Discussion in 'Phoenix Rising Articles' started by Mark, Aug 2, 2013.
Another post where the 'Like' button doesn't seem adequate - great stuff, Special!
I'd love to send this letter, but I don't have access to a printer. Does anyone have Dr. Unger's email address? I tried to google it, but could not find it. Thanks.
"Unger Dr. Beth" <email@example.com>
Thanks, Johnny, that was useful - I've just sent my email.
Dr. Unger should know that using these tests to confirm ME is endorsed in the ME Primer by clinicians and researchers on the ME International Consensus Panel:
Carruthers, Bruce M, MD, CM, FRCPC; clinician: internal medicine with focus on ME
Independent, Vancouver, British Columbia, Canada
De Meirleir, Kenny L, MD, PhD; clinician and researcher: physiology & medicine
Professor: Physiology and Medicine, Vrije Universiteit Brussel, Belgium
Director: Himmunitas Foundation, Brussels, Belgium
Klimas, Nancy G, MD; clinician and researcher: microbiology, immunology,allergy
Professor of Medicine and Director: Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale-Davie, Florida
Director: GWI and CFS/ME Research Center, Miami Veterans Affairs Medical Center, Miami, Florida, USA
Broderick, Gordon, PhD; researcher: systems biology, mathematical immunology, computational genomics – ME, CFS, Gulf War Illness (GWI)
Associate Professor: Pulmonary Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada
Mitchell, Terry, MA, MD, FRCPath; clinician:internal medicine - pathophysiology and haematology
Retired clinical haematologist with 28 years of experience of ME and chronic fatigue syndrome, Suffolk, UK
Staines, Don, MBBS, MPH, FAFPHM, FAFOEM; public health medicine, occupational and environmental medicine, researcher
Public Health Physician: Gold Coast Public Health Unit, Robina, Queensland
Associate professor: Faculty of Health Sciences and Medicine, Bond University, Robina, Queensland
Faculty of Medicine, Griffith University, Southport, Queensland, Australia
Powles, A C Peter, MBBS, FRACP, FRCPC, ABSM; clinician: internal medicine: sleep medicine, respirology
Professor Emeritus: Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario
Sleep Disorders Consultant: St. Joseph's Healthcare Hamilton, Ontario, Canada
Diplomate: American Board of Sleep Medicine
Speight, Nigel, MA, MB, BChir, FRCP, FRCPCH, DCH; paediatrics
Retired clinical paediatrician with many years of experience of ME and chronic fatigue syndrome. Durham, United Kingdom
Vallings, Rosamund, MNZM, MB, BS, MRCS, LRCP; clinician: primary care with focus on ME
Howick, New Zealand
Bateman, Lucinda, MS, MD; clinician: internal medicine with focus on ME & FM
Fatigue Consultation Clinic, Salt Lake City
Utah hospital affiliation: Salt Lake Regional Medical Center
Adjunct Instructor: Departments of Anesthesiology and Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USA
Bell, David S, MD, FAAP; clinician and researcher: paediatrics
Retired clinical paediatrician with many years of experience of ME and CFS, Lyndonville, New York
Department of Pediatrics, State University of New York, (SUNY – Buffalo) New York, USA
Carlo-Stella, Nicoletta, MD, PhD; clinician and researcher: immunology, immunogenetics of ME
Azienda Ospedaliera della Provinca di Pavia, Pavia
Primary care private practice with focus on ME, Pavia, Italy
Chia John,MD; clinician and researcher:internal medicine - infectious diseases, immunopathogenesis
Clinical assistant professor: Harbor-UCLA Medical Center, University of California, Los Angeles, CA
Director: EV Med Research, Lomita, California, USA
Darragh, Austin, MA, MD, FFSEM (RCPI, RCSI), FRSH, FI Biol I (Hon); clinician and researcher: endocrinology
University of Limerick, Limerick, Ireland
Gerken, Anne, MB, BS, D ObstRCOG, FRCPath: clinical microbiologist
Retired consultant microbiologist with many years of experience working with ME, Suffolk, United Kingdom
Jo, Daehyun, MD, PhD; clinician and researcher: pain and anesthesiology
Director: Pain Clinic, Konyang University Hospital, Daejeon
Professor: Department of Anesthesiology and Pain Medicine, Konyang University, Daejeon, Korea
Lewis, Don, MD; clinician: primary care with focus on ME
Donvale Specialist Medical Centre, Donvale, Victoria, Australia
Light, Alan R, PhD; researcher: Physiology, neuroscience, medical neurobiology and neuroanatomy, mechanisms of pain & fatigue
Professor: Anesthesiology and Neurobiology and Anatomy; Molecular and Cellular Neuroscience, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Light, Kathleen C, PhD; researcher: behavioral medicine – physiological dysregulation in chronic pain and fatigue disorders, behavioral factors in cardiovascular disease, health benefits of family support, minority and women’s health issues
Professor: Anesthesiology and Psychology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Marshall-Gradisnik, Sonya, PhD; researcher: immunology -natural killer cells, vasoactive neuropeptide dysfunction and receptor expression, T cell regulatory dysfunction
