Lipkin Study Press Conference 18th Sept

[Christopher]

I would appreciate comments on this, and especially would like to know if any of you have had any inherited immune deficiencies identified, or if you have had infections more or less continuously since an early age, or if you had a tonsillectomy at an early age.

Thanks.

Best regards,

Rich

I developed a sore throat during puberty that's never went away since then (15 years ago). Nothing showed up in testing. The CFS didn't start until 8 years ago after I moved into an apartment with newly installed carpet.

 

[SilverbladeTE]

I had stomach problems after being poisoned by weedkiller as a child
yeah great dad, put copper sulphate down on garden/grass when I was a toddler...doofus! acts as potent corrosive on soft, wet tissue...sparkly blue crystals...yeah...like I had drank acid.
Don't know if directly linked or not, but ended up with severe tonsilitis very often, could hardly breathe at times, so they eventually removed my tonsils aged about 10 or 11.

ME started after a severe flu-like nasty damn bug was going around, took 2+ months to get over, I remember damn near strangling on thick, tar-like phlegm (sorry, gross I know but hard fact, awful damn thing)
virus never identified at least to us the public, but was widespread here and GP said that lot of folk came down with ME after it.
AND
they put very toxic damp proofing down, made the workmen violently ill, took years for fumes ot fade, I was literally stoned out of my head for around 6 months from those fumes (NOT fun), too sick/brain fuzzed to do anything about it
and later, well we're poor, didn't know better to get it checked etc.

(can't recall which happened first to be honest, now, my entire memory of that period is hazy)

 

[SOC]

I'm not sure he would say 'a' single disease, but certainly that as a group something is up biologically. He said on a number of occaisions that CFS is likely to be multiple conditions with mulitple causes, and I think he meant that even using the strictest criteria definitions.

Multiple conditions or multiple "hits". I still suspect something of impairing our immune systems which then make us susceptible to many different infections. That would give the appearance of different causes because our symptoms would be the result of the various secondary infections.

The source of the immune dysfunction is entirely unknown at this point. Could be genetic, could be a virus that has come and gone, could be a chronic infection, could be a toxin exposure.....

OTOH, if we're thinking autoimmune, then I don't see that we could have multiple causes.

I could see subsets of us with different conditions, I suppose. Some of us are very herpes-virusy, others have more paralysis/muscle impairment, perhaps a different group that is severely OI....?

The PEM seems to be the central issue. That makes me think we have some common disorder. I'd be surprised if that's caused by multiple conditions, but I could certainly be wrong.

 

[Simon]

Multiple conditions or multiple "hits". I still suspect something of impairing our immune systems which then make us susceptible to many different infections. That would give the appearance of different causes because our symptoms would be the result of the various secondary infections.

The source of the immune dysfunction is entirely unknown at this point. Could be genetic, could be a virus that has come and gone, could be a chronic infection, could be a toxin exposure.....

OTOH, if we're thinking autoimmune, then I don't see that we could have multiple causes.

I could see subsets of us with different conditions, I suppose. Some of us are very herpes-virusy, others have more paralysis/muscle impairment, perhaps a different group that is severely OI....?

The PEM seems to be the central issue. That makes me think we have some common disorder. I'd be surprised if that's caused by multiple conditions, but I could certainly be wrong.

Talking about the sickness response (the host response to an infection: different people will react in different ways) he pointed out that sickness response is affected by things like your genes but also previous environemental exposure eg toxins, 'immune history' of previous infection and nutritional status. I think these findings come from animal model research.

If it is autoimmune, there could be still be multiple different triggers, or even multiple different form of autoimmune response eg B-Cell, T-cell or sub-types of each. However, I think autoimmune is a big IF at this stage, at least for everyone.

Not sure PEM is wholly unique to CFS: I think something similar can happen in other conditions eg MS and chronic pain (both of which are also poorly understood). But it certainly differentiates CFS from a lot of other possible causes of fatigue and I think it's a good thing the International criteria have made this a mandatory criterion.

 

[SOC]

Talking about the sickness response (the host response to an infection: different people will react in different ways) he pointed out that sickness response is affected by things like your genes but also previous environemental exposure eg toxins, 'immune history' of previous infection and nutritional status. I think these findings come from animal model research.

