This post has been copied and following posts moved from News from Aotearoa/New Zealand and the Pacific Islands At a recent webinar, Dr Lynette Hodges, Exercise Physiologist, Massey University, asked what pwME would like her to study. Any ideas here? and I can pass on.
I'd like to know whether short-term and long-term ME patients (vs LC vs HC) have low peripheral venous oxygen saturations. This was such a striking abnormality in many Long Covid patients (short-term by definition), yet Systrom's evaluations showed central measurements to be abnormally high. She almost certainly won't be in a position to evaluate SmcvO2, but peripheral is potentially doable and could be interesting. (I wonder if the metabolic abnormalities might vary with body site, such that limb muscles hyperextract, but central organs and brain aren't, for example. The net effect might be less O2 extraction as measured centrally. Perhaps impaired O2 or glucose availability is compensated for by lactate as the universal fuel for load balancing. Just an idea.)
I wonder whether she could work with Nicola Clague-Baker on developing ways to take equipment into people's homes to measure physical and physiological changes as people go through their normal daily activities as a way of developing assessment tools for severity and changes over time. I think one of the most important areas we need research on is following pwme over at least a year to capture data relating to increases and decreased in activity and changes in physiological measures when people report PEM and other symptom fluctuations. Nicola Clague Baker is at Liverpool University, is one of the @PhysiosforME and gave an interesting talk on her preliminary work on this at the recent IACFSME conference.
I'd like to see a straightforward 2 day CPET study, with all the details managed really well to produce an unassailable result. I'd like to see the CPETs combined with activity monitoring, so that it's possible to ensure that people have a stable activity level before undergoing the first CPET. One of the worries about CPETS is that some people are coming into the test already in PEM because of travel requirements, and the level of activity between the two tests might be unusual. With activity monitoring, you could ask the person to keep within 10% of their average daily step count from the previous month. And take the CPET to the people, by taking the van Massey University has with the CPET equipment to the participants' homes, so there is minimal travel. Have a large sample of people with ME/CFS, at least 50, and controls matched on activity level, sex, age, BMI range. Have a large sample of Long Covid people too. I'd also like to see some of the participants do a 3 day CPET - 3 tests on successive days, maybe even 4 day CPET, to see what happens. There could be blood tests before and after the CPETs, there are quite a few things in the blood that I think would be useful to look at. But most of all, I think we just need a great CPET study, with everything done really really carefully.
I would worry that repeatedly pushing and crashing in a 3 or 4 day CPET study would carry too much risk of long term deterioration. I think it would be unethical. But I agree we need a really good large 2 day CPET with all the conditions you mention. If they could get funding for such a big study I think it's vital they make the most of the data collection by coordinating with the team at Cornell University who are measuring all sorts of before and after biological information in their large study.
I think it depends on the person's threshold for PEM; I've exerted myself more strenuously than 8 minutes of cycling on successive days. I think it could be fine ethically if the participants were very well informed. I'd definitely do it if given the opportunity, because I really want to know what happens. If we could show that there is a cumulative effect on work rate at ventilatory threshold, I think that would have a big impact on management recommendations.
Given the notorious lack of funding in NZ, which leads to miniscule cohort sizes, I'd say collaborate with rigorous researchers overseas and use the same techniques to take the same measurements, to speed up replication. This could include what Physios4ME are developing for measuring the effects of ordinary day to day activities (see also Trish's post). We also need good studies on the effects of pacing. There'll be some headscratching involved trying to figure out a good way to do this. But since Lyn seems to have specialised in CPET, if she's doing more of those, then getting more data from other disease controls would be good. Lyn has already done this with MS but only small numbers. One control group I'd like someone to get their teeth into is badly overtrained athletes. @Snow Leopard might have some more technical suggestions about what sort of CPET measurements haven't yet been explored well enough
Not too keen on anyone repeating CPET daily 3 or 4 times, too risky. But wondering about mildly overexerting daily to study the effects of cumulative exertion, which is something I don't think has been studied much yet. My body seems to have a 3 day rule. I can mildly overexert 3 days in a row without it resulting in full-blown PEM (though on day 3 limbs may be starting to feel a tiny bit heavier if I pay attention), but on day 4 the shits hits the fan with PEM. Mild overexertion here means if I were to overexert at that level on day 1 and then go back to my normal activity level, I'd get away with it. The trick for any study would be to figure out the correct amount of exertion for each individual, and figure out suitable outcome measures. Maybe handgrip strength could be used, as well as bloods.
