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Endocrinological

I have replaced the text in this new section with the previous text about the HPA axis (which was deleted by IVI earlier this year). There was some discussion about restoring this section at the time, but it never happened. --sciencewatcher (talk) 17:13, 16 November 2016 (UTC)

I see Doc James replaced "there is a substantial body of evidence" with "there may be". That doesn't seem to tally with the review, which says "a substantial body of evidence now points to the following four main findings in patients with this condition: a degree of mild hypocortisolism; attenuated diurnal variation of cortisol; enhanced negative feedback; and blunted HPA axis responsiveness". --sciencewatcher (talk) 02:11, 17 November 2016 (UTC)

Um so it is a copyright infringement than?

We do not use the term patient generally and we must paraphrase as that is Elsevir. Doc James (talk · contribs · email) 03:42, 18 November 2016 (UTC)

Yikes. Sciencewater please don't restore the copyvio. Jytdog (talk) 03:53, 18 November 2016 (UTC)

I'm pretty sure copying 4 words is not a copy violation. In fact it would generally be preferred to copy the level of evidence verbatim (e.g. "moderately effective") rather than trying to use a different word which may not be the same. But Doc James' edit seems fine in this case. --sciencewatcher (talk) 15:19, 18 November 2016 (UTC)

Mitochondrial dysfunction?

Is this source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680051/ A reliable source? Everything seems to check out but something doesn't feel right. The journal "International Journal of Clinical and Experimental Medicine" has been controversial, and research for "ATP profile tests" don't come up with much. — Preceding unsigned comment added by Petergstrom (talk • contribs) 07:14, 18 November 2016 (UTC)

Given the recent study that shows higher than normal ATP in patients, it seems to contradict this study. That is a good example why we always use reviews where possible (see MEDRS). --sciencewatcher (talk) 15:20, 18 November 2016 (UTC)

Could you send that study to me?Petergstrom (talk) 16:11, 18 November 2016 (UTC)

I don't have it. Have a look on the reddit/healthrising/phoenixrising. I'm pretty sure I saw it there (probably reddit). Or look at recent research on google scholar. --sciencewatcher (talk) 16:42, 18 November 2016 (UTC)

Lead author is a controversial GP whose "science" in previous papers hasn't been, shall we say, rigorous. I would suggest a careful assessment of any paper authored by her. She has a wiki for patients advocating all sorts of dubious medicine. I'm not surprised that this study has been contradicted. It happens a lot! -Roxy the dog bark 11:51, 20 November 2016 (UTC)

More. Second author is the chief of the lab that performs the "ATP profile tests" that cost a considerable sum, as they cannot be done on the NHS, probably because they aren't accepted as telling anything significant. I don't think there is another lab in the world that does these tests, which were, I believe, invented by said second author. -Roxy the dog bark 13:44, 20 November 2016 (UTC)

Some of the Challenges to the PACE Trial

The article currently claims that:

"Evidence suggests that cognitive behavioral therapy and a gradual increase in activity suited to individual capacity can be beneficial in some cases. Exercise does not make people worse."

The former statement is doubtful, at best; I am not an expert, but have read that the main evidence for graded exercise therapy has been the PACE trial, and the methods and interpretation have been challenged. The latter statement is false as written, since chronic fatigue syndrome often involves post-exertional malaise. (See the symptom list.) 96.255.9.115 (talk) 04:32, 21 November 2016 (UTC)

Some of the challenges, this year, include:

• Frank Twist, "PACE: CBT and GET are not rehabilitative therapies"
• Sten Helmfrid, "Studies on Cognitive Behavioral Therapy and Graded Exercise Therapy for ME/CFS are misleading"
• James Charles Coyne and Keith R. Laws, " Results of the PACE follow-up study are uninterpretable"
• Mark Vink, "The PACE Trial Invalidates the Use of Cognitive Behavioral and Graded Exercise Therapy in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome: A Review"

The first ref is a letter to the editor, not a useful ref. The 2nd is published in a journal that is not indexed by pubmed or medline. Not useful. The third is another letter to the editor. Not useful. The last was published in a journal run by Sci Forschen, which is on Beall's list of predatory publishers. I was hopeful on that one, but it too is not useful. Jytdog (talk) 05:22, 21 November 2016 (UTC)

If you take a quick look at the edit history for this article, you'll see the info on CBT and GET was mostly written before PACE came out. Although we mention PACE, the evidence is mostly taken from reviews that cite a number of studies (and I'm not sure if they even include PACE). So, no, the main evidence for GET (or CBT) is not from the PACE trial.--sciencewatcher (talk) 06:33, 21 November 2016 (UTC)

What we currently have is supported by much better references than those criticizing it. Doc James (talk · contribs · email) 12:00, 22 November 2016 (UTC)

• Think the OP has a very good point, CFS is umbrella term. Sub groups of suffers do get worse when under going graded exercise. Many a doctor, is ignorant of the the many aetiologies, thus lumps it into Oh you just have CFS. WP is an encyclopedia in progress and there is plenty of research showing that in some sub groups, their mitochondria disfunction makes a program of graded exercise contra indicated. Ie. When the patents progress regresses, it is not the patents fault but inappropriate treatment. This was known and acknowledged since the times of Galen. Even then, doctors were still bleeding their patents to death because they were taught that it was the right thing to do, despite the evidence in front of their very eyes. Orthodoxy (definition: right thinking) is one thing but wontent ignorance (to wilfully ignore, due to knowing one is always right) and thus cherry pick to suit ones own received teachings on WP is another.--Aspro (talk) 18:37, 22 November 2016 (UTC)

The problem is that there is no reliable source showing this. There is also no evidence that some subgroups have mitochondrial dysfunction (recent research seems to have debunked that, as noted above). --sciencewatcher (talk) 18:47, 22 November 2016 (UTC)

The citation for the claim "Exercise does not make people worse." Is invalid. The Cochrane review states "no evidence suggests that exercise therapy may worsen outcomes" - this is not the same as exercise in general. Secondly, none of the articles reviewed by the Cochrane study used objective measures of activity/exercise. We literally have no evidence whether patients actually increased their activity levels, or simply substituted one type of activity (daily chores etc) for another. See: Does graded activity increase activity? A case study of chronic fatigue syndrome. Friedburg, Journal of Behavior Therapy and Experimental Psychiatry 33(3-4):203-15 · September 2002.

