Phoenix Rising - Cort Johnson's Column
...Presenting complex chronic fatigue syndrome (ME/CFS) research in a way we can all understand.
Tuesday, June 28th, 2010:
Dr. Nancy Klimas on Her New Clinic and More
by Cort Johnson
Dr. Klimas has been one of the central figures in CFS. A prominent AIDS researcher in the mid-1980′s she became acquainted with CFS when patients with another strange kind of immune dysfunction showed up on her door. In Oslers Web she recounts that she, like everyone else, tried not to believe in it (eg CFS) but (unlike others) she just couldnt push those strange immune abnormalities away. Other researchers brushed CFS patients off as depressed but Nancy Klimas had a background in psycho neuro- immunology and she knew that depression did not to that to the immune system.
Working together with Dr. Fletcher, Dr. Klimas helped to open up a new field of endeavor in CFS research as the two documented natural killer cell dysfunction, created new a test for it and linked it to other findings in ME/CFS. Indeed, over time, natural killer cell dysfunction has become the central immune finding in CFS. As she searched for natural killer cell problems Dr. Klimas ran one of the three federally funded CFS research centers in the US until the Centers programs were closed as the CFS program was moved from the the NIAID to the Office of Research on Womens Health.
CFS researcher is just one of the many hats she wears. Dr. Klimas is a past President of the IACFS/ME Association and is now a member of the federal advisory panel for CFS (CFSAC). A past AIDS researcher she gave most of it up up last year to concentrate on CFS she created some waves when she stated in the New York Times that her CFS patients were sicker than her AIDS patients, and if she had to chose, shed rather have AIDS than CFS! A frequent contributor to patient support groups in Miami, she also recently did a series of videos on CFS for the ME-CFSCommunity Center.
She has two offices, her new clinic and her longtime office in the Univ. of Miami as well as her work in the Veterans Administration on Gulf War Syndrome. Watching her work in the CFSAC meetings its obvious that Dr. Klimas has big goals for CFS, and her new clinic a doctors office/Research Facility packed into one is evident of that. With her plan to funnel her patients into research studies and use the facility to train doctors Dr. Klimas has created her own small Center of Excellence.
No easy answers- We know there are rarely easy answers for CFS patients even if they see an experts like Dr. Klimas. Occasionally some people get well, many improve and others may not. What experts like Dr. Klimas can offer is up to date knowledge of the disorder and the treatments used to treat it.
Dr. Klimas Interview (This interview was done earlier this year)
The New Clinic Why did you decide to do this? You already appear to be one of the busiest persons in the chronic fatigue syndrome world. You were the President of the IACFS/ME, youre on the CFSAC committee, youre a CFS and Gulf War Illness (GWI) researcher, you have your own medical practice, you until recently treated AIDS patients as well. Why not only a new clinic but possibly a nationwide series of clinics?
Well, I have done one of those step back and see where you can do the most good inventories, and decided to let go of much of my HIV work, to make room for the CFS/ME and GWI work.
Why the clinics? Try as I might I just couldnt expand the University clinics and consolidate/coordinate the multidisciplinary nature of the work enough to feel I was taking the very best care of my patients.
Dont get me wrong, at the University we have fabulous sleep, endocrine, autonomic and infectious disease experts, but I often have to deal with the insurance companys restrictions, scattered resources and my own understaffed clinic.
Thanks to a private donation to the University, we have added a doctor to my clinic (that makes two of us now!) and I am hoping to make headway through a tremendous backlog of people who need care, and my own patients who could really benefit from more frequent visits.
But even with the new doctor, Irma Rey, MD joining the faculty we can not take care of the number of patients that really need care. There are places in this country where the nearest expert is hundreds of miles away, so filling this national need seems urgent. And the model is very innovative a multidisciplinary assessment under one roof in a very cost effective fashion.
The other reason is the urgent need for clinical trials work in our field. There are far too few CFS/ME expert clinics, and the prospect of developing a model clinic using an electronic medical record system well suited for research needs as well as on site training for professional personnel was enticing. So thats what I am doing! If all goes well, I will use this clinic to develop some very cool clinical and research tools that can result in a very high quality assessment and treatment program. We can also use a series of very useful and objective tools to demystify the disability assessment, something that has already proved useful in our first month!