The thing is people have different thresholds. Some people can't or at least shouldn't do even one CPET. The CPETs I did with Lyn Hodges were each just 8 minutes of cycling, with some minutes of that very easy cycling. It's not necessarily going to trigger PEM, or at least PEM that lasts more than a day, in everyone with ME/CFS, certainly not if it isn't combined with a whole lot of other energy-requiring things. Maybe the result from the first CPET and second CPETs could guide who does the third test. If someone doesn't have a big drop in performance on the second one, what happens if they do a third one? If we found that there is a pattern of decreasing performance with cumulative activity, that would be pretty important.
I thought this when I first got sick. Wore a tomtom touch for 2-3yrs in hopes my doctor might want to look at the data. Nope. (Obviously, that would just have been anecdotal in studying ME/CFS. But I always think people will want data. I would. Much prefer data to having to report things. So very many times I’ve said I’ve not got symptoms or no to questions that should be yes, just due to being drained from getting there.)
NZ has a long history in shoestring research in other fields than medicine coming up with useful results. There’s a great deal that can be done with educating volunteers, self administration with postal or courier delivery, instructional videos and zoom type sessions, etc etc. I’d love to think that people could spend more of their budget on planning it brilliantly, and assessing it very critically beforehand to see if the method will fall down, before any rollout. So when the costs start mounting it’s going to give something other than ‘we need a larger sample’ or ‘this could do with more research’. And so that the preliminary study of a small, number of people can be easily rolled out with the same equipment over time to a much larger sample.
I’d happily take a CPET that brought on PEM. I think there are a lot of us who have triggered PEM many times for much smaller reasons than the potential to actually find something treatable about this disease. The idea that I can avoid PEM in my life is a lovely one but not realistic due to many factors but even when I do a great job and manage al sorts of things, it falls down due to my psychology (if I do a great job of pacing I imagine I might be able to do more, and of course overdo it - over and over again over the years). I’m not sure it’s necessity more unethical than asking people to participate in studies of smoking or drinking. If you’re going to do it anyway… Of course, participants need to be fully informed and that’s difficult as that’s exactly why these studies are needed. I do prefer the @Trish version where the monitoring is long term and part of normal life. So we’d be recording PEM events that happened because of life. But I suspect we need both. Not sure how to select for the people who could do the CPET without bias from that selection but others might.
No, not capillary (estimated arterial) oxygen saturation, I mean venous oxygen saturation from blood. We're still starting at 96-100% in oxygenated arterial blood, and it should be around 60-70% after it's been through the tissues. There is evidence of peripheral hyperextraction in many of us, eg I was walking (shuffling actually) around with sats of 15-46%. This is jaw-droppingly abnormal - as in my intensive care colleagues wanted to know "why I wasn't dead" as they typically see that late in resuscitation scenarios. (ETA finger pulse oximetry - ICU grade - was 99%.) However, the odd thing is that while many of us (LC) have seen this in peripheral blood draws (eg taken as usual from antecubital vein at the elbow), the formal CPET studies of mixed/central venous oxygenation show it to be normal or high. See the multiple studies by David Systrom. Another problem has been that medicine ignores this reading in clinical practice, as "we don't know what it means". However, there are studies to show that it has a useful relationship to mixed/central venous oxygenation (eg taken from a jugular central venous line, or better from a pulmonary artery Swan-Ganz catheter). See Peripheral measurements of venous oxygen saturation and lactate as a less invasive alternative for hemodynamic monitoring (2018) Also noted by Gez Medinger on Twitter. https://twitter.com/user/status/1566778102512066562