Professor: School of Medical Sciences, Griffith Health Institute, Griffith University, Southport, Australia
McLaren-Howard, John, DSc, FACN; clinical biochemistry, biochemistry of nutrition, biochemical features of ME, mitochondrial dysfunction, vascular disease & intestinal dysbiosis
Fellow: American College of Nutrition
Director: Acumen Medical Limited, Tiverton, Devon, United Kingdom
Mena, Ismael, MD; nuclear medicine
Director: Imagenologia Funcional Cerebral, Department of Medicina Nuclear, Clinica las Condes, Santiago, Chile
Professor Emeritus: Radiological Sciences, UCLA School of Medicine, California, USA
Doctor Honoris Causa: University, d'Auvergne, France
Miwa, Kunihisa, MD, PhD; clinician and researcher: internal medicine: cardiology, cardiovascular physiology
Director: Miwa Naika Clinic, Toyama, Japan
Murovska, Modra, MD, PhD; researcher: virology, medical microbiology, molecular biology
Director: A. Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia
Associate Professor: Riga Stradins University, Riga, Latvia
Stevens, Staci, MA; exercise physiology
Director: Workwell Foundation, Ripon, California, USA
With Dr. Broderick's having relocated to Florida, eight of these authors are based in the US. Drs. Klimas and Bateman are also involved in Dr. Unger's multi-site study.
A big thank you to Mark and the others who have worked on this. I think it is sooo important to be pointing out the issues with studies sooner rather then later.
Sorry if I missed the link, but is there a way to sign the petition online?
Thanks for sharing this Mark.
Hi Questus - it's not a petition, it's a letter - the email address was posted here:
From the CDC website regarding the ME/CFS multi site study:
How can they accurately sub group us if they don't take the relevant tests that are critical in the diagnosis of the disease?
What is their ultimate aim with this study? They are basically taking current patients from seven clinical sites. They are having them fill out a complete questionnaire. They are "studying" them, in a fashion that is not clear or disclosed to us.
I am afraid that the result of this study will show that there is very little to unify us. It will show that we are just a conglomerate of so many different issues resulting in "fatiguing" type of illnesses. It is not a real disease, they will say, it is just a syndrome of many symptoms which need to be treated symptomatically.
The reason why this is my fear is that if they were truly concerned in finding "the underlying biology', they would concentrate on the testing that have shown in past peer-reviewed studies, abnormalities in ME/CFS patients. They would also include severely affected patients as well as children.
The CDC are not great at keeping the community up to date with exactly what they are doing, but they have given out some information about their ongoing study.
The CDC don't seem to be engaging continuously with the wider ME community, but they are engaging with significant parts of the ME community, especially the experts and clinicians who are involving in their study.
It's a mistake to say that the CDC are only using questionnaires.
Their study is evolving and seems to be open-ended, and they have now gone beyond questionnaires, and physician reports, and are looking at some biomarkers.
Beth Unger seems to recognise that heterogeneity is the biggest problem. And she's looking for data to find well-defined subsets. Finding subsets seems to be her mission. I can't fault that mission.
She has said that, in the long term, none of the existing diagnostic criteria will be perfect, and she is looking towards defining subsets by looking at treatments, and finding out the differences between the patients who respond and those who don't respond. She gave Ampligen as an example of where some patients respond to treatment and others don't.
She says that finding out why some patients respond to treatments (what is different about them - are there any biomarkers?) will probably prove to be the best way forwards in terms of defining the disease. I think she's spot on.
Importantly, and very relevant to this thread, they are already taking the study to a new level, and looking at biomarkers. They are taking DNA/RNA samples, and testing for morning cortisol levels. And also doing cardiopulmonary testing during exercise tests, and cognitive testing post-exercise. (Although currently these are planned to be one-day and not two-day tests.)
So, to summarise, my understanding is that the CDC have already started carrying out further tests including:
DNA/RNA testing. (I'm not aware of the exact details.)
Morning cortisol levels.
Cardiopulmonary testing during exercise tests (one-day testing)
Cognitive testing post-exercise (one-day testing)
At the most recent CFSAC meeting, Beth Unger also expressed an apparent willingness to incorporate post-exertion resting heart-rate into the study, although she didn't make it a firm commitment.
