Dr. Jason Part 6: 55:52 to end
Slide - More Objective Measures
As you can see on the screen, for fatigue severity possibly using whats called actigraphs, which are able to measure behavioral abnormalities; for post-exertional fatigue and for pain possibly certain types of genes that following exercise, as the Lights have found, are nice indicators of this construct; for unrefreshing sleep or disturbance of sleep possibly a sleep study.
Slide Neurocognitive Manifestations
These are all cognitive manifestations by fMRIs; autonomic manifestations - ejection fraction decreases as has been found by this particular group (indicating Chemitiganti et al on slide); neuroendocrine manifestations abnormal cortisol levels; and immune manifestations by some of the work by Kevin Maher, Nancy Klimas, and Maryanne Fletcher.
Slide Scientific Enterprise
In summary, any scientific enterprise depends on reliable and valid ways of classifying patients into diagnostic categories. This critical research activity can enable investigators to better understand the etiology and pathophysiology of an illness. When diagnostic categories lack reliability and accuracy, the quality of treatment and clinical research can be significantly compromised. If ME/CFS is to be diagnosed reliably across healthcare professionals and scientists, its imperative to provide specific thresholds and scoring rules for the symptomatic criteria.
Slide In Conclusion
In conclusion, ME/CFS has gone from being considered a relatively rare illness in the 1990s, to one affecting about 1 million in the early 2000s. Now the CDC suggests as many as 4 million have this illness with the broadened criteria. These new estimates might include those with primary psychiatric illnesses, such as Major Depressive Disorder. Using a broad or narrow definition of ME/CFS will have important influences on ME/CFS epidemiologic findings, as weve suggested, on rates of psychiatric comorbidity, on how patients are treated, on risk factors as to what might be implicated in the cause of this illness, and ultimately on the likelihood of finding biological markers.
I hope that Ive been able to suggest that case definitions can be a major impediment to replicating findings across different laboratories. For if investigators select examples of patients who are different on fundamental aspects of this illness because of ambiguities with the case definition, then it will be exceedingly difficult for investigators to consistently identify biomarkers and this could lead to more psychogenic explanations of the illness.
Slide Interested in Participating?
Over the past hour, we have needed to probe deeply to find out where some of the problems with our case definition might arise. And I thank you for staying with me as weve had to cover many relatively complex material, including the field of epidemiology, issues of reliability including criterion variance, sensitivity, specificity, and even Bayes theorem. We often have people ask us if they can participate in one of our future studies. If you would like more information, you can contact us at the email on this screen (DePaulMECFSResearch@gmail.com). I now am available to answer some of your questions, and I am going to turn this over to Kim McCleary.
: Lenny, you have a couple more slides, is that right?
: I do have a couple more that I was going to use for maybe response to some of the questions.
: And the first question Im going to ask (and this is a bit of a plant because it came in through the registration process from many of the people who registered for todays program) is about the American Psychiatric Associations proposal to create a new construct of mental disorders called Complex Somatic Symptoms Disorders CSSD. and although CFS is not specifically named in that criteria, The CFIDS Association, IACFS, and many other organizations have seen the potential for that new classification to impact people with CFS, and I wondered if you could make some comments about that from your perspective?
: Sure, can you turn me back to my slides?
[Brief back and forth about technical difficulties]
: Ok, great. This is one of the modern miracles of technology. Ive got my screen up, but my other ones arent here. But I can talk briefly about that question (as I try to somehow get my slides to move). The DSM is undergoing a revision right now and as youve said this is a very controversial kind of diagnosis. In a sense, one of the issues that many people are concerned about is that while it doesnt explicitly say that Chronic Fatigue Syndrome can be placed into that category, its certainly possible it could. Basically, you have to have a symptom that lasts for 6 months; there has to be certain characteristics of it that Chronic Fatigue Syndrome could very much meet. So many people are concerned that this widened category could be used to identify individuals who have what we think of as ME/CFS. So I think that its very important for individuals and organizations to get their comments in, and I might add that The CFIDS Association has put together a very strong statement - Id encourage you to take a look at that. The IACFS/ME - Fred Freidberg and his board of directors - have also put together a very strong statement, and Id encourage those of you to take a look at that. Because I think both positions clearly suggest that there could be much harm done by this new diagnostic category.
Ok, Kim, I take it that I have some questions here?
