon-chrono (19.7±4.5 mL/kg/min and 24.3±5.8 mL/kg/min, respectively, p = 0.027). There was a positive correlation between peak heart rate during exercise and the change in systolic blood pressure from supine to standing (r = 0.365, p < 0.001). CONCLUSIONS: A subgroup of individuals with early PD not on dopaminergic medication had chronotropic incompetence and decreased VO2peak, which may be related to autonomic dysfunction. Evaluation of both heart rate responses to incremental exercise and orthostatic vital signs may serve as biomarkers of early autonomic impairment and guide treatment. Further studies should investigate whether cardiovascular autonomic dysfunction affects the ability to exercise and whether exercise training improves autonomic dysfunction.

Study in Parkinson's disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial.

BACKGROUND: To date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline. METHODS: This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60-65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80-85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity. DISCUSSION: SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health. TRIAL REGISTRATION: ClinicalTrials.gov NCT04284436 . Registered on February 25, 2020.

Prehabilitation-Driven Changes in Frailty Metrics Predict Mortality in Patients With Advanced Liver Disease.

INTRODUCTION: Frailty is a predictor of morbidity and mortality in cirrhosis. Although evidence for prehabilitation is promising, the data for liver transplant (LT) candidates are limited. The primary aim of this study was to evaluate the effect of a novel prehabilitation strategy on changes in frailty metrics and survival in LT candidates. The secondary aim was to determine liver-related and extrahepatic conditions associated with frailty. METHODS: In this ambispective cohort study, all patients underwent frailty assessment using the liver frailty index (LFI), 6-minute walk test, and gait speed test performed by a dedicated physical therapist. Home-based exercise prescription was individualized to each patient's baseline physical fitness. RESULTS: We included 517 patients (59% men, median age 61 years, and a model for end-stage liver disease score of 12) evaluated during 936 PT visits. Frailty metrics were affected by age, sex, and liver-related parameters, but not by model for end-stage liver disease. Patients with nonalcoholic fatty liver disease and alcohol-related cirrhosis had worse frailty metrics by all tools. We demonstrated the feasibility of prehabilitation in improving both LFI and 6-minute walk test, particularly in adherent patients. A median LFI improvement of 0.3 in frail patients was associated with improved survival in univariate analysis. Compliance with physical therapist visits (hazards ratio = 0.35 [0.18-0.67] for 2 visits and hazards ratio = 0.54 [0.31-0.94] for ≥3 visits) was independently associated with increased survival. DISCUSSION: Prehabilitation improves frailty metrics in LT candidates and is associated with a survival advantage. Our findings provide a framework for the standardized prehabilitation program in LT candidates while prioritizing compliance, adherence, and on-training LFI goal accomplishment.

Wearables, Physical Activity, and Exercise Testing in Liver Disease.

Physical inactivity is a major cause of deterioration in all forms of advanced liver disease. It is especially important as a driver of the components of the metabolic syndrome, with nonalcoholic fatty liver disease rapidly becoming the dominant cause of liver-related death worldwide. Growing realization of the health benefits of moderate-to-vigorous physical activity has captured the interest of persons who desire to improve their health, including those at risk for chronic liver injury. They are increasingly adopting wearable activity trackers to measure the activity that they seek to improve. Improved physical activity is the key lifestyle behavior that can improve cardiorespiratory fitness, which is most accurately measured with cardiopulmonary exercise testing (CPET). CPET is showing promise to identify risk and predict outcomes in transplant hepatology. Team effort among engaged patients, social support networks, and clinicians supported by web-based connectivity is needed to fully exploit the benefits of physical activity tracking.

Exercise in cirrhosis: Translating evidence and experience to practice.

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.

Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial.

Importance: Parkinson 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 Participants: The 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. Trial Registration: clinicaltrials.gov Identifier: NCT01506479.

Factors Associated With Ambulatory Activity in De Novo Parkinson Disease.

