Discussion in 'Institute of Medicine (IOM) Government Contract' started by alex3619, Feb 7, 2014.
I started this post in the IOM section. I consider this paper very relevant to the IOM debate.
Some snippets that caught my eye...
Thanks Alex - I hadn't (obviously) noticed the forum it was in.
Did the paper allow for the use of separate clinical and research definitions or the use of combined definitions in research? I wonder if there was any thoughts expressed as to the need for separate definitions in clinical diagnosis and research? Thanks
I sometime think we (those with ME) are the only group who takes this seriously. Well, us and the cleaning crew who have to sweep it all under the rug. Thanks for your post. Its helping me put 2 and 2 together. Iz
Actually, I think it's the main the basis for the opposition to the IOM process. We all know that if an evidence review of the literature is carried out, then it is likely to end up making the same sort of recommendations as this review paper*, because relatively little research has been carried out using the CCC or ICC. (This review paper rightly says that most research uses Oxford and Fukuda.)
*For example, the paper concludes:
(They are referring to Oxford and Fukuda.)
There is one thing that those opposed to the IOM process probably agree with this paper:
However, the authors assert that Fukuda and Oxford are preferable to the CCC.
It reviewed research related to both clinical and research practice, but the discussion seems to be devoted solely to clinical practice.
Here are alternative links to access the full paper...
Full paper in HTML format only:
PDF version (without the HTML window):
Hi Firestormm. I am not particularly familiar with all the details about the IOM and P2P efforts, but I would be a little surprised (or not) if after all the controversy and efforts they just merely endorsed the CDC 1994 criteria as good enough for now and regarded further developments as of low priority, as what Brurberg et al appear to have done.
A systematic review into case definitions should be a preliminary event to identity the strengths and weaknesses of the current data, in order to help guide further study. Then there needs to be massive collection of more empirical data, which is then made freely available to researchers to analyze it. Brurberg et al do have this to say about the Nacul et al study:
The systematic review above does not appear to mention the De Becker et al (2001?) study on which the Canadian criteria was based on. This study also collected data on the most common symptoms, which is obviously important data for developing a case definition. The CCC was the first definition to be based on such data.
I am not sure if using only population data is necessarily superior for developing a new definition. Do researchers use population studies to refine criteria for conditions such as multiple sclerosis or Parkison's disease, or do they rely more on the data from the clinical setting with actual patients? Maybe there are strengths and weaknesses of both approaches?
Some people may argue that CFS symptoms are just natural variations of the normal distribution of health among humans without classic disease, or on neat spectrums with arbitrary thresholds used to categorize as illness. I object to the notion that disease entities are black and white with obvious cut-off points, and I am not 100% convinced CFS symptoms are all on such a neat spectrum either. Sure, healthy people get tired and achy sometimes, but with enough data, analytical techniques can be used to fish out patterns of chronic symptom clusters which indicate a distinct clinical entity for further study.
I think we need both a broad approach and narrow approach, as well as clinical data and population data. A narrow approach should yield more homogeneous biological data once it is targeting known symptoms clusters, but the broad approach should eventually help to find other symptom clusters and also compare the broad approach to the narrow approach.
The original ME clinical entity has been drowned in the sea of broad CFS vagueness. Even if the recent ICC-ME does identify a distinct homogeneous group similar to the original ME clinical entity, we will never be free of the past baggage without a comparison to the broad approach and a resolution of the spectrum issue.
When you read about the ME outbreaks, there was obvious similarities but some degree of heterogeneity. ME was an acute condition, from which many people seemed to recover from. Once chronic it seemed to remain chronic for many. The Incline Village outbreak sounds like another ME epidemic. "CFS" was a botched loose construction in a botched response to the Incline Village outbreak. Then a whole bunch of psychobabble was imported into the concept of CFS from pre-existing concepts used in psychiatry and it became a wastebasket fatigue diagnosis and a poster-child of broadly-define psychosomatic functional illness which drowned out ME. ME and CFS became smeared together.
But it is also perhaps worth noting, that it doesn't seem to matter what the actual 'trigger' that initially leads to someone entering an acute phase, those of us who share this diagnosis have entered into this chronic phase i.e. a period beyond which usual recovery might be expected.