Secondly, the quality of harms reporting in clinical trials of graded exercise therapy has been reported as poor and does not meet the same standards of contemporary drug trials. Lastly, short term harms of exercise have been consistently reported, "Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome" "Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome" "Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome" etc.

Therefore The claim "Exercise does not make people worse" is not consistent with the current published body of evidence and needs to be removed from the article.

27.33.143.13 (talk) 01:43, 23 November 2016 (UTC)

Psychological subhead

The section on psychological factors has a very different tone to the other sections on possible causes. These other sections cite evidence for their respective causal factors. This section states outright: "Current data suggests that genetic, physiological and psychological factors work together to precipitate and perpetuate the illness." This is a speculation that goes well beyond the data. It is not yet clear on the current evidence that all of these factors "work together to precipitate and perpetuate the illness".

This section should cite any relevant evidence supporting psychological causal factors in the development and/or maintenance of CFS, without making any sweeping assertions as to causation.

Do others agree? --Wilshica (talk) 23:30, 21 November 2016 (UTC)wilshica

Well, that is what the Afari review says, and it looks like that statement is based on good evidence. Are you suggesting that the psychological section should be expanded to better explain the possible factors? --sciencewatcher (talk) 01:20, 22 November 2016 (UTC)

No. I'm saying we stick to evidence in these sections, no unsubstantiated claims (someone once making that claim in a publication does not make it WP-worthy). All the other sections on causation stick to the evidence. I think that's what we want to do here. I don't think there's any evidence to support the claim that "genetic, physiological and psychological factors work together to precipitate and perpetuate the illness". At best, its a rather empty statement; at worst, its misleading - we don't really know whether these factors work together or operate independently, or even which ones are most important at this stage. --Wilshica (talk) 08:32, 22 November 2016 (UTC)Wilshica

We should get rid of the ref from 2003 and use more contemporary sources more, is what we should do. The IOC and CDC don't talk about psyc causes at all. Jytdog (talk) 10:11, 22 November 2016 (UTC)

What about https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292451/ or http://www.nature.com/nrn/journal/v12/n9/full/nrn3087.html or https://www.researchgate.net/publication/7083503_Chronic_fatigue_syndrome_a_systematic_review? --sciencewatcher (talk) 17:30, 22 November 2016 (UTC)

Those are also all older than the 2015 IOM report (which reviewed everything to date) and the CDC criteria. The NHS Choices site which we also already cite is very reliable and is also more recent (2015) - it does mention possible psychiatric causes. So we do have one very good recent ref for psychiatric (not psychological) Jytdog (talk) 18:48, 22 November 2016 (UTC)

The systematic review Sciencewatcher refers to is probably not as up to date as we'd like (from 2006). The Nature ref is interesting because it represents multiple viewpoints. But it is fives years old too. The IOM report would seem to be a good tertiary ref here, and good to include something from outside the UK. The NHS choices webpage just says that many diverse theories have been proposed, and lists them all; it doesn't review any evidence or support any particular causal model. Its not much use to us here. --Wilshica (talk) 01:36, 23 November 2016 (UTC)Wilshica

Given the uncertainty and controversy in this field, we do need to keep evidence and claims separate. What we need to do here is describe the science, not the theories (there are other sections for that). — Preceding unsigned comment added by Wilshica (talk • contribs) 01:30, 23 November 2016 (UTC)

How about this for the "Psychological" subhead? It sticks to the evidence, and doesn't make any sweeping claims (the last version also made an implicit assumption that correlation=causation, I have made the causal reasoning explicit):

The disease profile in chronic fatigue syndrome is distinguishable from primary depression. (cite Zarouf ref here from Sciencewatcher). However, secondary anxiety and depression are common in patients with CFS.(cite Zarrouf ref again here) It is not yet clear whether anxiety, depression and other psychological factors are a cause or a consequence of the physical disability in CFS. Patients with more severe physical symptoms are also more likely to view their symptoms as having a physical basis. It is possible that such attributions may play a causal role in maintaining the disease; however, it may be the case that persons with more severe symptoms are more inclined to view them as physical. Uncertainties about the causes, prognosis, diagnosis and treatment, and the lack of clinical guidance for healthcare professionals, aggravate the impact of the disease both in those affected and their caregivers.--Wilshica (talk) 06:10, 25 November 2016 (UTC)

Should the opening sections on this page include the statement "Exercise does not make people worse"?

I am raising this comment from an unidentified WP editor to its own seciton

 The citation for the claim "Exercise does not make people worse." Is invalid. The Cochrane review states "no evidence suggests that exercise therapy may worsen outcomes" - this is not the same as exercise in general. Secondly, none of the articles reviewed by the Cochrane study used objective measures of activity/exercise. We literally have no evidence whether patients actually increased their activity levels, or simply substituted one type of activity (daily chores etc) for another. See: Does graded activity increase activity? A case study of chronic fatigue syndrome. Friedburg, Journal of Behavior Therapy and Experimental Psychiatry 33(3-4):203-15 · September 2002.
  Secondly, the quality of harms reporting in clinical trials of graded exercise therapy has been reported as poor and does not meet the same standards of contemporary drug trials. Lastly, short term harms of exercise have been consistently reported, "Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome" "Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome" "Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome" etc.
   Therefore The claim "Exercise does not make people worse" is not consistent with the current published body of evidence and needs to be removed from the article.

