Lonya and Jeremy take the TWiV team beTWIXt primate immunodeficiency virus proteins Vpx and Vpr and how they counteract transcriptional repression of proviruses by the HUSH complex.
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Show notes at microbe.tv/twiv
Lonya and Jeremy take the TWiV team beTWIXt primate immunodeficiency virus proteins Vpx and Vpr and how they counteract transcriptional repression of proviruses by the HUSH complex.
Become a patron of TWiV!
Show notes at microbe.tv/twiv
Yesterday I sent an email to Dr. Landa who had previously written to David Tuller about the 4th Columbia Psychosomatics Conference (link to David’s post). Like David, I was unhappy about Dr. Landa’s note so I decided to write her and see if she might respond better to a Columbia colleague. Apparently my faith in collegiality is misplaced – as of this writing I have not had a response. My email to Dr. Landa is reproduced below.
18 October 2018
Dear Dr. Landa:
I am writing to lend support to the protests surrounding Per Fink’s participating in this weekend’s Psychosomatic Conference, and to protest your email to my colleague, David Tuller.
Dr. Tuller is a Berkeley faculty and journalist who has been writing about ME/CFS on my blog, virology.ws. He has worked to expose bad research in the field, including the PACE trial. I fully support his work. Another Columbia faculty, Bruce Levin, has co-signed letters on these faulty studies on the blog. For you to write off David’s recent post is not acceptable. He has valid concerns should be addressed. Perhaps you are too busy to do so, but it’s not a good reason.
I want to join the voices who are complaining about having Fink participate in the conference. This is simply unacceptable. Having him speak at a Columbia conference is tantamount to validating his views – that is exactly how the outside world will perceive this. It’s why there will be a protest Saturday morning.
You wrote to Dr. Tuller that ME/CFS is not the focus of the conference. It doesn’t matter: even if there is just one mention of the disease in one talk, it will be a focus because there are so many patients and others who follow work in the field and will take note. And that comment ignores the real problem of Fink, who has had a hand in ME/CFS.
I’m sure you are aware of Fink’s poor record in dealing with persistent medical conditions. As just one example, I quote Dr. Tuller: “You have decided to invite to your gathering a man involved in what can only be called the kidnapping and torture of a vulnerable young Danish woman diagnosed with the illness you have just indicated is a serious organic disease. This kidnapping and torture, conducted with the full authority of the state, was considered justified based on the sorts of claims about functional somatic disorders being presented at Columbia this weekend.”
Given this record, it is quite clear that Fink should not be speaking at Columbia. It is your meeting and you can invite who you wish, but we also have the right to protest his presence.
Dr. Tuller has a very large following and merits a better response to his concerns and those of the ME/CFS community. Perhaps Columbia PR has advised you to send Dr. Tuller a form letter. As a Columbia colleague, I’m asking you to respond to his concerns, and those of the ME/CFS community. Thank you.
Vincent Racaniello, Ph.D.
Higgins ProfessorDepartment of Microbiology & Immunology
Columbia University, New York
virology.ws | microbe.tv
“Tanto sa ciascuno quanto opera”
By David Tuller, DrPH
In my earlier post about this issue, I accurately credited #MEAction but did not specifically make clear that Saturday’s demonstration has been organized by the movement’s New York arm. I apologize for the oversight.
So here’s an official New York #MEAction announcement about the event. I would be there tomorrow if I weren’t still in London trying to make my own noise.
ACTIVISTS PROTEST SPEAKER AT COLUMBIA UNIVERSITY CONFERENCE
Human Rights Abuser Per Fink is Not Welcome in New York
FOR IMMEDIATE RELEASE
October 18, 2018–New York, NY
Activists with NY #MEAction will converge on Columbia University Saturday, October 20that 8:00 a.m. to protest Danish Physician Per Fink’s appearance at the 4thColumbia Psychosomatics Conference and demand that he stop harming children and adults with Myalgic Encephalomyelitis (ME). ME is a serious complex neuro-immune disease which affects over one million Americans and approximately sixty thousand in New York. People with the disease suffer from severe and profound exhaustion, neurological, metabolic and immune system dysfunction. Most are left completely disabled and many are completely bedridden. Due to the lack of understanding of this disease, many are prescribed dangerous therapies like graded exercise therapy (GET) and cognitive behavioral therapy (CBT) with harmful results.
Per Fink is speaking at the Columbia University conference and believes that the neuroimmune disease ME is a psychosomatic illness. He teaches that physical ME symptoms are simply psychiatric manifestations, and claims that he can cure 25 percent of patients with CBT and GET. His treatment plan attempts to isolate patients from other doctors or specialists who might actually take the person’s symptoms seriously. Per Fink’s method has destroyed families in Denmark. His approach has led to children being removed from their homes and institutionalized. When a severely-ill ME patient, Karina Hansen, refused Fink’s treatment, he had the government forcibly remove her from her family. He treated her against her will for 3.5 years. Finally, she returned home in a much worsened state. So far, 55 patient complaints about his practices have been sent to the Board of Patient Safety in Denmark.
