Review Interventions for the management of long covid post-covid condition: living systematic review, 2024, Zeraatkar, Flottorp, Garner, Busse+

My rapid response has been published online.

I am just looking back at the REGAIN BMJ publication and it seems that they had to correct their main conclusions to state that the results were based on a specific population of patients, namely adults with post-covid-19 condition at least three months after hospital discharge for covid-19. The correction is here: https://www.bmj.com/content/385/bmj.q988

This is very important, and makes me think that originally they had left this out and conlcuded that their mental and physical rehabilitation programme works for all long covid patients.

Does anyone know what led to this change? I suspect this has come from someone contacting the editor. @ME/CFS Skeptic do you know anything about this?
 
ME/CFS Skeptic said:
In the protocol the authors said they were going to use intention-to-treat (ITT): "reviewers will preferentially extract the results from intention-to-treat analyses without any imputations for missing data, when reported.
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Been looking closer into this. One interpretation might be that including all randomized participants is assuming that those with missing data did not had the outcome (in our example improvement/recovery), so a form of imputation (non-responder imputation).

Cochrane seems to recommend not using the sample size randomized but instead the number with available data:
Although in theory this is equivalent to collecting the total numbers and the numbers experiencing the outcome, it is not always clear whether the reported total numbers are the whole sample size or only those for whom the outcome was measured or observed. Collecting the numbers of actual observations is preferable, as it avoids assumptions about any participants for whom the outcome was not measured
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https://training.cochrane.org/handbook/current/chapter-06

Not sure if I disagree with this. Lots of missing data will make the data look better with this approach.

I think a better conservative option would be to use the total amount randomized in case of a positive outcome (such as improvement, recovery etc.) and use the opposite approach with available data if the outcome is negative (like stroke, mortality, adverse effects etc.). Using this approach you assume that missing data are no improvers/recoveries but you do not make the assumption that missing data means no adverse effects.
 
Lead author's academic page at McMaster is https://experts.mcmaster.ca/display/zeraatd

In https://brighterworld.mcmaster.ca/a...ins-gairdner-early-career-investigator-award/ —

Zeraatkar completed her doctoral degree in Health Research Methodology, after which she completed a Banting Fellowship – a highly competitive fellowship intended to attract and retain top-tier postdoctoral talent, both nationally and internationally – at Harvard Medical School. 

Her research centres on evidence synthesis and evaluation to guide complex health care and public health questions. She often works in areas in which the evidence is complex or conflicting, or in areas in which the evidence is of low quality, such as COVID-19 therapeutics and nutrition.
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Some other publications —

The impact of blinding on trial results: A systematic review and meta-analysis (2023)
Tyler Pitre; Sarah Kirsh; Tanvir Jassal; Mason Anderson; Adelia Padoan; Alexander Xiang; Jasmine Mah; Dena Zeraatkar

BACKGROUND
Blinding—the concealment of the arm to which participants have been randomized—is an important consideration for assessing the risk of bias of randomized trials. A growing body of evidence has, however, yielded inconsistent results on whether trials without blinding produce biased findings.

OBJECTIVES
To conduct a systematic review and meta-analysis of the evidence addressing whether trials with and without blinding produce different results.

METHODS
We searched MEDLINE, EMBASE, Cochrane Reviews, JBI EBP, and Web of Science, from inception to May 2022, for studies comparing the results of trials with and without blinding. Pairs of reviewers, working independently and in duplicate, reviewed search results for eligible studies and extracted data. We pooled the results of studies comparing trials with and without blinding of patients, healthcare providers/investigators, and outcome assessors/adjudicators using frequentist random-effects meta-analyses. We coded study results such that a ratio of odds ratio < 1 and difference in standardized mean difference < 0 indicate that trials without blinding overestimate the beneficial effects of treatments.

RESULTS
We identified 47 eligible studies. For dichotomous outcomes, we found low certainty evidence that trials without blinding of patients and healthcare providers and trials without blinding of patients may slightly overestimate the beneficial effects of treatments. We found moderate certainty evidence that trials without blinding of outcome assessors overestimate the beneficial effects of treatments. For continuous outcomes, we found low certainty evidence that trials without blinding of patients and healthcare providers may overestimate the beneficial effects of treatments. We found moderate certainty evidence that trials without blinding of outcome assessors/adjudicators probably overestimate the beneficial effects of treatments.

CONCLUSIONS
Our systematic review and meta-analysis suggest that blinding may influence trial results in select situations—although the findings are of low certainty and the magnitude of effect is modest. In the absence of high-certainty evidence suggesting that trials with and without blinding produce similar results, investigators should be cautious about interpreting the results of trials without blinding.

Link | PDF (Cochrane Evidence Synthesis and Methods) [Open Access]

Instruments assessing risk of bias of randomized trials frequently included items that are not addressing risk of bias issues (2022)
Wang; Ghadimi; Wang; Hou; Zeraatkar; Iqbal; Ho; Yao; Hu; Ye; Couban; Armijo-Olivo; Bassler; Briel; Gluud; Glasziou; Jackson; Keitz; Letelier; Ravaud; Guyatt

OBJECTIVES
To establish whether items included in instruments published in the last decade assessing risk of bias of randomized controlled trials (RCTs) are indeed addressing risk of bias.

