Effects of a symptom-titrated exercise program on fatigue and quality of life in people with post-COVID condition, 2024, Barz+

[SNT Gatchaman]

Effects of a symptom-titrated exercise program on fatigue and quality of life in people with post-COVID condition – a randomized controlled trial
Barz, Andreas; Berger, Joshua; Speicher, Marco; Morsch, Arne; Wanjek, Markus; Rissland, Jürgen; Jäger, Johannes

Fatigue is the most prevalent symptom within the post-COVID condition (PCC). Furthermore, many patients suffer from decreased physical performance capacity and post-exertional malaise. Although exercise has been proposed as an effective therapeutic strategy for PCC, there is limited evidence on individualised and symptom-titrated exercise interventions in patients with fatigue and PEM. Therefore, we conducted a multi-centre randomised controlled trial to investigate the effectiveness of an individualised and symptom-titrated exercise program.

We measured fatigue, health-related quality of life, hand-grip strength, endurance capacity and PEM before and after the 10-week intervention. A total of 118 individuals with PCC were included in the final intention-to-treat analysis. All tests and training sessions took place in commercial fitness and health facilities.

We found significant effects on fatigue severity, health-related quality of life and physical performance capacity. Adjusting the individual exercise load to daily fatigue has proven to be an effective and safe strategy in PCC patients with fatigue.

Under the guidance of qualified professionals and by utilising symptom-titrated training recommendations, commercial fitness and health facilities present an appropriate setting for outpatient exercise rehabilitation in PCC.

Link | PDF (Nature Scientific Reports) [Open Access]

 

[SNT Gatchaman]

The purpose of this study was to investigate the effects of an individualized, symptom-titrated and feasible exercise program on fatigue, health related quality of life, The exercise program had a significant effect on fatigue in comparison to the control group but not on objective fatigability. Furthermore, the intervention had a significant effect on handgrip strength, endurance capacity and HRQoL. There were no effects on PEM as well as measures of objective fatigability.

The individualized and symptom-titrated exercise program significantly reduced fatigue in INT from 5.67 to 4.51 compared to CON (Pre: 5.49; Post: 5.29) on the FSS.

We observed no changes in objective fatigability as assessed by fatigue ratios as well as recovery ratio in either group. […] To our knowledge, this is the first experimental study to investigate changes in fatigue as well as objective fatiguability after an exercise intervention in PCC.

While exercise in our study has reduced the subjective fatigability during activities of daily living as evidenced by the reduction in FSS scores, it did not improve the objective fatigability (fatigue ratio1/2, recovery ratio) in tasks requiring consecutive maximum exertion of effort such as the repeated HGS test. Our findings also allude to deconditioning not being the cause for objective fatigability in PCC. Given the increase of maximum (1.45 ± 3.43 kg) and mean strength (1.97 ± 3.40 kg) in INT, muscular fatigability is likely not an effect of a lack of overall strength.

 

[SNT Gatchaman]

One major limitation of this study is the relatively high attrition rate. In particular, the number of individuals who did not commence the study despite being included or who dropped out of the intervention must be acknowledged. Possible reasons for non-participation or discontinuation might be a generally low expectancy of improvement or previous negative experiences with physical activity.

 

[Nightsong]

Saw this one earlier - only very briefly skimmed, but: there are substantial dropout rates across both groups amounting to 32.2% of all participants (despite exclusion both of patients with significant functional disability and those hospitalised due to COVID-19). No power calculation, & no mention of sensitivity analyses etc for missing data that I can see? The more objective measures of fatiguability did not show improvement, nor was there improvement on DSQ-PEM. Waitlist control.

This study also illustrates a different problem that I've mentioned on S4ME before. 174 patients were randomised, 118 included in the analysis. The inclusion criteria were:

(a) age between 18 and 79 years, (b) confirmed SARS-CoV-2 infection (positive PCR test) ≥ 12 weeks before, (c) mild to moderate course of COVID-19, (d) presence of fatigue symptoms for ≥ 12 weeks, (e) < 1 h/week of physical exercise within the last 3 months, (f) no contraindications for physical training (pre-existing conditions, medication) and (g) a medical certificate for physical activity readiness. Exclusion criteria were a Post-COVID-19 Functional Status (PCFS)-score of 4 as this indicates an inability to perform activities of daily living and thus exercise without assistance[47] and hospitalization due to COVID-19.

And yet:

The DSQ-PEM indicated PEM in all participants in CON at study onset. In INT, two participants were below the threshold for PEM at PRE. Mean PEM frequency and intensity showed overall mild to moderate PEM in CON (PEM: 2.39 ± 0.68) and INT (PEM: 2.43 ± 0.75) at study onset.

