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Comments on Lombardi, et al in Science

Dolphin

Senior Member
Messages
17,567
since when has it been ok to not undertake research, so that it wont effect patients emotions. What horse doo.
Good point. And who are they to judge which emotions I'd like to be given, anyway? Maybe I'd prefer false hope to no hope.
Yes, although I have read a lot of ME/CFS papers, I haven't heard this type of argument made much in print. Is it mentioned much in psychiatry or psychology, for example or often mentioned as a bad thing in journals (as opposed to people complaining amongst themselves)?
With "no hope", some people might die by suicide* I would have thought. Of course, I think it helps if there is research in a few different directions at any one time that gives hope - one can still be hopeful even if one direction "fails".

* "commit suicide" is not PC here (as it's not a crime) although I'd prefer if the term wasn't seen as being negative
 

ixchelkali

Senior Member
Messages
1,107
Location
Long Beach, CA
Well, if this was pending publication maybe it explains why Judy Mikovits may have been hesitant to elaborate on their patient cohorts. I dont know if the same keep your mouth shut before publication rules apply to technical comments as to papers.

But, POW! BIFF! BAM! BAM! this sure answers the naysayers.

Some of the remarks are such bunk Im surprised theyd submit them to a scientific journal. I guess they figure probably rightlythat most of the people reading it dont know enough about ME/CFS to sort out whats codswallop. And I guess thats the point, to surround the subject with smoke in the form of lies, half-truths, and innuendo in order to make it more difficult for the truth to be heard.

The 101 patients studied in (Lombardi, et al) were patients fulfilling the 1994 CDC Fukuda criteria for chronic fatigue syndrome and the 2003 Canadian Consensus Criteria for chronic fatigue syndrome/myalgic encephalitis (CFS/ME) and presenting with severe disability [supporting online material for (1)], but the latter requires physical signs precluded in the former.
Um, since when?

It is unusual to find such a strong association between an infectious agent and a well-defined chronic disease...
Really? Right off the bat I think of polio, malaria, Helicobacter pylori & ulcers, hepatitis B with chronic liver disease, Hansens disease (leprosy), tuberculosis, HTLV1 with T-cell leukemia, HHV8 with Karposis sarcoma, Epstein-Barr with Burkitt lymphoma, HPV with warts, rheumatic heart disease with strep or scarlet fever, Rocky Mountain spotted fever, and of course, HIV/AIDS. Maybe if they were microbiologists instead of psychologists theyd know that.

Other plausible alternative explanations for the findings are not explicitly discussed. Foremost among these is reverse causality: Patients with poor general health because of CFS may be more susceptible to viral and other infections.
Right. 100% of people with warts have HPV infection and only 26% of people without warts have HPV infection. So maybe warts arent caused by HPV. Maybe people who handle frogs are more susceptible to HPV infection, or maybe having warts makes you susceptible to HPV infection. Or maybe not. (Besides the fact that, as Judy Mikovits points out, the Lombardi, et al paper did raise the possibility that XMRV could be a passenger virus in the immunosuppressed CFS patient population. But you notice that Sudlow et al carefully used the phrase poor general health rather than mention immunosuppression.

researchers exploring an exciting new hypothesis of a viral cause for CFS in a laboratory established to explore biological causes of CFS will be understandably eager for positive results. This so-called "expectation bias" may lead to completely unconscious and nondeliberate differences in sample handling and data interpretation between cases and controls
Funny, I dont remember them mentioning expectation bias in their much-touted CBT and GET studies. I guess they psychiatrists arent subject to unconscious differences in data interpretation the way virologists are. But since the study was blinded it kinda shoots down this theory, doesnt it?

Hmm, I guess this kind of stuff upregulates my sarcasm gene.
 

Dolphin

Senior Member
Messages
17,567
I and two others from the ME community had our rapid responses published in BMJ USA which was circulated to 100,000 physicians:

Nowadays, I know papers to reference so I probably wouldn't write a response like that.

Unfortunately with Science, they say e-letters won't be considered for consideration to the print journal.

Thanks for this Tom

the 'rapid response team', is this team still in operation?
Thanks flybro.

