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Jo Nijs
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==Exercise therapy== === Exercise limits === Nijs tested the use of exercise limits as a method to prevent post-exertional setbacks in ME/CFS patients.<ref name="Prevent2008" /> In a 2008 study, patients had to estimate the amount of exercise (walking) they could handle without triggering post-exertional malaise. Because it was assumed patients would overestimate their capacities, this amount was reduced by 25% if the person was having a good day and 50% if she was having a bad day. Another exercise limit involved a maximal heart rate (the heart rate that corresponded with a respiratory exchange ratio of 1 on an exercise test), that patients could not exceed during walking. Despite these precautions, patients still experienced a worsening of their symptoms after exertion. Because this relapse was short-lived, Nijs concluded that the exercise limits had worked and prevented important health status changes. Two years later the Nijs’ research group conducted a similar study. Twenty-two ME/CFS test-subjects had to perform a submaximal exercise test and a paced cycling regime. Patients could only do 75% (on a good day) or 50% (on a bad day) of what they thought they could handle without triggering a relapse, while a maximal heart rate was set at 80% of their anaerobe threshold. Once again, despite these precautions, patients experienced a worsening of their condition after both pacing and the submaximal exercise test, a deterioration that was not seen in healthy controls.<ref name="Unravelling2010" /> === A symptom-contingent exercise program === In 2008, Nijs collaborated with Karen Wallman and Lorna Paul to work out an exercise program for ME/CFS that took into account post-exertional malaise. Although it was still instructed to exercise progressively and to build up stamina, the key advice was that patients should listen to their body while doing so. They could for example change their schedule if they were having a bad day. Nijs et al. criticized earlier approaches that used a time-contingent approach where patients have to follow a pre-set plan, regardless of how they were feeling. <blockquote>"Early approaches to graded exercise therapy advised patients to continue exercising at the same level when they developed symptoms in response to the exercise. This led to exacerbation of symptoms and adverse feedback from patients and patient charities."<ref name="NijsSM2008" /></blockquote>To prevent relapses, Nijs, Paul and Wallman advised to build in a long stabilization phase in which patients had to find the right balance between rest and activity. With this approach, symptom fluctuation has to be reduced to a manageable level first. Only when the patient feels that she can cope with a certain level, can it be decided to build up exercises. This form of self-management combined with graded exercise was criticized by Lucy Clark and Peter White. They emphasized that a graded exercise program has to be time-contingent to be effective: <blockquote>"[…] a central concept of GET is that patients maintain their level of exercise as much as possible even after a CFS/ME setback. This is to reduce the many negative consequences of rest and allow the body to habituate to the increase in activity."<ref name="Letter2008" /></blockquote> In 2011, Nijs & Wallman collaborated with Leonard Jason, who had helped develop the [[Energy Envelope Theory]], and [[Ellen Goudsmit]], who had studied the use of pacing. Together they worked out a 'consensus document' about the main principles of the pacing in ME/CFS. According to the authors there was a "lack of information on the efficacy of time-contingent protocols in people with evidence of neurological or immunological disease."<ref name="Pacing2012" /> Nijs and colleagues proposed an approach where patients limited their activities in response to internal cues of post-exertional malaise. Patients were only advised to gently increase their activity levels if their health had stabilized and they were close to about 60 to 70% of their former functioning. === A U-turn towards time contingent-exercise === In 2012 (after the first results of the controverial [[PACE trial|PACE-trial]] were published) the research group of Nijs made a U-turn and started advocating a time-contingent form of graded exercise.<ref name="Cauwenbergh2012" /> This position was criticized by [[Tom Kindlon]]<ref name="Kindlon2012">{{Cite journal | last = Kindlon | first = Tom | authorlink = Tom Kindlon | date = 2012 | title = Objective compliance and outcome measures should be used in trials of exercise interventions for Chronic Fatigue Syndrome | url = https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2362.2012.02724.x|journal=European Journal of Clinical Investigation|language=en|volume=42|issue=12|pages=1360–1361|doi=10.1111/j.1365-2362.2012.02724.x|issn=1365-2362}}</ref> who pointed out that studies supporting graded exercise therapy were almost solely based on subjective measures. Nijs et al. responded: <blockquote>"We agree with [[Tom Kindlon]] that such evidence is based on self-report rather than on objective measures, but in the end of the day, patients prefer treatments that make them feel better (subjectively) over treatments that improve objective blood results (but at the same time leave them feeling sick)."