If it is autoimmune, there could be still be multiple different triggers, or even multiple different form of autoimmune response eg B-Cell, T-cell or sub-types of each. However, I think autoimmune is a big IF at this stage, at least for everyone.

Not sure PEM is wholly unique to CFS: I think something similar can happen in other conditions eg MS and chronic pain (both of which are also poorly understood). But it certainly differentiates CFS from a lot of other possible causes of fatigue and I think it's a good thing the International criteria have made this a mandatory criterion.

I don't know enough about autoimmunity, but I see your point. Autoimmunity is very complicated.

I'm pretty sure PEM/PENE (as opposed to exhaustion/fatigue or relapses) is unique to ME/CFS, but I'll have to do some more research to be sure.

 

[Bevbh]

Rich, you might want to start a separate thread on this genetic immune dysfunction/childhood infections topic. I'm guessing there are a lot of us here.

I had a severe emotional trauma followed by chicken pox and then measles when I was 3. Had frequent earaches, tonsilitis, strep throat as a child and into my 20s. Added yeast infections too after years of being on tetracycline for acne. I had some allergies but didnt realize it until they got much worse in my 30s. Also mono during college. My half-sister and mother are both lifelong asthmatics with lots of allergies and a fibromyalgia diagnosis. Dad has bad allergies and scarlet fever as a kid.

 

[Bevbh]

New Post from Dr Snyderman in the comments:

Quote

It would be nice to be able to double quote when you want to.

I havent heard anyone explain how Dr. M got EMs of budding viruses yet. I did get the impression from Lipkin, cant remember if it was the press conference or TWIV, that he said something about other retroviruses are not ruled out. He was very specific about saying this study was designed to follow up on the Mikovits XMRV paper and the Lo/Alter paper. It was not fishing expodition for new viruses. Science moves forward in incremental steps that have rules for evidence. I'm looking forward to his new paper on expanding Koch's rule, how the rules of evidence work in today's world with chronic, multi-cause diseases.

I read a subtext from Lipkin's performance at the press conference that went something like: "I am one of the good guys, I have helped Drs. Mikovits and Ruscetti save face and move forward. I play by the rules of science but I am not part of the anti-science political machine that ignored this disease. I really want to get to the bottom of it. Good science is now being done on it. Trust me if I gloss over some of this stuff in public." I dont know if he deserves this trust or not. That remains to be seen but I am a little hopeful.

Dr. M knows that she had pictures of budding viruses and antibody results. I bet she wants to find out what those were. Will she get a chance now? Will someone else follow up on that?

 

[Sasha]

I read a subtext from Lipkin's performance at the press conference that went something like: "I am one of the good guys, I have helped Drs. Mikovits and Ruscetti save face and move forward. I play by the rules of science but I am not part of the anti-science political machine that ignored this disease. I really want to get to the bottom of it. Good science is now being done on it. Trust me if I gloss over some of this stuff in public." I dont know if he deserves this trust or not. That remains to be seen but I am a little hopeful.

That was my take. I was very impressed by him. We're really lucky to have him on the case.

 

[Simon]

This has its own thread but thought I'd post it here too:

Patricia Carter has set up a collective e-card to send to Ian Lipkin to thank him for his impressive efforts on the XMRV study and beyond.

Sign card here​

 

[waiting]

Does anyone know if someone has done a transcript of the press conference?

 

[Simon]

Does anyone know if someone has done a transcript of the press conference?

Wildaisy has helpfully transcribed the first half at mecfsforums wiki. Someone else was planning to transcribe the second half but it hasn't happened yet. I think there is a lot in this conference.

 

[waiting]

Wildaisy has helpfully transcribed the first half at mecfsforums wiki. Someone else was planning to transcribe the second half but it hasn't happened yet. I think there is a lot in this conference.

Thanks, Simon! (and Wildaisy -- a lot of work there).