27.33.143.13 (talk) 01:43, 23 November 2016 (UTC)

Its perhaps not fair to say that this claim is invalid (it has some empirical basis), but I do agree that we should be cautious more when commenting on possible adverse/side effects of treatments. And behavioural treatments should be no exception. As the editor above noted, exercise physiology studies show that some patients can have an adverse reaction to intense exertion, at least over the short term. Informal patients surveys also report a high incidence of adverse effects from exercise programmes in general (and these sorts of reports are part of any consideration of treatment adverse/side effects). A more cautious phrasing would be preferred. The suggested edit looks acceptable to me. --Wilshica (talk) 02:06, 23 November 2016 (UTC)

The blanket claim "Exercise does not make people worse." is invalid. The cited reference stated that there were no major harms in the context of supervised exercise therapy of those who agreed to participate in a clinical trial (eg there is selection bias involved). This is very different from the Carte blanche claim that exercise is not harmful. It is not ethical for a doctor, nor this article to make such a broad claim given there is evidence of harm of exercise in other studies. Not only exercise physiology studies, but simple exercise programme studies. eg Black et al 2005 (DOI: 10.1186/1476-5918-4-3) Arch 14:37, 24 November 2016 (UTC) — Preceding unsigned comment added by Architectonic (talk • contribs)

Sure changed to "exercise therapy"

We do not use a more than 10 year old primary source to refute a recent high quality secondary source. Doc James (talk · contribs · email) 03:06, 25 November 2016 (UTC)

The statement "Exercise therapy does not make people worse." is still a non-sequitur based on the cited reference. First of all, the Cochrane review only considered "serious averse effects" not "making people worse" in general. The Cochrane review specifically stated "Serious adverse reactions were rare in both groups, but sparse data made it impossible for review authors to draw conclusions." Only two studies were considered when reviewing serious adverse effects and the quality of harms reporting in those two studies has been questioned compared to the quality expected of drug trials, see the feedback section of the Cochrane review. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003200.pub5/full

What part about "sparse data made it impossible for review authors to draw conclusions" leads you to think this is high quality evidence? Arch 03:44, 25 November 2016 (UTC) — Preceding unsigned comment added by Architectonic (talk • contribs)

It states "no evidence suggests that exercise therapy may worsen outcomes" so what we have is a good enough summary. Doc James (talk · contribs · email) 06:38, 25 November 2016 (UTC)

No, what you have added is your own point of view, not a fair summary of the evidence presented. The article explicitly states that it is impossible to draw conclusions due to sparse data. If insufficient evidence has been collected/reviewed, then you cannot conclude the converse that "exercise therapy does not make appear to make people worse".Arch 12:31, 25 November 2016 (UTC) — Preceding unsigned comment added by Architectonic (talk • contribs)

That is not Doc James POV, but from the authors conclusion of the review, which you probably haven't read. it states " ... no evidence suggests that exercise therapy may worsen outcomes" Which part of that don't you understand. Seems pretty clear, dont you think. -Roxy the dog. bark 14:09, 25 November 2016 (UTC)

The context was that they stated "sparse data made it impossible for review authors to draw conclusions" in the review. A lack of evidence (due to sparse data) for efficacy of a treatment is not the same as saying that treatment is effective. Likewise, a lack of evidence for adverse effects (due to sparse data) of a treatment is not the same as saying that treatment is safe.Arch 15:20, 25 November 2016 (UTC) — Preceding unsigned comment added by Architectonic (talk • contribs)

By the way, if this sparse data (when cited in systematic reviews) is acceptable, then using this logic one could conclude that Hydrocortisone, Ritixumab "appear to be effective" (they have shown benefit in blinded randomised trials) according to "A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis." doi: 10.1016/j.clinthera.2016.04.038. But I would not add such statements because the evidence is currently lacking. Arch 15:38, 25 November 2016 (UTC) — Preceding unsigned comment added by Architectonic (talk • contribs)

• Have removed statement “Exercise therapy does not make appear to make people worse” for the obvious medical philosophical reason that medical scientific reason conforms and upholds to well accepted scientific methodology. CFS has become an umbrella term for more than one aetiology (the whole point in creating the International Classification of Diseases was so that each disease had both a definition and best proven treatment protocol). If some studies select a cohort of subjects according to one definition of CFS and they appear to benefit from an exercise regime that does not (using the scientific method) equates in any form nor medical sense, that all CFS subjects benefit from an exercise regime without suffering harm. Thus, it can't be stated that Exercise therapy does not make appear to make people worse If any editor wants to revert that, then may they kindly state a Cochrane study or some such, that states that one can just pick and choose cohorts to prove a mere hypothesis. Some editors here appear to have free access to med libraries and belong to medical orgs that provide them with free access to med journal and databases. They should not be pontificating the dogma they were taught in med school but using their learning during their long hours of studies ( unless the went to parties every night like a lot of med students did) an expounding the latest up to date encyclopedic information. Cross examined of course by the knowledge they gained by declining invitation to parties when they knew they should be studying --Aspro (talk) 14:40, 25 November 2016 (UTC)

We follow high quality secondary sources. Doc James (talk · contribs · email) 22:59, 25 November 2016 (UTC)

When the secondary source explicitly states that there is an ABSENCE OF EVIDENCE for a claim "but sparse data made it impossible for review authors to draw conclusions", you cannot use this to make a positive claim about the safety of that treatment. The addition "Exercise therapy does not appear to make people worse" is POV statement that is not justified by the secondary source. Arch 01:27, 26 November 2016 (UTC) — Preceding unsigned comment added by Architectonic (talk • contribs)

The content added is supported by the reference in question. Doc James (talk · contribs · email) 01:33, 26 November 2016 (UTC)

Doc James, I'm asking you a specific question: What do you think "no evidence" and "but sparse data made it impossible for review authors to draw conclusions" means in context? If I cited a secondary study that said "sparse data made it impossible for review authors to draw conclusions" in reviewing the efficacy of a treatment, would you let that edit stand? Arch 01:38, 26 November 2016 (UTC) — Preceding unsigned comment added by Architectonic (talk • contribs)

Doc James, we have discussed your proposed edit on this talk page as requested (adding "exercise does not make people worse"), and various editors have given their views and do not think it appropriate. I think this would be a good time to stop your attempts to reinsert this statement each time it is deleted, and focus on other WP material that needs improvement.

--Wilshica (talk) 03:49, 26 November 2016 (UTC)

Okay will start a RfC. The removal of a very recent Cochrane review is concerning. Doc James (talk · contribs · email) 04:54, 26 November 2016 (UTC)

RfC: Suggested addition to the lead

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We have a June 2016 Cochrane review that states "Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes."

Option 1

As this is an important point I propose we add "Exercise therapy does not appear to make people worse." to the third paragraph of the lead.

Option 2

Other wording could include "There is no evidence of harm from exercise." Doc James (talk · contribs · email) 05:01, 26 November 2016 (UTC)

Option 3 (proposed by Architectonic)

"In a systematic review of exercise therapy, no evidence of serious adverse effects was found, however data was insufficient to form a conclusion." The Cochrane review explicitly stated they could not form a conclusion on adverse effects, so a point along those lines needs to be stated. Arch (talk) 04:28, 27 November 2016 (UTC)

Option 4 (proposed by RexxS}

"There is no evidence of worsened outcomes from exercise therapy compared with other interventions, but data on serious adverse effects is insufficient to form any conclusions." The Cochrane review explicitly stated they could not form a conclusion on serious adverse effects, but the authors were able to reach a conclusion on worsening outcomes in general: no evidence for it.

