Cardiopulmonary Exercise Test Methodology for Assessing Exetion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Background: Concise methodological directions for administration of serial cardiopulmonary exercise testing (CPET) are needed for testing of patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Maximal CPET is used to evaluate the coordinated metabolic, muscular, respiratory and cardiac contributions to energy production in patients with ME/CFS. In this patient population, CPET also elicits a robust post-exertional symptom flare (termed, post-exertional malaise); a cardinal symptom of the disease. CPET measures are highly reliable and reproducible in both healthy and diseased populations. However, evidence to date indicates that ME/CFS patients are uniquely unable to reproduce CPET measures during a second test, despite giving maximal effort during both tests, due to the effects of PEM on energy production. Methodology: To document and assess functional impairment due to the effects of post-exertional malaise in ME/CFS, a 2-day CPET procedure (2-day CPET) has been used to first measure baseline functional capacity (CPET1) and provoke post-exertional malaise, then assess changes in CPET variables 24 h later with a second CPET to assess the effects of post-exertional malaise on functional capacity. The second CPET measures changes in energy production and physiological function, objectively documenting the effects of post-exertional malaise. Use of CPET as a standardized stressor to induce post-exertional malaise and quantify impairment associated with post-exertional malaise has been employed to examine ME/CFS pathology in several studies. This article discusses the results of those studies, as well as the standardized techniques and procedures for use of the 2-day CPET in ME/CFS patients, and potentially other fatiguing illnesses. Conclusions: Basic concepts of CPET are summarized, and special considerations for performing CPET on ME/CFS patients are detailed to ensure a valid outcome. The 2-day CPET methodology is outlined, and the utility of the procedure is discussed for assessment of functional capacity and exertion intolerance in ME/CFS

Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Post-exertional malaise (PEM) is the hallmark clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PEM involves a constellation of substantially disabling signs and symptoms that occur in response to physical, mental, emotional, and spiritual over-exertion. Because PEM occurs in response to over-exertion, physiological measurements obtained during standardized exertional paradigms hold promise to contribute greatly to our understanding of the cardiovascular, pulmonary, and metabolic states underlying PEM. In turn, information from standardized exertional paradigms can inform patho-etiologic studies and analeptic management strategies in people with ME/CFS. Several studies have been published that describe physiologic responses to exercise in people with ME/CFS, using maximal cardiopulmonary testing (CPET) as a standardized physiologic stressor. In both non-disabled people and people with a wide range of health conditions, the relationship between exercise heart rate (HR) and exercise workload during maximal CPET are repeatable and demonstrate a positive linear relationship. However, smaller or reduced increases in heart rate during CPET are consistently observed in ME/CFS. This blunted rise in heart rate is called chronotropic intolerance (CI). CI reflects an inability to appropriately increase cardiac output because of smaller than expected increases in heart rate. The purposes of this review are to (1) define CI and discuss its applications to clinical populations; (2) summarize existing data regarding heart rate responses to exercise obtained during maximal CPET in people with ME/CFS that have been published in the peer-reviewed literature through systematic review and meta-analysis; and (3) discuss how trends related to CI in ME/CFS observed in the literature should influence future patho-etiological research designs and clinical practice

A Double-Blind, Placebo-Controlled, Randomized, Clinical Trial of the TLR-3 Agonist Rintatolimod in Severe Cases of Chronic Fatigue Syndrome

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a severely debilitating disease of unknown pathogenesis consisting of a variety of symptoms including severe fatigue. The objective of the study was to examine the efficacy and safety of a TLR-3 agonist, rintatolimod (Poly I: C(12)U), in patients with debilitating CFS/ME. METHODS AND FINDINGS: A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites. The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET). Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS), Activities of Daily Living (ADL), and Vitality Score (SF 36). Subjects receiving rintatolimod for 40 weeks improved intra-patient placebo-adjusted ET 21.3% (p = 0.047) from baseline in an intention-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo-adjusted ET improvement to 28% (p = 0.022). The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies. The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048). Placebo subjects crossed-over to receive rintatolimod demonstrated an intra-patient improvement in ET performance at 24 weeks of 39% (p = 0.04). Rintatolimod at 400 mg twice weekly was generally well-tolerated. CONCLUSIONS/SIGNIFICANCE: Rintatolimod produced objective improvement in ET and a reduction in CFS/ME related concomitant medication usage as well as other secondary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00215800