 

[Mark]

Hi Mark, sorry going slightly of topic, RE your high white blood cell count, yes it can be a sign of infection or immune activation but it is also found in many other diseases such as Addison’s and leukemia, 365 diseases are listed as causing high white blood cell count see http://en.diagnosispro.com/differential_diagnosis-for/infected-organ-abscesses-wbc-white-blood-cell-count-leukocytes-lab-increased/10100-154-90.html white blood cell count is one of the tests that nobody with CFS or ME is supposed to fail because they are not supposed to fail these kinds of common tests, High white blood cell counts was also never found in any of the ME epidemics. This kind of failed tests result should lead to an extensive investigation to find the cause of it, because many of the diseases that can cause it will ultimately be fatal. So I would recommend that you don’t see it as confirmation of immune activation in ME but as a sign to tell your doctor to get there a into g and start looking for the cause. There is more information on this test here http://labtestsonline.org/understanding/analytes/wbc/tab/test

Sorry to go of topic but failing that tests can be very serious and is highly unlikely that your results are caused by ME.

Hope this helps

All the best

Thanks for prompting me to follow up on this rlc. I should mention that I have never been diagnosed with ME. I have been diagnosed with MCS (and told by an MCS support person that they think that's the same thing as "ME/CFS") and I have, for a few years in 17 years of illness, fit the CCC (by my careful reading), but I do believe that I don't actually have the illness properly referred to as ME, I accept that there are probably alternative diagnoses for me that haven't been excluded, and I am here partly on the basis that I think there are very probably other people with the same illness as myself who have been diagnosed with ME/CFS.

So in that sense I'm quite receptive to your general point that there is a huge amount of misdagnosis and missed diagnosis in people who have been diagnosed with ME/CFS. Two recent studies put that UK wrong diagnosis level at 40-50% and I think we have to take that as a minimum, though I doubt it's as high as 90% or more as some seem to think. I also find that, when I look through the lists of conditions you supply, the alternatives broadly fall into two categories: very severe conditions like leukaemia that I seriously doubt are relevant to me, and syndromatic symptom-based conditions like IBS that, having no known cause, seem dubious to me as exclusionary for ME/CFS. If I were diagnosed with IBS instead - well, I have IBS in the broad sense, for sure - but I have a whole lot of other symptoms too, and having a different syndromatic diagnosis wouldn't seem to make a whole lot of difference. With so many related, neuro-immune, syndromatic conditions on Dr Hyde's exclusionary list, I do wonder whether there is really any meaning to changing the labels in this way. One thing I always wonder, when you mention how Dr Hyde is brilliant at finding different diagnoses for 90% of people diagnosed with ME/CFS, is whether these other diagnoses are actually treatable conditions and whether the re-labelling makes any difference to those patients in terms of treatment options (not to mention how much it costs for these hundreds of tests to get labelled with a different syndrome). That may be unfair, it's just a suspicion. These complex, multi-symptom autoimmune or neuro-endocrine-immune illnesses seem to have an awful lot of overlap, and until they're all better understood the labels are probably pretty arbitrary at the moment, IMO.

Anyway, I will follow up on what I found from your links, which is that a differential white blood cell test should now be performed to start to identify specifically which white blood cells are elevated. That's what I guessed anyway and I think you're right that I should pursue that more actively; I think I just presumed that the follow-up wouldn't be available since it wasn't offered...still trusting the doctors too much...

By the way, I just checked and I'd forgotten there were some other results that were outside reference range. If anyone has any clues on where to go next with these results I'd be interested to hear them...I'll start a fresh thread for that if I get a few replies because I'm taking this thread off-topic...sorry...

Total white blood count (XaldY): Above range 11.4 10*9/L (4.0 - 11.0) - tested 4 times last year at similar level
Serum triglyceride levels (XE2q9) Above range 2.3 mmol/L (0.4 - 1.8) - above high reference limit
Serum folate level (42U5.) Below range 3.7 ug/L (3.9 - 14.0) - again consistent on several tests

 

[rlc]

Hi Mark, RE

still trusting the doctors too much

My advice is never trust a doctor, always double check on the internet what they are saying, I have been told so many things over the years that are completely false, and know many people who have been given the wrong diagnosis which has almost killed them, including one person I know who had a raise white blood cell count for years and their doctor ignored it, turns out that they do have Leukemia and are going to die, because it has been left to long to have any chance of being treated.

So it is very important to double check on what doctors are doing and follow up on all failed test results, ME patients are not supposed to fail any standard medical tests, it is for this reason that ME is a mystery.

