THE CROI INSIDER

An HIV clinician who attended last week’s CROI (Conference on Retroviruses and Opportunistic Infections) in Boston told CFS Central that it was pretty much a bust all around, but that would be par for the course with CROI, which is “notoriously good at keeping out those they don’t want in.”  As far as the XMRV presentations, the physician said it was glaringly obvious to him and to others that the opposing side—those who have found the retrovirus XMRV in ME/CFS patients and in prostate cancer patients—wasn’t being heard. 

His impressions of the discussions in the hallways were that the HIV researchers thought XMRV was a joke, but that many clinicians were taking XMRV seriously.  It reminded him of the early days of HIV when the doctors who were treating these sick patients knew something was seriously wrong with them, while the official word from government was much ado about nothing. “The feeling that I got,” he said, “was the same underlying sense of information being tightly controlled.”

THE DEVIL MADE ME DO IT

Below is my response to CFIDS Association board member Jennifer Spotila's comments from yesterday.  Spotila was responding to my "Bad Company" blog post, particularly to my commentary on CAA President Kim McCleary's statement to CNN about the PACE trial.  McCleary told CNN:  “I think it would be challenging, at least in the U.S. system, to purchase the services that they've tested in this trial,” adding this:  The alphabet soup of acronyms that represent the interventions used in Britain is “just not something that our health care service offers, is reimbursable, or is really available here.” And, finally, this: “It's kind of a shame that we're still limited to talking about approaches to coping mechanisms as the only therapy that's available.” 

Spotila's comments are below mine.

Jennifer Spotila,

If McCleary hadn't made those comments to CNN, CNN wouldn’t have included those comments. No one held a gun to McCleary’s head or laid a cattle prod to her feet and forced her to utter those problematic remarks. She did that all on her own. Granted, it’s difficult to articulate a string of perfect quotes, but McCleary’s endorsement of cognitive behavioral therapy (CBT) and graded exercise therapy (GET) was inexcusable in my view and the view of many patients. After all these years, there is no excuse for defending these ineffective therapies.

Defending McCleary’s statements, you wrote: “Both reporters had also been prepped by the authors of the PACE trial to expect and dispute the objections raised by McCleary and other advocates to the study.”  Prepped?  Says who?  Jennifer, each side makes his or her case.  You’re an attorney.  Think of it like the defense and the prosecution in a murder trial. That’s how it works.  McCleary’s job was to make her points, not to endorse those of the opposing side.

Kim McClearly could have told CNN something like this:  “The PACE trial is problematic, and here are some reasons why. The selection process eliminated most bona fide CFS patients.  Instead, the PACE patients had idiopathic fatigue and depression. Cognitive behavioral therapy and graded exercise therapy are primarily helpful for those with idiopathic fatigue and depression, not those with Chronic Fatigue Syndrome. In fact, the hallmark of CFS is post-exertional crashing, so graded exercise therapy would make the symptoms of most CFS patients worse.

“Many patients with CFS are severely ill and suffer from seizures; swollen lymph nodes; fevers; autonomic dysfunction that makes it difficult or impossible to sit or stand; heart failure; immune dysfunction, including reactivation of herpes viruses; and rare cancers. Some patients are dying, others are consigned to a living death, and compelling evidence points to a newly discovered retroviral infection in these patients that’s similar to the one that causes HIV. 

"Despite its trivial name, this is not a trivial disease.  To suggest that patients can power through CFS through GET or CBT would be as incorrect as suggesting that those with Parkinson’s disease or multiple sclerosis or AIDS can be restored to health simply with exercise and a positive attitude.”

Jennifer Spotila, even if I had been on hallucinogens, I couldn’t have said something as unhelpful as what McCleary told CNN.

On another note, you wrote, “The Association did make changes to its website and operations in response to feedback we received through Khaly's postings and other venues.”  Khaly Castle posted a reply to you that said in her view there were no significant changes (see her response, below). Jennifer, I would appreciate if you would tell the readers of CFS Central what those changes were, and let the patients weigh in on their significance.