Support option 1

• Support as proposer. Cochrane reviews are high quality sources and it was recently published. Doc James (talk · contribs · email) 05:01, 26 November 2016 (UTC)
• support it is a new review and is from Cochrane reviews (usually they are the best...IMO)--Ozzie10aaaa (talk) 11:44, 26 November 2016 (UTC)
• Support: the best quality evidence we have on "the effects of exercise therapy for patients with CFS as compared with any other intervention or control" is from the Cochrane review. The authors' conclusions begin with the sentence "Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes." This conclusion is relevant to the subject and is not contradicted by another equivalent secondary source. There can be no doubt that the proposed text should be included in the article. --RexxS (talk) 22:29, 26 November 2016 (UTC)
• Support - Cochrane reviews are top sources and they tend to get more weight. Option 1 adds better detailed content for the reader. Option 2 is shorter and okay. QuackGuru (talk) 23:54, 26 November 2016 (UTC)

Support option 2

• Support happy with this version aswell. Doc James (talk · contribs · email) 06:58, 26 November 2016 (UTC)

Support option 4

• Support as reasonable aswell. Doc James (talk · contribs · email) 05:36, 27 November 2016 (UTC)
• Support. This is the best one.--Literaturegeek | T@1k? 07:06, 27 November 2016 (UTC)

Oppose

The statement "Exercise therapy does not appear to make people worse." takes the quote "no evidence suggests that exercise therapy may worsen outcomes." out of context and does not reflect the evidence provided in the article that was cited.

·The cited Cochrane review only reviewed a single study (compared to "‘Passive control’ (treatment as usual/waiting-list control/relaxation/flexibility") and simply re-stated the results without meta-analysis. The authors conclusion that there was "no evidence" is to be taken literally, that there is an absence of evidence in studies that met the review criteria. The meaning of this statement is not ambiguous as the authors explicitly clarified in the article that "sparse data made it impossible for review authors to draw conclusions." specifically about adverse effects. The fact that the authors stated that it was impossible to draw conclusions means the proposed statement "Exercise therapy does not appear to make people worse." reflects a personal point of view and does not reflect the evidence in the cited article.

·This review only reported "serious adverse effects", this is much more specific than "make people worse", which could involve any type of temporary or long term adverse effects as a result of a treatment. The statement "make people worse" is far too non-specific. Arch 05:44, 26 November 2016 (UTC) — Preceding unsigned comment added by Architectonic (talk • contribs)

Per the paper "We have included eight randomised controlled studies and have reported data from 1518 participants in this review." Doc James (talk · contribs · email) 06:14, 26 November 2016 (UTC)

Yes and if you look closely under the table "Comparison 1. Exercise therapy versus treatment as usual, relaxation or flexibility", you will see only one study was included in the adverse events analysis compared to "treatment as usual/waiting-list control/relaxation/flexibility". The effect size was stated as "Totals not selected" in the table. Here is the direct link to the figure: http://onlinelibrary.wiley.com/enhanced/figures/doi/10.1002/14651858.CD003200.pub5#figure-viewer-CD003200-fig-00103 Arch 06:30, 26 November 2016 (UTC) — Preceding unsigned comment added by Architectonic (talk • contribs)

Sure but they looked for evidence of harm in all the avaliable RCTs. Doc James (talk · contribs · email) 06:33, 26 November 2016 (UTC)

Yes and the other RCTs did not meet the quality criteria for inclusion in the adverse effect analysis. Anyway, the unavoidable bottom line is that the article clearly states "sparse data made it impossible for review authors to draw conclusions." on the point of adverse effects. To conclude in the Misplaced Pages article is inserting your own point of view. Arch (talk) 06:49, 26 November 2016 (UTC)

No, the sparse data made it impossible for the authors to draw conclusions on "serious adverse reactions". They clearly saw enough data concerning all adverse reactions to conclude that "no evidence suggests that exercise therapy may worsen outcomes", because that's exactly what they concluded. That conclusion carries the weight not only of the authors, but of the Cochrane review. Your bit of amateur analysis carries no weight whatsoever. --RexxS (talk) 22:40, 26 November 2016 (UTC)

Option 2 lacks clarity. It is dishonest to imply something is safe due to "no evidence", when that means lack of evidence. It would be much more accurate to say "Evidence is currently lacking on whether exercise (or exercise therapy) leads to harm". Arch (talk) 07:06, 26 November 2016 (UTC)

As such, I oppose both option 1 and option 2. I may consider other options. Arch (talk) 09:06, 26 November 2016 (UTC)

For reasons outlined above and below (see discussion subsection), I oppose both current options. Option 2 is even worse than Option 1. Alternatives should be focused on caveats with the evidence rather than presenting poorly evidenced statements as fact while ignoring the context provided in the same source. Perhaps "Patient surveys consistently report harms from exercise therapy, but a general lack of data from randomised trials makes it difficult to draw conclusions about the safety of exercise therapy for CFS." -- Tekaphor (TALK) 11:54, 26 November 2016 (UTC)

(just adding my discussion points from below in here under "oppose" for clarity) My feeling is that proper explanation and qualification is needed, and all that would suggest a separate, later section, perhaps one dedicated to graded exercise therapy. This is an opening paragraph. I would rather not see treatments discussed at all at this stage. But if they are the statement needs to be very brief: the presence/absence of adverse effects of a treatment requires care and caution. I also do not want to encourage patients to go out and exercise madly, that's reckless. The statement in the Cochrane review is meant to be interpreted within the context of certain specific supervised programmes, and even then they never claim there is "no risk". I am unclear why we are still discussing this, as the overwhelming consensus is that the statement should not appear.--Wilshica (talk) 07:27, 26 November 2016 (UTC) --Wilshica (talk) 23:40, 26 November 2016 (UTC)