The problem with all these syndromes be it CFS, Fibro, MCS or IBS is that they are supposed to be diseases of exclusion, there are often many known causes of these types of symptoms and they are supposed to be ruled out before the diagnosis is given, but either uninformed or lazy doctors just hand out these diagnoses without ruling out other diseases that can cause these symptoms, there is about 100 diseases that cause the symptoms of CFS, IBS symptoms can be caused by many things like Crohns disease, Celiac, H Pylori etc Dr Mirza claims 70% of the patient he sees with fibro actually have Vitamin D deficiency and can be quickly cured.

So we end up with a situation where lots of people are given these diagnoses without having all the other possibilities ruled out, and many of them are misdiagnosed, then researchers study these people without checking them for the other diseases and come up with completely confusing results because of mixed cohorts, this pattern is being repeated in this Lipkin retrovirus study, the patients haven’t even been checked for very common diseases that cause these symptoms and statistically there is no chance that they all have CFS, so further research will be done on mixed cohorts and the results will be worthless as I have pointed out in this tread http://forums.phoenixrising.me/index.php?threads/a-multicenter-blinded-analysis-indicates-no-association-between-cfs-me-and-either-xmrv-or-pmlv.19420/

I think it is right to be suspicious of anyone making any claims in this field because virtually nothing has been scientifically replicated; Nobody has replicated the methods of the likes of Drs Hyde and Mirza, but I have read a lot of Dr Hyde’s publications and most of the things he finds are very serious known conditions such as heart defects, other infections, brain abscesses etc, he’s not just changing the name of the patients diagnosis to some other largely meaningless syndrome, many of the diseases he finds will be treatable some, will have been found to late and the patient will die. Again we have to take his word for it because it hasn’t been replicated, but I can say I know quite a lot about medicine and the conditions that the likes of Drs Hyde and Mirza claim to be finding will cause the kind of symptoms attributed to ME and the tests that they do are not being done by the vast majority of doctors seeing assumed ME patients.

I do wish that someone would replicate these things, if you got the patients who have been selected for this study, who it has been decided that they have CFS by the various CFS doctors involved without testing them properly to rule out other diseases, and then put them through the testing regimes of Drs Hyde and Mirza it is very likely to bring out lots of very useful information. And prove what kind of testing is needed to find the misdiagnosed patients.

The other problem we have is that there is no agreement on what the symptoms of ME are so how can someone be diagnosed on the symptoms, the ME epidemics, which are after all what ME was named after and got its WHO classification from, have very different symptoms then are found in the CFS criteria, in fact some of the symptoms found in the ME epidemics like depression and emotional liability are now used to exclude people from having a ME diagnosis, including the patients in this study! All the CFS criteria have different sets of symptoms, so how can anyone say with any certainty that because you have a certain set of symptoms you have ME, we have no agreement on something as simple as what the symptoms of this disease are. So in your case you say you have IBS and MCS, but some reports say these are symptoms of ME, so are your IBS and MCS caused by ME or do you have these two conditions separate of ME, nobody knows without properly testing people. So all anyone can do is stick to the basics of Medicine and say have you had all other possible diseases ruled out, and do you have any other test results that indicate the possibility of other diseases.

In your case you obviously haven’t had all other diseases ruled out and you do have test results that indicate that you probably do have another disease, so as it would be a tragedy for you to be suffering needlessly when you may have a treatable disease. I highly recommend giving your doctor a kick in the butt and getting them to do their job properly or just get another doctor.

So what is making you sick, well I can’t give you the full answer to that, but I can tell you that your test results show you have a serious missed condition Folate deficiency!! Symptoms of which are explained here http://suite101.com/article/folic-acid-folate-deficiency-a79897 Folate deficiency can cause gastrointestinal disorders and maybe an explanation for your IBS, certain diseases like Crohns diseases and ulcerative colitis can also cause the symptoms of IBS and Folate deficiency see http://www.vitamin-mineral-info.com/folic-acid-folate-vitamin-b9-benefits-signs-of-deficiency.php

So your tests show you have Folate deficiency and it is very likely causing a lot of your symptoms. So it needs to be investigated to see if you have some other condition that is causing low folate or if it is just Folate deficiency, and it needs to be treated.

Like I say your consistently high Total white blood count could be being caused by a large number of different conditions some of which are fatal, and your doctor should have been investigating this not ignoring it.