STUDY DESIGN AND SETTING
We searched Medline, Embase, Web of Science, and Scopus from 2010 to October 2021 for instruments assessing risk of bias of RCTs. By extracting items and summarizing their essential content, we generated an item list. Items that two reviewers agreed clearly did not address risk of bias were excluded. We included the remaining items in a survey in which 13 experts judged the issue each item is addressing: risk of bias, applicability, random error, reporting quality, or none of the above.

RESULTS
Seventeen eligible instruments included 127 unique items. After excluding 61 items deemed as clearly not addressing risk of bias, the item classification survey included 66 items, of which the majority of respondents deemed 20 items (30.3%) as addressing risk of bias; the majority deemed 11 (16.7%) as not addressing risk of bias; and there proved substantial disagreement for 35 (53.0%) items.

CONCLUSIONS
Existing risk of bias instruments frequently include items that do not address risk of bias. For many items, experts disagree on whether or not they are addressing risk of bias.

Link (Journal of Clinical Epidemiology)

Minimal important difference estimates for patient-reported outcomes: A systematic survey (2021)
Carrasco-Labra; Devji; Qasim; Phillips; Wang; Johnston; Devasenapathy; Zeraatkar; Bhatt; Jin; Brignardello-Petersen; Urquhart; Foroutan; Schandelmaier; Pardo-Hernandez; Hao; Wong; Ye; Yao; Vernooij; Guyatt

OBJECTIVES
The objective of the study was to develop an inventory summarizing all anchor-based minimal important difference (MID) estimates for patient-reported outcome measures (PROMs) available in the medical literature.

STUDY DESIGN AND SETTING
We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database internal library (January 1989eOctober 2018). We included primary studies empirically calculating an anchor-based MID estimate for any PROM in adults and adolescents. Pairs of reviewers independently screened and selected studies, extracted data, and evaluated the credibility of the MIDs.

RESULTS
We identified 585 eligible studies, the majority conducted in Europe (n 5 211) and North America (n 5 179), reporting 5,324 MID estimates for 526 distinct PROMs. Investigators conducted their studies in the context of patients receiving surgical (n 5 105, 18%), pharmacological (n 5 85, 15%), rehabilitation (n 5 65, 11%), or a combination of interventions (n 5 194, 33%). Of all MID estimates, 59% (n 5 3,131) used a global rating of change anchor. Major credibility limitations included weak correlation (n 5 1,246, 23%) or no information regarding the correlation (n 5 3,498, 66%) between the PROM and anchor and imprecision in the MID estimate (n 5 2,513, 47%).

CONCLUSIONS
A large number of MIDs for assisting in the interpretation of PROMs exist. The MID inventory will facilitate the use of MID estimates to inform the interpretation of the magnitude of treatment effects in clinical research and guideline development.

Link (Journal of Clinical Epidemiology)
 
SNT Gatchaman said:
Interventions for the management of long covid post-covid condition: living systematic review
Dena Zeraatkar; Michael Ling; Sarah Kirsh; Tanvir Jassal; Mahnoor Shahab; Hamed Movahed; Jhalok Ronjan Talukdar; Alicia Walch; Samantha Chakraborty; Tari Turner; Lyn Turkstra; Roger S McIntyre; Ariel Izcovich; Lawrence Mbuagbaw; Thomas Agoritsas; Signe A Flottorp; Paul Garner; Tyler Pitre; Rachel J Couban; Jason W Busse

OBJECTIVES
To compare the effectiveness of interventions for the management of long covid (post-covid condition).

DESIGN
Living systematic review.

DATA SOURCES
Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023.

ELIGIBILITY CRITERIA
Trials that randomised adults (≥18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care.

RESULTS
24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation.

Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference −8.4, 95% confidence interval (CI) −13.11 to −3.69; Checklist for Individual Strength fatigue subscale; range 8-56, higher scores indicate greater impairment) and probably improves concentration (mean difference −5.2, −7.97 to −2.43; Checklist for Individual Strength concentration problems subscale; range 4-28; higher scores indicate greater impairment).

Moderate certainty evidence suggested that, compared with usual care, an online, supervised, combined physical and mental health rehabilitation programme probably leads to improvement in overall health, with an estimated 161 more patients per 1000 (95% CI 61 more to 292 more) experiencing meaningful improvement or recovery, probably reduces symptoms of depression (mean difference −1.50, −2.41 to −0.59; Hospital Anxiety and Depression Scale depression subscale; range 0-21; higher scores indicate greater impairment), and probably improves quality of life (0.04, 95% CI 0.00 to 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; range −0.022-1; higher scores indicate less impairment).

Moderate certainty evidence suggested that intermittent aerobic exercise 3-5 times weekly for 4-6 weeks probably improves physical function compared with continuous exercise (mean difference 3.8, 1.12 to 6.48; SF-36 physical component summary score; range 0-100; higher scores indicate less impairment).

No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, a mobile application providing education on long covid.

CONCLUSIONS
Moderate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid.

