The Timeline of Post Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2018, Nielsen

https://mro.massey.ac.nz/bitstream/handle/10179/14653/02_whole.pdf?sequence=2&isAllowed=y

New Zealand study of PEM using 2xCPETs at 48 or 72 hours.

ABSTRACT

PURPOSE: To investigate the timeline of post-exertional malaise (PEM) using objective and subjective measures in Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The primary aim was to determine whether PEM extends beyond 24-hours, and if a 48-hour or 72-hour repeated exercise protocol would provide additional information as a diagnostic tool. The secondary aim was to analyse subjective patterns of fatigue during PEM.

METHODS: Sixteen ME/CFS and 16 age and gender matched controls participated in the study. Participants were randomly assigned to either a 48-hour or 72-hour repeated cardiopulmonary exercise test protocol on a cycle ergometer. Objective measures were recorded at anaerobic threshold (AT), respiratory exchange ratio (RER) and maximal exercise.

All ME/CFS participants recorded their subjective fatigue 7-days prior to and 10-days post exercise utilising the daily diary of fatigue.RESULTS: Results from the 48-hour and 72-hour protocol indicated no decline in functional capacity in any group across days.

There was a significant increase in workload and %VO2max at AT within the 72-hour ME/CFS group only. Subjective timelines of fatigue showed significant differences between the 48-hour and 72-hour protocol, with the 48-hour ME/CFS group taking significantly longer to recover (mean 11 days) than the 72-hour ME/CFS group (mean 5 days). Conversely, both control groups were recovered in less than a day. However, there was high variation across measures of subjective fatigue among ME/CFS participants.

CONCLUSIONS: The results of this study further support the use of 24-hour repeated protocols to determine functional decline during PEM. Results also provide new information regarding a potential improvement in function 72-hours after an initial exercise bout in ME/CFS. Subjective results indicate no identifiable pattern in relation to subjective fatigue during PEM. Future research should focus on a larger clinical trial to further understand the implications and consistency of the data from this study.​

 

This study was done by a student of Lyn Hodges of Massey University. An earlier study is discussed here.
https://www.s4me.info/threads/hodge...thy-controls-following-repeated-exercise.860/

I participated in this study. I'm only part of the way through reading the paper. The literature review is disappointing, there's a lot of positivity about CBT and GET, and mention of associations with OCD behaviours. It's hard to understand how people can read the literature and come away with these views.

 

My brain's having a holiday. Can anyone explain what this means? Is it good or bad?

 

Yes, I haven't got into the meat of the study yet either.

But yes, I feel the same.
Dr Hodges has done other work on ME/CFS. She's been in contact with Professor Tate. It is my understanding that she became interested in ME/CFS when a colleague at Massey University had family members develop ME/CFS. The colleague is a psychologist. So, I don't think there is any excuse for Dr Hodges not having a good appreciation of the literature around ME/CFS and understanding the problems around the evidence base for GET, CBT and correlations with psychological problems.

So it becomes very hard to understand how she could let a student make the following statement in a paper:

Surely Dr Hodges would not want a student to go out into the world, theoretically with specialist knowledge of ME/CFS, thinking this is true.

Maybe we need to have a whip round and send her a copy of Brian Hughes book.

 

A quick glance through her reference list and I feel sorry for her trying to get her head around all that lot and produce a coherent report. Lots of the papers listed have nothing to do with ME at all. And on PACE the only paper listed questioning it is Keith Geraghty's initial PACE gate paper. Perhaps the re-analysis came out too late to influence this thesis.

 

Don't get me wrong, I'm really appreciative of Dr Hodges and her team being interested enough to do this work. Tessa Nielsen is a very nice person who seemed to want to be helpful to people with ME/CFS.

I spent quite a bit of money to travel to participate in this study and it was an effort. I have communicated with both Dr Hodges and Tessa, including after the MS study came out. And yes, I will send a polite email. I just had hoped the team had moved beyond needing feedback on some of the issues in the literature review.

 

Here's two PR threads where we discussed the first study (with an MS cohort) and initial aspects of this second study.
https://forums.phoenixrising.me/threads/distinguishing-cfs-new-zealand-research.51357/
https://forums.phoenixrising.me/thr...yndrome-multiple-sclerosis-and-healthy.53341/

Here's a post I made on PR about my first communications with Dr Hodges, dated 16 May 2017.