There was never really a team although in the early 2000s, there were fewer forums so things were more concentrated on certain lists so one did get to know people - some forums were the e-groups/yahoogroups MEActionUK (still going at: http://health.groups.yahoo.com/group/MEActionUK/ - Doug is one of the mods), IMEGA-e [which Ellen Goudsmit was on - it was for group leaders and was quite a lively list - it eventually closed in 2008 when the list owner had enough (I certainly didn't agree with a lot of his views on ME politics but he did well keeping it going for so long)], etc.

Anyway, Doug Fraser is still very active - he was one of the two people who took NICE to court over the NICE guidelines which was a huge task to take on and kept him very busy for a long time.

Ellen Goudsmit is still active. Her CV is at: http://freespace.virgin.net/david.axford/ellen-cv.htm where one can see she has published quite a bit on ME, CFS etc over the years. She's a patient so has that perspective. She has lots of interesting articles at: http://freespace.virgin.net/david.axford/me/me.htm which people can learn from. She knows the ME and CFS literature very well and I have learned a lot from her over the years although, like with quite a few people on lists, I have disagreed with her and she has disagreed with me at different stages.

http://www.bmj.com/cgi/eletters/325/7378/1449

Looking at other rapid responders for that article:
Abhijit Chaudhuri - neurologist - he is still working in the field but he no longer sends rapid responses. He did his PhD on ME/CFS around then so was probably more interested.

Gurli Bagnall - a patient from New Zealand. Gurli is "no spring chicken" but still writes the odd piece. Not sure if she sends in many rapid responses.

Paul Lynch - patient who disappeared from the scene maybe 5 years ago and I haven't seen on the Internet since

Hayley Klinger - is still severely affected with ME. Is the PR person for the 25% ME Group. Has had some letters published in national newspapers.

Jane C Colby - still head of the TYMES Trust

Suzy Chapman - still very active on the internet. She uses a username a lot now so don't know if everyone knows who she is.

Over the years, plenty of people have sent rapid responses to the BMJ. But oddly, out of the few dozen patient/carer activists, or anyone else in other countries very very few sent replies to any other journal including all the open access journals.

I'm hoping some of the people from Phoenix Rising will start writing in and keep authors on their toes.
 

Dolphin

Senior Member
Messages
17,567
“It is unusual to find such a strong association between an infectious agent and a well-defined chronic disease...”
Really? Right off the bat I think of polio, malaria, Helicobacter pylori & ulcers, hepatitis B with chronic liver disease, Hansen’s disease (leprosy), tuberculosis, HTLV1 with T-cell leukemia, HHV8 with Karposi’s sarcoma, Epstein-Barr with Burkitt lymphoma, HPV with warts, rheumatic heart disease with strep or scarlet fever, Rocky Mountain spotted fever, and of course, HIV/AIDS. Maybe if they were microbiologists instead of psychologists they’d know that.
Yes.

Their comment on this was a bit similar to what Bill Reeves said:
From: http://www.nature.com/news/2009/091008/full/news.2009.983.html
William Reeves, principal investigator for the Centers for Disease Control
and Prevention (CDC)'s CFS public health research programme, says the
findings are "unexpected and surprising" and that it is "almost unheard of
to find an association of this magnitude between an infectious agent and a
well-defined chronic disease, much less an illness like CFS"
Bill Reeves was said to be in regular contact with Peter White (one of the authors of the letter). I wouldn't be surprised if he rang Peter White and asked him for advice about how to deal with the XMRV study.

“researchers exploring an exciting new hypothesis of a viral cause for CFS in a laboratory established to explore biological causes of CFS will be understandably eager for positive results. This so-called "expectation bias" may lead to completely unconscious and nondeliberate differences in sample handling and data interpretation between cases and controls”
Funny, I don’t remember them mentioning expectation bias in their much-touted CBT and GET studies. I guess they psychiatrists aren’t subject to unconscious differences in data interpretation the way virologists are. But since the study was blinded it kinda shoots down this theory, doesn’t it?"
Yes, was thinking the same about the CBT and GET studies.
 

Dolphin

Senior Member
Messages
17,567
Most FUKUDA presentations do not even include PEM which is not mandatory.
In the population-study by Leonard Jason, 75% of the people found to have CFS had PEM: http://archinte.ama-assn.org/cgi/reprint/159/18/2129 (Table 4).
Only around 9% of this group had been diagnosed - these random studies tend to pick up milder cases.

