Who Are Those Guys? Gazing at the distant cloud of dust raised by his dogged but mysterious pursuers Butch Cassidy turned to the Sundance Kid and with some awe muttered Who are those guys? Despite all their tricks that posse had stuck on their trail like glue.
Has the Whittemore Peterson Institutes posse caught one of the slippiest preys in all medicine? Or will a significant subset of ME/CFS patients slither through their hands?
A good part of that answer depends on Who are those guys? Specifically when WPI researchers called the subjects of their study chronic fatigue syndrome (ME/CFS) patients just who were they talking about? Answering that question may determine if the WPI posse can corral the whole disease or just a portion of it.
Lets take a close look at just who was in the little study that shook the ME/CFS world.
Stacking the Deck - The WPI did not choose your garden-variety chronic fatigue syndrome patients for their first study. To put it bluntly they stacked the deck. Stacking the deck is actually standard procedure in the research world. In their first study researchers usually include patients they think will best make their case. Those patients still fit the definition of the disease but theyll often have less than subtle differences. (Given the vague definition of this disease make that very large differences. This is presumably one reason the CDC went to a random sampling scheme.)
An immune researcher would probably try to include pathogen loaded, cytokine upregulated, fluey patients. A endocrine researcher might fit in patients with hormonal problems. Perhaps not surprisingly that first study usually works out pretty well but the second one by an independent researcher who didnt try and gild the lily, so to speak, often doesnt.
A Special Group of Patients - In this case Whittemore Peterson Institute was refreshingly direct in how they stacked the deck. They stated the study participants hadsevere disability, low natural killer cell functioning, increased pro-inflammatory cytokine levels (primarily IL-6, IL-8), extremely low VO2 max during exercise testing and RNase L dysfunction. During a radio interview we learned that 20% of the patients had lymphoma. Without knowing their functional status it sounds like they are housebound and many very well may have been bedridden.
Outbreaks! (Outbreaks?) - They also came from areas where outbreaks had occurred. The WPI took a page from the distant past when they included outbreaks in the parameters. No one to my knowledge has officially reported an outbreak in several decades. Why therefore specifically go back to where outbreaks had begun (and therefore not include non-outbreak areas)?
Was this to highlight the possibly infectious nature of this pathogen or to draw attention to an important but mostly forgotten era of ME/CFS thinking? Or was it central to their case? Was limiting the participants of the study to known infectious events one way the WPI gilded their lily? (Will non-outbreak patients fit the WPIs scenario?)
Whatever the answer to that question its clear that these are NOT your normal chronic fatigue syndrome patients. A recent Pacific Fatigue Lab study, for instance, found low VO2 max levels in about half their participants. A considerable number of those participants came from Dr. Montoyas and Dr. Petersons pathogen studded patients. Given that low VO2 max was required for the WPI study its possible that a significant number of even pathogen ridden patients might not have gotten into this study.
Pathogens? Given all the speculation about XMRV opening the door like an HIV-like Puppet Master consider what these patients apparently didnt have: high pathogen loads. There is no mention of high pathogen loads the description of these patients.
The 25 Percenters - This was clearly Dr.Petersons special subset; a group hes been reported to say that he believes makes up somewhere around 25% of all ME/CFS patients.
The Big Question - Do I have an XMRV infection? Taking a very conservative view of this question and going strictly off this paper youd have a good chance of testing positive for it if you had the following characteristics; an infectious onset, extremely low VO2 max levels, low natural killer cell functioning, RNase L. problems and increased inflammatory cytokines. (If you have all of those plus lymphoma youre almost certainly in - but in a very bad way). Even in these very poorly off patients only two thirds of them tested positive for the virus (but see below).
The Last Breakthrough - If you go strictly by the study its beginning to sound pretty disappointing for the average ME/CFS patient. One is reminded of the last breakthrough to hit ME/CFS - Dr De Meirleirs H2S finding of a few months ago. H2S may very well constitute a breakthrough for chronic fatigue syndrome but only about half the self-reported chronic fatigue syndrome patients on the (admittedly limited) poll on the Phoenix Rising Forums were positive. Dr. De Meirleir also focused on very severely ill patients. He asserted hed found a biomarker for ME/CFS but his verson of ME/CFS may not fit the typical ME/CFS patient.