What seems now to be happening, in large part, is that we all have arrived at this diagnosis from multiple points of origin. Now when we are being studied as a cohort, they are finding similar - perhaps - degrees of immune activation.
Whether or not you can tease from the cohort all the different triggers - assuming you can still identify them - and then determine different or slightly different, persisting factors - I don't know.
Perhaps those differences would mean slightly different treatments - personalised medicine - but again it's hard to say at this stage.
I think though we have moved beyond - a long time ago - keeping those patients who had this chronic illness triggered by the same pathogen together.
Different patients may have arrived at a CFS diagnosis from multiple points of origin, but it does not necessarily mean they are generally at the same end-state or have the same pathophysiology. CFS still functions as a waste-basket diagnosis. Until the end-state(s) is better elucidated, how do we know we are all generally at the same end-state?
Lots of patients in the broad approach do not even report cardinal symptoms associated with ME. And as I mentioned on another thread, reporting similar symptoms is not a guarantee of sharing the same explicit symptoms.
How do we know that people don't have the same e.g. immune activation problems, and only don't seem to share the same symtoms because they don't have them to the same degree of severity as others, or are unable to separate one symptom from another e.g. fatigue after minimal or no exertion from PEM which can be variously interpreted to mean a worsening of symptoms following over exertion from the 'norm' following a delay?
If e.g. Lipkin's work, is showing a similar degree of this immune activation across a cohort of mixed triggers - then how do you explain it and is it necessary to explain it? The findings with cytokine activity do not seem to relate to individual or sub-group triggers for example. There is the strong suggestion that once a process has been initiated it then continues for some reason, and that process and that reason may be the same across a population.
Is my ME any different to yours, because my own was triggered by a parva b infection? It's important perhaps that research continues into the triggering mechanisms, and I am also of the opinion, that the period where we all seem unable to recover from this initial infection, appears to incur significant stress which also may be a factor in prolonging the 'state' of ME; but I think now that evidence is being produced which suggest we all do share similarities regardless of individual triggers.
My real reservation is with psychological triggers but then we could also be talking about a similar mechanism that is 'looping' I suppose, and who's to say that the 'stress' caused by an infection is not the same as the stress caused by a significant psychological event.
If ME - for a large group - is proven to be autoimmune in origin, then could a psychological event or trauma also initiate a fluctuating symptom cycle?
How sure are we that immune activation and cytokine activity is similar across a broad cohort of mixed triggers? Even if that is true, we would also need to know what is causing it, as some of it may be simply the generic effects of chronic symptoms such as sleep deprivation and compensatory sympathetic nervous system activation etc.
Regarding triggers for ME and CFS, we are usually going by what the patient reports. How many other disease populations are expected to know exactly how their condition was triggered? In my own case, IIRC, exercise became more difficult in the months after receiving a booster shot for MMR in highschool, then the onset of symptoms coincided with a close relative being diagnosed with suspected EBV. At the time I did not link either possible trigger to my own experience.
Obviously some people are perfectly fine one day and suddenly come crashing down literally instantly after an obvious trigger, while for others it is gradual and not clear cut, or they fail to recover from an otherwise "ordinary" infection.
It is of course possible that triggers and the speed of onset are less important than the end-state, but then I would still suspect an underlying biological vulnerability to those triggers. A recent study suggested a EBV-specific immune deficiency. Others, usually psychobabblers, suspect a vulnerability of the HPA-axis to stresses.
As per the recent study which reported Clonidine did not improve symptoms and worsened activity levels in adolescents with CFS despite quelling down the stress response, I have always felt from my own personal experiences that the sympathetic nervous system activation in CFS was compensatory in response to symptoms and pathophysiology.
I have doubts that psychological stresses and the biological stresses are the same. No doubt there is much overlap and mental stress involves physical mechanisms with downstream effects, but still. I think the stress response appears to be affected in ME and CFS patients because of chronic biological stresses (with psychological stress added on top). I vaguely recall a study which reported (somewhat surprisingly) that current self-reported stress is not a predictor of outcome.
