Saturday, May 23, 2015

Conflict of Interest: CDC Accepts Millions from Corporations

Jeanne Lenzer is the associate editor of the The BMJ (British Medical Journal), USA. The BMJ is one of the world's oldest medical journals. As a peer-reviewed publication of the British Medical Association, it has tremendous clout, and is widely read by medical professionals all over the world.

In this BMJ article, Lenzer discusses the conflict of interest generated by an infusion of millions of dollars from private corporations into the CDC. Although she only presents a few cases in which the CDC has shifted policy in order to aid corporate interests, given the enormous amount of money it has received there are obviously many more.

The demise of the CDC as a public institution began in the 1980s during the Reagan-era period of privatization. In 1995 the CDC Foundation, which was created by Congress, began to accept "gifts" on behalf of the CDC. This funding arm has not only led to skewed treatment recommendations - the most recent of which is the narrow window of antibiotic treatment allowed to Lyme disease patients - but has opened the door to strong-arm tactics, such as the NRA's withdrawal of funds after the CDC began an investigation of gun violence.

The CDC will not bite the hand that feeds it. In the case of ME/CFS the hand is most likely insurance companies, which (as in the case of Lyme disease) don't want to pay for expensive long-term treatments. As long as the CDC promotes criteria for ME/CFS that are vague enough to fit into the generally accepted definition of depression, doctors will prescribe therapy and exercise, patients will be misdiagnosed, and it goes without saying that Ampligen will never be approved.

The concept that the CDC represents the public good needs to be seriously re-evaluated.
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Centers for Disease Control and Prevention: protecting the private good?

By Jeanne Lenzer, associate editor, The BMJ, USA

BMJ 2015;350:h2362 doi: http://www.bmj.com/content/350/bmj.h2362 (Published 15 May 2015)

The Centers for Disease Control and Prevention (CDC) includes the following disclaimer with its recommendations: “CDC, our planners, and our content experts wish to disclose they have no financial interests or other relationships with the manufacturers of commercial products . . . CDC does not accept commercial support.”1

The CDC’s image as an independent watchdog over the public health has given it enormous prestige, and its recommendations are occasionally enforced by law.

Despite the agency’s disclaimer, the CDC does receive millions of dollars in industry gifts and funding, both directly and indirectly, and several recent CDC actions and recommendations have raised questions about the science it cites, the clinical guidelines it promotes, and the money it is taking.

Marcia Angell, former editor in chief of the New England Journal of Medicine, told The BMJ, “The CDC has enormous credibility among physicians, in no small part because the agency is generally thought to be free of industry bias. Financial dealings with biopharmaceutical companies threaten that reputation.”2

Industry funding of the CDC has taken many doctors, even some who worked for CDC, by surprise. Philip Lederer, an infectious diseases fellow at Massachusetts General Hospital and Brigham and Women’s Hospital in Boston, Massachusetts, and a former CDC epidemic intelligence service officer, told The BMJ he was “saddened” to learn of industry funding.

The CDC’s director, Tom Frieden, did not respond to a question about the disclaimer. He told The BMJ by email, “Public-private partnerships allow CDC to do more, faster. The agency’s core values of accountability, respect, and integrity guide the way CDC spends the funds entrusted to it. When possible conflicts of interests arise, we take a hard, close look to ensure that proper policies and guidelines are followed before accepting outside donations.”

Since its inception in 1946, the CDC has had a pivotal role not only in the prevention of infectious diseases but in reducing workplace hazards, motor vehicle injuries, and tobacco related deaths and in ensuring food safety.

One of the CDC’s most important contributions, with an estimated eight million lives saved to date,3 has been its work to educate the public about the dangers of tobacco. CDC spokesperson Thomas Skinner says the surgeon general’s first report on smoking in 1964 was a “tipping point,” when tobacco was first clearly identified as a health hazard by the US government. Skinner said the CDC’s anti-tobacco campaign “serves as an important counter to the more than $950 000 [£630 000; €860 00] that the tobacco industry spends each hour—more than $23m a day—on cigarette advertising and promotion.”

Opening up to private money

Funding of CDC took a turn in 1983, when the CDC was authorised to accept external “gifts” from industry and other private parties. In 1992, Congress passed legislation to encourage relationships between industry and the CDC by creating the non-profit CDC Foundation, which began operations in 1995.

The CDC Foundation raised $52m in fiscal year 2014, of which $12m was from corporations. The CDC itself in fiscal year 2014 received $16m in conditional funding from sources such as corporations, individuals, and philanthropy, including the CDC Foundation. Conditional donations are earmarked for specific projects. For example, in 2012, Genentech earmarked $600 000 in donations to the CDC Foundation for CDC’s efforts to promote expanded testing and treatment of viral hepatitis. Genentech and its parent company, Roche, manufacture test kits and treatments for hepatitis C.