: You do - a couple of them while youve still got the controls. One of them asked if the 6 factors in the DePaul study that you presented were presented in order of the percentage variance accounted for, so I thought maybe you would want to go back to that slide if you can.
: You know, I would go back to the slide except my screen is frozen. But thats a good question, and what that suggests is that - in a sense - which factors basically account for the most variance. And what that indicates is that - and unfortunately I dont have those numbers in front of me, so I dont want to give out any misinformation - but certainly they all had at least an eigenvalue of one, and they would all explain at least a certain amount of variance that would make sense to look at them beyond a particular item.
But I think whats interesting rather than answering that particular technical statistical question its a very good one is alright, I am no longer the presenter so basically Im back here. But actually whats nice about that particular model is that its really an attempt, and I think that theres a number of research groups around the world that are really trying to use statistical efforts rather than a group of people coming together and saying this is what we think this illness is. I think ultimately using these types of things like factor analysis and other strategies to figure out what symptoms are really characteristic of this population - I think thats going to really push our field forward and we can see just some really interesting work thats occurring even at the genetic level at this point.
: A couple people asked about the distinction between primary psychiatric disorders and depression in particular, and the kind of depression that many people with CFS experience, often at the hands of unknowledgeable or uncaring medial providers who either dismiss or downplay the severity of the illness, and how you can distinguish between those symptoms.
: Thats a great question. You know, theres just lots of people who look at someone with classic depression and classic ME/CFS and they dont get it. They dont see the difference between these two groups. And if you dont understand the difference between these groups, then you ultimately put them together into one category and this can have really some significant issues.
You know, individuals with depression have actually different cortisol levels, thats usually higher. Those with ME/CFS usually have lower cortisol levels, so in a sense you have different neuroendocrine functioning just on that one dimension, but many many others. What I try to suggest is that self-reproach - people with depression have a lot of negative types of things they say to themselves in self-reproach. Theyre very upset with themselves in different ways. People with Chronic Fatigue Syndrome and ME generally dont have that self-reproach. Theyre basically wanting to have their life back. Theyre wanting to get on with their life. Theyre basically seeing themselves as being limited.
So in a sense, if you think about the kind of the difference - one of my students, a graduate student at DePaul, just actually looked at that situation of those who have kind of different types of psychiatric issues. Some individuals with ME/CFS do have depression. I mean, the reality is any kind of chronic illness that you have is probably going to cause you tremendous losses, and those losses could cause depression. Whats interesting is when you talk to people - theres folks who have primarily a major affective disorder like Major Depressive Disorder, others who have really different ME/CFS. So really, theres a lot of physiological differences.
On self-report measures, as I suggested, you can make 100% separation. The ME/CFS - to make a generalization - usually feel in a sense demoralized, usually feel kind of upset that they cant do things. Thats different from clinical depression, so thats the key difference. But if youre a primary care physician, and you have someone coming into your office and youve got 10 minutes to try to figure out what to do - too often those individuals are going to make a claim of saying oh this person must be just depressed because theyre fatigued. And fatigue is one of the primary things that people come into healthcare settings complaining of, so theres many many people coming in with fatigue problems. But not everyone has ME/CFS, which is different, as I tried to suggest in this presentation, from many other types of chronic fatigues, as well as chronic fatigue that is caused by depression. And that certainly needs to be differentiated.
Its a great question - very complex issue. I think it is one of the basic challenges to our field to ultimately try to collect homogeneous samples. And if we can get less heterogeneous samples and more homogeneous samples with the key characteristics of this illness, we have a chance of not only producing better - I think - prevalence numbers, but also of identifying those people who then we can look at these biological markers and see if theyre common across labs. To the extent that different laboratories have different people with different primary characteristics, and one group of people might have more affective depression in their group (and maybe not even ME/CFS) Well, that sample is never going to have the same biological markers, if you have another group that has really primarily ME/CFS symptoms in that sample.
: Well, lets kind of turn that one on its side, if you dont mind, and talk about - several of the questions have asked about biomarkers and how biomarkers will affect the definition of CFS. And thinking about things like XMRV, you mentioned the Light study of post exercise markers in CFS, can you speak to the effect of how different biological findings may regroup or redistribute the way that the case definition is shaped?
: Yeah. I think thats as I said, really, at the beginning of my presentation, I think that these are exciting times. I think that there are people doing work with proteomics, with genetics - people who are giving challenges. It really seems like whether its in the nasal area or whether its in peripheral blood, that were seeing really challenges that seem to kind of elicit these types of changes in some of the genetic markers or some of the receptors. So thats exciting and I think ultimately thats why the last slides I really started talking about more biological measures.