Strongly oppose: Cochrane reviews may be of high quality, yet one has to judge and place them into context to gain any benefit from them. The review is of studies where the cohort had be selected from the umbrella term that covers CFS in all its manifestations. Not to put to finer point on it, five out of those eight used the used the Oxford Criteria. Hardly a random CFS cohort! Therefore, to promote these inclusions in this article (as if it was a matter of fact) is a bit like saying that “ A Cochrane review found that a few patients selected for a certain type of cancer benefited from a ce'rtain type of chemotherapy and thus all cancer patents will suffer no harm at all from this type of treatment”. The supporting review provided - even states - that "Serious adverse reactions were rare” I.e. not totally absent. Although some editors may have enough medical degrees to get a job as a clinical thermometer they appear to be ignorant of the science concerning aetiology and the work that gets done to find the best treatments. So the sentence proposed can not stand as worthy of inclusion in this article. --Aspro (talk) 12:37, 26 November 2016 (UTC)

To further the comparison of exercise for CFS to chemotherapy for cancer, the evidence shows harms are not recorded and patients are not receiving chemotherapy, yet blanket statements are still being made about its safety. In clinical trials, patients are told that they need it and how beneficial it is, instructed on how receive it if they want it, and a small proportion even report benefit from being in the programme, but there is no objective evidence of the chemotherapy being regularly administered (i.e. no objective evidence that CFS patients are sustaining gradual increases in activity, actually the evidence shows no such increases). Meanwhile thousands of patients outside the clinical trials are reporting the 'chemotherapy' (exercise) makes them worse but these are dismissed as not "MEDRS". The current options are dangerous and misleading. -- Tekaphor (TALK) 13:33, 26 November 2016 (UTC)

Aspro has a good point about the safety issue being further complicated by the use of the Oxford criteria to select CFS patients and then making blanket statements about safety that may not apply to other patients. US health authorities have called for the Oxford criteria to be retired because "using the Oxford case definition results in a high risk of including patients who may have an alternate fatiguing illness or whose illness resolves spontaneously with time" and "continued use of the Oxford (Sharpe, 1991) case definition may impair progress and cause harm" . -- Tekaphor (TALK) 13:33, 26 November 2016 (UTC)

No, forming your own judgements about the content of a reliable secondary source is precisely what WP:MEDRS says not to do: "Do not reject a high-quality type of study (e.g., a meta-analysis) ... because of personal objections to the inclusion criteria, references, funding sources, or conclusions in the higher-level source." We can make judgements about what type of review it is, but Misplaced Pages editors are not qualified to critique the details of a systematic review to advance their own point-of-view as you're doing. Criticism of a secondary source is valid when published in an equally authoritative publication, but not just on the say-so of a Misplaced Pages editor. If you have found an authoritative published refutation of the Cochrane review, then by all means, refer to it. Otherwise, your self-produced analysis carries no weight here. --RexxS (talk) 22:59, 26 November 2016 (UTC)

Oppose the lead already states "The fatigue of CFS is not due to ongoing exertion, is not much relieved by rest, and is not due to any other medical condition." ( not sure if this was inserted post discussion), no need to state this twice--Tom (LT) (talk) 21:53, 26 November 2016 (UTC)

They are different statements. One is looking at the cause the other is looking at the side effects of a treatment. Doc James (talk · contribs · email) 23:09, 26 November 2016 (UTC)

Oppose either misleading summary - I think it's important people read the review before deciding on this, including the comments from Tom Kindlon and Robert Courtney, and the author's response. Ideally people would be aware of the public exchange between James Coyne and David Tovey too. Other than with the PACE trial, reporting of harms has been recognised as being generally poor for exercise trials of CFS: https://www.ncbi.nlm.nih.gov/pubmed/26112761 Considering the current controversy surrounding the PACE trial (the studies authors recently losing a court case in which they had argued that Cochrane's review of their data was not independent as they themselves had been involved in the process, so still had control) it seems odd to place such a bold statement founded on this trial so prominently, eg: https://www.statnews.com/2016/09/21/chronic-fatigue-syndrome-pace-trial The Cochrane review only looked at outcomes for RCTs, so any summary of its findings must recognise this, particularly given the negative reports seen from patients receiving exercise therapy and the research seeming to indicate abnormal responses to exercise. A lack of evidence of harm from one type of evidence is not the same as there being no evidence of harm. I don't know much about wikipedia, and was told about discussion by someone using it as an example of how wikipedia's rules seem to actively discourage critical thinking. This Cochrane review classed the PACE trial as having a low risk of selective reporting - a judgement by the authors that always seemed to defy Cochrane's own guidelines, and one that has now been left looking absurd following the partial release of data from the trial. — Preceding unsigned comment added by 146.90.86.66 (talk) 03:36, 27 November 2016 (UTC)

The way it works on Misplaced Pages is explained at WP:WEIGHT. It would be very beneficial for this discussion if those like yourself who don't understand Misplaced Pages's sourcing policies familiarise themselves with them before attempting to comment further. Where a high quality type of source, like a Cochrane review, reaches a conclusion such as "no evidence suggests that exercise therapy may worsen outcomes", we follow the guidance "Neutrality requires that each article or other page in the mainspace fairly represent all significant viewpoints that have been published by reliable sources, in proportion to the prominence of each viewpoint in the published, reliable sources." That means that the Cochran review's viewpoint on ET worsening outcomes will be reported along with any other equally authoritative sources that have a view on the issue. It does not mean that a bunch of anonymous editors can decide that they don't like the way a review was conducted and can exclude it. That's not critical thinking, that's a recipe for anarchy and POV-pushing. Misplaced Pages does indeed discourage editors thinking that their analysis of data supersedes that of reliable sources. An expert here is defined as somebody who knows what the best sources are. So, please check the review you adduce: as far as I can see, Marques et al, 2015 looks at the effectiveness of different interventions and says nothing conclusive about harms as you seem to think. If you believe the proposed summaries are misleading, then please explain how we should be summarising a conclusion that states "no evidence suggests that exercise therapy may worsen outcomes". If you are asserting that the conclusions of the Cochrane review are misleading, then name for us the equally reliable source which states that those conclusions are misleading. If you haven't grasped WP:No original research yet, that means we go by what reliable secondary sources tells us, not what amateur analysis by editors might come up with. --RexxS (talk) 04:37, 27 November 2016 (UTC)

Discuss

I remember reading a bit about this some months ago, when the activists were outraged at the recommendation. My (possibly faulty) impression was that it's a bit more complicated than that:

• Statistically, on average, graduated exercise is good.
• But that only means that it helps more people than it hurts (or more people than other options). It doesn't mean that it won't hurt anyone. Exercise for a CFS/ME patient may be the equivalent of chemotherapy for a cancer patient: Cytotoxic chemotherapy saves lives, but it kills people, too.
• Exercise is good in the medium- to long-term. Nobody says that CFS/ME people never feel bad during or shortly after exercise. (In fact, lots of people feel "worse" in some respects the day after exercising, especially if they've been sick and haven't felt up to exercising in recent months.)
• CFS/ME may not be a single disease, and it's certainly not a single experience, and therefore exercise may help (or hurt) one group of CFS/ME patients, but not another group. It's possible, for example, that graduated exercise is almost always helpful and non-harmful for a person with a mild, recent-onset CFS/ME, but that the same program would be harmful for the rare person with long-standing and severe CFS/ME.