And high triglyceride can be caused by all these diseases http://en.diagnosispro.com/differential_diagnosis-for/triglycerides-lab-increased/10540-154.html

So you have a lot of things that need to be investigated to find the cause or causes of your symptoms. Now I know that the NHS can be bad and that if anyone has ever stuck ME on your file as a diagnosis, then you have basically been branded as insane, which makes it difficult to get the extra testing that you have to get done. If you find that you can’t get a doctor to take your case seriously, I’d suggest you one or both of these options.

You can complain to the General Medical council, the complaints procedure is explained here http://www.gmc-uk.org/concerns/making_a_complaint/faqs.asp

The second option is in the UK although not many people seem to know about this, patients can sue their doctors for medical negligence. I’m not recommending that you start by suing anyone, but if you can afford a couple of hundred to get a lawyer to write a letter to your doctor saying that, you have had failed tests that indicate the possibility of serious and life threatening diseases and these test results have not lead to further investigation to find the cause, and a treatable condition folate deficiency that hasn’t been treated or causes of low folate investigated, and get the lawyer to advise them that unless there is an immediate improvement in the way that you are being treated legal action for medical negligence is likely to follow. Send this letter to your doctor and be prepared to be amazed as you find yourself being referred to many specialists and getting every test under the sun. Even just saying to your doctor if you don’t see an improvement in the way you are being treated you will be talking to a lawyer and sending a complaint to the General medical council is likely to get you all the testing that you need.

Medical Negligence is punishable in the UK both by the medical council and by legal action, doctors may act like they are bullet proof gods, but they are very vulnerable to action being taken against them and stand to lose their jobs and large sums of money if found guilty of medical negligence. The failure to follow up on your test results stands a very good chance of being seen as negligence!

If you have other test results or want to post what other tests you have had done, to see what hasn’t been done, myself and I’m sure some of the other knowledgeable members of the forum would be happy to help, but we may need a new tread, rather than hijacking this one.

Like I say you have test results that need to be followed up on! And when properly investigated and treated there is a good chance you will feel substantially better, maybe even cured.

Hope this helps

All the best

 

[Bob]

Here is one of those recent research papers about alternative diagnoses, and misdiagnosis, in the UK:
http://forums.phoenixrising.me/inde...als-to-a-specialist-servic.14480/#post-238707


This study is also summarised in the latest edition of:

ME Research UK's Breakthrough magazine - Autumn 2012
http://www.meresearch.org.uk/information/breakthrough/index.html

LONDON
Who the heck has ME/CFS?

As the Editorial on page 2 points out, there
is both anecdotal and research evidence
that some GPs are diagnosing ME/CFS
inaccurately, and a recent study has added
to the mounting concern. The investigation,
conducted by clinicians at the London School
of Medicine, examined the prevalence of
alternative diagnoses in patients referred
by GPs to a hospital clinic with a definite
or provisional diagnosis of ‘CFS’ between
March 2007 and September 2008.
The major finding was that a diagnosis
of ‘CFS’ was eventually confirmed in only
137 of 250 patients (54%) assessed at
the clinic. Of the rest, 53 patients (21%)
were given alternative medical diagnoses
(most commonly primary sleep disorders,
endocrine disorders, nutritional disorders
and pain disorders), while 54 patients (22%)
received alternative psychiatric diagnoses
(most commonly a depressive illness or
anxiety disorder). As around 9,300 people
are newly diagnosed with ME/CFS every
year in the UK, mostly by GPs, it makes you
wonder how many of them actually have
another, treatable condition, doesn’t it?

 

[Bob]

By the way, I just checked and I'd forgotten there were some other results that were outside reference range. If anyone has any clues on where to go next with these results I'd be interested to hear them...I'll start a fresh thread for that if I get a few replies because I'm taking this thread off-topic...sorry...

Total white blood count (XaldY): Above range 11.4 10*9/L (4.0 - 11.0) - tested 4 times last year at similar level
Serum triglyceride levels (XE2q9) Above range 2.3 mmol/L (0.4 - 1.8) - above high reference limit
Serum folate level (42U5.) Below range 3.7 ug/L (3.9 - 14.0) - again consistent on several tests

Mark, these results are burried at the end of a long post, in a long thread...
Maybe you should post them in a new thread, so people can easily find them?
You might get some interesting responses.
Bob

 

[currer]

You should always get any new symptom investigated.
Unfortunately having ME does not mean you cannot develop another disease.

