Brief Outpatient Rehabilitation Program for Post-COVID-19 Condition, Nerli et al, 2024 - with comment from T. Chalder

Abstract

Importance Post–COVID-19 condition (PCC) is emerging as a common and debilitating condition with few treatment options.

Objective To assess the effectiveness of a brief outpatient rehabilitation program based on a cognitive and behavioral approach for patients with PCC.

Design, Setting, and Participants Patients with mild to moderate PCC were randomized 1:1 to an established transdiagnostic rehabilitation program or care as usual at a single referral center recruiting from the region of the South-Eastern Norway Regional Health Authority. Participants were followed up after treatment completion and 12 months after enrollment using participant-reported outcome measures. Data were collected from February 22, 2022, until April 15, 2024. Intention-to-treat analysis was performed.

Intervention The program consisted of 2 to 8 outpatient encounters with approximately 2 to 6 weeks between each encounter. The intervention was theoretically grounded in the cognitive activation theory of stress, and physicians and physiotherapists were trained in cognitive and behavioral approaches with targeted negative stimuli and response outcome expectancies being particularly important.

Main Outcomes and Measures Participant-reported physical function assessed by the Short-Form Health Survey 36 Physical Function Subscale (SF-36-PFS) served as the primary outcome. Secondary outcome measures were the remaining subscales of the SF-36, return to work self-efficacy and symptom scores on fatigue, postexertional malaise, breathlessness, cognitive difficulties, sleep problems, anxiety and depression symptoms, and smell and taste abnormalities. Safety measures included primary health care contacts; hospital admissions; initiation of pharmacologic and/or nonpharmacologic therapy; occurrence of novel disease, illness, or other health problems; worsening of selected key symptoms; working abilities; and thoughts of suicide.

Results A total of 473 patients with mild to moderate PCC were assessed for eligibility (n = 364 physician referred; n = 109 self-referred); 314 were included (225 females [72%]; mean [SD] age, 43 [12] years) and 231 completed the primary end point evaluation. The SF-36-PFS scores improved statistically and clinically significantly in the intervention group (score difference between groups, 9.2; 95% CI, 4.3-14.2; P < .001; Cohen d = 0.43; intention-to-treat analysis). The effect was sustained over time. Most secondary and safety measures favored the intervention.

Conclusions and Relevance In this randomized clinical trial, a brief outpatient rehabilitation program with a cognitive and behavioral approach in patients with PCC was effective and safe. This trial adds to the evidence supporting such interventions in routine clinical care. Future research should investigate which elements of this approach are the most effective and identify subgroups for which the current treatment is most relevant.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2828267

 

Invited comment by Trudie Chalder

Quote:

This randomized clinical trial found that theoretically informed CBT rehabilitation improved more than care as usual on physical functioning as well as secondary outcomes, with a relatively small number of sessions.

This adds to the emerging body of evidence observing that CBT and rehabilitation are effective and safe treatments for improving symptoms and functioning after COVID-19 infection.

Postexertional malaise also improved, which suggests that postexertional malaise should not prevent people from participating in these interventions.

As this was a single-center study, future effectiveness studies should include multiple centers.

Embedded within the intervention were clear messages about safety and possible mechanisms. It is possible that the information provided reassured the patient that what they were being encouraged to do was potentially helpful.

The nocebo effect (expectation of harm) is hugely powerful. However, this study demonstrated the opposite of this, that is, it provides information about the potential benefits of rehabilitation that resulted in improved outcomes for those in the intervention group.

Outcomes were self-reported. Future studies would benefit from objective behavioral and physiologic assessments as well as an investigation of mediators and moderators.
Controlling for health care professional time and attention would provide clarity about active ingredients.


https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2828271

 

One of the authors, Selvakumar, was first author of the study "Prevalence and Characteristics with Post-COVID-19 Condition Among Non-hospitalized Adolescents and Young Adults", which also Wyller was part of.

That study is still making the rounds in the media as the study where lots of Long Covid patients turned out to never even having had Covid. This is how it was summarised just a few weeks ago in a news discussion segment on Long Covid.

What it actually showed was that the WHO criteria for LC might be too lax.

Thread for that study:
https://www.s4me.info/threads/jama-...olescents-selvakumar-wyller-et-al-2023.32677/

 

How is PEM defined - seems to be moving goalposts with LC and rarely anything approaching PE

 

Which safety measures didn't?

 

Wyller is also the senior author of this paper.

 

The third example in three days of why the DSQ PEM scales are problematic:

 

The more I think about it and review the De-Paul Symptom questionnaire, the more I think it’s appropriate to say using the DSQ to measure PEM is the equivalent of using the Oxford criteria to measure ME/CFS.