“Human Rights violations are happening right now by Per Fink. His unscientific approach to healthcare has been responsible for children and adults being harmed. All you have to do is google the name Karina Hansen to read what he is capable of,” said Terri Wilder, a New York ME activist. “We are sending a clear message that Per Fink is not welcome in New York.”
New York State has recognized ME as a biological disease on their Department of Health website. The Department of Health also lists CBT and GET as inappropriate treatments based on the myriad of objective scientific evidence proving these treatments are harmful and ineffective. In 2017, Health Commissioner Dr. Howard Zucker sent a letter to over eighty-five thousand physicians in New York urging them to take their patient’s complaints seriously and to make ME a part of their differential diagnosis when evaluating patients with these symptoms.
“Per Fink perpetuates the debunked and demoralizing falsehood that ME is psychosomatic rather than a serious biological disease. This has ramifications, including inappropriate treatments and inadequate funding for research. I’m proud to stand with those who suffer from ME, and the advocates and doctors who work on their behalf against this cruel and dangerous practitioner,” stated New York State Senator Brad Hoylman.
The protest is organized by New York #MEAction. New York #MEAction is a network of people with and affected by ME fighting for health equality. www.meaction.net.
Press Contact: Terri Wilder firstname.lastname@example.org 404-502-4710
By David Tuller, DrPH
*The headline has been changed to indicate that Cochrane has decided to withdraw the review but had not yet done so at time of posting.
Cochrane has decided to withdraw, at least for now, its fatally flawed review of exercise treatments for ME/CFS—or CFS, as the review calls the illness. This review, which reported that graded exercise therapy was an effective treatment, was first published in 2014 and republished last year. The more recent version included extensive exchanges between two very smart patient-advocates—Tom Kindlon and the late Robert Courtney—and Lillebeth Larun, the lead author. The Kindlon and Courtney arguments were cogent, persuasive and unassailable. Larun’s responses were not.
Powerful forces in the UK academic and medical establishment have pushed back hard against those calling for change in Cochrane’s approach to ME/CFS. At the same time, many patients have understandably expressed serious concerns about the methodological lapses that mar the exercise review. Moreover, clinicians, scientists and academics engaged with the issue, including me, have also made their strong opinions known to Cochrane as well to as other organizations with decision-making authority.
Just last month, I wrote a lengthy and widely read post titled “The Cochrane Controversy.” I have reposted it below in full.
Cochrane–formerly called the Cochrane Collaboration–is respected worldwide for its systematic reviews of medical treatments. These reviews are often cited as the definitive source of information about treatment efficacy and safety. In taking on the thankless task of assessing the data on commonly used interventions, Cochrane performs an invaluable public health service and has advanced the cause of evidence-based decision-making in medicine.
But like any organization, Cochrane can get things wrong—as it has in the case of chronic fatigue syndrome. (Cochrane generally uses the term CFS, so I will also when referring to these systematic reviews.) Cochrane’s review of cognitive behavior therapy for CFS was published in 2008, pre-PACE. The most recent review of exercise therapies for CFS, which mainly included studies of graded exercise, was published in 2014. These systematic reviews and previous versions, all of which reported benefits from the treatments, were conducted by Cochrane’s Common Mental Disorders group.
Last month, The Times and The BMJ covered the growing international concerns about the PACE trial. Both publications ran articles about Virology Blog’s most recent open letter to The Lancet, which cited PACE’s “unacceptable” flaws and called for a fully independent reanalysis of the trial data. The letter was signed by 114 experts, ten members of Parliament, and 70 patient and advocacy organizations. To counter this sort of public criticism and support their unwarranted claims, the CBT/GET ideological brigades and their enablers regularly cite Cochrane’s systematic reviews.
Most recently, Professor Fiona Watt, executive chairwoman of the UK Medical Research Council, released a statement in response to The Times’ coverage of the Lancet open letter. The MRC, the main funder of PACE, has previously defended the conduct of the study. In her letter, Professor Watt reaffirmed this support without providing any response to the specific concerns raised about PACE—such as the paradox that 13 % of the participants were already “recovered” on the key outcome measure of physical function at baseline, before any treatment at all.
Professor Watt’s defense of PACE rested heavily on the fact that other researchers have similarly reported benefits from CBT and GET. She noted pointedly: “This evidence is summarised in three Cochrane reviews. Cochrane reviews are systematic reviews of primary research in human healthcare and health policy, and are internationally recognised as the gold standard in evidence-based healthcare.” [It is not clear which is the third Cochrane review being referenced here.]
It takes nothing away from Cochrane’s reputation to note that systematic reviews are only useful if the studies they include provide valid and reliable data. If the studies themselves are fundamentally flawed, and if the purported experts conducting and writing the reviews refuse to acknowledge or cannot understand these shortcomings, then any synthesis or summation will generate similarly problematic conclusions. This is what appears to have happened with the systematic reviews for CFS treatments conducted by the Common Mental Disorders group.