Also, ric is quite correct in suggesting that abnormal blood results should not automatically be put down to ME.
Anything abnormal, or that you are concerned about should always be properly investigated.

 

[rlc]

Hi all, here is a more detailed explanation of the high misdiagnosis rates in the UK and links to the research from ME Research UK article Misdiagnosis on a grand scale http://www.meresearch.org.uk/information/publications/misdiagnosis.html
Misdiagnosis on a grand scale?

Around 190,000 people have a diagnosis of ME/CFS in the UK, and there are approximately 9,300 newly diagnosed cases each year. Yet, how valid a diagnosis of ME/CFS really is depends crucially on the rigour of the initial clinical assessment, and the efforts made to exclude other treatable conditions that might be causing the collection of symptoms. If the examination is cursory – and if the clinician is sceptical, alienated or just plain disinterested – the “diagnosis” can easily become a convenient lay-by for clinically complex cases that don’t fit into any other category.

Every year ME Research UK gets about 400 calls or e-mails from patients. A small number of these – not a flood, but a regular trickle – are from patients reporting that they have improved after being re-diagnosed with and treated for another condition. These conditions have included Addison’s disease, multiple sclerosis, sleep apnoea, primary mitochondrial disease, primary liver disease and paranoid schizophrenia – and in every case the caller has been content with the re-diagnosis and/or the new treatments it has brought.
So, there is certainly anecdotal evidence that something is amiss with the diagnosis of ME/CFS at the GP surgery. Thanks to two good scientific papers from reputable clinical research groups in the UK, we now have formal research evidence to back up these patients’ anecdotes.

In the first – originally published in 2010 in the Journal of the Royal College of Physicians Edinburgh (1) – researchers examined the records of every patient referred by local GPs to the Newcastle CFS/ME Clinical Service. The key finding was that 103 (40%) of referrals were eventually diagnosed with other conditions which could explain the concatenation of symptoms. The main alternative diagnoses in these patients were fatigue associated with a chronic disease (47% of all alternative diagnoses); a primary sleep disorder (20%); psychological/psychiatric illnesses (15%, most commonly, depression, anxiety and post-traumatic stress disorder); and cardiovascular disorders (4%).

The second, recently published report examined the prevalence of alternative diagnoses in patients referred by GPs to the specialist clinic at St Bartholomew’s Hospital, London (2). Its major finding was that a diagnosis of “CFS” was eventually confirmed in only 54% of patients. Of the rest, 53 patients (21%) were given alternative medical diagnoses (most commonly primary sleep disorders, endocrine disorders, nutritional disorders and pain disorders), while 54 patients (22%) received alternative psychiatric diagnoses (most commonly a depressive illness or anxiety disorder).

These reports provide clear, formal evidence that almost half of patients referred from primary care with a diagnosis of ME/CFS actually have something else wrong with them – a fact that is not discovered until they are lucky enough to be seen at a specialist clinic. This seems like misdiagnosis on a grand scale.
Something has to change. In the short term, continuing education for GPs should be beefed up – ideally with input from ME/CFS charities and experts. In the longer term, the problem could be resolved by the creation of ME/CFS Centres of Excellence at key points throughout the UK, offering biomedical assessment, proper diagnosis, treatment and onward referrals, all under one roof. As well as improving patient care, these centres would become validated “research resources” of properly diagnosed patients for biomedical studies of the future.

References

•Newton et al. The Newcastle NHS Chronic Fatigue Syndrome Service: not all fatigue is the same. J R Coll Physicians Edinb 2010; 40:304–7. http://www.rcpe.ac.uk/journal/issue/journal_40_4/newton.pdf

•Devasahayam A et al. Alternative diagnoses to chronic fatigue syndrome in referrals to a specialist service: service evaluation survey. JRSM Short Rep 2012; 3(1):4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269106/

When you read the studies that this article is based on you see that many of the alternative diagnoses are things like heart defects, sleep apnea, Auto immune conditions, Hemochromatosis, celiac. All things that have not been tested for in this XMRV studies patient cohort selection.