If one looks at the Canadian Clinical guidelines, we are given information on the following study in Appendix 2:
(These prevalence and severity figures are from A definition-based analysis of symptoms in
a large cohort of patients with chronic fatigue syndrome, P. De Becker, N. McGregor, and K.
De Meirleir. Journal of Internal Medicine 2001;250:234-240.) A total of 2,073 consecutive
patients with major complaints of prolonged fatigue were assessed. Among them 1,578 met
the Fukuda criteria and of those, 951 met the Holmes criteria. The figures indicate the differences in prevalence and severity of symptoms between these patient groups.
97.3% of those satisfying the Fukuda criteria had PEM (at an average severity of 2.7 on a 0-3 scale which was the second highest figure for a symptom - the highest was for fatigue).

Did you have you any evidence for what you said or did you just make this up?
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
Thanks flybro.

There was never really a team although in the early 2000s, there were fewer forums so things were more concentrated on certain lists so one did get to know people - some forums were the e-groups/yahoogroups MEActionUK (still going at: http://health.groups.yahoo.com/group/MEActionUK/ - Doug is one of the mods), IMEGA-e [which Ellen Goudsmit was on - it was for group leaders and was quite a lively list - it eventually closed in 2008 when the list owner had enough (I certainly didn't agree with a lot of his views on ME politics but he did well keeping it going for so long)], etc.

Anyway, Doug Fraser is still very active - he was one of the two people who took NICE to court over the NICE guidelines which was a huge task to take on and kept him very busy for a long time.

Ellen Goudsmit is still active. Her CV is at: http://freespace.virgin.net/david.axford/ellen-cv.htm where one can see she has published quite a bit on ME, CFS etc over the years. She's a patient so has that perspective. She has lots of interesting articles at: http://freespace.virgin.net/david.axford/me/me.htm which people can learn from. She knows the ME and CFS literature very well and I have learned a lot from her over the years although, like with quite a few people on lists, I have disagreed with her and she has disagreed with me at different stages.

http://www.bmj.com/cgi/eletters/325/7378/1449

Looking at other rapid responders for that article:
Abhijit Chaudhuri - neurologist - he is still working in the field but he no longer sends rapid responses. He did his PhD on ME/CFS around then so was probably more interested.

Gurli Bagnall - a patient from New Zealand. Gurli is "no spring chicken" but still writes the odd piece. Not sure if she sends in many rapid responses.

Paul Lynch - patient who disappeared from the scene maybe 5 years ago and I haven't seen on the Internet since

Hayley Klinger - is still severely affected with ME. Is the PR person for the 25% ME Group. Has had some letters published in national newspapers.

Jane C Colby - still head of the TYMES Trust

Suzy Chapman - still very active on the internet. She uses a username a lot now so don't know if everyone knows who she is.

Over the years, plenty of people have sent rapid responses to the BMJ. But oddly, out of the few dozen patient/carer activists, or anyone else in other countries very very few sent replies to any other journal including all the open access journals.

I'm hoping some of the people from Phoenix Rising will start writing in and keep authors on their toes.

I'd like to add myself to the list of people who have been responding both in rapid responses and one of those who HAVE been sending replies to other journals including open access journals, including two of the recent XMRV negative studies.

My responses to various journals over the years are located on a dedicated Yahoo group I keep: "APK-papers", which can also be accessed as a link on the MEAgenda website.
 
G

Gerwyn

Guest
In the population-study by Leonard Jason, 75% of the people found to have CFS had PEM: http://archinte.ama-assn.org/cgi/reprint/159/18/2129 (Table 4).
Only around 9% of this group had been diagnosed - these random studies tend to pick up milder cases.

If one looks at the Canadian Clinical guidelines, we are given information on the following study in Appendix 2:

97.3% of those satisfying the Fukuda criteria had PEM (at an average severity of 2.7 on a 0-3 scale which was the second highest figure for a symptom - the highest was for fatigue).

Did you have you any evidence for what you said or did you just make this up?