"I emailed Dr Hodges yesterday (email address easily found on Massey University website) and she replied very promptly with the screening questionnaire and the participant consent form for the next study.

"I've completed the questionnaire and this morning I sent an email to Dr Hodges about a few issues. She rang me to discuss the issues I raised. I didn't ask if I could share what she said but as my comments are pretty positive, I don't think she will mind.

"She became interested in CFS when a colleague asked if she would give his wife and children (with CFS) an exercise test. The tests were all perfectly normal. But she started reading the CFS literature and became interested.

"She explained a bit about the first study. It was pretty small - the CFS component was only 10 participants plus matched controls. And it sounds as though the results were variable. Some people with CFS actually performed poorly on the first test as well as the second. Dr Hodges mentioned that they seemed to be finding two groups of people in the CFS/ME cohort. Some got over the exercise in a couple of days but others took four weeks. Some of the people travelled quite a long way to do the study and so might have been exhausted before that first test. Dr Hodges said that they are now travelling to some of these people to test them in their home town and see if the results are replicable. So, this first study may not have very robust findings but it has obviously raised enough questions to allow this next larger study to proceed.

"The patient consent form had a definition of CFS/ME as 'a complicated disease characterised by extreme fatigue that cannot be explained by an underlying medical condition'. I mentioned in my email that no one knows if it is actually complicated, it might just be currently poorly understood, and that the word 'complicated' tends to be used by the BPS crowd to indicate that our thoughts and behaviours are involved in maintaining the illness. I also said that extreme fatigue wasn't really the main characterising feature, rather PEM is. And I queried the statement that our fatigue can't be explained by a medical condition, which is probably nit-picking, but some readers could assume from that definition that our fatigue must therefore explained by a 'non-medical condition'.

"Dr Hodges said that she hadn't had a definition to start with but her ethics committee had required one. I got the impression that she didn't necessarily place much importance on the definition and didn't think we should either.

"I questioned the statement 'The fatigue may worsen with physical or mental activity but it doesn't improve with rest'. It isn't a big step from saying that rest doesn't help, to saying that pushing through the fatigue is the right way to go. Of course rest (as opposed to more activity) does help with the return to a baseline during PEM.

"The participant consent form says that knowledge of how people with CFS/ME respond to exercise will 'be valuable in creating solutions for exercise prescription in the future'. And it is 'anticipated that there will be an intervention study aimed at investigating the effect of vibration training on biomarkers of fatigue'. So that sounded like there was an underlying belief in exercise potentially being a cure for CFS/ME. I questioned that in the email but we didn't properly cover it in the phone conversation. I understand that an exercise physiologist has certain tools and probably comes with a mindset that exercise helps with a lot of things.

"Dr Hodges did state that she knows that there were problems with the PACE trial and that there are problems with studies into the effect of exercise and the effectiveness of exercise therapy in this illness in general. This is when she mentioned the complicating issues that they had come across in her initial trial.

"I also asked about a question in the survey about what we attribute our illness to (100% physical cause; 100% psychological cause and various combination in between). Dr Hodges replied that that question was just part of a survey characterising the illness that was taken from Leonard Jason's work. She said that they were thinking of shortening the survey and that she didn't think that answers to that question would be used anywhere. She has a PhD student working for her so she may not be totally hands on with every part of the work.

"She is interested in lactic acid levels and in heart rate variability in people with ME. I get the sense that she can see a lot of interesting questions to be answered.

"Dr Hodges seems very keen to find participants and to do the studies on this illness properly. She and I might disagree on some underlying beliefs such as the value of exercise in curing ME or CFS/ME. But my sense is that she is curious and compassionate and willing to engage productively with people with the illness. She is reading the literature and criticisms of past work and I think she will be open to whatever conclusion the data points to.