BACKGROUND AND PURPOSE: Objective ambulatory activity during daily living has not been characterized for people with Parkinson disease prior to initiation of dopaminergic medication. Our goal was to characterize ambulatory activity based on average daily step count and examine determinants of step count in nonexercising people with de novo Parkinson disease. METHODS: We analyzed baseline data from a randomized controlled trial, which excluded people performing regular endurance exercise. Of 128 eligible participants (mean ± SD = 64.3 ± 8.6 years), 113 had complete accelerometer data, which were used to determine daily step count. Multiple linear regression was used to identify factors associated with average daily step count over 10 days. Candidate explanatory variable categories were (1) demographics/anthropometrics, (2) Parkinson disease characteristics, (3) motor symptom severity, (4) nonmotor and behavioral characteristics, (5) comorbidities, and (6) cardiorespiratory fitness. RESULTS: Average daily step count was 5362 ± 2890 steps per day. Five factors explained 24% of daily step count variability, with higher step count associated with higher cardiorespiratory fitness (10%), no fear/worry of falling (5%), lower motor severity examination score (4%), more recent time since Parkinson disease diagnosis (3%), and the presence of a cardiovascular condition (2%). DISCUSSION AND CONCLUSIONS: Daily step count in nonexercising people recruited for this intervention trial with de novo Parkinson disease approached sedentary lifestyle levels. Further study is warranted for elucidating factors explaining ambulatory activity, particularly cardiorespiratory fitness, and fear/worry of falling. Clinicians should consider the costs and benefits of exercise and activity behavior interventions immediately after diagnosis of Parkinson disease to attenuate the health consequences of low daily step count.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A170).

Frailty as Tested by Gait Speed is an Independent Risk Factor for Cirrhosis Complications that Require Hospitalization.

OBJECTIVES: Frailty is a known risk factor for major life-threatening liver transplant complications, deaths, and waitlist attrition. Whether frailty indicates risk for adverse outcomes in cirrhosis short of lethality is not well defined. We hypothesized that clinical measurements of frailty using gait speed and grip strength would indicate the risk of subsequent hospitalization for the complications of cirrhosis. METHODS: We assessed frailty as gait speed and grip strength in a 1-year prospective study of 373 cirrhotic patients evaluated for or awaiting liver transplantation. We determined its association with the outcome of subsequent hospital days/100 days at risk for 7 major complications of cirrhosis. We tested potential covariate influences of Model for Endstage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores, age, sex, height, depression, narcotic use, vitamin D deficiency, and hepatocellular carcinoma using multivariable modeling. RESULTS: Patients experienced 2.14 hospital days/100 days at risk, or 7.81 days/year. Frailty measured by gait speed was a strong risk factor for hospitalization for all cirrhosis complications. Each 0.1 m/s gait speed decrease was associated with 22% greater hospital days (P<0.001). Grip strength showed a similar but nonsignificant association. Gait speed remained independently significant when adjusted for MELD, CTP, and other covariates. At hospital costs of $4,000/day, patients with normal 1 m/s gait speed spent 6.2 days and $24,800/year; patients with 0.5 m/s speed spent 21.2 days and $84,800/year; and patients with 0.25 m/s speed spent 40.2 days and $160,800/year. CONCLUSIONS: 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.

The gap between clinically assessed physical performance and objective physical activity in liver transplant candidates.

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.

Surgery versus nonsurgical treatment of lumbar spinal stenosis: a randomized trial.