Let’s dispense with one issue right away: This illness should not be housed in the Common Mental Disorders group. Whatever the historical reasons for this arrangement, it undoubtedly must lead observers to assume that Cochrane as an organization endorses the framing of CFS as a psychiatric illness. Patients object to the situation not because they are prejudiced against psychiatry and people with mental disorders–as the PACE authors and others have claimed—but because their illness is not a mental disorder and because the Common Mental Disorders group has already demonstrated its inability to assess the research accurately.
(Cochrane editor-in-chief David Tovey and psychologist James Coyne have previously engaged in a public debate over issues related to conflicts-of-interest of Cochrane reviewers in this domain. I am not addressing those issues in this post.)
The Common Mental Disorders group’s most recent version of the exercise systematic review drew skeptical scrutiny from very smart advocates soon after its 2014 publication. Patient-researchers Tom Kindlon and the late Robert Courtney, in particular, submitted cogent and comprehensive comments that exposed the systematic review’s serious flaws and refuted its unfounded claims. When Cochrane republished the review last year, it included the exchanges between the correspondents and Lillebeth Larun, the lead author.
Larun, a researcher and associate professor in the department of assessment interventions at the Norwegian Institute of Public Health, provided inadequate defenses to the concerns raised by Kindlon and Courtney. I won’t dissect the arguments here. But Larun’s response to one problem is worth highlighting for its audacity in re-purposing English to justify poor methodology.
In PACE, the investigators switched their methods of assessing their primary outcomes from those detailed in their protocol. These outcome switches—which produced numbers that favored a more positive interpretation of the results—took place after data collection. The PACE investigators have nonetheless referred to these revised assessment measures as “pre-specified” because, as they have explained, the changes were made before they examined their data.
The issue is significant because it impacts how Cochrane reviewers should assess PACE’s risk of bias. In Cochrane’s own guidelines for assessing a study’s risk of biasacross multiple domains, the requirements for being considered at “low risk” of bias when it comes to reporting results include the following: “The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way.”
That sentence seems clear. “Pre-specified” in this case means “specified in the protocol before the beginning of the trial.” It is indisputable that PACE was not reported in this “pre-specified” way. Yet Larun, parroting the PACE authors, has chosen to re-define the word so that it can encompass what actually happened in the trial. Here is what she wrote about the outcome-switching: “These changes were drawn up before the analysis commenced and before examining any outcome data. In other words they were pre-specified, so it is hard to understand how the changes contributed to any potential bias.” She assessed PACE as having a “low risk” of bias.
Larun’s position is unsustainable. Clinical trial investigators write protocols so that everyone understands what the goal-posts are. No matter what Larun and the PACE authors might argue, “pre-specified” does not mean “specified post-data-collection-but-pre-data-viewing”—and that’s per Cochrane’s own risk-of-bias guidelines, which Larun apparently decided she could ignore. Moreover, PACE was an open-label trial relying on subjective outcomes. In such cases, investigators are likely to know the outcome trends long before they look at any actual data. In this context, to define the reported PACE outcome measures as “pre-specified” is ridiculous.
With more than 600 participants, PACE was the largest treatment trial for the illness. Even so, removing it from the exercise systematic review would not change the overall conclusions. But both the exercise and CBT systematic reviews suffer from other deficiencies that render their findings suspect and essentially meaningless. Putting aside PACE’s outcome-switching and other unique flaws, the trial exemplifies two major problems that plague much or most of the CBT/GET research for this illness. The first is that many studies use overly broad case definitions. The second is that the studies are open-label trials that rely on subjective outcomes.
The first problem means that study samples are likely to include a heterogeneous collection of people suffering from chronic fatigue for any number of reasons, including depression and anxiety disorders, but not necessarily the illness supposedly being investigated. It is possible that some of these other participants could benefit from CBT and GET, complicating any efforts to interpret the findings.
The second problem—combining open-label status with subjective outcomes–means that positive self-reports from participants in treatment arms could easily be due to bias. Since participants know their treatment allocation as well as whether the treatment is supposed to help them, their responses are likely to be influenced by hopes and expectations. It is not clear why systematic reviews should include such trials at all, just as it is not clear why anyone would spend much money conducting them in the first place.
Do systematic reviews of pharmaceuticals generally include such trials and assess them as providing robust evidence with a low risk of bias? If not, why is that appropriate in the case of this illness and these studies? In any event, if Cochrane feels it must include these inherently unreliable trials in systematic reviews, then its guidelines should automatically designate them as having a high overall risk of bias, even if they boast other laudatory traits.
Systematic reviews that includes studies with these thorny problems will feature some of the same defects themselves. Unfortunately, such reviews will provide little or no information about people suffering from the illness in question as defined through more precise definitions. In this case, that means not only the CDC’s 1994 Fukuda definition (for CFS) but also two superior ones drawn up by international committees of experts–the 2003 Canadian Consensus Criteria (for ME/CFS) and the 2011 International Consensus Criteria (for ME). (There is also the US Institute of Medicine’s 2015 clinical case definition for systemic exertion intolerance disease, or SEID, but that’s another issue.)