This is my understanding of it anyway. I may have misinterpreted something, because I've gleaned the information mainly from the chatter in CFSAC meeting videos.
I think prompting the CDC to look at two-day exercise testing is helpful, but keep in mind that Dr Snell has had some mixed results from two-day exercise testing, and has only carried out relatively small studies, and he has suggested that his work has not been reliably replicated by others. So two-day exercise testing may or may not prove to be as helpful as we hope.
My own interpretation is that Beth Unger and her team are moving in exactly the right direction, but still have a very long way to go. I don't think we should assume that Beth Unger is like previous CDC employees. She seems to be wiping the slate clean, and starting from scratch and approaching ME/CFS with an open mind, and basing her work on the data outcomes. This is absolutely the best way to go about it. But it's something that should have been done 30 years ago, so the CDC is behind schedule. My own interpretation is that Unger is taking her job seriously, and treating this illness seriously. Of course, I might be wrong, and perhaps I have a tendency to be over-optimistic, but I'm trying to be fair minded, and base my opinions on my interpretation of the evidence. The evidence suggests to me that she is doing the right stuff, but has a long way to go, and the CDC is at least 30 years behind schedule. I'm sure that others might disagree with me.
I've previously posted about these issues in a jumble of posts, if anyone is interested in reading further (but I've copied the essential information into this post):
Bob thank you for that. I had asked what they were actually up to with the testing before on this thread I think. All tends to get muddled across the forums. Very useful summary
Their study might have evolved even further now. I'm basing my info on what was available at the last CFSAC meeting, whenever that was.
I guess we have different perspectives, looking at the same data.
So far, from my understanding the CDC first phase of the study has been accomplished.
This included 450 patients from 7 clinical sites.
-physical exam (not clear if this was done by the clinicians or CDC reps)
-patient questionnaires - including measure of fatigue, sleep, pain and function
-data abstraction of medical records by clinic personnel
They have collected all (95%) of the data and analyzed it, comparing the different sites and comparing some of the data with different illnesses.
The second phase, we are told, involves:
From all clinical sites
-saliva morning cortisol collection (??? this will find subsets?)
-blood DNA & RNA (sounds important but, what is it?)
Additional studies at some clinics:
-comparing healthy controls
-cognition and exercise testing
"final dataset will allow comparison of instruments measuring domains of CFC illness"
I wish someone can explain to me what this means exactly.
I don't have anything personal against Dr. Unger. I don't think that she has the power to "wipe the slate clean". I think that she is just doing the job she is told to do.
Why is the CDC totally ignoring all the scientific studies that are already out there?
They give the impression that this is a legitimate and important study because they are involving patients who are part of major clinical practices. In what way, are they going to find a biomarker for ME/CFS with this study as it is?
I don't feel that heterogeneity is the biggest problem. I feel that finding a biomarker and diagnostic criteria are. Many other illness are heterogenic, that doesn't necessarily mean that it is not one disease. Any multi-system illness will be heterogeneous. Lupus, for example will appear totally different in each patient. Separating the patients into different illnesses, would have been a major mistake.
Why am I so disillusioned with the CDC? Because they are totally ignoring the fact that we have the CCC and the ICC. They are acting as if they don't exist. I don't have any medical or science background but, from my knowledge of the history of this disease, what they are doing now in this study, does not make sense to me.
Nielk just confirm for me that they are assessing patients using their own (CDC) criteria. Thanks.
According to Dr. Unger, the patients they are studying are the ones that each clinician has diagnosed with CFS, Post Infective Fatigue (?),ME - it doesn't say by which criteria.
No particular criteria is necessary for the study. The clinicians just have to diagnose the patient in their own way, according to their expert knowledge. I expect that each patient will subsequently be diagnosed as per various criteria, for the purposes of gathering extra data.
This was to have been my next comment. I hope that the data gathered will be used in 'research' as we might better understand it; and those who are sub-grouped in this initial business are then studied under the microscope as it were. I may well be wrong of course.
I'm assessing Beth Unger's progress relatively from a standing start, and not from where we want the CDC to be. I'm not trying to pretend that everything at the CDC is wonderful, but there has been change, and I'm quite impressed with what I've seen recently, in terms of attitude. I imagine that many people will be shouting at their computers whenever I say anything positive about the CDC, and I totally understand that.
Of course there is a huge distance that they need to travel, but this is not Beth Unger's fault. So I'm assessing her progress from a standing start, and not from where the CDC should be. And I'm not suggesting that we shouldn't be critical of the CDC, and or that we shouldn't put pressure on them. We should be critical, and we should put pressure on them. I just think that it's helpful to observe what they are actually doing.