BACKGROUND: Primary care management decisions for patients with symptomatic lumbar spinal stenosis (LSS) are challenging, and nonsurgical guidance is limited by lack of evidence. OBJECTIVE: To compare surgical decompression with physical therapy (PT) for LSS and evaluate sex differences. DESIGN: Multisite randomized, controlled trial. (ClinicalTrials.gov: NCT00022776). SETTING: Neurologic and orthopedic surgery departments and PT clinics. PARTICIPANTS: Surgical candidates with LSS aged 50 years or older who consented to surgery. INTERVENTION: Surgical decompression or PT. MEASUREMENTS: Primary outcome was physical function score on the Short Form-36 Health Survey at 2 years assessed by masked testers. RESULTS: The study took place from November 2000 to September 2007. A total of 169 participants were randomly assigned and stratified by surgeon and sex (87 to surgery and 82 to PT), with 24-month follow-up completed by 74 and 73 participants in the surgery and PT groups, respectively. Mean improvement in physical function for the surgery and PT groups was 22.4 (95% CI, 16.9 to 27.9) and 19.2 (CI, 13.6 to 24.8), respectively. Intention-to-treat analyses revealed no difference between groups (24-month difference, 0.9 [CI, -7.9 to 9.6]). Sensitivity analyses using causal-effects methods to account for the high proportion of crossovers from PT to surgery (57%) showed no significant differences in physical function between groups. LIMITATION: Without a control group, it is not possible to judge success attributable to either intervention. CONCLUSION: Surgical decompression yielded similar effects to a PT regimen among patients with LSS who were surgical candidates. Patients and health care providers should engage in shared decision-making conversations that include full disclosure of evidence involving surgical and nonsurgical treatments for LSS. PRIMARY FUNDING SOURCE: National Institutes of Health and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Links between osteoarthritis and diabetes: implications for management from a physical activity perspective.

Osteoarthritis (OA) and type 2 diabetes mellitus (T2DM) often coexist in older adults. Those with T2DM are more susceptible to developing arthritis, which has been traditionally attributed to common risk factors, namely, age and obesity. Alterations in lipid metabolism and hyperglycemia might directly impact cartilage health and subchondral bone, contributing to the development/progression of OA. Adequate management of older persons with both conditions benefits from a comprehensive understanding of the associated risk factors. We discuss common risk factors and emerging links between OA and T2DM, emphasizing the importance of physical activity and the implications of safe and effective physical activity.

Comparing physical activity programs for managing osteoarthritis in overweight or obese patients.

Obesity is a well-known modifiable risk factor for osteoarthritis (OA) in weight-bearing joints, and is present in approximately 35% of individuals with OA. Obesity adds significant burden to individuals with OA and is associated with poorer functional status and greater disability. In addition to tackling OA-related impairments, such as pain and functional limitations, interventions in this population need to address bodyweight reduction, as well as promotion of active lifestyle behaviors. While exercise and regular physical activity participation are both recommended and beneficial for OA and obese populations, our current understanding of optimal strategies to improve function and health status in those who have both OA and obesity is limited. This review will summarize the current available evidence related to effectiveness of various physical activity interventions to reduce pain, improve function and overall health-related quality of life in overweight or obese individuals with OA.

Optimizing long-term weight control after bariatric surgery: a pilot study.

BACKGROUND: Although bariatric surgery is associated with significant overall weight loss, many patients experience suboptimal outcomes. Our objective was to document the preliminary efficacy of a behavioral intervention for bariatric surgery patients with relatively poor long-term weight loss and to explore the factors related to outcome at an academic medical center in the United States. METHODS: Patients with a body mass index (BMI) ≥ 30 kg/m(2) who had undergone bariatric surgery ≥ 3 years before study entry and had <50% excess weight loss were enrolled. The participants were randomly assigned to a 6-month behavioral intervention or wait list control group. The assessments were conducted at baseline (before intervention) and 6 months (after intervention) and 12 months (6-mo follow-up). RESULTS: On average, the participants (n = 36) had undergone surgery 6.6 years before study entry. The average age was 52.5 ± 7.1 years, and the BMI was 43.1 ± 6.2 kg/m(2); most participants were women (75%) and white (88.9%). The intervention patients had a greater percentage of excess weight loss than did the wait list control group at 6 (6.6% ± 3.4% versus 1.6% ± 3.1%) and 12 (5.8% ± 3.5% versus .9% ± 3.2%) months. However, the differences were not significant and the results varied. The intervention patients with more depressive symptoms (P = .005) and less weight regain before study entry (P = .05) experienced a greater percentage of excess weight loss. CONCLUSION: Behavioral intervention holds promise in optimizing long-term weight control after bariatric surgery. More research is needed on when to initiate the intervention and to identify which patients will benefit from this type of approach.