And such systematic reviews will provide no information about whether objective measures support the positive subjective reports. Larun has acknowledged that including objective outcomes in the exercise systematic review would be helpful. However, to justify having excluded them from the current exercise review, she noted that they were excluded from the systematic review protocol. Of course, that reasoning just raises the question of why objective findings were excluded from the protocol.
When it comes to this illness, objective findings have generally not supported the published subjective results. Including objective data in the systematic review would therefore have required a downward reassessment of the reported benefits of the interventions. Perhaps that is one reason it was decided to leave these data out of both the protocol and the review.
The Common Mental Disorders group has written a second exercise systematic review, using individual participant data from the various trials rather than just the published results. This IPD review was reportedly supposed to have been published last year, but it remains unpublished. It was known that Cochrane—to its credit—sent it out for peer review to people beyond the usual orbit. These further peer reviews were said to have been scathing. This would not be a surprise to anyone outside the biopsychosocial bubble-think.
Cochrane is aware that concerns about PACE and this entire field of research have extended beyond the patient and advocacy communities. It knows the US National Institutes of Health and the Institute of Medicine (now the National Academy of Medicine) released major reports three years ago that declared the illness to be organic and not psychological in nature. It knows that the US Centers for Disease Control has rejected CBT and GET as treatments for what it now calls ME/CFS; that the US Agency for Healthcare Research and Quality has downgraded its recommendations for CBT and GET after stratifying the analysis by case definition; and that the UK National Institute for Health and Care Excellence is pursuing a “full update” of its guidance.
In other words, international support for the CBT/GET paradigm is crumbling. Yet members of the Common Mental Disorders group still champion these treatments, basing their arguments on deficient research. This presents a challenge for Cochrane. The challenge involves not just what to do with the unpublished IPD review but how to handle the published reviews as well. These reviews, and in particular the exercise review, continue to exert a harmful impact on patient treatment options, as I noted in a recent post about the Mayo Clinic. That will continue as long as CBT/GET promoters can hide behind Cochrane’s skirts.
In the near future, Cochrane needs to make some tough decisions, announce its plans, and then clean up the mess created by the Common Mental Disorders group. Should the current systematic reviews be withdrawn? (Absolutely, from my perspective, with the reasons clearly outlined.) Or should they be slapped with warning labels while experts unaffiliated with the Common Mental Disorders group reconsider the entire enterprise and develop a new strategy for assessing studies and analyzing the data?
Would any subsequent systematic reviews be required to differentiate results based on case definition? Would these reviews highlight objective outcomes? If open-label trials relying on subjective outcomes are to be included, would they be appropriately assessed as having a high overall risk of bias?
Professor Watt’s recent defense of PACE suggests that deference to authority still outweighs scientific reasoning in powerful sectors of the UK medical-industrial complex. Cochrane will likely face pushback for seeking to address the flaws of these systematic reviews, so taking corrective action won’t be easy. But to protect patients’ health, it must be done.
All immune responses, from intrinsic to adaptive, need to be regulated – if left on indefinitely they will damage the host. The innate immune response is no exception, and a cellular RNA has been identified that binds to a sensor of viral RNA and regulates the production of interferon (IFN).
The innate immune response, an early response to viral infection, depends on sensors that can distinguish self from non-self. One sensor of non-self RNA is RIG-I, a cytoplasmic protein that binds to short, blunt ended dsRNAs containing a 5′-triphosphate. Such RNAs are not typically found in the cell cytoplasm, and hence are a signature of virus infection. The RIG-I protein contains two N-terminal caspase recruitment domains (CARDs), a central helicase/ATPase domain, and a C-terminal regulatory domain (RD) (Figure). In an uninfected cell, the CARD domains are blocked by interaction with other parts of the protein (Figure). When RNA binds RIG-I (black spring in figure) it induces a conformational change, exposing the CARDs. The released CARDs bind MAVS, a mitochondrial outer membrane protein, to start a signaling cascade that leads to the synthesis of IFN.
A long non-coding RNA called Lsm3b has been identified in mouse cells that binds RIG-I but does not lead to the synthesis of IFN (link to paper). Instead, Lsm3b dampens IFN production late in RNA virus-infected cells. When Lsm3b is removed, IFN production increases.
Lsm3b synthesis is induced by IFN, but only after IFN is produced after 12-16 hours. Then levels of Lsm3b rise to sufficient levels to shut down IFN synthesis.
Lsm3b RNA is a competitive inhibitor of viral RNA binding to RIG-I. Furthermore, its mechanism of binding is completely different from that of viral RNA, and it binds with greater affinity. Binding of Lsm3b to RIG-I does not lead to exposure of the CARD domains (Figure) and therefore does not induce IFN synthesis.
As Lsm3b levels rise late in infection, the RNAs bind up all the free RIG-I in cells, shutting down IFN production. This regulation is achieved because IFN is toxic: if cells have survived infection, there is no point in having them killed by IFN!