Our group in Chicago is now trying to write a paper where were going to try to take every symptom and try to say this is what we have, level one, level two. You know, basically this is self-report and this is one level, and thats ok, but heres the next level if you basically meet criterion on this, for example, exercise challenge. That will basically be the gold standard, and I think ultimately thats what our field is going to go to. Its happened in other fields like MS where ultimately, you come up with kinds of measures that basically say, yes we think this is kind of the illness and these are the types of characteristics that fulfill it. Thats where our field will go, I think in the next 5 to 10 years. Theres no question that the genetic work is a sign for tremendous hope among the people who are out there in the audience. We are close to making breakthroughs. And the hope is that scientists will select the right people, carefully defined, so they can find these biological markers. And once these markers are better understood, we will ultimately begin to understand some of the basic central processes that are basically causing the many symptoms of these illnesses.
: Lenny, theres a lot of interest in the symptom of post-exertional malaise/fatigue/exhaustion, and I have to admit I was responding to questions when you were focusing on that part of the presentation, but a question came in about whether the new measures that your group is proposing and the way that youre asking about that symptom - whether it also incorporates not just physical effort but also mental and cognitive effort, and the relapse that many people experience after trying to do their taxes, or help their kid with third grade math even, that has almost the same effect as physical effort does.
: Thats a great question. Theres no question that its not just physical activity that can cause these types of symptoms and mental activity can also do this. There has been work that has been done in that area, and certainly I think that the reason the exercise challenges are so interesting, you know - Staci Stevens and the Lights and many others who are doing such incredible work in this area - are that its really much easier to quantify basically having a person kind of do sub-maximal or maximal exercise depending on, you know, Gaines work is also very important.
So the key question is how do you operationalize it, so that you can actually have a person go through a procedure and then see these types of changes, biological changes. And ultimately, probably a little bit more work now has been done with the physical challenges. I hope that the other types of challenges will also be more explored. Theres some preliminary work in that area. Theres no question that both of these types of challenges are going to have physiological changes that could be used by us to help, again, identify patients who have this very interesting phenomenon of post-exertional malaise.
Its just such an interesting phenomenon. Remember with depression, getting back to the depression vs. MS/CFS category, you take a person with Major Depressive Disorder and you tell them to start working out, do some aerobic exercise, get more active - they feel better. They will come back and report, gee this is making me feel better. Isnt it interesting that the ME/CFS person whos told to start getting a little bit more active and to start pushing themselves a little bit, they will experience post-exertional malaise. So you have, again, two fundamental different kinds of events occurring for two different type patients. So why would you want to put them both together? You put them together and youre never going to find those types of biological markers that are specific for ME/CFS. So again, an excellent question and I think that very similar types of genetic changes probably could occur. Again, this is something that we need more research on.
: Several questions about the Canadian Case Definition and how it might be more widely distributed and circulated. When it was published, it was published in the Journal of Chronic Fatigue Syndrome which is no longer active and wasnt ever Medline or PubMed searchable. I know youve been working with the authors of that definition, and maybe you can share some of your thoughts about how to get that into the hands of more clinicians and researchers?
: Sure. The Canadian criteria were developed in 2003, and our group in Chicago looked at them very closely. And we tried to take what they stated in their manuals as well as in the Journal of Chronic Fatigue syndrome and just operationalize it, and tried to get real specific about whether you count it or dont count it with a particular person, and we have some difficulties. I mean the reality is that operationalizing the Fukuda criteria and the Carruthers - the Canadian criteria - is not always the easiest for researchers. Now with the Canadian criteria, that didnt stop them from using it - the Canadian clinical case definition - because they say its a clinical case definition. Some people said, well maybe it shouldnt be used for research purposes. We have been struggling for the last few years trying to figure out why its not being used more, and our first effort in this area was with the pediatric criteria, which we really used a template of the Canadian folks to work on that. And we had some success with that criteria. And now were trying to concretize the work - the really excellent work - that the Canadian authors put together.
Now, it might sound simple but its very difficult. We have a questionnaire that we have developed. Weve sent it out to probably about 25 people around the world. You know, we have a team that sits down and sort of says, well how should we phrase this? you know, how do we capture it? And we had one group from Great Britain that were saying well they use this word a little differently there, so how do we use that particular word? Very hard to operationalize things so everybody will use the same stems, (?) the same questions, so that we can have everybody on board and thats what were hoping.