I am skeptical that "psychological stress" alone is sufficient for triggering ME or CFS in healthy individuals. Perhaps severe and ongoing mental stresses can trigger chronic end-states which overlap with or resemble CFS symptoms and can be self-perpetuating i.e. being in a depleted state is itself stressful. That seems to be the basis of the Lightning Process and the Gupta training, both approaches of which I have serious doubts about for most patients.
I will draw on an analogy I like to use. Some neurological diseases such as Parkinson's disease and Alzheimer's disease develop slowly over time. Research suggests that depression presents a several-fold "risk" of developing Parkinson's disease, which is usually taken as an early sign of PD (dopaminergic neuron death), not a casual risk.
Similarly, I suspect that for some people, the pathophysiology of their ME or CFS is already in motion before obvious symptoms appear, but certain events appear to precede it, or triggers may even accelerate the full manifestation of the disease. Perhaps post-exertional symptomatology/pathophysiology kicks in and the patient is immediately or gradually brought down by their previously normal levels of activity, so whatever was happening at the time is blamed as a trigger?
Some patients of other diseases e.g. breast cancer blame their illness on stress too even though it is untrue. Also, not everyone has obvious symptoms of mononucleosis when infected with EBV, so EBV could still have been the main trigger for those who do not report mononucleosis or glandular fever as their obvious trigger.
I think there is very limited research suggesting that although psychological stress is more commonly (retrospectively) reported to have occurred in the 3 months preceding the onset of CFS, infections are more commonly reported in the preceding 12 months, predating psychological stress. Patients may be reporting psychological stress not because of unusual circumstances but because their stress response has already been compromised biologically, so things appear more stressful as a result. Despite decades of psychobabble and speculation about stress, there is no well-conducted prospective research on people who ended up with medically diagnosed ME or CFS.
@biophile You know I have been thinking a lot of late about other illnesses and wondering at their complete lack of understanding. I mean even though for example, it is known what MS is, they are still far away from understanding it completely, and the same goes for cancers etc. So I think that we will never truly understand everything there is to know about ME either. Doesn't mean that we should stop looking of course.
Whether or not we will ever be able to answer all the questions I don't know. Some days it seems to me there are simply too many, and if you chose one or even two possible explanations, they don't encompass the whole picture. Chances are there are a number of things at play other than the initial triggering event. What you say is perfectly true - how do I or my doctors really know that para-b was the actual trigger? Why not the glandular fever I had at 21 or the recurrent throat infections I suffer before and after puberty? And for a great many folk, I suspect also, that they can't point to an actual event - even though for most of the main clinical definitions such an event is necessary for diagnosis.
Maybe it really will be treatment that defines us all. If, if, Rituximab comes on line, then chances are it might help only a fraction of the affected numbers. If, if, something comes of the microbiome work that leads to a treatment, it might help but a fraction of patients. Same is true I am sure of a carefully structured management plan - though perhaps learning how best to live with any illness can be more effective for more people. Maybe research that continues to pursue the allegedly known triggers will unearth some treatment that can again be directed at those who can be tested, and perhaps further work on autopsies might better establish grounds for the development of even more targeted treatments.
Are 10 people with MS ever the same? Is it wrong to expect 10 people with ME to be the same? If the similarity of MS is erosion of the myelin sheath, and for ME is some measure of immune activation: maybe that is all that we can hope for. But I don't yet understand how immune activation might also affect my muscles in the way they are affected, or have such an impact on our exercise and exertion: but then again in comparison to the flu - perhaps the same mechanisms are involved and immune activation can account for them. If so, then even the mitochrondria could be effected - as I think they are when fighting the flu - which is something that again is mentioned in relation to ME of course.
Dunno my friend. Just have to wait and see I suppose. I do hope that these larger and collaborative projects though will be the ones to break the camel's back, and will even now begin to try and replicate the other, smaller but interesting studies our history has been dominated by.
Some e-letters have been posted on BMJ Open in response to the Brurberg et al. paper:
Jennifer M. Spotila
R Simpson (Invest in ME)
Tom P Kindlon
Ellen M Goudsmit
Nasim Marie Jafry
Frank N.M. Twisk
More letters have been posted:
@jspotila has posted a blog entry about this paper:
New response to the paper by Jennifer M. Spotila:
You can also try a Google Site Search
Separate names with a comma.