Lsm3b is a negative regulator of RIG-I signaling during RNA virus infection. Immune homeostasis is therefore achieved by self-recognition of host RNAs.
One can imagine using the human version of Lsm3b to control autoimmune inflammatory diseases. However, human cells do not produce Lsm3b! All the work described above was done in mouse cells. Perhaps human cells produce a different lncRNA, or maybe utilize a completely different mechanism to regulate RIG-I activation.
W. Ian Lipkin, Director of the Center for Infection and Immunity and the Center for Solutions for ME/CFS at Columbia University, has written the following letter several days before the Fourth Annual Conference on Psychosomatics at Columbia University this weekend. The original letter can be found at this link.
18 October 2018
Dear Colleagues and Friends,
The Center for Infection and Immunity (CII) has been committed to ME/CFS research since 2010. We began this research with generous support from the Chronic Fatigue Initiative of the Hutchins Family Foundation, the National Institutes of Health, and the Microbe Discovery Project.
In 2017, the CII was selected to host one of three NIH centers funded for collaborative research into the biology of this disease. The Center for Solutions for ME/CFS (CfS for ME/CFS) includes representatives from #MEAction and Solve ME/CFS as well as clinical and basic scientists drawn from leading academic institutions and clinical sites across the United States.
Our studies of blood, cerebrospinal fluid, saliva and feces, using state-of-the-art methods that include microbial gene sequencing, metabolomics, proteomics, and immunological profiling, confirm that patients with ME/CFS have biological abnormalities that cannot be characterized as psychosomatic.
Committees convened by the National Academies of Sciences, the National Institutes of Health, and the Centers for Disease Control and Prevention have also concluded that ME/CFS is not a psychosomatic disorder.
We are committed to actively investigating the causes of immunological and metabolic abnormalities in ME/CFS. Our hope is that this work will enable insights that lead to treatments.
W. Ian Lipkin, MD
Director, Center for Infection & Immunity
Director, Center or Solutions for ME/CFS
By David Tuller, DrPH
After I posted yesterday’s blog about Per Fink’s upcoming appearance at the fourth annual Columbia Psychosomatic Conference being held this weekend, I received the following e-mail from Columbia’s Alla Landa. She is an assistant professor of “clinical psychology in psychiatry”–whatever that means–and director of the conference.
I found her note unsatisfactory on multiple fronts, and responded accordingly. My e-mail to her follows below.
Dear Mr. Tuller,
Thank you for sharing with us you concerns about these important matters. I can assure you that the conference committee and I received your email and are taking what you expressed to us very seriously.
As a clinician and researcher, I am aware that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) brings severe suffering to millions of people around the world, and truly hope that biomedical research will help find cures for this condition. I also want to share that the Organizing Committee of the 4th Psychosomatics Conference and the Columbia University Department of Psychiatry affirm our support for the ME/CFS community and state unequivocally that we agree that ME/CFS is a serious multi-system disease associated with neurological, immunological, and energy metabolism impairment. We also support our colleagues at Columbia University’s Center of Infection and Immunity who are using the latest precision-medicine approaches to study the underlying pathophysiology for ME/CFS, with the goal of developing new treatments.
The 4th annual Psychosomatics Conference hosted by the New York State Psychiatric Institute and Columbia University Irving Medical Center will not focus on ME/CFS. This conference will address how multidisciplinary approaches in medicine can help patients with persistent somatic symptoms by bringing together clinical researchers with expertise in brain-body interaction in the fields of psychosomatic medicine, gastroenterology, cardiology, and neuropsychiatry.
Unfortunately, we are unable to answer emails about this matter on an individual basis and to, therefore, address in detail all the points you have raised.
I am hopeful that recent biomedical research initiatives will move the field forward and lead to the development of new treatments for ME/CFS.
Dear Alla Landa–
Thank you for your e-mail, but I’m not sure why I’m getting this message. I did not “share” my concerns with you–I wrote a post on Virology Blog, a site hosted by one of your Columbia colleagues. Perhaps someone else decided to send my post to you.
In any event, it is clear that you and the other organizers have created a public relations disaster for Columbia, New York mental health officials, and the field of psychosomatic medicine. Your generic e-mail to me does nothing to address the specifics of this situation, since it is non-responsive to the particular concerns raised about Per Fink.
I’m glad you agree that ME/CFS has an “underlying pathophysiology.” But to say that the conference does not “focus” on this illness is obviously not the same as saying it won’t be discussed. For reasons known only to you and the other organizers, you have decided to invite to your gathering a man involved in what can only be called the kidnapping and torture of a vulnerable young Danish woman diagnosed with the illness you have just indicated is a serious organic disease. This kidnapping and torture, conducted with the full authority of the state, was considered justified based on the sorts of claims about functional somatic disorders being presented at Columbia this weekend.