It is backwards You can make Oxford look like Fukuda because PEM is not manatory and you dont need PEM to satisfy a FUDUKA criteria.How many had abnormal cytokines which was the point I was making.I was also making the point that every patient who qualifies for CCC will also qualify for. Fukuda.If some one is only diagnosed by FUKUDA criteria then none of Those patients will qualify for CCC beacause neuroimmune symptoms are mandatory In CCC and excluded under FUKUDA



So I am not making it up .That is absolute fact.The data you referred to had patients diagnosed by the CCC criteria. That they also happened to qualify for fukuda was as a result of being diagnosed under CCC guidelines and not that 97.3 % of patients diagnosed according to Fukuda alone have PEM! I have never been known to make anything up!

These are the criteria under Fukuda et al(1994)

A case of the chronic fatigue syndrome is defined by the presence of the following: 1) clinically evaluated, unexplained, persistent or relapsing chronic fatigue that is of new or definite onset [has not been lifelong]; is not the result of ongoing exertion; is not substantially alleviated by rest; and results in substantial reduction in previous levels of occupational, educational, social, or personal activities; and 2) the concurrent occurrence of four or more of the following symptoms, all of which must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue: self-reported impairment in short-term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social, or personal activities; sore throat; tender cervical or axillary lymph nodes; muscle pain, multijoint pain without joint swelling or redness; headaches of a new type, pattern, or severity; unrefreshing sleep; and postexertional malaise lasting more than 24 hours.

That would not even be close to qualifying for a diagnosis under CCC .Of course if they qualified under CCC they would automatically qualify for FUKUDA.So when Lombardi et al said that their patients qualified under CCC and FUKUDA they were diagnosed according to CCC guidelines and the European cohorts were not
 

Dolphin

Senior Member
Messages
17,567
I'd like to add myself to the list of people who have been responding both in rapid responses and one of those who HAVE been sending replies to other journals including open access journals, including two of the recent XMRV negative studies.
Yes, well done Angela. That list was just of those people who had replied to that particular article - I didn't try to do other people.
 

Dolphin

Senior Member
Messages
17,567
It is backwards You can make Oxford look like Fukuda because PEM is not manatory and you dont need PEM to satisfy a FUDUKA criteria.How many had abnormal cytokines which was the point I was making.I was also making the point that every patient who qualifies for CCC will also qualify for. Fukuda.If some one is only diagnosed by FUKUDA criteria then none of Those patients will qualify for CCC beacause neuroimmune symptoms are mandatory In CCC and excluded under FUKUDA



So I am not making it up .That is absolute fact.The data you referred to had patients diagnosed by the CCC criteria. That they also happened to qualify for fukuda was as a result of being diagnosed under CCC guidelines and not that 97.3 % of patients diagnosed according to Fukuda alone have PEM! I have never been known to make anything up!

These are the criteria under Fukuda et al(1994)

A case of the chronic fatigue syndrome is defined by the presence of the following: 1) clinically evaluated, unexplained, persistent or relapsing chronic fatigue that is of new or definite onset [has not been lifelong]; is not the result of ongoing exertion; is not substantially alleviated by rest; and results in substantial reduction in previous levels of occupational, educational, social, or personal activities; and 2) the concurrent occurrence of four or more of the following symptoms, all of which must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue: self-reported impairment in short-term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social, or personal activities; sore throat; tender cervical or axillary lymph nodes; muscle pain, multijoint pain without joint swelling or redness; headaches of a new type, pattern, or severity; unrefreshing sleep; and postexertional malaise lasting more than 24 hours.

That would not even be close to qualifying for a diagnosis under CCC .Of course if they qualified under CCC they would automatically qualify for FUKUDA.So when Lombardi et al said that their patients qualified under CCC and FUKUDA they were diagnosed according to CCC guidelines and the European cohorts were not
Gerwyn, what you said was:
Most FUKUDA presentations do not even include PEM which is not mandatory.

That sounds like a statistical fact. But it seems you just made it up. You should be clearer what you are saying as you're not just talking to yourself but to other people.

Those studies were done quite a bit before the Canadian Clinical Criteria. For example, the Chicago prevalence study was published in 1999.

Leonard Jason re-assessed the data and found that of the 32 who satisfied the Fukuda criteria, 20 (62.5%) satisfied the Canadian Criteria and 12 did not.