SYSTEMATIC REVIEW REGISTRATION
Open Science Framework https://osf.io/9h7zm/


Link | PDF (BMJ) [Open Access]
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This is funded by the Long Covid Web (as well as Canadian institute fir heakth research)

does anyone know much about what this is?
The about us has blurb about values and mission but I’ve not spotted details about who they are

so intrigued if they are a patient org or government type thing or what?
 
Mij said:
"I suddenly believed I would recover completely" and avoiding pwME experiences is what he thinks saved him.
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The part that bothers me is that he doesn't seem to grasp the fact that his body might have been improving already (natural remission) and it was that improvement itself that could have led to the idea that he could recover quickly.

The same goes with those who claim increasing activity levels led them to recover when the reverse could be true - natural recovery allowed them to increase activity levels over time.
 
The persistent decades-long failure to both discriminate between correlation and causation, and the failure to account for plausible alternative interpretations, is inexcusable. Especially as these fundamental failures have been pointed out since the start, including in the formal peer-review literature.

Nobody claiming to be doing serious science based research can plead ignorance of this stuff. This is Methodology 101, FFS. :grumpy:

The only plausible conclusion left now is that these critical issues are being deliberately ignored because those doing the ignoring know they are fatal to their hypotheses/models/claims.

Anti-science is alive and flourishing within the medical profession. And its name is biopsychosocial.
 
bobbler said:
This is funded by the Long Covid Web (as well as Canadian institute fir heakth research)

does anyone know much about what this is?
The about us has blurb about values and mission but I’ve not spotted details about who they are

so intrigued if they are a patient org or government type thing or what?
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It's the official professional network for LC. Funded by the federal government.

There are credible names attached, but they seem to be all over the place. Looking at the research that was funded, it's a mix of good and bad things seemingly with no intelligence involved.

Having funded this, and the disaster that is the Cochrane guideline development, basically screams to me that this initiative is a complete waste of everything. Nor surprisingly, we have literally nothing good going on in Canada. Zero relevant research either. I guess this is why, they have no idea what they're doing. Even though some of the people involved seemed to have at least some clue.

But clearly they don't. What a total disaster. And it makes it clear that the problem was never limited to some small fringe cabal. They may have done most of the work, but they also never put any effort into it and it still ended up dominating everything. That only happens when the whole system fails, and if it wasn't them, it would have be someone else. The failure is fractal, the same at all levels, and wherever you look, it's there, in all directions.
 
I have a feeling this review will be instrumental in pushing CBT/'rehab' programmes into the future. The review is terrible, and I'm not saying that just because I don't like its conclusions. It's really badly done — they've broken numerous standards for systematic reviews and evidence synthesis. @ME/CFS Skeptic will put them right, but we need this crap correcting, or, better still, completely pulled. It's that bad.
 
Nightsong said:
"Trial By Error: Yet Again BMJ Recommends CBT and Exercise for Long Covid":

https://virology.ws/2024/12/03/tria...j-recommends-cbt-and-exercise-for-long-covid/
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Indeed a good question, what is a "living systematic review"? Well, it's not what this review is:
Cochrane handbook said:
We define an LSR as a systematic review which is continually updated, incorporating relevant new evidence as it becomes available.

Practically, this means that LSRs:
  • Are underpinned by continual, active monitoring of the evidence (i.e. monthly searches)
  • Immediately include any new important evidence (meaning data, studies or information) that is identified
  • Are supported by up-to-date communication about the status of the review, and any new evidence being incorporated
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I know this is BMJ and not Cochrane but I doubt their definition would be much different. This review has been published at the 4.5 year mark with a tiny few trials reporting nothing worth writing about, and we know that it will definitely not be updated based on active monitoring, since the point here is not to review the evidence but to push for a particular version of reality.

Of course it will be months before this can be exposed as a sham. Then the damage will have been done. Corrections will have been issued, minimized and likely without affecting the conclusions, even though their evidence will have been debunked.

It's explained to be of use in a field that is rapidly changing. This is not the case. In fact we have seen nothing worth writing about beyond apathetic monitoring. There are dozens of trials underway that should report in the next two years, but this is still not rapidly changing as literally nothing has changed from day 1. In fact those two are the treatments that were used, without a valid reason, emphasizing how nothing has, in fact, changed.

They even write this in their review, which David has noted, that CBT and GET are offered to people with LC not on the basis of credible evidence, but on the same misunderstanding fueled by their insistence that there is no actual illness:
CBT and graduated physical activity are offered to patients with long covid and ME/CFS based on the observation that patients often reduce activity in response to their symptoms. Consequently, patients may become physically deconditioned, develop disrupted sleep-wake patterns, and hold unhelpful beliefs about fatigue. Interventions such as CBT and supervised physical activity which gradually reintroduce patients to activity may help with reconditioning, regularising patterns of activity, optimising rest and sleep, and addressing patients’ unhelpful beliefs about fatigue and activity.
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This is not a valid reason. It's pure speculation, a belief system debunked by real life data. Obviously. Hence nothing has changed from day 1. So while a living systematic review would be useful if the field were rapidly changing, it is instead static and borderline comatose.

But words and their meaning, who can be bothered with them?
 
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