If you and the other organizers were aware of these actions and decided to invite Fink anyway, shame on you. If you and the other organizers were not aware of these actions, that would suggest that none of you engaged in sufficient due diligence to vet those being invited. Neither explanation reflects well on you and your colleagues. The invitation would also seem to violate some key principles of developing CME activities, according to the guidelines promulgated by the Accreditation Council for Continuing Medical Education.
Here’s what those guidelines say about “dealing with controversial topics”:
To protect the integrity of accredited CME and of the clinician/patient relationship, all patient care recommendations must be based on evidence that is accepted within the profession of medicine and all scientific research used to support patient care recommendations must conform to generally accepted standards of experimental design, data connection, and analysis.
Thus, CME providers need to develop activities that encourage free and rigorous scientific discourse — while ensuring that faculty do not advocate or promote unscientific treatments and that clinical care recommendations are based on established scientific consensus. When a CME activity includes information about an approach to diagnosis or treatment that is not generally accepted, it is allowable to facilitate debate and discussion about the approach, but it is not allowable to advocate for the test or treatment, or teach clinicians how or when to use it.
It goes without saying that the kidnapping and torture of Karina Hansen was not grounded in “evidence that is accepted within the profession of medicine” or on “established scientific consensus”–nor are Fink’s treatment recommendations for this illness overall. As the international scientific community has now recognized, describing ME/CFS as a functional somatic disorder or an example of so-called “bodily distress syndrome” is neither appropriate nor acceptable. This framing of the illness rests on flawed research that cannot in any way be claimed to “conform to generally accepted standards of experimental design, data connection and analysis.” Your invitation to Fink is a disgrace–an insult to millions of patients around the world confronted daily with the sort of nonsense he and his collaborators in the UK and elsewhere have promulgated for many, many years.
I see nothing in the schedule that suggests the presentations at issue here will be balanced by any effort “to facilitate debate and discussion” about the advocated approach to treatment. It is immaterial that ME/CFS is not the “focus” of these presentations. As you must understand, those in the audience will certainly be likely to apply the recommended “treatments” to ME/CFS patients, regardless of whether that particular illness is even mentioned. So you cannot alleviate yourself and the other organizers of responsibility for this debacle by vaguely suggesting that the gathering is somehow irrelevant to the concerns of those who plan to attend the Saturday protest organized by ME Action New York or the more than 9,000 people who have signed the online petition.
All that is apart from the larger questions of whether these purported disorders or syndromes or the categories of “medically unexplained symptoms” or “persistent physical symptoms” should be construed as discrete illnesses rather than somewhat useful descriptive phrases. The evidence for such claims seems to reside in the absence of current pathophysiological explanations for the symptoms, not in any scientific proof that these purported diagnoses represent actual clinical entities. But perhaps that is a discussion for another day.
David Tuller, DrPH
Senior Fellow in Public Health and Journalism
Center for Global Public Health
School of Public Health
University of California, Berkeley
By David Tuller, DrPH
Someone uninformed or stupid or maybe both decided to invite Danish physician Per Fink to present at a conference on so-called psychosomatic medicine being held this weekend at Columbia University. Fink—I won’t dignify him by using an honorific–is a scary guy. He should never have been provided with this prestigious platform—in my home town, no less. (I’ve lived in San Francisco for 30 years but I’ve always identified as a New Yorker living in San Francisco—an expat of sorts.) I’m overseas until late October, so I can’t even go to the event and ask him a few pertinent questions about his treatment of people with ME/CFS—or whichever name people choose to use for this disease.
Fink is the most prominent member of the Danish wing of the cult of MUS (“medically unexplained symptoms”), but his pernicious influence reaches far beyond that, as the invitation to this gathering demonstrates. His basic position, as I understand it, is that anyone experiencing persistent physical symptoms for which Per Fink can’t find an organic cause must be suffering from a mental illness. This mental illness might require them—especially if they are Danish–to be sequestered from their families against their will for years.
Moreover, if they reject Per Fink’s recommended treatments they must be suffering not from whatever they have deluded themselves into believing they have but from an obscure condition referred to as “pervasive refusal syndrome”—for which the main symptom seems to be a rejection of Per Fink’s advice. (Can someone please explain to me the difference between “pervasive refusal” and “non-pervasive refusal”? Is “non-pervasive refusal syndrome” also a purported psychiatric illness?)
This weekend’s two-day event for clinicians, co-sponsored by New York mental health officials, is the fourth annual Columbia Psychosomatic Conference. This year’s program is called “Healing ‘Unexplainable’ Pain: Advances in Multidisciplinary Integrated Psychosomatic Care.” Fink’s upcoming appearance has not gone unnoticed by the ME/CFS community. MEAction is organizing a demonstration at 8:00 AM on Saturday. The group has also sponsored a petition demanding that Fink be uninvited. So far more than 9,000 people have signed it.
(I am personally uncomfortable with uninviting people—even horrible people—once they have been invited to talk somewhere. But I understand why others feel differently. Fink is not just giving a speech. In this case, conference attendees can receive continuing medical education credits, which they need to maintain their professional standing. Fink will undoubtedly be offering harmful and unscientific advice to clinicians unaware of his background. So I am sympathetic to the request to remove him from the schedule, despite my own overall uneasiness about such a strategy.)