Does anyone believe that in a patient cohort defined by the very broad inclusion criteria above, almost all of them are going to "crash" as pwME do? All this really illustrates is that DSQ-PEM is not an ideal instrument for measuring PEM. If you look at the questions it seems more a metric of exertional intolerance & there is no real attempt to draw out just how disproportionate it is relative to the trigger:



In the absence of better alternatives, PEM is now effectively being defined by this scale, which has led to a study in which nearly all of a very broadly defined group of patients were initially thought to have "PEM". And there is now a push to create a consensus around such outcome measures...

 

[rvallee]

Another turd for the turd-polishing industry.

Still no one has ever come up with a reason why exercise has anything to do with the problem outside of the debunked nonsense about deconditioning, which this clearly isn't. It's just a mindless reflex.

Pathetic. There has never been a group of professionals better suited for the old "addition by subtraction". Firing every single one of the people involved in this nonsense would be a net positive.

 

[Eleanor]

So we have 'PEM' being used as a vague and muddy term for any general post-activity tiredness, understood to be one possible feature of 'post-Covid condition' used as a vague and muddy term for any general post-Covid illness.

Getting nowhere fast. But I'm sure the 'commercial fitness and health facilities' will appreciate the plug.

 

[Sean]

substantial dropout rates across both groups amounting to 32.2%

That alone renders the conclusions dodgy, at best.

 

[SNT Gatchaman]

Speaking of plugging, there's a post on Bluesky from the journal "Clinical Rehabilitation". I'm not giving it oxygen on Bsky by commenting, but noting here for reference.

DW. People with chronic fatigue avoid exercise through fear of increasing post-exertional malaise (PEM). A trial in 118 people with Long Covid found a tailored exercise programme benefited them without worsening PEM - it was reduced. www.nature.com/articles/s41... NICE should recommend exercise.

https://bsky.app/profile/clinicalrehab.bsky.social/post/3ldirkpefa22o

The account has a small number of followers (currently 25) and the post has 2 likes. It follows 2 accounts, 1 is Bsky and the 2nd is Derick Wade (https://bsky.app/profile/derickwaderehab.bsky.social). This is presumably the "DW" preceding the post and suggests he (partly/wholly) runs the journal's Bsky account. Listing for Derick T Wade as Editor Emeritus. Probably well known here, he was an author of the infamous anomalies paper.

Contemporaneously, DW posted from his personal account —

Chronic fatigue syndrome and Long Covid are associated with post-exertional malaise (PEM), which leads some people to avoid exercise despite its benefits; a new trial shows that tailored exercise benefits most symptoms, and PEM was reduced, NOT increased. www.nature.com/articles/s41...
#neurorehab

(currently 1 like)

https://bsky.app/profile/derickwaderehab.bsky.social/post/3ldirchprkc2o

I presume he hasn't actually read the paper.

 

[dave30th]

This is the paper cited for the MCID range for the Fatigue Severity Scale: https://pmc.ncbi.nlm.nih.gov/articles/PMC4937582/

"Three cross-sectional studies reporting MIDs for the FSS were identified [33, 46, 50]. Diagnostic groups included SLE, RA and multiple sclerosis (MS). Anchor-based approaches were applied in all the three studies and a distribution-based approach (viz. effect size, ES, of at least 0.25) was also applied in one [50]. Two used a patient global rating scale as an anchor [33, 46] whereas the third used clinical anchors and baseline data from a clinical trial to establish MIDs [50] MIDs ranged from 0.5 to 1.2 for global change, 0.08 to 0.4 for improvement and 1.0 to 1.2 for deterioration."

The sentence in the new paper that references that earlier paper is this: "The decrease of fatigue in INT (−1.14; 20.1%) is within the range of the minimal clinically important difference for a global change (0.5 to 1.2)."

Of course, the decrease of fatigue in the internvention group isn't on its own the point. The point is the difference from the "waitlist" group, who had a much more modest reported reduction of fatigue of 0.2 on the same scale--so the change is somewhere around .95 rather than 1.14, although they don't seem to provde an exact measure of the difference.

Can someone smarter than me explain the difference between the MCIDs for "global change" and "improvement" and "deterioration." Would relying on the MCID for improvement make more sense than citing the one for global change--the one mentioned in the new study?

 

[Kitty]

Chronic fatigue syndrome and Long Covid are associated with post-exertional malaise (PEM), which leads some people to avoid exercise despite its benefits; a new trial shows that tailored exercise benefits most symptoms, and PEM was reduced, NOT increased.

So as PEM is defined as worsening after activity, they seem to have demonstrated that none of them have PEM.

I suppose you could call that useful.

 

[bobbler]

Saw this one earlier - only very briefly skimmed, but: there are substantial dropout rates across both groups amounting to 32.2% of all participants (despite exclusion both of patients with significant functional disability and those hospitalised due to COVID-19). No power calculation, & no mention of sensitivity analyses etc for missing data that I can see? The more objective measures of fatiguability did not show improvement, nor was there improvement on DSQ-PEM. Waitlist control.