Also 3 who had idiopathic chronic fatigue (but did not satisfy the Fukuda criteria) satisfied the Canadian Clinical criteria. That means that 20/23 (87%) of those who satisfied the Canadian criteria, satisfied the Fukuda definition. Ref: Jason LA, Torres-Harding SR, Jurgens A, Helgerson J. Comparing the Fukuda et al. Criteria and the Canadian Case Definition for Chronic Fatigue Syndrome. J CFS 12(1):37-52, 2004. http://www.cfids-cab.org/cfs-inform/CFS.case.def/jason.etal04.pdf
 

Dolphin

Senior Member
Messages
17,567
Thanks Tom, those are excellent responses and I hope at least some of the 100,000 docs read them and took them to heart.

Adam said:
Thanks from me as well. You are one of our stalwarts. I wonder where we would be now if it wasn't for the likes of Tom and others like him?
Thanks oerganix and Adam.

I'm not sure if I made much of a difference internationally up to a few years ago although I feel I made a difference in Ireland. Most of my BMJ rapid responses were at times when lots of other people were also writing in.

But when you see a bad paper, and nobody else responds but you, I feel in that situation I might be making a bit of a difference. If people write enough rapid responses and e-letters, one might get to the stage that one can write full letters - I've had 6 published in the last 18 months or so and have one more in press. Writing e-letters/rapid responses is probably good training for writing full letters.

We need people writing e-letters/rapid responses (and full letters) to keep researchers on their toes. I think for example we had studies claiming CBT was leading to "full recovery" because for years nobody was challenging claims authors were making.

Anyway, I hope some people will write e-letters in reply to the letters in Science.
To find a reference, go to: http://www.ncbi.nlm.nih.gov/pubmed/
 

Francelle

Senior Member
Messages
444
Location
Victoria, Australia
Editing error?

I haven't read all the responses in this thread so don't know if anyone else has commented on this.....but am I correct in noticing that Mikovits and Ruscetti let a double negative slip through the editing process in this sentence below? Pity, if so!

"We contend that the three recently published negative PCR studies (1315) do not qualify as being studies that fail to replicate our study,........."
 
G

Gerwyn

Guest
Thanks oerganix and Adam.

I'm not sure if I made much of a difference internationally up to a few years ago although I feel I made a difference in Ireland. Most of my BMJ rapid responses were at times when lots of other people were also writing in.

But when you see a bad paper, and nobody else responds but you, I feel in that situation I might be making a bit of a difference. If people write enough rapid responses and e-letters, one might get to the stage that one can write full letters - I've had 6 published in the last 18 months or so and have one more in press. Writing e-letters/rapid responses is probably good training for writing full letters.

We need people writing e-letters/rapid responses (and full letters) to keep researchers on their toes. I think for example we had studies claiming CBT was leading to "full recovery" because for years nobody was challenging claims authors were making.

Anyway, I hope some people will write e-letters in reply to the letters in Science.
To find a reference, go to: http://www.ncbi.nlm.nih.gov/pubmed/

I have draughted one Tomk.Do you have access to the paper which originally diagnosed the Dutch cohort ? It,s he one that I originally found and Parvofighter used in his original article

BTW.There is an option at the bottom of the FUKUDA paper that allows a researcher the option of including patients in which they have a special interest.The paper especially mentions immune abnormalities.So when White and Wallies say that a diagnosis of CCC precludes a diagnosis of Me,cfs under FUKUDA they are totally wrong! a diagnosis of CCC would preclude a diagnosis under Oxford only!
 
Messages
85
Good catch

Functional Symptoms in Neurology: Diagnosis and Management

Jon Stone, Alan Carson, Michael Sharpe

http://www.acnr.co.uk/pdfs/volume4issue6/v4i6reviewfunctional.pdf

Functional Symptoms = Psychiatric, for anyone who hasn't come across this term before.

Happy reading :D

Orla

It should also be noted that not only is Jon Stone a permanent fixture in journals with Alan Carson and Simon Wessely colleague Michael Sharpe, but Michael Sharpe was the lead author of the 1991 Oxford definition used in the Dutch study.
 
Messages
85
Wesselly and co have no knowledge of virology or epidemiology.