The CAA survey on the patient forum Phoenix Rising gives patients the choice of voting that the CAA is doing great, or needs some minor changes, or needs changes in direction, or needs changes in both direction and leadership.  So far, 143 out of 153 patients—that’s 93 percent—have voted for changes in direction and leadership.  I would argue that the CAA is doing poorly on the Phoenix Rising survey because it’s not representing what the patients want and need. 

Patients deserve better representation.  Patients deserve a CAA that strongly opposes the money spent on CBT and GET studies/treatment for ME/CFS. Patients deserve bona fide biomedical research, not this appalling, make-believe, psychoneurotic PACE study.  Patients, in my view, deserve an advocacy organization that actually advocates for them.

You wrote: “I strongly encourage you to balance your reporting on the advocate point of view by interviewing a diverse sample of us.”  Jennifer, I strongly encourage you to hear what the patients are saying and to stop defending the indefensible:  McCleary’s statements to CNN are inexcusable.

Jennifer Spotila's remarks:

Mindy, If you had contacted me, I would have been happy to answer any questions you have about the Association or the incidents you cite here. I did respond to Khaly Castle in 2009. The Association did make changes to its website and operations in response to feedback we received through Khaly's postings and other venues. 

Kim McCleary gave a very lengthy interview on PACE to CNN, and another to NPR. Both reporters chose to use only one quote from those interviews. Both reporters had also been prepped by the authors of the PACE trial to expect and dispute the objections raised by McCleary and other advocates to the study. Their questions to McCleary and the pieces they produced reflect this. 

I strongly encourage you to balance your reporting on the advocate point of view by interviewing a diverse sample of us. Reasonable minds can and do differ on many aspects of CFS advocacy. I continue to believe that dialogue serves us better than monologue.   

Khaly Castle's response to Jennifer Spotila:

Jennifer, to say that the CAA responded would be accurate. To say that the CAA responded in a meaningful way would be inaccurate. In 2009, a thread was started on Phoenix Rising. The discussion over there continues to this day, about basically the same issues.

After we tried to have a meaningful dialogue, CAA was asked to help us fight the DSM5 issues. The response was meager and meaningless, basically boiling down to the suggestion that we should go ask the IACFS/ME as CAA did not feel informed enough to take a stance. I notice the same conversation evolving regarding ICD codes right now.

Mindy already cited and linked to two of my articles voicing some of the concerns we had in 2009. We are still facing the same concerns...lack of adequate response to ill-defined cohorts in X-negative studies, inability to take a stand that CFS is NOT what the CDC likes to describe, inability to advocate for the sickest of us, inability to verbalize a distinction between this illness and the grab bag of fatiguing illnesses....on and on.

For more on some of these issues, see: http://www.cfsuntied.com/archivedblog4.html#caaxmrv

You will notice that not much has changed.

A few months ago, after the "Inside Voices" article was presented to us, I asked the CAA on Facebook if the CAA still considered itself an advocacy organization, or if it had decided to become a science and research organization. You answered, that they were indeed an advocacy organization, but that there were many ways to advocate. The conversation and surrounding events are documented here: http://cfsuntied.com/blog2/2010/10/07/be-vewy-vewy-quiet-im-hunting-wabbits/

This can no longer be about promotion of promotion. It has to be promotion of what will save us. Many of us are facing not only the end of our ropes, but the end of our time. The clock is ticking. 

FLIP WILSON on ED SULLIVAN: THE DEVIL MADE ME DO IT

BAD COMPANY

Why Some Patients Have Had Enough 
of the CAA

When it comes to the CFIDS Association of America, patients Khaly Castle, Otis Quila and Liz Willow have reached critical mass.  They’ve just devised a “Petition to disassociate from CFIDS Association of America as our advocacy representative” because they believe that the CAA isn’t doing its job.  In one day, 205 patients have signed the petition, with a goal of one thousand signatures from all over the world.