So with these thoughts in mind, I'm slightly concerned about the statement that "it doesn't make people worse". I wouldn't insist that this one sentence explain everything, though, as this is a bit more than the lead should handle. But perhaps a different phrasing would be more precise. WhatamIdoing (talk) 06:23, 26 November 2016 (UTC)

Well evidence does not support harm from exercise therapy. This is notable as many claim harm from it. And feeling bad is different than making people worse in the long term. Doc James (talk · contribs · email) 06:36, 26 November 2016 (UTC)

"Does not make people worse in the long term" is not the same as "does not make people worse". Arch (talk) 06:51, 26 November 2016 (UTC)

Added a second option. Doc James (talk · contribs · email) 06:57, 26 November 2016 (UTC)

My feeling is that proper explanation and qualification is needed, and all that would suggest a separate, later section, perhaps one dedicated to graded exercise therapy. This is an opening paragraph. I would rather not see treatments discussed at all at this stage. But if they are the statement needs to be very brief: the presence/absence of adverse effects of a treatment requires care and caution. I also do not want to encourage patients to go out and exercise madly, that's reckless. The statement in the Cochrane review is meant to be interpreted within the context of certain specific supervised programmes, and even then they never claim there is "no risk". I am unclear why we are still discussing this, as the overwhelming consensus is that the statement should not appear.--Wilshica (talk) 07:27, 26 November 2016 (UTC)

I agree. The Cochrane review on exercise therapy was already included and discussed in its own section of article, before the recent addition by Doc James as an additional reference in the opening paragraph. Arch (talk) 07:56, 26 November 2016 (UTC)

Yes the Cochrane review seems to have been used in the section on Exercise therapy, smeared with an unsupported piece of original research: "The evidence for this however comes only from studies of people who are well enough to attend outpatient clinics and that this in turn limited who could be recommended exercise therapy as an intervention." Where is that stated in a reliable source? The section also omitted the first conclusion from the review - I wonder why that is? --RexxS (talk) 23:06, 26 November 2016 (UTC)

Both supporting options are unacceptable. Option 2 is even worse than the original Option 1.

Cherry picking poorly evidenced statements from a systematic review while ignoring the context given in the same source is not consistent with WP:MEDRS. Misinformed content in relatively high profile articles also puts the health of patients at risk. But a limitation of WP:MEDRS is that it does tend to encourage a blind adherence to Cochrane reviews, which is a serious issue when such reviews can merely reflect the biases inherent in the primary studies. Experts such as John Ioannidis are concerned that "evidence-based medicine has been hijacked" and Cochrane reviews "may cause harm by giving credibility to biased studies of vested interests through otherwise respected systematic reviews" . Figure 2 of the Cochrane review of exercise for CFS documents the high risk of bias in exercise studies. James Coyne has expressed concerns about conflicts of interest present in the Cochrane review in question .

The Cochrane review in question is specifically referring to serious adverse events (e.g. hospitalisation and death), and the evidence is poor because most trials did not record adverse events in general and when they did it was not reported adequately. The Cochrane review itself states that "sparse data made it impossible for review authors to draw conclusions". In the NIH P2P systematic review is a similar conclusion: "Harms were rarely reported across studies (insufficient evidence)." Older reviews make similar statements. It is negligent to omit this context when placing a questionable and controversial statement at the top of the Misplaced Pages article: "Exercise therapy does not appear to make people worse." The proposed alternative is worse: "There is no evidence of harm from exercise."

WP:MEDRS states that reports from US government agencies such as the Agency for Healthcare Research and Quality provide trustworthy mainstream views for health content on Misplaced Pages. This is what a recent AHRQ report (Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) has to say about the current subject : "Harms were not well reported, although in one trial patients receiving GET reported more adverse events compared with those receiving cognitive behavior therapy (CBT), adaptive pacing, or usual care; one trial reported more withdrawals of patients receiving GET, one trial had a high percentage of patients refusing repeat exercise testing, and several other trials reported more withdrawals of patients receiving GET, all compared with controls." "Although harms were not well reported across trials, GET was associated with a higher number of reported harms and withdrawals in some trials." "Studies also need to report harms more completely to help identify patients negatively affected by certain treatments."

(The AHRQ recently published an addendum that downgrades the general quality of evidence for CBT and GET to "low strength of evidence" and "insufficient evidence" for various outcome measures once studies that use the poor quality Oxford criteria are excluded, as such studies may not reflect CFS patients.)

Reports of harms from exercise are very common outside clinical trials, on the order of 50-75% of those surveyed . The number of patients who have reported harms from exercise therapy is much greater than the number of patients who participated in trials that recorded harms. Symptoms becoming worse after exertion is a characteristic feature of any serious definition of ME or ME/CFS, and exercise stress tests show symptoms and biological parameters worsening abnormally after exercise; these facts prompted the Institute of Medicine to suggest a name change to Systemic Exertion Intolerance Disease .

The claim that a medical condition characterized by intolerance to exertion can be safely treated with graded increases in activity is an extraordinary claim that is contradicted by the available evidence: there is no good evidence that CBT or GET safely increases activity in the medium or long term . Evidence from a meta-analysis and a large trial shows no increases of fitness or objectively measured activity. Therefore wording of the first sentence is also misleading and should be changed: "Evidence suggests that cognitive behavioral therapy and a gradual increase in activity suited to individual capacity can be beneficial in some cases." It is important to distinguish between the lofty goals of GET and the actual achievements of patients who have done GET. ME/CFS patients are generally unable to sustain increases in activity when instructed to do so; claiming otherwise, against the evidence, is essentially quackery.

