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Post-exertional malaise
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=== Loss of functional capacity === A fourth distinctive element of PEM is often described as a loss of stamina and/or functional capacity. This refers to the results of the 2-day cardiopulmonary exercise test (CPET) procedure. A CPET is usually reproducible and normally has a test-retest difference of 7-12%<ref name="Stevens2018">{{Cite journal | last = Stevens | first = Staci | authorlink=Staci Stevens | last2 = Snell | first2 = Chris | authorlink2 = Christopher Snell | last3 = Stevens | first3 = Jared | last4 = Keller | first4 = Betsy | last5 = VanNess | first5 = J. Mark | authorlink5 = Mark VanNess | date = 2018 | title=Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00242/full|journal=Frontiers in Pediatrics|language=English|volume=6|doi=10.3389/fped.2018.00242|issn=2296-2360}}</ref>. ME/CFS patients however show strikingly lower results on several measures at the second CPET compared to the first, despite meeting objective markers of maximal effort. These results have been replicated by several research teams, though there is inconsistency on which measure (VO2 or maximal workload, at peak or ventilatory threshold), the decline in functional capacity is best represented. {| class="wikitable" ! colspan="8" |Physiological changes between first and second exercise test during 2-day CPET procedure in patients with ME/CFS |- | |Number of ME/CFS patients |VO2 peak |VO2 at VT |Workload peak |Workload at VT |HR peak |O2pulse at VT |- |[[Mark VanNess|VanNess]] et al. 2007.<ref name="VanNess2007" /> |6 | -22% | -26% |? |? |? |? |- |Vermeulen et al. 2010.<ref name="Vermeulen2010" /> |15 | -6.3% | -7.0% | -5.3% | -7.0% | -1.9% | -8.8% |- |[[Christopher Snell|Snell]] et al. 2013.<ref name="Snell2013" /> |51 | -5% | -10.8% | -7.2% | -55.2% |? |? |- |[[Betsy Keller|Keller]] et al. 2014.<ref name="Keller2014" /> |22 | -13.8% | -15.8% | -12.5% | -21.3% | -5.9% | -12.6% |- |Hodges et al. 2018.<ref name="Hodges2018" /> |10 | +5.3% | +6.1% | -6.7% | -11.4% | -0.6% |? |} The drop in functional capacity on the second CPET is usually not seen in other diseases. According to [[Betsy Keller|Keller]] et al. (2014) "ME/CFS patients currently represent a unique class of ill patients who do not reproduce maximal CPET measures, unlike individuals with cardiovascular disease, lung disease, end-stage renal disease pulmonary arterial hypertension and cystic fibrosis".<ref name="Keller2014">{{Cite journal | last = Keller | first=Betsy A. | last2 = Pryor | first2 = John Luke | last3 = Giloteaux | first3 = Ludovic | date = 2014-04-23 | title = Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment|url=https://www.ncbi.nlm.nih.gov/pubmed/24755065|journal=Journal of Translational Medicine|volume=12|pages=104|doi=10.1186/1479-5876-12-104|issn=1479-5876|pmc=4004422|pmid=24755065}}</ref> A preliminary study from [[New Zealand]] suggests that patients with MS do not display the same decline on the second day of exercise testing, as do patients with ME/CFS.<ref name="Hodges2018">{{Cite journal | last = Hodges | first = L. D. | authorlink = Lynette Hodges | last2 = Nielsen | first2 = T. | last3 = Baken | first3 = D. | date = Jul 2018 | title = Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/28782878|journal=Clinical Physiology and Functional Imaging|volume=38|issue=4 | pages = 639–644|doi=10.1111/cpf.12460|issn=1475-097X|pmid=28782878}}</ref> Questions have however been raised about the clinical use of the 2-day CPET procedure. [[Christopher Snell|Snell]] et al. (2013) suggested it might be unethical to use this method since many ME/CFS patients might suffer a serious relapse as a result of exercise performance.<ref name="Snell2013" /> Others have noted that the CPET- procedure is not practical either. It cannot be used in patients with severe ME/CFS (thus excluding these patients from study) and because of cost and expertise, may not be available to most clinicians.<ref name="CDC-PEM-comments" /> CPET for ME/CFS is usually not covered by insurance and can cost hundreds of dollars.<ref name="Cotler2018" /> For these reasons PEM is usually assessed using self-reporting questionnaires.
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