Room For Hope - There is room for hope, however. Dr. Mikovits reported that 95% of a larger set of patients (n=330) tested positive to an antibody tests. The antibody test did not measure active infection but it did indicate that these patients have been exposed to the pathogen. Thankfully the number of healthy controls testing positive has remained very low throughout; this pathogen - in contrast to all the others associated with ME/CFS - appears to to be quite rare in the general population - an important finding.
Still we dont know who those antibody positive patients are either. Given Dr. Petersons reported propensity for focusing on a particular subset of patients those findings may not apply to most patients. Dr. Mikovits gave many ME/CFS patients hope when she stated that she expects most ME/CFS patients to test positive for the virus but to be bit nitpicky its unclear just what she means by ME/CFS. Since the Canadian Consensus Definition refers to this disease as ME/CFS she may mean cognitively challenged patients who demonstrate postexertional malaise. That would probably be a very large group of patients. Or is she referring to the patients shes most familiar with - the Incline Village Cohort type?
Dr. Cheney is our only independent guide to the prevalence question right now. He contributed 14 patients to the study and reported that his results were similar to the group as a whole. But we dont know how selective he was in his patient selection.
Professional Recomendations - Given all this it wasnt surprising that the first recommendation from the ME Association was for the WPI to begin
Dr. Vernon echoed this when she stated that
Who Are Those Guys? So we dont really know who those guys are yet. Sure we have some tantalizing hints that the virus is found in more types of patients than the Science paper can show but before most patients should pop the bubbly they should wait to see studies that contain patients that look like them. The good news is that those studies should already be underway.
Beachhead Established - the Jungle Awaits - This is not to criticize the Whittemore Peterson Institute. Its about being wary in the face of a complex issue. Given how research happens these problems are inevitable. The WPIs first job was to establish a beachhead and theyve established the most biggest beachhead yet in this disease. Their next job is even more difficult - to try and work their way deeper into the jungle that has been ME/CFS. Hopefully theyll be able to.
Has the Whittemore Peterson Institutes posse caught one of the slippiest preys in all medicine? Or will a significant subset of ME/CFS patients slither through their hands?
A good part of that answer depends on Who are those guys? Specifically when WPI researchers called the subjects of their study chronic fatigue syndrome (ME/CFS) patients just who were they talking about? Answering that question may determine if the WPI posse can corral the whole disease or just a portion of it.
Lets take a close look at just who was in the little study that shook the ME/CFS world.
Stacking the Deck - The WPI did not choose your garden-variety chronic fatigue syndrome patients for their first study. To put it bluntly they stacked the deck. Stacking the deck is actually standard procedure in the research world. In their first study researchers usually include patients they think will best make their case. Those patients still fit the definition of the disease but theyll often have less than subtle differences. (Given the vague definition of this disease make that very large differences. This is presumably one reason the CDC went to a random sampling scheme.)
An immune researcher would probably try to include pathogen loaded, cytokine upregulated, fluey patients. A endocrine researcher might fit in patients with hormonal problems. Perhaps not surprisingly that first study usually works out pretty well but the second one by an independent researcher who didnt try and gild the lily, so to speak, often doesnt.
A Special Group of Patients - In this case Whittemore Peterson Institute was refreshingly direct in how they stacked the deck. They stated the study participants hadsevere disability, low natural killer cell functioning, increased pro-inflammatory cytokine levels (primarily IL-6, IL-8), extremely low VO2 max during exercise testing and RNase L dysfunction. During a radio interview we learned that 20% of the patients had lymphoma. Without knowing their functional status it sounds like they are housebound and many very well may have been bedridden.
Outbreaks! (Outbreaks?) - They also came from areas where outbreaks had occurred. The WPI took a page from the distant past when they included outbreaks in the parameters. No one to my knowledge has officially reported an outbreak in several decades. Why therefore specifically go back to where outbreaks had begun (and therefore not include non-outbreak areas)?