Castle, Quila and Willow will present the petition at the May 2011 Chronic Fatigue Syndrome Advisory Committee meeting and also let the NIH and the CDC know that the CFIDS Association no longer speaks for the majority of patients. Explains Liz Willow, “[NIH administrator] Dennis Mangan realizes the patient community is diverse and reaches out to a number of individual advocates, Facebook page founders and bloggers on a regular basis.  But the CAA still seems to be perceived by many government officials as representative of patient wishes.  We didn't feel we could wait for a new organization to establish itself before rolling out the petition.  Patient sentiment for this type of petition is high, and we wanted to capture that momentum.”

Brewing dissatisfaction
The dissatisfaction with the CAA has been brewing for a long time but deepened after the first paper linking XMRV to ME/CFS was published in October of 2009.  Khaly Castle observed that the CAA maintained “an air of skepticism when they could have instead taken this new piece of science and turned it into a platform for some pretty powerful advocacy. In my mind,” Castle contends, “it just confirmed that this group is nothing but an arm of the entity it had contracted itself to for so long:  the CDC.”

Brian Smith and Jennifer Spotila 
A blogger as well as a patient, Castle in 2009 wrote two articles on the CAA that garnered huge response from patients.  (To read the articles, click here and here.)  After Castle posted them, CAA board member Brian Smith told her on Facebook that the CAA was listening.  “Then I never heard from him again, despite friend-requesting him,” Castle recalls.  However, Jennifer Spotila, who at the time was board president, contacted Castle directly, asking her to forward whatever patients wanted to tell the CAA. 

That’s when Castle started a new post, “CFIDS Association— What do you want to say to them?”  Gathering the hundreds of patient comments and questions that resulted, she forwarded them to Spotila.  But in the end, says Castle, “We got very little feedback and little or no visible change from the CAA.”

McCleary's response to the PACE trial
Most recently, it’s been CAA President Kim Kenney McClearly’s reaction to the PACE trials that Castle, Quila and Willow have found problematic. Of the PACE trial, which endorsed cognitive behavioral therapy and exercise for CFS, McClearly rattled off to CNN a peculiar commentary that appeared to endorse the bogus findings: “I think it would be challenging, at least in the U.S. system, to purchase the services that they've tested in this trial,” McClearly stated, adding this:  The alphabet soup of acronyms that represent the interventions used in Britain is “just not something that our health care service offers, is reimbursable, or is really available here.” And, finally, this lackluster shrug: “It's kind of a shame that we're still limited to talking about approaches to coping mechanisms as the only therapy that's available.”

Castle says that with McCleary’s response to the PACE trial, it’s clear that the CAA’s advocating for a chronic fatigue light kind of illness that’s primarily about generalized fatigue—as opposed to the serious neuroimmune disease that ME/CFS really is.  The result is “muddying the diagnostic waters,” Castle says.  “This is not only unhelpful, it's extremely harmful.”

Suzanne Vernon and spinal fluid
McCleary isn’t the only CAA representative who’s been a problem.  Last week Dr. Steven Schutzer’s team at the University of Medicine and Dentistry of New Jersey published on a distinct abnormal protein signature in the spinal fluid of ME/CFS patients, which apparently was a yawn to CAA Scientific Director Suzanne Vernon, who told the Wall Street Journal’s Amy Dockser Marcus: “It’s difficult to have a diagnostic test based on spinal fluid. You can’t just go poking everyone in the spine.” 

Vote to be heard
On the Phoenix Rising patient forum, so far 147 patients have participated in a new CAA poll, with 138 voting that it’s time for a change in direction and leadership. Cast your vote on Phoenix Rising and be heard.  If you believe the CAA doesn’t speak for you, cast your vote on the “Petition to disassociate from CFIDS Association of America as our advocacy representative.”

Training Day

Dog day afternoon at the NIH as Dr. Fred Gill, who hails from the psychoneurotic school of CFS, questions whether CFS is even a disease.  He’s pitted against Dr. Harvey Alter and Dr. Shyh-Ching Lo, who believe in science.