Fink has most famously deployed his theoretical approach to MUS or what he often calls “bodily distress syndrome” in the horrendous case of Karina Hansen, a young woman from Holstebro, Denmark. Karina was essentially kidnapped from her family’s home five years ago and held incommunicado while her condition drastically deteriorated. Her case has become a cause celebre among ME/CFS patients around the world.
My friend and colleague, UK barrister Valerie Eliot Smith, has comprehensively documented Karina’s situation over the years on her blog, Law and Health. Her coverage of the situation has been indispensable. It has also put Danish medical authorities on notice that others were and are keeping tabs on their actions. Here is a link to all Valerie’s posts about Karina: https://valerieeliotsmith.com/category/karina-hansen/
The following is from a 2016 post on Law and Health:
Karina first became ill as a teenager. After much debate and disagreement between various health professionals, she was eventually diagnosed in 2008 with a severe case of Myalgic Encephalomyelitis (ME). However, as often happens with this illness, the diagnosis was disputed. Her parents continued to care for her in the family home.
Given her vulnerable state and the disputed diagnosis, Karina and her family arranged for her parents to be granted power of attorney on her behalf. At this time, she was deemed competent to make the decision.
In February 2013, Karina (by now aged 24) was forcibly, and without warning, removed from her home in Holstebro, Denmark. This process was carried out by a large team of people consisting of police officers, social workers, doctors and a locksmith. There had been a similar but unsuccessful attempt at removal some months earlier. She made desperate phone calls for help to her family until the battery in her phone died.
Karina was taken to Hammel Neurocenter (described as “The Research Clinic for Functional Disorders”) which treats patients with neurological damage and diseases. It seems that a number of doctors have been involved in Karina’s case but psychiatrists Nils Balle Christensen and Per Fink have dictated the overall course of her treatment.
As is frequently the case with ME patients (in Denmark and elsewhere), Drs Balle Christensen and Fink believe that ME is a “functional disorder” ie. effectively a psychosomatic condition. As a result, their recommended treatments are exercise therapy/physical rehabilitation, psychotherapy, “sensory” (occupational) therapy and psychotropic medication. Whilst these treatments can sometimes help patients with apparently similar conditions (who are often misdiagnosed with ME or – so-called – “chronic fatigue syndrome“), patients who genuinely have ME are very likely to deteriorate with these treatments – often with serious and long-lasting effects.
After her admission to Hammel, Karina was diagnosed with PAWS – also known as pervasive refusal syndrome. This is characterised by a patient engaging in obstructive behaviour which is designed to resist treatment. It is usually applied to children rather than adults and is not a formally-recognised psychiatric condition. It is also tantamount to blaming the patient for the failure of inappropriate or dangerous treatment.
In 2016, Karina was returned to her parent’s care–where she always belonged–but in much diminished health. Moreover, the court appointed a guardian to monitor decisions made about her care and other matters. Earlier this month, the court finally dismissed the guardian, leaving Karina free from the state’s clutches for the first time in years. However, the consequences of the torture she and her family went through at the hands of Per Fink and other health and legal authorities will remain with them for the rest of their lives.
The website for this weekend’s psychosomatic conference provides the following description of the purported problem under discussion:
Persistent somatic symptoms (i.e., chronic pain, fatigue, gastrointestinal and neurologic symptoms) that are associated with stress are highly prevalent and cause much suffering to millions of people all over the world. “Somatic symptom disorders,” “functional disorders,” “fibromyalgia,” “irritable bowel syndrome,” “somatization,” or “medically unexplained symptoms”–are just some of the many terms patients hear in the medical offices regarding their symptoms. Patients with psychosomatic distress often dwell at the interface between psychiatry and medicine, and can’t find needed help in either discipline. Physicians of multiple specialties often struggle to find ways to help their patients; and we still have a paucity of mental health clinicians trained to provide specialized psychosomatic treatments.
Fink is presenting twice. One of his sessions is called “Bodily Distress Syndrome or Functional Somatic Syndromes: How to diagnose and treat.” The second is called “How to Treat Functional Disorders in Primary Care and General Medical Hospitals: A brief introduction to a training program for family physicians and other medical doctors.”
It is difficult if not impossible to prove or disprove the presence of BDS or FSS or whatever else this diagnosis is called, since the main evidence for its existence as a discrete illness entity rather than just a descriptive term appears to be an absence of identified organic causes. An unknown number of people, of course, might experience symptoms that are delusional or non-organic or generated through some psychological condition. But it is critical to regard such claims with extreme caution and to acknowledge the very real possibility that underlying pathophysiological processes might have simply not yet been identified.