Sorry, but you are partially incorrect. Wessely is not a virologist, but he is an epidemiologist which is a public health degree. Below is a bio from Harvard University when he was a speaker there.

Simon Wessely is a professor of epidemiological and liaison psychiatry at the Institute of Psychiatry, King's College London; a consultant psychiatrist at King's and Maudsley hospitals, and director of the King's Center for Military Health Research Unit at King's College London. His main research interests are in the grey areas between medicine and psychiatry, clinical epidemiology, and military health. He has published more than 400 papers on many subjects, including epidemiology, post-traumatic stress, medicine and law, the history of psychiatry, chronic pain, somatization, Gulf War illness, chronic fatigue syndrome, chemical and biological terrorism, and deliberate self-harm. He is currently running a study on the health of 20,000 UK military personnel who took part in the invasion of Iraq. Wessely is a consultant advisor in psychiatry to the British Army.
 
G

Gerwyn

Guest
Gerwyn, what you said was:


That sounds like a statistical fact. But it seems you just made it up. You should be clearer what you are saying as you're not just talking to yourself but to other people.

Those studies were done quite a bit before the Canadian Clinical Criteria. For example, the Chicago prevalence study was published in 1999.

Leonard Jason re-assessed the data and found that of the 32 who satisfied the Fukuda criteria, 20 (62.5%) satisfied the Canadian Criteria and 12 did not.

Also 3 who had idiopathic chronic fatigue (but did not satisfy the Fukuda criteria) satisfied the Canadian Clinical criteria. That means that 20/23 (87%) of those who satisfied the Canadian criteria, satisfied the Fukuda definition. Ref: Jason LA, Torres-Harding SR, Jurgens A, Helgerson J. Comparing the Fukuda et al. Criteria and the Canadian Case Definition for Chronic Fatigue Syndrome. J CFS 12(1):37-52, 2004. http://www.cfids-cab.org/cfs-inform/CFS.case.def/jason.etal04.pdf

if you work out the possible permutations of Fukuda you will see that the majority of oresentations do not contain PEM

jasons study had no statistical powering at all.When you look at the patient numbers 32 out of some 23.000 interviwed by phone by self report.20 said they qualified for Fukuda.Quoting naked percentage gigures are meaningless unless accompanied by P values and confidence intervals.The point is that none of those would qualify for a diagnosis under CCC guidelines.But if someone qualifies for a diagnosis under CCC guidelines they automatically under FUKUDA.

I hope that this is clear enough for you
 
G

Gerwyn

Guest
Sorry, but you are partially incorrect. Wessely is not a virologist, but he is an epidemiologist which is a public health degree. Below is a bio from Harvard University when he was a speaker there.

Simon Wessely is a professor of epidemiological and liaison psychiatry at the Institute of Psychiatry, King's College London; a consultant psychiatrist at King's and Maudsley hospitals, and director of the King's Center for Military Health Research Unit at King's College London. His main research interests are in the grey areas between medicine and psychiatry, clinical epidemiology, and military health. He has published more than 400 papers on many subjects, including epidemiology, post-traumatic stress, medicine and law, the history of psychiatry, chronic pain, somatization, Gulf War illness, chronic fatigue syndrome, chemical and biological terrorism, and deliberate self-harm. He is currently running a study on the health of 20,000 UK military personnel who took part in the invasion of Iraq. Wessely is a consultant advisor in psychiatry to the British Army.

Post traumatic stress is a neurobiological disorder which Dr wesselly classifies as psychiatric.He is not an epidemiologist.An epidemiologist concentrates on the origin and propagation of medical diseases.Dr Wesselly has published no papers on that subject.Somatisation chemical and biological terrorism have nothing to do with epidemiology.Dr Wesselly has simply changed the meaning of the word as he so often does and given himslf that title.

In the study of communicable and non-communicable diseases, the work of epidemiologists ranges from outbreak investigation to study design, data collection and analysis including the development of statistical models to test hypotheses and the documentation of results for submission to peer-reviewed journals. Epidemiologists also study the interaction of diseases in a population, a condition known as a syndemic. Epidemiologists rely on a number of other scientific disciplines such as biology (to better understand disease processes), biostatistic