_Tekaphor (TALK) 12:53, 26 November 2016 (UTC)

The sky is pink. -Roxy the dog. bark 11:53, 26 November 2016 (UTC)

The review you link to says "Although CBT effectively reduced fatigue, it did not change the level of physical activity."

Not sure why one would think counselling would change fitness levels? It did lead to improvements just not in this aspect. All people have trouble increasing activity levels for a sustained period of time when instructed to do so, nothing special about CFS there. Doc James (talk · contribs · email) 18:38, 26 November 2016 (UTC)

5BX exercises got Canadian air crews up to super-fit by taking it slowly without the trouble that you speak of. Why keep injecting non sequiturs? You appear to be now flogging a dead horse. So dead, that editors are politely suggesting that the lifeless carcass or cadaver of your argument is now beginning to smell.--Aspro (talk) 19:56, 26 November 2016 (UTC)

Yup that exercise program is supported by sources such as "celebsnow.co.uk"  :-) Doc James (talk · contribs · email) 21:28, 26 November 2016 (UTC)

Are you agreeing with me or trying to take a side-wipe by bring up the web site Celebs Now as if you can belittle me by referencing (and there by trying to associate me with popular twaddle) to such a web site. You may have had the opportunity and profession privilege to dig bullets out of people but William's brother served twice in Afghanistan where he was a prime target. To atempt to downgrade and ridicule 5BX, (like you have done above) is like ........ P.S. in my late twenties my resting heart rate was still 54-56 and lower than a cardiac surgeons heart rate so don't try an' bull-shit me any more. --Aspro (talk) 22:36, 26 November 2016 (UTC)

The claim that a medical condition characterized by intolerance to exertion can be safely treated with graded increases in activity is an extraordinary claim that is contradicted by the available evidence. That's simply untrue. You have produced no reliable secondary source that finds that graded exercise therapy is unsafe as a treatment. You've cherry-picked one cell of a table in the AHRQ report which notes that in one trial patients receiving GET reported more adverse events, but the AHRQ report draws no conclusions whatsoever about the safety of GET as a treatment. So what evidence do you have to validly contradict the Cochrane report conclusion, "no evidence suggests that exercise therapy may worsen outcomes"? The answer is "none". --RexxS (talk) 23:25, 26 November 2016 (UTC)

I would be greatful if people would actually read the Cochrane review and the context before forming their opinions. It is not the quality of the review that it is being questioned, but the proposed points will be quoting the article out of context. The Cochrane review specifically states "but sparse data made it impossible for review authors to draw conclusions" on the point of adverse effects. This means it is deliberately misleading to include a non-specific point that implies the treatment has no adverse effects. Any point will need to specifically state something along those lines, eg use words along the lines of "sparse data" or "lack of data" or "insufficient data to conclude". Arch (talk) 04:14, 27 November 2016 (UTC)

And I would be grateful if you stopped trying to impose your own views on the Cochrane review and let the authors speak for themselves rather than deciding that you know better than they do. The quality of the review is the ONLY thing that you can question per WP:MEDRS. The proposed points will not be quoting the article out of context because those are the authors' own conclusions and the context is the section of the review labelled "AUTHORS' CONCLUSIONS". The Cochrane review states precisely "Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions." So the sparse data is referring only to serious adverse reactions, which we all agree are rare - hence 'sparse', but does not say the data on other adverse outcomes is sparse. You are the only one quoting out of context. The authors do not qualify their generalised conclusion, and we should not be doing so either. It is deliberately misleading to take a comment about rare events like "serious adverse reactions" and pretend it applies to a conclusion about all potential adverse effects. --RexxS (talk) 04:55, 27 November 2016 (UTC)

Again, please read the article and look at what was reviewed. No other measures of adverse effects were reviewed. The only specific adverse effects reviewed in the article were the "serious adverse reactions" we have been discussing this whole time. Arch (talk) 05:05, 27 November 2016 (UTC)

Yet again, please read WP:MEDRS and try to understand why we don't let editors' own views and conclusions dictate content. Anybody can read what the review said about adverse effects in the MAIN RESULTS summary: Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate. The authors reviewed: (1) physical functioning; (2) depression; (3) anxiety; (4) sleep; (5) pain; (6) self-perceived changes in overall health; (7) use of health service resources; and (8) drop-out rate. They found little or no difference between the ET group and the controls regarding the first four adverse reactions, and were unable to draw conclusions on the latter four. They summarised that in the AUTHORS' CONCLUSIONS section as Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. What problem are you having with reading what the authors wrote about the multiple possible adverse reactions? --RexxS (talk) 05:27, 27 November 2016 (UTC)

Added option 3, which is most consistent with what is presented in the Cochrane review. Arch (talk) 04:28, 27 November 2016 (UTC)

I've added option 4, which is even more consistent with what is presented in the Cochrane review. I've also respected WP:ASF which tells us to write in Misplaced Pages's own voice when summarising the view of a reliable source that is not contradicted by an equal source, and to reserve attribution for where different sources hold different views. --RexxS (talk) 05:10, 27 November 2016 (UTC)

Arch, it seems you are correct that serious adverse reactions (SARs) are the only specific, individual adverse effects reviewed. Under "Primary outcomes", it lists "Adverse outcomes: measured using any reporting system (e.g. serious adverse reactions (SARs) (European Union Clinical Trials Directive 2001))." Then under each section of the review it has a subsection on "Adverse effects" but only SARs are covered. Then under "Summary of main results" in the "Discussion" section it repeatedly states that it is difficult to draw conclusions about this issue, and this point is repeated in the Abstract. This is consistent with multiple systematic reviews conducted over the past ten years which conclude that harms are poorly reported in general.