In your new clinic patients meet with a nurse practitioner trained by you in the ins and outs of CFS for the first hour. The nurse practitioner will order up a series of tests and then at the next visit a month later the patient will meet with you to go over their test results and plan out their protocol. This is different from other practices where the patient meets with the Doctor first. Why did you do it this way?
Well what is actually happening is 1-2 hour initial with the ARNP or the clinic MD, then another half hour with me and the provider, the followup visit including both of us again. The idea is to get through an extensive and thorough review on ever patient that is not time constrained in the usual fashion. If there are any diagnostics needed to complete the assessment they are sorted out quickly, and as soon as that all comes together then the visit to sort out a treatment plan. Sometimes this can be as short a a week the month is an estimate if there are labs that take a while or another clinic has to be involved (like a sleep lab assessment).
As the clinic has more time to become established there will be a fulltime MD or two, but we are just getting off the ground, and starting with part time hours.
Do you have a standard battery of tests that all patients will receive and if so what does it consist of?
No it varies by need, and also by what the patient has had done before they come here. But in general there is a very comprehensive medical assessment, some effort to assess autonomic function (at a minimum a BP/pulse log, but sometimes a tilt table study), an immune/infectious disease screen (this varies by exposures and prior blood work), endocrine screening, cognitive assessment (this is a computerized study that focuses on the areas most impacted in CFS/ME and really helps assess the degree of impairment and the variability over time). We also have the ability to assess VO2 max and some basic metabolic studies. If there is a disability assessment involved, we do this with day 1 and day 2 cognitive testing, a very powerful tool to measure objective impairment.
New Patient Initial Visit: What does the clinic charge for a visit?
The 2 hour assessment without any additional studies runs about $700. If we need the cognitive, the tilt, etc, then additional costs are added in. The fees are actually about 40% less than that charged at the University, and are attached to the appropriate codes in a superbill that is submitted by the patient to their insurance company for reimbursement.
Most insurances pay very near the cost of the assessment, less the usual copay. Because insurance policies vary greatly, in some cases the insurance would have paid more if we had charged more, but the clinic tried to keep it near the average of a PPO reimbursement.
By not having to see several different clinics each step of the way, the actual cost of the work up is far less overall than it would have been, if say, you saw the provider, was referred to cardiology, endocrinology, sleep, neuropsychology then back to the provider to put it all together.
You also dont have to convince any of those other doctors that the illness is real, and you have an evaluation that is tuned to the condition. For instance, in our version of the tilt, we do not use the medications that race the heart , we also take our time, and get a true reading of your bodys reaction to an upright posture 30 minutes after tilt. If you have a drop in blood pressure or speeding heart beat, because we are monitoring with sophisticated research equipment in addition to the standard monitors and are watching everything from heart beat to heart beat, we can put the table flat before you feel the extremes of the symptoms (dizzy, passing out etc). We can then administer saline and re-tilt, and see if manipulating the volume alone is good enough to reverse the problem.
You go home with both a diagnosis and a tested treatment plan much better than a best guess approach.
If I got this right lab tests plus the appointment will not bring the total to over $3300?
We are using an outside lab, and we are sending the blood and insurance information to the lab to collect separately. We list the lab costs because some patients come from out of country and their insurance can not be billed directly. For the most part we are using the very best immunology lab in the country (my bias) the EM Papper Lab at the University of Miami. The lab is an internationally acclaimed for it rigorous standards, and has done much of the work that put I in CFIDS.
When they do not offer a test, or if someones plan will only cover Quest or Labcorp, then we will send out there as well. The XMRV assays are only available at two sites right now, and the assay quality is likely to change quite a bit over the next few months. For the moment I am drawing an extra tube of blood and storing it for XMRV testing once the quality control issues have been worked out.
A Nationwide Series of Clinics? You envisioned a nationwide series of clinics. How would your clinics differ from other CFS clinics of this sort?
There are several clinics with similar approaches, though they are limited to a single place and provider. There are others that have radically different approaches. One tenet is that we arent selling products, just providing very good health care.
We are in a western and multidisciplinary model, using evidence based medicine from this field or related illnesses as much as is possible. The clinic providers are open to eastern and alternative approaches, but always always always will distinguish between care that has a level of scientific certainty behind it, and that which is less evidence based, whether western or eastern in origin.