Was this to highlight the possibly infectious nature of this pathogen or to draw attention to an important but mostly forgotten era of ME/CFS thinking? Or was it central to their case? Was limiting the participants of the study to known infectious events one way the WPI gilded their lily? (Will non-outbreak patients fit the WPIs scenario?)
Whatever the answer to that question its clear that these are NOT your normal chronic fatigue syndrome patients. A recent Pacific Fatigue Lab study, for instance, found low VO2 max levels in about half their participants. A considerable number of those participants came from Dr. Montoyas and Dr. Petersons pathogen studded patients. Given that low VO2 max was required for the WPI study its possible that a significant number of even pathogen ridden patients might not have gotten into this study.
Pathogens? Given all the speculation about XMRV opening the door like an HIV-like Puppet Master consider what these patients apparently didnt have: high pathogen loads. There is no mention of high pathogen loads the description of these patients.
The 25 Percenters - This was clearly Dr.Petersons special subset; a group hes been reported to say that he believes makes up somewhere around 25% of all ME/CFS patients.
The Big Question - Do I have an XMRV infection? Taking a very conservative view of this question and going strictly off this paper youd have a good chance of testing positive for it if you had the following characteristics; an infectious onset, extremely low VO2 max levels, low natural killer cell functioning, RNase L. problems and increased inflammatory cytokines. (If you have all of those plus lymphoma youre almost certainly in - but in a very bad way). Even in these very poorly off patients only two thirds of them tested positive for the virus (but see below).
The Last Breakthrough - If you go strictly by the study its beginning to sound pretty disappointing for the average ME/CFS patient. One is reminded of the last breakthrough to hit ME/CFS - Dr De Meirleirs H2S finding of a few months ago. H2S may very well constitute a breakthrough for chronic fatigue syndrome but only about half the self-reported chronic fatigue syndrome patients on the (admittedly limited) poll on the Phoenix Rising Forums were positive. Dr. De Meirleir also focused on very severely ill patients. He asserted hed found a biomarker for ME/CFS but his verson of ME/CFS may not fit the typical ME/CFS patient.
Room For Hope - There is room for hope, however. Dr. Mikovits reported that 95% of a larger set of patients (n=330) tested positive to an antibody tests. The antibody test did not measure active infection but it did indicate that these patients have been exposed to the pathogen. Thankfully the number of healthy controls testing positive has remained very low throughout; this pathogen - in contrast to all the others associated with ME/CFS - appears to to be quite rare in the general population - an important finding.
Still we dont know who those antibody positive patients are either. Given Dr. Petersons reported propensity for focusing on a particular subset of patients those findings may not apply to most patients. Dr. Mikovits gave many ME/CFS patients hope when she stated that she expects most ME/CFS patients to test positive for the virus but to be bit nitpicky its unclear just what she means by ME/CFS. Since the Canadian Consensus Definition refers to this disease as ME/CFS she may mean cognitively challenged patients who demonstrate postexertional malaise. That would probably be a very large group of patients. Or is she referring to the patients shes most familiar with - the Incline Village Cohort type?
Dr. Cheney is our only independent guide to the prevalence question right now. He contributed 14 patients to the study and reported that his results were similar to the group as a whole. But we dont know how selective he was in his patient selection.
Professional Recomendations - Given all this it wasnt surprising that the first recommendation from the ME Association was for the WPI to begin
Dr. Vernon echoed this when she stated that
Who Are Those Guys? So we dont really know who those guys are yet. Sure we have some tantalizing hints that the virus is found in more types of patients than the Science paper can show but before most patients should pop the bubbly they should wait to see studies that contain patients that look like them. The good news is that those studies should already be underway.
Beachhead Established - the Jungle Awaits - This is not to criticize the Whittemore Peterson Institute. Its about being wary in the face of a complex issue. Given how research happens these problems are inevitable. The WPIs first job was to establish a beachhead and theyve established the most biggest beachhead yet in this disease. Their next job is even more difficult - to try and work their way deeper into the jungle that has been ME/CFS. Hopefully theyll be able to.