 

So he is! Thanks. I just saw the first three names of the authors. Also now see Maria Pedersen there who is often in the media with her BPS approach to fatigue.

 

Haven't read the full paper yet but noticed this:

The difference between groups was 9.2 (95% CI, 4.3-14.2).

 

The real trend here is the claiming of benefits even when researchers' own data show findings do not reach the clinical significance threshold. As I mentioned in my talks in Ireland, this is one of the strategies these people use over and over.

 

Only briefly skimmed. Despite the multiple imputation & per-protocol analyses, 35% isn't trivial. Numerous secondary outcomes were tested without correction for multiple comparisons. At T1, the between-group difference on the SF-36-PFS was approximately 9.2 points (95% CI, 4.3–14.2 points) & at T2 (12 months), the difference was 9.0 points (95% CI, 4.0–13.9). Although the confidence intervals include 10, the point estimate does not, so the interpretation of the intervention as effective is somewhat optimistic.

 

Classic Chalder!
431 were assessed eligible and 231 completed

At first I was shocked she was using an actual physical function measure (having read Crawley eg al 2013 which was basically another arm of the pace trial except they found no result for physical function even then just the Chalder fatigue scale so … recommended it was important to stop measuring physical function) even if it is self-report and highly infkuencable by ‘cognitive methods to change … bla bla’ .. and also what people might self-report even if they were objectively just as unwell.

but then I realised effectively it’s just the 50% who actually completed enough sessions and did the follow up - and it’s a broad long covid group who would all have this point have been well-aware of the dangers of increased-focused courses if you have PEM/ the ‘PEM-type long covid’ thanks to it being much better disseminated than it was before civid) and likely all the therapists did too (and might have suspected where that was heading if people were getting worse)

so I guess the question is , how many other likely methodological issues are there or is it just that their conclusions only apply to a population / are only externally valid for a group who can only be identified by being run through this same set-up where 50% complete so probably the non-PEM form

and you’ve the same influences/attitude to drop outs (in who is encouraged to or not to drop out perhaps ) by way of therapists and design and what their aims were.

and it’s that last but that I find most interesting: did they harm the other 200+? Did they get worse? Did at least they let them drop out before it happened too badly? Why do they never get reported on? It’s just like a repeat of ME/CFS clinics that treat ‘everyone but ‘ people with me/cfs who have PEM - are we now heading towards only treating non PEM fatiguey long covid and the rest can get stuffed because they don’t exist?

I know nothing about non-PEM long covid at 12months after enrolment (or if diagnosed at xweeks then how quickly were they enrolled ?) but I get the impression they should have had a control of people they’d also identified with non-PEM long covid but who didn’t do this to compare improvements over a year averaged over 200people’ to?

and maybe given the obvious influence these cognitive treatments mainly seem to have on encouraging people to ‘answer positively’ there should also be a real control arm - ? a plain non-Chalder not-pretending-to-treat-anything plain ‘sales technique to answer more positively’ arm which did all the things (having watched the therapists) to do with ‘encouraging not to be negative in answers’ and forcing people to ‘be optimistic’ in their function and best-friending etc

so it’s like with like on everything except the actual ‘claimed treatment part’ with the ‘icing on the cake bbit’ directly copied for the real control arm?

 

\

I'm not clear how they are claiming the primary outcome results are clinically significant when 9.2 is below the threshold of clinically important threshold of a 10-point difference. In the paper, they mention the 10-pt threshold only in discussing power calculations but not elsewhere, unless I missed it elsewhere.

 

Summary on Twitter from one of the authors, Joel Selvakumar

 

Signe Flottorp, research director at the Norwegian Institute for Public Health (FHI) writes:

In this randomised trial from Norway, a brief outpatient rehabilitation program with a cognitive and behavioral approach in patients with post-COVID-19 condition was effective and safe. Fits well with previous studies. Well done
@nerlitom
@jp_selvakumar

 

https://www.youtube.com/watch?v=R6diiifcSQs

Garner has just posted this video about the trial.

 

Medpage Today

Long COVID Symptoms Improve With Outpatient Intervention

quote:

"Patients can recover from post-COVID condition," Nerli said. "This intervention is effective and safe. The treatment is brief, but giving patients an explanation they can relate to -- an explanation for their symptoms -- is important," he told MedPage Today.

For over a decade, Nerli and his team have treated other patients with persistent physical symptoms -- mainly, fatigue and pain -- with this intervention.

"For us, it is essential to foster a belief that the body has the potential to adapt, and that a positive adaption towards a normal health state requires an active pursuit of physical and mental tasks that are individualized, suitable, feasible, and enjoyable," he said. "We differ a lot from others with our way of working, but our experience over years has made us confident."