Were hoping to begin collecting data know with the . . . questionnaire that weve developed (unintelligible) written that well eventually be sending off. Were hoping to present some of the initial data at the next major IACFS/ME conference. By that time well have some of our data collected. But we think that we certainly would encourage people who want to collect data to think about maybe using the Fukuda and the Canadian criteria and seeing what they find, and seeing if they are finding similar groups or if they find slightly similar groups. And I think that using both case definitions is something that I would encourage, and I hope that it comes to a point where you see the Canadian criteria actually used. At this point, theres really only been a handful of studies that have actually used it and wed like to see that changed.
Slide SolveCFS BioBank
: And I would note that (and Im actually going to advance my slide to make this point) the Association just launched the SolveCFS BioBank and we are enrolling patients for the first study using the BioBank. And the eligibility requirements use both the Fukuda and Canadian definition, because as you say it is not as easy to operationalize as one might hope. But were hoping through the eligibility criteria weve established to really encircle a more homogeneous group of patients, as you suggested earlier in your presentation. And so were excited about what that opportunity to look at a really well characterized group of patients will bring to advance the research.
If youre not familiar with the BioBank, Ill just put a plug in to visit our website at www.cfids.org
. And I did have a slide with some URLs on it and Im not sure what happened to it. But weve also been working with Lenny on the questionnaires that will collect the information directly from patients about their symptoms and medical history, medication history, etc. and hope that the BioBank will be a resource for the expansion of his research on how those tools and operationalization through questionnaires might be enhanced as well. So weve enjoyed that partnership on this new BioBank.
According to my watch, were a little bit over time. Im just astounded we still have 185 people on the line, so bravo to all of you who have lasted for 90 minutes. I know that even though you may be reclined or in a comfortable chair, and you dont have to be in a hotel ballroom in an uncomfortable straight chair at a desk somewhere sitting to listen to this, it is still exertion and requires your attention to focus in on the computer and the dialogue as well, so thanks for hanging with us. Lenny any parting comments before I make some closing remarks?
: I just want to thank you and The CFIDS Association. I certainly have enjoyed this webinar, and I look forward to hearing more about other webinars you do in the future.
: Great. Well, thanks for helping us pioneer this series and this was Dr. Jasons first webinar, and it is a bit of an odd experience. I mean all of us are sitting here, probably by ourselves, but when youre speaking and looking at a computer screen it makes you feel just a little bit like an out of body experience. But you did a great job and one person even sent a comment that they teach public presenting, and that you were doing a fantastic job from that standpoint, so Ill pass that on to you by email.
For those of you still hanging with us, I just want to make sure that everybody is aware that our webinars have expanded. We had initially planned to do one program a month, and we were able to get some support from a family that wishes to remain anonymous to expand that - and to really utilize that technology and this opportunity to bring really dynamic speakers to you. We have three upcoming webinars on sort of more medical research topics, for those who sent questions about some of the things like biomarkers and treatment issues on the clinical side. Coming up on May 4th with Suzanne Vernon, who will talk about three of the six projects were funding; Dr. Charles Lapp here in Charlotte at the Hunter-Hopkins clinic will describe his approach to treatment of CFS; and then Suzanne will be back with us on June 8th with Dr. Liz Horn from Genetic Alliance to talk about the SolveCFS BioBank. We have a list of the other topics that will be coming on our website. We have another program planned for next week, but were having a little bit of scheduling difficulties, so that one may be rescheduled for the future. But were just real excited about this series. Already weve had more than 1500 people participate, and thats something we couldnt do without this technology and people being willing to take us up on this offer.
We will be sending a follow-up email to everybody that participated today with some of the URLs that were mentioned. I know a couple people missed the email address if youre interested in participating in Dr. Jasons groups studies, for the BioBank, for the upcoming webinars, for where to find the recordings of this program and the slides after the fact, and some other resources that came up in the content of the program. So well be getting that out to you later today or tomorrow morning, so you have all those things in your email, in case you didnt catch them as we were going through. So on behalf of everyone here at the Association, we really appreciate your participation, your support, and your engagement in this, and thanks so much for participating. Have a good afternoon/ rest of your day/ evening or whatever you have left of the day before U.S. tax day. Thanks again, Lenny, and take care.