The CDC currently appears to be very resistant to suggestions from the ME patient community, but I think this is because they have a very bureaucratic and specific way of doing things, and their plans take a long time to implement. I think this can give the appearance that they are not listening and that they don't care. But I think we should be aware of their bureaucratic processes, and not assume that they are ignoring our community to spite us. I saw evidence of flexibility, engagement and receptiveness, from Beth Unger at the recent CFSAC meeting, although it wasn't obvious.
Before Beth Unger, I had no respect for the CDC at all. And it took me a long time to learn what Beth Unger's approach would be. Only recently have I really learned what her approach is, and I've only learned it by listening carefully to what her team have said at the CFSAC meetings.
Like I said earlier, I may well have misinterpreted, and I may be far too optimistic, but I am optimistic about their direction of travel. Of course, they yet have to prove themselves. I'm also aware that many will strongly disagree with my assessment.
Beth Unger seems to be approaching the subject without preconceived ideas, and she has stated that she is following the data. I think that's the best way for her to go about it. It really does seem to me that she's made a fresh start of ME/CFS at the CDC. I'm basing this on what she's said, and on the project that they are carrying out. She has a very long way to go, but that's not her fault. What she is doing now should have been done 30 years ago.
My understanding is that it is because they require a certain standard of evidence. Yes, there is research out there, but is any of it conclusive? I'm not aware of any conclusive top-quality research in terms of objectively defining ME/CFS. Are you? There is some evidence re exercise testing, tilt-table tests, brain scans and immune activity, but none of it is of a high enough standard to be widely accepted, as far as I am aware. Unless I'm forgetting something.
The CDC needs data from studies with large numbers of participants. And any objective biomarkers need to be reliably reproducible in further research studies. The CDC have now started looking at large numbers, and have also started looking at potential biomarkers. But, yes, they've yet to demonstrate exactly what they are studying in terms of biomarkers.
Beth Unger has acknowledged that she's yet to get to grips with PEM, in terms of defining it for research purposes, and she's acknowledged that it could be a useful biomarker if she is able to define it to her satisfaction for research purposes. Sure, this sort of thing seems very basic to us, but she's got to define it in a way that is reliable and replicable in research studies. Should she use self-reported questionnaires, immune biomarkers, exercise testing, or something else? What reliable biomarkers are there for PEM? Is there any top quality research that defines reliable biomarkers for PEM or PENE? I'm not aware of any. Dr Snells recent research is very promising, but it's just one small study.
I get the feeling that it's an open-ended, evolving, exploratory study. So far, there are some potentially decent biomarkers involved, although the details are sketchy. Exercise testing, post-exertional cognition testing, DNA/RNA analysis, and post-exertional resting heart rate testing seem like pretty good objective biomarkers to be starting with. Two-day exercise testing, immune signatures, viral testing and protemics are maybe the next step.
Likpin is doing an extensive viral and proteomic study, and it is something that the CDC should have been doing years ago. If we compare Lipkin's study with the CDC study, then the Lipkin study puts the CDC to shame. But I'm assessing Unger from a standing start. I hope that the CDC will be funding research similar to Lipkin's after they have done their current basic biomarker research.
Yes, the CDC is doing far too little, far too late. But I'm not assessing Unger on where I want her to be. I'm assessing her on where she is, based on a standing start. So I'm trying to assess her motivation, rather than her accomplishments.
I think that many of us would accept that CFS may not be a single disease, and some of our community would like ME to be distinguished from CFS. Unger is attempting to identify subsets. She has said that she is open minded to defining ME separately, if her data leads her that way. Without getting to grips with heterogeneity, if there is any, and defining subsets, then biomarkers and objective diagnostic criteria would be impossible to define. Defining subsets is the best way to start, or biomarkers will be impossible to find.
I think that the CDC has accepted that research should be carried out with Fukuda and CCC, haven't they? The reason that they are partially ignoring the CCC is that they don't believe that it is evidence based. Not to the standard that they require. So they have set about finding subsets for themselves, using their newly gathered data. Whether it's the right or wrong approach, the CDC requires a certain quality of empirical evidence.
It makes sense to me. And I like what they are doing. It's just not enough, and not fast enough.
I like what I've heard Beth Unger say recently.
She does sometimes seem resistant to suggestions from the ME community, but I don't think she ignores us.
Anyway, it's just my own assessment, and I know that many won't agree, but I haven't seen any evidence of cynicism from Beth Unger.