By Charlotte von Salis

Curious to find out the National Institute of Health’s take on CFS these days, I attended the agency’s in-house lecture "Chronic Fatigue Syndrome:  Is there a virus?" on February 22.  One in a series in the NIH’s Demystifying Medicine presentations, the lecturers were the NIH’s Harvey Alter and the FDA’s Dr. Shyh-Ching Lo, co-authors of the 2010 paper "Detection of MLV-related virus gene sequences in blood of patients with Chronic Fatigue Syndrome and healthy controls.”   

The third speaker was Dr. Fred Gill, a medical doctor and chief of the Internal Medicine Consultation Service at the NIH.  He’s the self-proclaimed protégé of NIH psychobabbler extraordinaire, the late Dr. Stephen Straus.  In addition, Seabiscuit author Laura Hillenbrand is a former patient of Gill’s.

So there I was, the sole member of the public, along with about fifty other NIH attendees.  The good news:  Lo and Alter were terrific.  Lo, in particular, went to great lengths to explain how they carefully ruled out contamination in their study. 

Gill: worse than expected

The bad news:  Gill was even worse than I expected, touting graded exercise therapy as the best treatment for CFS.  That wasn’t terribly surprising, as Gill worked with Stephen Straus and treated Straus's patients. Gill remarked that when he was in private practice, he asked his patients to exercise, and they improved. He noted that many patient advocates feel that exercise exacerbates their symptoms, but he believes exercise is the right treatment for CFS.

Gill gave kudos to the just-released PACE study. "For those of us who've been preaching this [graded exercise therapy],” he said, “it's nice to show this study." Gill was particularly pleased that the same fatigue questionnaires used by the CDC were also used in the PACE study.

Gill’s a big fan of the Centers for Disease Control’s Empirical case definition, AKA the Reeves definition. He loves the—gasp—"excellent" questionnaires that the Reeves definition used, as well as the CDC's 2006 gene study.

The clinician's approach, he said, should mirror the CDC's toolkit recommendations.  Gill’s big on reassuring the patient, avoiding unnecessary tests, avoiding debate over whether it’s psychological, and above all, getting patients to remain active and exercise no matter what.

And the topper?  Gill’s condescending presentation of a CFS patient whom he called Velma (a pseudonym).  A middle-aged former pharmacist, Velma had a sudden CFS onset in 2006.  She reported the classic CFS symptom of suddenly needing to sit down and then lie down.  The next day Velma said she could barely get out of bed to go to the bathroom. Like many patients, she saw several doctors before getting a diagnosis, including physicians at the Mayo Clinic.  (Given the center’s piss-poor track record with CFS, it’s not surprising that they couldn’t find anything wrong.)

Velma admitted to secondary depression.  “It’s depressing when you’re debilitated, but I’m not a depressed person,” she summed up to the audience.  While she’s better than she was five years ago, she still has crashes. She’s not concerned whether CFS is caused by a virus; she just wants to get well.

Velma explained that she takes fludrocortisone— a steroid that treats low blood pressure and neurally mediated hypotension, common autonomic nervous system problems in CFS.  However, the patronizing Gill deemed this drug “useless” for CFS patients—despite that Velma said the drug helps her. 

Velma reported feeling feverish and having swollen lymph glands, but Gill said he found no discernible fever or lymphadenopathy.

Pushing herself to exercise

Velma isn’t the typical CFS patient, as post-exertional crashing isn’t a big issue for her.  She claimed, for instance, that she feels “much better” after she pushes herself to exercise on her “bad days.”  That made Gill smile.

Gill, who looks to be well into his 60s, went through a series of ancient slides from the 1980s. Oh joy—he started by pointing out that CFS was first recognized as neurasthenia by Beard in 1869, and it went downhill from there.  He went through the different names for CFS and selected case definitions (ignoring the Canadian).

Just in case anyone in the audience still thought there might be a real disease buried under the CFS construct, Gill ran through all the studies done by Straus that rebutted any positive treatment trials. Resurrecting his BFF Straus once again, he gave a big thumb’s up to studies done on stress and CFS. As to "pacing,” Gill oddly claimed that “he didn't fully understand pacing.”