This study also illustrates a different problem that I've mentioned on S4ME before. 174 patients were randomised, 118 included in the analysis. The inclusion criteria were:

And yet:

Does anyone believe that in a patient cohort defined by the very broad inclusion criteria above, almost all of them are going to "crash" as pwME do? All this really illustrates is that DSQ-PEM is not an ideal instrument for measuring PEM. If you look at the questions it seems more a metric of exertional intolerance & there is no real attempt to draw out just how disproportionate it is relative to the trigger:

View attachment 24531

In the absence of better alternatives, PEM is now effectively being defined by this scale, which has led to a study in which nearly all of a very broadly defined group of patients were initially thought to have "PEM". And there is now a push to create a consensus around such outcome measures...

It’s a very important point that the patient and scientific community need to very swiftly draw up a minimum quantitative definition as what can count as people with PEM fir any study

otherwise we have the same issue where either real pem is being skirted by pef fatiguability etc often deliberately sometimes due to patients being misled into thinking that’s a term for them

and even more likely we have fir PEM:

- a severit of crash
- a threshold of what we can do without causing PEM eg 12-48hrs later
- cumulative often bigger crashes from having people skirt being just over this limit and just getting enough rest to perform (but it is sort of PEM just harder to measure whilst we don’t have objective measures eg haven pathed what might be a blood test or bodily measure that happens in PEM so it’s based on symptoms and said people will be ‘in a state of momentum ) that falls outside what is put under that PEM but is big and does damage health and limit life


I suspect it’s very easy to if not recruiting people with cf being encouraged to state/imagine being tired is PEM we have people very mild ie with higher thresholds not being actively triggered into that 48hr PEM but it catching up with them outside the follow-up period.

in a sense the 2day cpet stuff is indicative because it’s an individual MAX. Then on day two you see the deterioration for example but also there will be symptoms and debility in the days and weeks around and beyond this.

I don’t know enquire what we do because of course we are being played

I don’t think it’s unreasonable that given all sorts of filters are used to keep the illest out of their experiments there should be limits out in of being excluded if too mild. And within that PEM being quantified for any research


It’s useless having a load of research being allowed when on the mild end it’s how long is a piece of string.

it would also stop those dodgy fatigue clinics from being fertile recruitment onto rubbish studies if most their participants don’t reach the research bar.

but we’ve left PEM too lose. There needs to be a minimum on this ?

 

[SNT Gatchaman]

Glasziou on Bsky —

Several new randomised trials on activity/exercise for long-covid out last month - all suggesting benefits - eg German trial of "symptom-titrated exercise program" pubmed.ncbi.nlm.nih.gov/39681609/

As with DW's post mentioned above, not planning to interact there to give it oxygen — FWIW its social media "SpO2" is 0% an hour after posting, with 0 likes or reposts. (After 3 weeks DW's post above got 4 likes and 2 reposts, which look to be from uninvolved colleagues, probably auto-liking, as well as our old friend cfsresearch.)

It does suggest that he hasn't read the paper or is unable to recognise its plainly spelled out limitations in terms of drop-out rate and lack of objective improvement. Neither of those scenarios would be a particularly good look for a professor of EBM, although on par with colleagues.

Again, to quote the paper —

While exercise in our study has reduced the subjective fatigability during activities of daily living as evidenced by the reduction in FSS scores, it did not improve the objective fatigability (fatigue ratio1/2, recovery ratio) in tasks requiring consecutive maximum exertion of effort such as the repeated HGS test. Our findings also allude to deconditioning not being the cause for objective fatigability in PCC.

One major limitation of this study is the relatively high attrition rate. In particular, the number of individuals who did not commence the study despite being included [21/314 = 6.7%] or who dropped out of the intervention [50/224 = 22.3%] must be acknowledged.

 

[bicentennial]

Glasziou

It does suggest that he hasn't read the paper or is unable to recognise its plainly spelled out limitations in terms of drop-out rate and lack of objective improvement.

Neither of those scenarios would be a particularly good look for a professor of EBM, although on par with colleagues.

So is he reducing the science into blurb to impress some undiscerning amateur audience, expecting professorial EBM status to carry it to the finishing line, and if so what is his target audience being sign-posted to his post, is it for trade, and does it amount to an advert ?

"He is Professor of Evidence-Based Medicine at Bond University, where he is also Director of the Faculty of Health Sciences and Medicine.

He was the director of the Centre for Evidence-Based Medicine at the University of Oxford in England from 2003 to 2010.

In July 2010, he received an NHMRC Australia Fellowship at Bond University.

In March 2015, he was elected a fellow of the Australian Academy of Health and Medical Sciences.

He was appointed an Officer of the Order of Australia in the 2021 Queen's Birthday Honours.

https://pubmed.ncbi.nlm.nih.gov/?term=Glasziou+P&cauthor_id=19935040

Thats a lot of misleading eminence in the evidence bringing his profession and institutions into untrusted disrepute, and undermining also the standards of compliance

His name is stuck on 737 papers ? The titles look like he is a compliance expert