What is most important is the frank and open partnership with the patient. Diagnostic and treatment plans are discussed, the relative merits and risks weighed,and decisions made together, clinician and patient. When there is a hole in our medical knowledge, the CFS Clinics are keen to correct the problem.
By setting up from the beginning with a medical record system that can double as a research record, we will be asking our patients permission to track everyone and develop a clean data set.
This kind of data can be used to track outcomes: which medicines worked best to help induce restorative sleep? Is there a lab result that predicts an increased risk of a particular outcome from gingivitis to cancer? And of course, with the patients permission we can use this sort of record to find out who is eligible for a drug trial, who should be called back in because of a dramatic change in therapeutic approach, etc.
I have heard a number of patients worrying that there are so few good doctors, and that we are getting older. The clinics are designed to train up the next generation of experts, and the next. If we get beyond this model stage, I would hope to bring well respected experts to review and improve on the model, serve as visiting or on line second opinions, and pool the years of knowledge.
But for now we are relying on my own expertise and experience, and I am doing my utmost to see that the care that is received is of the highest caliber.
Natural Killer Cell Dysfunction One thing I imagine youll be looking for, giving your long history of research in this area, is natural Killer cell dysfunction. Is there a natural killer cell subset in ME/CFS; ie a set of ME/CFS patients meet your criteria for natural killer cell dysfunction and a group that dont and, if so, do they differ clinically?
Well, yes the low NK cell function group are sicker, have more inflammation, more evidence of viral reactivation. But it is not a static thing, and remit/relapse patterns emerge, with NK cell function fluctuating. NK cells are important, but they also reflect cytotoxic T cell function and that may be even more important. The genomics work by our group and the work on mechanisms of cell dysfunction are very important. It is also interesting that XMRV virus may target these cells.
Having said that most CFS/ME patients have poor NK cell function, there is poor and poorer still. There may be other important immune subgroups, and cytokines may be the best way to define them. I tend to look at people through a what can I fix lens so I look for patterns that suggest treatment strategies.
AIDS and CFS. You reported that you got some grief for stating in the New York Times that your AIDS patients were a lot better off than your CFS patients. I was recently rereading Oslers Web and Hilary Johnson quoted you saying the same thing and that was over 10 years ago! As I remember researchers pretty quickly found evidence of massive immune dysfunction in the T-helper cells of AIDS patients but nothing in the immune system of ME/CFS patients has really turned the heads of the traditional medical establishment.
Yet the natural killer cell evidence is there. Is natural killer cell dysfunction in ME/CFS the T-helper cell dysfunction of AIDS and if so, why doesnt it get more attention? Or is it that CFS is just much, much more complex than AIDS ever was?
Well, you have to agree that having so many people die of AIDS was impossible to ignore, and that early on the diagnosis was considered a death sentence. In 2010 things are so much different, and my CFS/ME patients are much more ill day to day, and yes some of them die from CFS/ME related conditions. But the misery quotient in CFS/ME is terribly high day in and day out.
I think the XMRV work is already attracting interest from some fabulous new scientists to our field. But do not ignore another group of amazing scientists systems biologists. They take our complex data describing immune, endocrine autonomic, sleep, add in the genomics and do computational magic that should lead to new therapies and approaches. I would suggest you interview Gordon Broderick sometime, you would enjoy the process.
Immune System In past talks and interviews youve talked about how difficult it is to give a blank prescription for ME/CFS patients regarding their immune functioning; patients can exhibit immune activation and/or immune inhibition in different areas of the immune system and care really has to be taken when prescribing immune regulating drugs. Are you able to identify different immune subsets and treat them accordingly?
Yes, I think so. But to change the standard of care we need clinical trials that test this experience in proper placebo control studies. So we need research minded clinics, and thousands of patients and potential research subjects in data bases
This kind of sophisticated fine tuning selects out, say the patients with very high levels of TNF or TNF inhibitors, or patients clearly replicating EBV or HHV6 for antivirals. Some of this work can be done as case series, like Dr. Lerners work with valgangcyclovir(valcyte). But eventually we have to be able to go to the pharmaceutical companies, with enough willing patients in hand, to propose cost effective phase 2 and 3 studies that result in labels on drugs.
Beyond the obvious gains to patients when providers have proven treatment strategies, affordable treatments also matter. The wide practice of prescribing off label is more and more being shut down by insurance reimbursement policies, and many of the proposed therapies have very steep costs.