Unfortunately these reports don’t give much detail on what testing the patient had to be rejected as having CFS, but in the first one which was done in Newcastle it doesn’t report finding any cases of Vitamin D deficiency, Newcastle has atrocious weather so it would be safe to assume that the reason they didn’t find any cases of vitamin D deficiency is they didn’t look. The CFS clinics that these studies are done by are NHS clinics which is not famous for extensively testing people and do not use the new up to date reference ranges for things like B12, TSH, and Vitamin D etc, So it is likely that if more extensive testing was done and the new reference ranges were used the misdiagnosis rate is likely to be substantially higher than the already terrible misdiagnosis rates that they have found so far.

All the best

 

[Bob]

Recruitment Criteria

Someone, somewhere, on this forum, said that Lipkin's recruitment criteria (for Lipkin's XMRV study, and his sample bank) required the patients to have 'night sweats' to be included in the study.

I've just had a look at the paper, and it seems that this is a misunderstanding.
I think the misunderstanding comes from a description of ME which is included in the paper:

"Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a disabling disorder characterized by persistent unexplained fatigue in association with impaired memory or cognition, muscle or joint pain, headache, sore throat, tender lymphadenopathy, and night sweats."

I've just had a look at the recruitment criteria details, and they include the following:

Patients were required to have "reported a viral-like prodrome prior to the onset of CFS, defined as three or more of the clinical features: fever, headache, gastrointestinal discomfort/upset, malaise, sore throat, myalgias, arthralgias, and tender lymph nodes"

So these symptoms were not required to be present currently, but three or more were required to be present prior to onset of ME. (Night sweats were not included in the recruitment criteria.)


Exclusion Criteria

There were also quite a number exclusion criteria, which included the following:

"Assays included screens for human immunodeficiency virus infection (HIV), syphilis (rapid plasmin reagin [RPR] test), hypothyroidism (T4 and thyroid-stimulating hormone [TSH] tests), hematocrit, white blood cell count, erythrocyte sedimentation rate, electrolytes, glucose, blood urea nitrogen, creatinine, and transaminases. Potential cases were excluded if screening laboratory values were not within the ranges shown in Table 1 or were HIV or RPR positive."

Table 1, is to be found here:
http://mbio.asm.org/content/3/5/e00266-12/T1.expansion.html

Full paper:
http://mbio.asm.org/content/3/5/e00266-12.full#T1


Note: The 'white blood cell count' exclusionary criteria is relevent to Mark's and rlc's discussion.

 

[rlc]

Hi bob, it is interesting to see them re defining CFS into what they think it is and ignoring the criteria that they claim they are using.

"Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a disabling disorder characterized by persistent unexplained fatigue in association with impaired memory or cognition, muscle or joint pain, headache, sore throat, tender lymphadenopathy, and night sweats."

Because both the CCC and Fukuda have multiple choices of what the symptoms can be and the patients don’t have to have all of them, they do not demand that all the patients have to have many of the symptoms that the authors of this study are defining CFS as, e.g. you do not need to have tender lymphadenopathy, night sweats, sore throat, headache, muscle pain, joint pain or impaired memory or cognition to qualify to have CFS by either the CCC or Fukuda they are options that they say some patients may have but the patients can have different combinations of symptoms which may or may not include some of these symptoms.

I have to say that I’m not very impressed with the multi choice options that you find in some many of these studies and diagnostic criteria. If you look at what their saying

Patients were required to have "reported a viral-like prodrome prior to the onset of CFS, defined as three or more of the clinical features: fever, headache, gastrointestinal discomfort/upset, malaise, sore throat, myalgias, arthralgias, and tender lymph nodes"

Firstly they say viral LIKE not viral onset many non infectious diseases cause these symptoms and can start suddenly.

These multi choice options mean one patient can have qualified by having a headache, malaise and myalgias, which are symptoms that are found in many conditions that are not infectious, another could have gastrointestinal discomfort/upset, myaligias and malaise again symptoms that can be found in many non infectious conditions, another patient could have fever, tender lymph nodes and headache these symptoms can be caused by many conditions that are not infectious or the patient could have just had flu.

The problem is that when you say a patient has to have three out of six symptoms, is that in throws up a vast number of different combinations, so you end up with selecting patients who actually could have many different conditions because of the many different combinations of symptoms that they can have to qualify.