<ref name="Time2012">{{Cite journal | title = Time-contingent pacing and exercise therapy accounting for postexertional malaise and central sensitization in chronic fatigue (central sensitivity) syndrome | date = 2012-09-15 | url = https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2362.2012.02722.x|journal=European Journal of Clinical Investigation|volume=42|issue=12|pages=1363–1365 | last = Nijs | first = Jo | last2 = Van Cauwenbergh | first2 = Deborah | last3 = De Kooning | first3 = Margot | last4 = Ickmans | first4 = Kelly|doi=10.1111/j.1365-2362.2012.02722.x|issn=0014-2972}}</ref></blockquote>Regarding the argument that numerous patients surveys had shown that GET can have detrimental effects on the health of ME/CFS patients, Nijs et al. replied: <blockquote>"Such surveys have value, but from a scientific viewpoint, it remains an unanswered question who filled out these surveys (nothing but patients with ME/CFS diagnosed by a physician?), to what extent selection bias, suggestion and recall bias have contributed to the study findings, etc. One cannot exclude the possibility that the survey results reflect the difficulty of clinicians around the globe to apply exercise therapy for patients with ME/CFS."<ref name="Time2012" /></blockquote> ===Activity pacing self-management (APSM) === According to Nijs, the PACE-authors made a mistake by placing GET in opposition to pacing. He argues the two can and should be used together, in what he calls 'Activity Pacing Self-Management' (APSM). In a first phase, pacing is used to stabilize the health condition of the patient and let her know that exercise doesn't always have to result in a relapse. Only when this is achieved (and this can take several weeks) is it advised to move on to a second, graded phase where a progressive time-contingent approach is used. According to APSM, activities should only be increased incrementally according to a personalized, pre-set schedule. Sufficient rest periods are included after each activity to prevent serious [[relapse]]s. Nijs tested his APSM approach in a 2015 randomized controlled trial in which the control group received relaxation therapy. The results were favorable, though no objective performance measures were used. The study was also rather small as only 16 ME/CFS patients were involved in the experimental APSM group, of which 4 (25%) stopped the treatment prematurely.<ref name="Kos2015" /> === Kinesiophobia and catastrophizing: testing the fear-avoidance model === Nijs has investigated the fear avoidance model in ME/CFS. In this model, originally developed for chronic low back pain, it is believed patients worsen their condition by holding an irrational fear of movement called kinesiophobia. When Nijs tested this in 64 ME/CFS patients, the results contradicted the theory:<blockquote>"Our data do not support the view that kinesiophobia is associated with disability (ie, activity limitations and participation restrictions) in patients with CFS who experience pain. Our results, therefore bring into question the clinical importance of kinesiophobia."<ref name="NoKin2004" /></blockquote>Two other studies by Nijs, both published in 2004, did find a relationship between kinesiophobia and activity limitations measured with the CFS-APQ, but there was no correlation with exercise test results.<ref name="Kinesiophobia2004" /> Another concept of the fear avoidance model is catastrophizing, a tendency to interpret events negatively or to assume the worst will happen. In a group of 36 ME/CFS patients, Nijs found that “catastrophizing accounted for 41% of the variance in bodily pain."<ref name="performance2018" /> These results were questioned by [[Tom Kindlon]] who pointed out the study could not prove the assumed direction of causation. The lack of correlation between catastrophizing and the large drop in employment rate seen in the ME/CFS patients studied, suggests other factors might be more important in determining their condition."<ref name="Kindlon2009">{{Cite journal | last = Kindlon | first = T | authorlink = Tom Kindlon | title = Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing|journal=Pain Med | date = 2009 |volume=10|issue=6|pages=1144 | url = https://www.researchgate.net/publication/26802501_Response_to_Exercise_Performance_and_Chronic_Pain_in_Chronic_Fatigue_Syndrome_The_Role_of_Pain_Catastrophizing}}</ref> In 2011, Nijs collaborated with Gijs Bleijenberg to test the effect of kinesiophobia and catastrophizing in ME/CFS before a threatening activity, in this case, stair climbing. Both factors were unrelated to symptom expectancies, but they did correlate with actual stair climbing performance, i.e. the time required to complete the task.<ref name="Stair2012" /> Two years later the study was repeated using a larger sample of 49 ME/CFS patients. Findings contradicted those of the previous study as kinesiophobia and catastrophizing were no longer related to stair climbing duration.<ref name="Heins2013" /> In 2012, Nijs' research group concluded that catastrophizing is a long-term predictor of pain in ME/CFS patients.<ref name="Psych2012" /> In a 2013 review Nijs concluded that fear of movement was a highly prevalent and a clinically relevant factor in ME/CFS.<ref name="Avoidance2013" />
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