Physical activity and physical function in individuals post-bariatric surgery.

BACKGROUND: A better understanding of the physical activity behavior of individuals who undergo bariatric surgery will enable the development of effective post-surgical exercise guidelines and interventions to enhance weight loss outcomes. This study characterized the physical activity profile and physical function of 40 subjects 2-5 years post-bariatric surgery and examined the association between physical activity, physical function, and weight loss after surgery. METHODS: Moderate-to-vigorous intensity physical activity (MVPA) was assessed with the BodyMedia SenseWear® Pro (SWPro) armband, and physical function (PF) was measured using the physical function subscale of the 36-Item Short Form Health Survey instrument (SF-36(PF)). Height and weight were measured. RESULTS: Percent of excess weight loss (%EWL) was associated with MVPA (r = 0.44, p = 0.01) and PF (r = 0.38, p = 0.02); MVPA was not associated with PF (r = 0.24, p = 0.14). Regression analysis demonstrated that MVPA was associated with %EWL (ß = 0.38, t = 2.43, p = 0.02). Subjects who participated in ≥150 min/week of MVPA had a greater %EWL (68.2 ± 19, p = 0.01) than those who participated in <150 min/week (52.5 ± 17.4). CONCLUSIONS: Results suggest that subjects are capable of performing most mobility activities. However, the lack of an association between PF and MVPA suggests that a higher level of PF does not necessarily correspond to a higher level of MVPA participation. Thus, the barriers to adoption of a more physically active lifestyle may not be fully explained by the subjects' physical limitations. Further understanding of this relationship is needed for the development of post-surgical weight loss guidelines and interventions.

Physical activity and physical function changes in obese individuals after gastric bypass surgery.

BACKGROUND: Little is known about the effects of gastric bypass surgery (GBS) on physical activity and physical function. We examined the physical activity, physical function, psychosocial correlates to physical activity participation, and health-related quality of life of patients before and after GBS. METHODS: A total of 20 patients were assessed before and 3 months after GBS. Physical activity was assessed using the 7-day physical activity recall questionnaire and a pedometer worn for 7 days. Physical function was assessed using the 6-minute walk test, Short Physical Performance Battery, and the physical function subscale of the Medical Outcomes Short Form-36 (SF-36). The Physical Activity Self-Efficacy questionnaire, the Physical Activity Barriers and Outcome Expectations questionnaire, the SF-36, and the Numeric Pain Rating Scale were also administered. RESULTS: Physical activity did not significantly increase from before (191.1 +/- 228.23 min/wk) to after (231.7 +/- 230.04 min/wk) GBS (n = 18); however, the average daily steps did significantly increase (from 4621 +/- 3701 to 7370 +/- 4240 steps/d; n = 11). The scores for the 6-minute walk test (393 +/- 62.08 m to 446 +/- 41.39 m; n = 17), Short Physical Performance Battery (11.2 +/- 1.22 to 11.7 +/- .57; n = 18), physical function subscale of the SF-36 (65 +/- 18.5 to 84.1 +/- 19.9), and the total SF-36 (38.2 +/- 23.58 to 89.7 +/- 15.5; n = 17) increased significantly. The Numeric Pain Rating Scale score decreased significantly for low back (3.5 +/- 1.8 to 1.7 +/- 2.63), knee (2.4 +/- 2.51 to 1.0 +/- 1.43), and foot/ankle (2.3 +/- 2.8 to 0.9 +/- 2.05) pain. No significant changes were found in the Physical Activity Self-Efficacy questionnaire or the Physical Activity Barriers and Outcome Expectations questionnaire. CONCLUSION: GBS improves physical function, health-related quality of life, and self-reported pain and results in a modest improvement in physical activity. These are important clinical benefits of surgical weight loss. Long-term follow-up is needed to quantify the ability to sustain or further improve these important clinical outcomes.