Pathogens - Pathogens are a huge topic of interest for chronic fatigue syndrome patients, many of whom got sick following an infectious event. I hear all sorts of different findings regarding pathogens. XMRV aside can you give us a general percentage of patients test positive for EBV or HHV6 or Borrelia or other pathogens in your practice?
Well I am estimating a bit I havent analyzed the data in a while, but using Montoyas cut points for reactivation, about 60% of my population would have met entry criteria for the valcyte study. Lyme is less so, partly because South Florida has far few cases than the NE, though upstate Florida is catching up. Still I see a cases, and screen for Lyme in all of my patients if they have not already been tested,
Some doctors do long term antiviral therapy and others dont. Will long term antiviral therapy a year or so in length be a part of your clinic?
Thats a case by case decision. Dr Lerner was kind enough to publish his experience with a large series of patients, and that was very helpful. Dr. Montoyas studies have also lent credence to the use of antivirals in the right cases. But the drug is expensive, potentially toxic and clearly did not help patients with borderline or low antibody titers. So each case needs to review risk/benefit , other options, whether it will be covered on insurance etc.
XMRV Are you testing your patients for XMRV now or waiting for a validated, standardized test? If you are getting test results back can you give us insight as to what percentage are testing positive for PCR or the culture test? Do you see any patterns emerging? (this question was asked several months ago)
I am for the most part waiting for better tests. We are likely going to set one up in the University lab but it involves quite a bit of quality control work before it would be a good study. I asked the lab director from Clinical Diagnostics, and they have about a 10% rate of positive, though they may have set their cut point for positive a bit high. VIP Dx, affiliated with WPI is testing the negative samples with further studies involving culturing and activating viral expression. I dont know what their rate of positives in CFS in the commercial samples might be.
Were still up in the air to some extent about XMRV. Questions have lingered in the patient community for almost 20 years whether Dr. DeFreitas retrovirus in the early 1990s was really disproven. Do you think that,given all the attention to XMRV, that over the next couple of years as research proceeds that, however it turns out, well at least have a clear answer regarding this virus; ie parts of the patient community will be wondering if XMRV was given a fair shake?
Crystal ball time. I dont think Dr DeFreitas was given a fair deal back in the 90s. All of that early work was done with fairly small sample sizes, and with techniques that have improved tremendously. But the pictures of budding retrovirus from both her work and Mike Holmes in New Zealand are images that are hard to explain away.
XMRV will be a hot bed of controversy for a while, as there may be big regional differences, sampling differences, and assay differences. One very exciting technology just around the bend is whole genome assays. In these studies you sequence all of the DNA in the cell -be it viral or human, then get the data banks to try to read the code .you dont have to know the name of the virus you are searching for. Its new enough that we dont know all of that code quite yet, but it is a very rapidly growing field. We are planning a study like that right now for the Gulf War Syndrome patients, and I hope to submit another to the NIH for CFS in the spring.
Behavioral Therapies Youve worked with Dr. Antoni on cognitive behavioral-like therapies (which he calls stress management) and youve noted that they can make a difference in some patients. In the Reno conference Dr. Antoni stated he was trying to reregulate the HPA axis and thereby improve immune functioning. Will CBT-stress management be part of the treatment regimen for some patients?
I know that CBT is a dirty word to some folks, based on sweeping health care policies that deny other options. But when used together with a medical approach it can be very helpful indeed. Pacing is one of the key tenets in CBT, energy banking another phrase for the same thing.
Definitely discussions on pacing, small group CBT and one on one CBT will be offered to patients who are interested. We are lucky enough to have psychologists with lots of CFS experience affiliated with the clinic, and with Dr. Antonis recent success using a telephone based group therapy for more house bound patients, we will offer phone or videoconferencing based treatment as well.
From the Reno Conference on Dr. Antoni:
Dr. Antoni noted that CBT has proven effective in improving immune functioning in HIV-AIDS and other diseases. His goal was to use stress management techniques (he called his therapy cognitive behavior stress management (CBSM)) to reregulate the stress response (HPA axis) and thereby improve immune functioning. He used two techniques cognitive behavioral therapy to improve coping skills, cognitive appraisals, etc., and relaxation therapies such as progressive muscle relaxation, breathing exercises, mindfulness meditation and visualization to reduce stress.
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