Gill concluded his presentation by recommending the CDC's CFS website as well as that of the CFIDS Association of America (CAA). Gill said that he has a high regard for the CAA because he agrees with their views.  So now it’s abundantly clear the kind of scientists whose thinking dovetails with the CAA’s. 

I quickly and loudly called out that for real information, as opposed to misinformation, attendees should check out mcwpa.org and iacfsme.org. I actually got the attention of those present, many of whom copied down the URLs.

Alter’s talk

Alter explained that XMRV and related murine leukemia viruses (MLVs) aren’t yet accepted as human invaders or pathogens by most of the scientific community. (Sad, but true.)  Alter also noted that scientists are still debating whether CFS is physiological or psychological. (Sad, but true.)  He went through his slides, which unfortunately have been taken down from the course material website.  My favorite was the last slide, which indicated that clinical trials with antiretroviral drugs could potentially prove whether XMRV causes CFS.

Alter said that XMRV is a simple retrovirus (compared to the more complex HIV) that could be passed on to progeny.  He didn’t specify whether this infection occurred in utero, during breastfeeding or both.

Infection with XMRV, Alter said, can lead to viremia, which affects the immune and neurological systems.  Alter explained that it made sense to look for XMRV in CFS because many patients have an acute onset that leads to a chronic illness, cluster outbreaks had been reported, concomitant herpes infections are common, and defects in the antiviral RNASE-L pathway have been found. He briefly addressed the XMRV and MLV studies to date, including the negative ones. To my relief, everything he said indicated that he continues to believe CFS is a serious, physiological disease.

Lo’s talk

Lo, too, followed his slide presentation.  I'm kicking myself for not downloading the slides—I was surprised to find them gone from the course material website.  Lo reviewed the methodology and findings in the joint FDA/NIH study in extreme detail (to this non-scientist).

His research team, Lo explained, developed a "highly sensitive assay targeting mitochondria DNA, mouse DNA, that are well-conserved in multiple copies" and used that assay to re-test the positive samples before publishing the study. Lo then brilliantly rebutted the contamination articles.  As to the negative studies, he pointed out that differences in methodology, assays, and sample preparation were among the contributing factors that could explain the disparate results.  He noted that two CDC samples tested positive for MLVs using the FDA assay.

Questions and answers

In the Q & A session that followed the talks, Gill was hopelessly out of touch, invoking the Simon Wessely school of misinformation about CFS, circa 1988, by insisting that the disease is "not common" in children.

During the Q & A, I said that the Canadian Consensus Criteria (CCC) should be used to select patient cohorts and that audience members should read it as well as Dr. Lenny Jason's "Development of a Revised Canadian Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Case Definition.”

I was cut off as I was making a statement rather than asking a question.  So I don't know if what I said will make it to the edited videotape.

I did ask Gill a detailed question (mainly for the audience's benefit) about the Pacific Fatigue Lab's findings with repeat exercise testing, as well as the Lights’ exercise studies in CFS patients.  Both groups of researchers found objective, measurable and significantly abnormal biomarkers that distinguished the sick from the healthy controls after exercise.  Their findings allowed me to bring up post-exertional malaise as the hallmark of CCC-defined patients.

Gill replied that he disagreed with those studies but didn’t explain why.

In the Q & A, I told Gill that I was on the drug Midodrine for neurally mediated hypotension, and that was the only reason I was functional enough to attend the lecture.

Gill’s response was that studies have shown that there’s no orthostatic intolerance in CFS.  Earth to Gill:  Have you not read any of the formidable research by cardiologist Hugh Caulkins’ and pediatrician Peter Rowe’s group at Johns Hopkins?

Harvey Alter spoke again, pointing out that CFS has a viral-like “picture.” 

Gill asked Alter, “Is CFS a real disease—and if so, what’s its etiology?”  

Alter replied cryptically, as if he were the wisest of fortune cookies:  “The answer depends on the effort to find the cause.”

--------------

Charlotte von Salis, an attorney, has lived with ME/CFS for 20 years.