Forgive me for butting in my 2 cents since over the years here at PR my comments have become extremely sporadic due to the Damn Disease (not that they would be worth more than the aforementioned 2 cents anyway ;-) ), but I cannot agree with Bob more. All CCC and ICC give us is a dim picture that some very good clinicians & researchers have been able to cobble together using a relatively tiny bit of money to do tiny studies that have not been adequately replicated for the purposes of helping other clinicians trying to provide some sort of support for patients with a disease that cannot yet be treated beyond palliative care. None of the diagnostic testing mentioned in CCC and ICC (or Fukuda, for that matter) has been clinically validated, i.e. they have been studied in thousands of patients and replicated so consistently that almost everybody agrees they will reliably diagnose (or assist in treatment of) this disease. There are simply all the authors of those criteria had/have at the present. But they do not have nearly enough data to be definitive because they have not had the funding nor the infrastructure to do the studies needed to produce enough data one way or the other (thanks NIH and CDC!). We simply do not know with anything close to certainty that CCC or ICC or Fukuda can definitely diagnose this/these illness(es).
However the CCC/ICC group do have years of clinical experience, which Dr Unger and the current CFS program at CDC appear to acknowledge and are trying to utilise with a far bigger cohort than any one of these clinician-researchers could muster on his or her own. Moreover each of these clinicians have their own approach to diagnosing this disease. By collecting data from their patients (who have already ostensibly been diagnosed using CCC/ICC since all the clinicians in this study were involved in creating those criteria) and comparing/contrasting this data, it will either show that CCC/ICC are good at distinguishing this disease from depression and other co-morbidities, or it will show that there are tests/symptoms that are more helpful than those listed in CCC/ICC. It may be that NK cell function testing or 2-day CPET only catches a subgroup and misses a huge swath of patients that has hitherto been missed because of the tiny cohorts used in testing thus far. It may be that vertigo or delayed gastric emptying or some other random symptoms end up being more definitive than NK cell function or CPET (I strongly doubt it but without a large enough data set, who knows?). But the data from this CDC study will be far more robust than anything CCC, ICC, or Fukuda can provide.
If we do not deal with the issue of heterogeneity, we will get no where (we HAVE gotten no where). Whether this is one disease with multiple presentations or multiple diseases with similar presentations, we must, must, must start subgrouping. It's what Fukuda called for nearly 20 years ago. It's what just about every one of the clinician-researchers we talk about (Peterson, Klimas, etc.) mention at every ME/CFS conference they speak at -- big or small. It has been THE problem impeding progress in figuring out biomarkers and establishing diagnostic criteria with which every researcher can agree and -- more importantly -- use for further research (as well as finally put a cork in the psychogenists!). And from what I've seen of Unger's CDC study, it appears to be finally -- FINALLY!! -- addressing this issue (30 years late but I'd prefer it now than in another 30 years).
I agree that there should absolutely be transparency in how CDC is carrying out the test and would think CFSAC should be seeing to that (note I say "should"; given the last meeting, god only knows what they're doing). While I'm cautiously hopeful about this big study, I haven't forgotten the last 30 years (half of which I've spent wasting away my 20s and 30s). That they have much to prove to us is an understatement. But, aside from some sort of an exercise and cognitive stressor, I'm rather agnostic on what tests CDC must use. I think they need to have the flexibility to go where what they find (i.e. data) tells them would be the best place to go so that we don't spend precious time and money chasing theories that look promising but just don't produce consistent findings.
Sorry. I'll return to radio silence. I get way too wordy when I comment (though it probably helps me get to sleep to write this down rather than spend hours talking to myself about what I would say if I was going to comment...yes, that IS sad...lol).
Michelle, I agree with nearly all of your post, but I wouldn't have quite used your wording with the following:
I think you make a half-valid point here, and I agree that without biomarkers and treatment, that the CCC and ICC are of limited value. But they are based on expert observation of patients, and I think these criteria have an important purpose. The CCC is now widely being used for research, and it's an extra way to subset patients, which might prove to be very helpful. I also think it's helpful to define a disease, or a subset of patients, in a more precise way than the more inclusive CFS criteria, based on careful clinical observation. It hopefully will give the illness and patients more credibility, over time, and it better informs clinicians about the nature of the disease.
But yes, proper empirical data, based on objective observations of large number of patients, has the potential to transform the field.
But I acknowledge that I have a very optimistic view of the future of CDC. And I make the assumption that the CFS division of the CDC is no longer corrupt. It might be the case that the CDC produces absolutely nothing useful. Their study is not yet ambitious enough, and they appear as if they are dragging their feet. They have to prove themselves.
You can also try a Google Site Search
Separate names with a comma.