Joint action aesthetics

Synchronized movement is a ubiquitous feature of dance and music performance. Much research into the evolutionary origins of these cultural practices has focused on why humans perform rather than watch or listen to dance and music. In this study, we show that movement synchrony among a group of performers predicts the aesthetic appreciation of live dance performances. We developed a choreography that continuously manipulated group synchronization using a defined movement vocabulary based on arm swinging, walking and running. The choreography was performed live to four audiences, as we continuously tracked the performers’ movements, and the spectators’ affective responses. We computed dynamic synchrony among performers using cross recurrence analysis of data from wrist accelerometers, and implicit measures of arousal from spectators’ heart rates. Additionally, a subset of spectators provided continuous ratings of enjoyment and perceived synchrony using tablet computers. Granger causality analyses demonstrate predictive relationships between synchrony, enjoyment ratings and spectator arousal, if audiences form a collectively consistent positive or negative aesthetic evaluation. Controlling for the influence of overall movement acceleration and visual change, we show that dance communicates group coordination via coupled movement dynamics among a group of performers. Our findings are in line with an evolutionary function of dance–and perhaps all performing arts–in transmitting social signals between groups of people. Human movement is the common denominator of dance, music and theatre. Acknowledging the time-sensitive and immediate nature of the performer-spectator relationship, our study makes a significant step towards an aesthetics of joint actions in the performing arts

The impact of a mandatory wellness program in a fire protection district

A mandatory two year fitness, health screening and education program was conducted in a fire protection district to assess the impact on selected fitness, medical and absenteeism variables. The study evaluated the archival data from a program that had already been conducted. Absenteeism measured as occupational injury and personal illness were reviewed two years prior to the program and during the two year program period. Medical evaluation and fitness testing were also conducted during the program. Individualized exercise prescriptions were developed for each participant from the fitness profiles derived from testing. The firefighters were given two hours each work shift to complete their prescribed physical training. Wellness education topics were provided during training sessions at the fire stations. A quasi-experimental factorial design was used to evaluate the program. All fitness measures showed improvement. Total cholesterol, triglycerides and diastolic blood pressure declined as well. A repeated measures MANOVA showed a significant multivariate effect for the linear combination of variables consisting of physical fitness, health screening and absenteeism. A reduction in injury-related absenteeism resulted in a decline in the workers\u27 compensation premium and saved this fire district an estimated $68,741 over two years. It appears that this mandatory health promotion program improved physical fitness and reduced absenteeism due to occupational injury

Functional outcomes of anaerobic rehabilitation in an individual with chronic fatigue syndrome: case report with 1-year follow-up

This case study aimed to document the effect of pacing self-management and short-duration exercise on physiological functioning and disability in an individual with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). A 28-year-old woman with CFS/ME received a rehabilitation program that involved: (1) pacing self-management using a heart rate monitor to maintain heart rate below ventilatory threshold and (2) a pragmatic approach to restorative strengthening and flexibility exercises conducted at an intensity below anaerobic threshold, which were completed 3 times weekly. Cardiopulmonary exercise testing (CPET) with analysis of expired gases and functional self-report were obtained before and 1 year after initiation of intervention. At 1-year follow-up, the patient reported she was able to complete daily activities without reproducing symptoms and 75% improvement in time to recover from CPET. Prior to intervention, patient demonstrated impaired cardiovascular and pulmonary responses at peak and anaerobic threshold, which improved at 1-year follow-up. Pacing self-management combined with short-duration restorative exercise resulted in a favorable clinical outcome in this patient with CFS/ME. Additional research is necessary to determine the efficacy and mechanism of action for this treatment

Functional outcomes of anaerobic rehabilitation in an individual with chronic fatigue syndrome: case report with 1-year follow-up

This case study aimed to document the effect of pacing self-management and short-duration exercise on physiological functioning and disability in an individual with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). A 28-year-old woman with CFS/ME received a rehabilitation program that involved: (1) pacing self-management using a heart rate monitor to maintain heart rate below ventilatory threshold and (2) a pragmatic approach to restorative strengthening and flexibility exercises conducted at an intensity below anaerobic threshold, which were completed 3 times weekly. Cardiopulmonary exercise testing (CPET) with analysis of expired gases and functional self-report were obtained before and 1 year after initiation of intervention. At 1-year follow-up, the patient reported she was able to complete daily activities without reproducing symptoms and 75% improvement in time to recover from CPET. Prior to intervention, patient demonstrated impaired cardiovascular and pulmonary responses at peak and anaerobic threshold, which improved at 1-year follow-up. Pacing self-management combined with short-duration restorative exercise resulted in a favorable clinical outcome in this patient with CFS/ME. Additional research is necessary to determine the efficacy and mechanism of action for this treatment