However, as RexxS seems to be saying, the statement about there being no evidence that exercise therapy worsens outcomes could be based on the other outcome measures reported. If that is what the Cochrane review authors are saying, then we should be clear in the Misplaced Pages article that this is what they mean. Unfortunately, most of the other outcomes received a quality rating of either very low or low, so their conclusion is still based on low quality evidence according to the authors. Also almost all of the other outcomes are group averages of continuous scores, not binary outcomes for individuals, and such outcomes simply do not detect the number of adverse events for individuals. That said, RexxS's Option 4 is a significant improvement over Option 1 and Option 2, but I think further clarification or caveats is needed. -- Tekaphor (TALK) 09:18, 27 November 2016 (UTC)

Doc James, the version of CBT studied in the meta-analysis was not simply counselling but included graded activity/exercise. Also the most studied version of CBT for CFS encourages graded activity/exercise, as avoidance of activity is speculated to be one of the main maladapative behaviours arising from patients' unhelpful beliefs that exercise makes them worse. We should certainly expect such a therapy to increase activity if it works as claimed, as it is part of the process and goal of the therapy. Just because people in general have trouble increasing activity does not mean we should expect such a dedicated programme to completely fail to produce any significant increases in activity, unless of course the target population are unable to do it: CFS patients are generally less active than sedentary controls, they commonly report a low "activity ceiling", intolerance to exertion is a hallmark, and exercise testing shows abnormalities. -- Tekaphor (TALK) 09:18, 27 November 2016 (UTC)

RexxS, the available evidence of objective outcomes clearly shows that CFS patients have not increased their fitness or activity during or after graded exercise therapy. This comes from a meta-analysis of three CBT(/GET) trials, two additional large trials of CBT, GET, or pragmatic rehabilitation, and a few smaller trials of activity management. I am not aware of relevant evidence that contradicts this. Perhaps there is a high-quality secondary source summarising all this. If graded increases in activity are not actually occurring, then it is an unsupported leap of faith to claim such increases are safe.

For randomised trials of ambulatory CFS patients meeting loose criteria, GET enrollment does not appear to cause a significant increase of SAEs (e.g. hospitalisation and death) or worse outcomes on average for the entire group, but there is no objective evidence of increased exercise, activity, or fitness, while most trials do not properly record or report individual harms so the evidence is limited. The types of harms from exercise therapy reported by patients outside trials are generally not recorded in trials either. The purpose of me quoting the AHRQ report was not to show that GET is unsafe but to further show that harms or adverse effects are poorly reported in the research literature. -- Tekaphor (TALK) 11:25, 27 November 2016 (UTC)

I disagree with RexxS's interpretation that "sparse data" means "low number of SAEs". Sparse data is likely referring to the general lack of data on the subject, not the low number of SAEs. Why would a low number of SARs make it difficult to draw conclusions? If anything the low number of SARs would only serve to show it can be concluded that exercise therapy is safe. But the authors state it is "impossible" to draw conclusions, because of sparse data. -- Tekaphor (TALK) 09:18, 27 November 2016 (UTC)

Tekaphor, If graded increases in activity are not actually occurring, then it is an unsupported leap of faith to claim such increases are safe. You are making the mistake of confusing efficacy with safety and your conclusion is a non-sequitor. As a simple analogy, nobody but a handful of cranks believes that homeopathy is effective, but nobody believes it is unsafe, either. I don't need a leap of faith to accept that ET doesn't worsen outcomes compared with other treatments, I just need to read the authors' conclusions in the Cochrane review, as you should.

Why should sparse data mean anything other than what it is? Serious adverse reactions are a rare occurrence - surely we all agree on that? The implications for trials are clear: you need massive sample sizes to be able to do any meaningful statistical comparisons between two groups when the event you are comparing is rare; the usual sample sizes make it impossible to draw conclusions. That's just stats 101. If two samples each of size 10,000 are made of treatment A and treatment B, and 1 SAR occurs in the A group, while 2 SARs occur in the B group, can you say that treatment B is less safe than treatment A? No, the difference in frequencies is less than 1 standard deviation and that's not significant. Whereas if two samples each of size 10,000 are made of treatment A and treatment B, and 100 SARs occurs in the A group, while 200 SARs occur in the B group, can you say that treatment B is less safe than treatment A? Of course you can - the difference between the frequencies is over 8 standard deviations. Now do you understand why a low number of events ("sparse data") make it difficult to draw conclusions on any comparison?

But I'm not trying to read anything into the sparse data of SARs, unlike your colleague. I am merely concerned by the rejection of the conclusions concerning all adverse outcomes of one of the highest quality type of sources we have by editors who do not bring forward sources that disagree. These editors merely argue ad tedium that the authors of the Cochrane review didn't meant what they wrote: "no evidence suggests that exercise therapy may worsen outcomes." Please re-read what I quoted above about WP:WEIGHT. If Misplaced Pages policies and guidelines continue to be flouted like that, at some point soon this will tip over from a content dispute into a behavioural one. --RexxS (talk) 21:45, 27 November 2016 (UTC)

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"Onset" section on the Chronic Fatigue syndrome: Some thoughts

I am bumping this from the archived talk pages - some editors would like to discuss further before any change is implemented.

The main review article that’s cited in this section is reliable (citation ), but the current phrasing is lifted word-for-word from that review, so needs to be either in quotes or rephrased. Also, there’s a final statement at the end, which is taken word-for-word from an earlier, poorer quality source (a conference abstract). I suggest omitting that.

I also suggest adding a line from the main review article already cited about the findings of prospective studies. This approach compensates partially for the problem of recall bias in retrospective studies.

So here’s a suggested rephrase:

It has been estimated that between 25 and 80 percent of adults with CFS report a sudden illness onset, initiated by a flu-like illness or other acute infection. ". In contrast, one population study that identified individuals meeting CFS criteria from a randomly selected population sample found that the majority of cases had a more gradual onset. Such discrepancies may derive from variations between the groups surveyed, as well as different interpretations of the meanings of "acute" and "gradual".

Prospective studies have also examined the proportion of patients with acute, documented infections later develop CFS. 1 to 22 percent of patients with various documented acute infections (which included Epstein-Barr virus (EBV) associated glandular fever, non-EBV-associated glandular fever, Ross River virus, Giardia duodenalis enteritis, parvovirus B19, and Q fever) go on to develop CFS. --Wilshica (talk) 05:07, 25 November 2016 (UTC)

1. Cite error: The named reference pmid:12562565 was invoked but never defined (see the help page).
2. Kindon, Tom (2011). "Reporting of harms associated with graded exercise therapy and cognitive behavioural therapy in myalgic encephalomyelitis/chronic fatigue syndrome". Bulletin of the IACFS/ME. 19 (2): 59–111.

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