Yet as the description of the Columbia program suggests, those in this field often make assertions that go far beyond such tentative approaches. These claims erase any distinction between “medically unexplained symptoms” and “medically unexplainable symptoms”—a point discussed at length by journalist Maya Dusenbery in her excellent new book, Doing Harm: The Truth About How Bad Medicine and Lazy Science Leave Women Dismissed, Misdiagnosed, and Sick. The certainty with which these health care professionals impose their ideas on vulnerable patients—who are disproportionately female–reflects a troubling arrogance about their own diagnostic acumen and healing powers. That they are viewed as authorities in deciding whether others suffer from mental illness–based solely on symptoms that are currently unexplained–can lead at times to serious abuse. Just ask Karina Hansen and her family.
Jennie Spotila has recently written about the situation on her blog, Occupy M.E. For those not familiar with Jennie’s important and excellent work, I highly recommend reviewing previous posts as well. She always provides cogent analysis and smart insights into the politics and debates involving this disease. Here’s what she wrote last week about the decision to invite Per Fink to dispense his dangerous ideas to other clinicians:
When researchers and institutions offer the microphone to ME-denialists like…Fink, we have to speak out against it. When a university of Columbia’s caliber invites one of the people responsible for holding Karina Hansen–against her will and incommunicado for years–to speak at a conference on psychosomatic illness, we have to speak out against it.
This is not an example of academic freedom and divergent points of view. Fink will speak about “bodily distress syndrome,” the landfill he invented for ME and CFS and a number of other medical conditions. This is like inviting a climate change denier to give the keynote address at a UN Climate Change Conference, or inviting Andrew Wakefield to speak at the National Immunization Conference. There is no justifiable reason for it. Academic freedom is an essential principle in science, but it is not an impenetrable shield to be deployed in defense of every misinformed or misguided speaker invitation.
I hope some smart clinicians, scientists and advocates are present not only outside at the protest but inside at the event itself to hold Fink to account by asking tough questions and follow-ups. Here are a few of the questions I would like to ask him myself:
Do you agree that other illnesses presumed in the past to be psychological or psychiatric in nature have now been shown to be physiological illnesses? If so, what makes you so sure that the same is not true of the various conditions you have dumped into the MUS category?
What is the evidence for claiming that the conditions in the MUS category are functional somatic disorders or bodily distress syndrome (or whatever), beyond the lack to date of definitive identification of an organic cause? Why should the default presumption be that people are expressing psychological distress in this manner? How can that presumption ever be proven? How can it be disproven?
What is the evidence for “pervasive refusal syndrome”? Isn’t this a diagnosis designed to explain why therapies based on the presumed presence of functional somatic disorders or bodily distress syndrome have often failed to make people better and often appear to make them worse?
If your diagnosis of Karina Hansen’s illness was correct, why did she leave the state’s care worse off than when she went in?
The TWiV team notes the passing of Tom Steitz, an outbreak of acute flaccid myelitis in the US, a continuing Ebola virus outbreak in DRC, respiratory vaccinia due to inhalation of ground up rabbit skin, and how a human papillomavirus capsid protein directs virus-containing endosomes towards the nucleus.
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Show notes at microbe.tv/twiv
At the First Annual Lab Coat Ceremony for Ph.D. and MD/Ph.D. students at Icahn School of Medicine at Mount Sinai, at which I delivered the Keynote Address, the students and their mentors were asked to recite oaths pledging their dedication to the field. Such oaths have been called ‘Hippocratic oaths for Scientists’, similar to the Hippocratic oath taken by medical professionals at the onset of their training.
I strongly endorse the idea of having a Lab Coat Ceremony for Ph.D. students (the one at Icahn School of Medicine was the first in New York). While similar oaths for scientists have been previously proposed, I reproduce those from the Mt. Sinai event below to help guide other programs in developing their own ceremonies.
I willingly pledge to uphold the highest levels of integrity, professionalism, scholarship and honor.
I will conduct my research and professional endeavors with honesty and objectivity.
I will apply the highest standards of rigor and respect for the generation and application of knowledge, and fully acknowledge the contributions of others.
I will not allow financial gain or ambition to cloud my judgment or decision-making nor cause harm to society or subjects of research.
I will embark on the furthering of knowledge through respectful interaction and collaboration with my colleagues and community, without prejudice or exclusion.
I will be a role model, and use my skills to inspire, mentor and empower future generations, instilling in them the highest principles of ethical behavior.
As witnessed by all present today, and in the tradition of graduates before me, i do affirm to uphold these guiding principles.
As teachers and mentors for our students, we pledge to maintain the highest professional standards in all of our interactions with students, patients, colleagues, and staff.
We pledge our utmost effort to ensure that all components of the educational program for students will be of the highest quality.
We will respect all students as individuals, without regard to gender, race, national origin, religion, or sexual orientation; we will not tolerate anyone who manifests disrespect or who expresses biased attitudes towards any student. We will not tolerate any abuse or exploitation of students.
In an effort to nurture personal development, we pledge that students will have adequate time for reflection as well as personal and family obligations.
In nurturing both the intellectual and professional development of our students, we will celebrate achievement of academic excellence and demonstration of the highest virtues of our profession.