"And so, if my family gets through the screening process, we will try to participate in this next study. Dr Hodges, if you read this, you and/or your PhD student are very welcome to come onto Phoenix Rising anytime to discuss things, get a sense of whether what you are finding is common in a broader population and/or let us know how things are going and when papers or articles are published."​

 

And here's a post of mine, written after I participated in this study:

"I finished mine two weeks ago. I guess the objective exercise and circulation system metrics are what the researchers will focus on, so maybe it's ok to say how I went? If you don't want to read it, stop now.

"I was quite busy in the days before the first session, preparing to leave my family and travelling. I felt ok after the test, I mean a little bit dizzy and sick but that passed quickly. I was actually surprised what relatively little effort the researchers were asking for - they just seemed to take things a little beyond where the anaerobic threshold was reached? And it's just a couple of minutes of work. Because I was away from home with nothing else to do, I was able to rest a lot between sessions.

"The night of the first session, I had chills, couldn't get warm, hurt all over quite badly and couldn't sleep for quite awhile. It wasn't muscle aches from the cycling, it was the flu-type pain and my feet burned.

"The next day, I woke up feeling ok and had a stroll into the city, had lunch and walked back to where I was staying. The walk home got harder and harder, my legs became heavier and heavier. I then rested in bed for the rest of the day.

"So, a bit less than 48 hours after the first session, I did the second CPET. My anaerobic threshold dropped from previously 156 to 137 bpm from memory. The evening was ok.

"The next day I travelled home, and it was pretty much ok.

"The next few days were ok-ish. I was quite busy, catching up on housework, getting ready for visitors and then hosting them. I thought that the CPET had not had much of an effect. I wondered if maybe I didn't really have PEM, or ME.

"However, after the visitors left, I've pretty much fallen in a heap. My days are much harder to get through. My heart rate is high in the evenings (120 bpm resting on the sofa for goodness sake) and I'm getting a lot of sore throats, glands up, headaches, neurological odd things, my ear drum burst, mouth ulcers and I'm periodically getting bad all-over pain and chills. I normally wake up at 6.30 am but I'm waking up around 8 am and have to really fight to get out of bed and do what I have to do. I'm collapsing on the sofa and then bed for the day much earlier than usual. My activity levels have dropped right down to a bare minimum.

"I doubt that the CPET itself is the major reason for this. I think, for me, it's more of a cumulative thing - more the impact of total activity over a period of time. I think studies of this kind would be better if we wore fit bits for two weeks before and for some time after.

"The researchers were lovely and committed to understanding the disease better. Hopefully the drop in anaerobic threshold means something. They didn't do the blood testing, which was a shame as I really want to see something solid that explains why I'm sick.

"Having experienced this, it brings home to me the very many factors that confound any study, even ones with objective outcomes.

"These factors include:
*other activity (e.g. I think standing for 15 minutes in the cold waiting to be picked up (not the researchers' fault) had a big impact on my blood pressure and ability to think in the first session; also activity before, between and after the sessions)
* menstrual cycle
* medication (I had had quite a lot of nurofen in the days prior to the first session for neuralgia and a migraine)
* difficulty in remembering and rating subjective impacts. Unless there is some sort of a real time method for gathering impressions, I think subjective ratings aren't worth much at all.
* technical issues (e.g. I was slow getting the mouthpiece in with the bag of oxygen for one test)."​

 

So yes, the study didn't find that the people with ME/CFS performed worse on a second test than on a first test when there was 48 or 72 hours between tests. In fact, if anything, performance on the second test after 72 hours was better rather than worse.

It's a shame there wasn't a graph of changes at the individual level. My data with the 48 hour testing protocol, emailed to me by the researchers soon after the study shows a substantial drop:
VO2Max - VO2 (day1 >day 2)
Mine: 24.0 >17.8
ME/CFS 48 average: 25.9 >24.5
Control 48 average: 38.8 >36.7

Anaerobic Threshold - VO2
Mine: 19.5 >14.7
ME/CFS 48 average: 14.8 >14.9
Control 48 average: 22.5 >21.7

Anaerobic Threshold - Workload (watts)
Mine: 90 > 75
ME/CFS 48 average: 54 >58
Control 48 average: 71 >68

I should note however, that I did do a significant walk on the day between my tests to get food. So perhaps my test really was more like a test 24 hours after exertion.

A graph of individual changes would give us a better idea of how variable CPET performance is even in controls.