What they’re saying is, to be selected the patients had to have what are basically the symptoms of flu like syndrome which is caused by 938 different conditions see http://en.diagnosispro.com/differential_diagnosis-for/vegetative-autonomic-endocrine-disorders-flu-like-syndrome/40945-154-220.html many of which are not infectious and many are diseases that they have not ruled out.

You have the same problem with the diagnostic criteria they have used, Fukuda for example says you only have to have four of eight symptoms and this throws up many different combinations of symptoms that the patients can have to qualify, raising the strong possibility that the patients have different conditions.

The CCC appears at first glance that it is stricter but a close reading of it shows that it has a very large number of multi choice options, the CCC symptom criteria are on page eleven here http://www.co-cure.org/ccpccd.pdf And what it shows is that the patients can have post exertional malaise or post excertional fatigue, fatigue and malaise are very different symptoms. Sleep dysfunction can be unrefreshed sleep or rhythm disturbances again very different. Pain can be in the muscle or joints. Neurological/Cognitive Manifestations says that you only have to have two of a multitude of options. So one patient can have confusion and overload phenomena another may have Ataxia and spatial instability. Category six say that the patient only has to have one symptom from two of the three categories but there are about thirty different symptoms to choose from which allows an almost wndless aray of possibilities.

All of this throws up hundred of possibilities of the symptoms the patient can have and still qualify for a CCC diagnosis, which is one of the reasons why it authors have rejected it and written the ICC which by saying that the patients must have PENE to qualify helps to stop it being a random list of a large number of symptoms which could be caused by a large number of diseases which is what the CCC is.

So by using the viral prodrome criteria for this study and the CCC and Fukuda means that the patients can have a vast array of very different onsets symptoms and symptoms but still qualify for the study, which raises the strong possibility that they have many different diseases and yet they all still have qualified for this study.

People really need to stop using these multi choice definitions and use a far narrower set of symptoms to select the patients, but the most important thing is to check the patients for all other diseases that can cause these symptoms something that they have failed to do!!!

RE

Exclusion Criteria

There were also quite a number exclusion criteria, which included the following:

"Assays included screens for human immunodeficiency virus infection (HIV), syphilis (rapid plasmin reagin [RPR] test), hypothyroidism (T4 and thyroid-stimulating hormone [TSH] tests), hematocrit, white blood cell count, erythrocyte sedimentation rate, electrolytes, glucose, blood urea nitrogen, creatinine, and transaminases. Potential cases were excluded if screening laboratory values were not within the ranges shown in Table 1 or were HIV or RPR positive."

Table 1, is to be found here:
http://mbio.asm.org/content/3/5/e00266-12/T1.expansion.html

Full paper:
http://mbio.asm.org/content/3/5/e00266-12.full#T1

The exclusionary criteria used for this study is very flawed and fails to even check for the most common cause of fatigue, muscle pain and weakness in the western world which is also shown to damage the immune system cause gastro upsets and effect sleep patterns Vitamin D deficiency. There are many other common causes of these types of symptoms that they have failed to check for such as Celiac, hemochromatosis, B12 deficiency, folate deficiency, sleep apnea, pre diabetes etc, etc. plus many other rarer conditions such as Lupus and Addison’s disease. The exclusionary criteria for this study is so bad it will not find a large percentage of the diseases that the NHS is managing to find that people have, that are being misdiagnosed as CFS see ME research article in my post above.

Their exclusionary criteria is so weak that I feel it is an insult to both the patients and medical science for them to have called it a Exclusionary criteria. The patients because of the methods they have used in this study could have anything and statistically there has to be many people in their patient cohort who have the other common diseases that they have failed to rule out. Which will lead to future research being done on the samples from this patient cohort being a waste of time because it will be being done on a mixed cohort.

I would recommend that if the patient community want to have good science and have a chance of getting better, that they divert their energies from things like complaining about what some journalist opinion on ME is to contacting the authors of this study and asking them to start using proper exclusionary criteria that will actually rule out all other diseases in the patient cohorts. I also think it would be a good idea for the patients in the UK to send the ME research article in my post #178 above plus this article http://www.bmj.com/rapid-response/2011/11/01/chronic-fatigue-syndrome-nice-and-cdc-miss-boat to every new outlet and politician in the country and let them know that there is scientific evidence provided by the NHS that shows that people are being misdiagnosed with CFS on an epic scale and try and get things changes.

All the best