Numerous manufacturers give donations to the CDC Foundation. Janssen also contributed $1.5m in 2012-13,1 and in 2011-12 contributors included Merck ($915 149), Genzyme ($762 000), Sanofi-Aventis ($600 000), and Abbott Laboratories ($550 000).

The CDC has recently issued controversial recommendations for screening tests and drugs,2 4 and is currently overseeing several equally controversial studies.5 Some of these are associated with “conditional” industry funding, as the three examples below show.

Cohort screening for hepatitis C

The CDC issued guidelines in August 2012 recommending expanded (cohort) screening of everyone born from 1945 to 1965 for hepatitis C virus.1 The agency cited new direct acting antiviral drugs and protease inhibitors to treat hepatitis C as part of its rationale for cohort screening, saying the drugs “can halt disease progression and provide a virologic cure (ie, sustained viral clearance following completion of treatment) in most persons.”

The science behind cohort screening has been challenged4 and is said to be “the subject of major debate.”6 The scientific debate along with the price tags of the newer drugs (over $84 000 per treatment course for the new drug sofosbuvir), raise questions about CDC’s industry funding.

In 2010, the CDC, in conjunction with the CDC Foundation, formed the Viral Hepatitis Action Coalition, which supports research and promotes expanded testing and treatment of hepatitis C in the United States and globally. Industry has donated over $26m to the coalition through the CDC Foundation since 2010. Corporate members of the coalition include Abbott Laboratories, AbbVie, Gilead, Janssen, Merck, OraSure Technologies, Quest Diagnostics, and Siemens—each of which produces products to test for or treat hepatitis C infection.

Conflict of interest forms filed by the 34 members of the external working group that wrote and reviewed the new CDC recommendation in 2012 show that nine had financial ties to the manufacturers.1

A report by the Office of the Inspector General in December 2009 found that external advisors to the CDC “play an influential role in decision making for the federal government.” The inspector general evaluated conflicts of interest of advisors and concluded, “CDC has a systemic lack of oversight of the ethics program”: 97% of disclosure forms filed by advisors were incomplete, and 13% of advisors participated in meetings without filing any disclosure at all.7

Although the CDC states it has addressed all of the deficiencies cited in the report, the agency did not restrict participation of the nine conflicted external advisors in the recommendation to broaden hepatitis C screening.1 However, the CDC told The BMJ that external advisors acted in an “individual capacity” and are not designated as “special government employees.” It said that their financial ties to industry didn’t comprise a conflict of interest as the participants “had no relationships directly related to the task-reviewing evidence as a basis for an HCV testing guideline. The reported financial activities represent activities not directly related to this work but involving commercial and non-commercial entities that could be perceived to influence involvement in the task.”

Oseltamivir for flu

Following criticism of the CDC and its foundation for accepting a directed donation from Roche for the agency’s Take 3 flu campaign (Step 3 tells the public to “take antiviral medicine if your doctor prescribes it”),2 the CDC posted an article on its website entitled, “Why CDC Recommends Influenza Antiviral Drugs.”8 The agency cited multiple observational and industry funded studies, including the recent meta-analysis by Dobson and colleagues,9 which it described as an “independent” study. However, the study was sponsored by Roche, and all four authors had financial ties to Roche, Genentech, or Gilead (the first two sell oseltamivir and Gilead holds the patent).10

Despite its extensive list of studies, the CDC did not cite the systematic review and meta-analysis by the Cochrane Collaboration.11

The CDC told The BMJ that it didn’t include the Cochrane review because Cochrane “did not consider any data from uncontrolled observational studies of oseltamivir treatment. While such studies have inherent design limitations, they can inform clinical practice and public health, especially when data from RCTs [randomized controlled trials] are unavailable or have not been conducted among high-risk groups or hospitalized influenza patients, or because having a placebo group would be unethical since antiviral treatment is recommended for these groups.”

The US Food and Drug Administration issued a warning to Roche that it could not claim that oseltamivir reduces pneumonia or deaths since it has never provided evidence to the FDA to support that claim.2 Manufacturers are prohibited by law from making off-label claims about their drugs. However, doctors can legally recommend drugs for off-label uses. By funding the CDC’s Take 3 campaign, Roche and other companies are not claiming their antivirals will reduce pneumonia or death. CDC director, Frieden, however, did make the off-label claim, telling the public that it could “save your life.”2

Shannon Brownlee, senior vice president of the Lown Institute and former journalist covering the CDC, told The BMJ, “This looks like classic stealth marketing, in which industry puts their message in the mouths of a trusted third party, such as an academic or a professional organization.”

CDC and the sugar industry

The CDC has also been criticised for its role in a series of studies into an epidemic of chronic kidney disease among men working in the sugar fields of central America.5 The sugar industry is paying $1.7m to fund the studies, and critics say the fact the research is being funded by the men’s employers raises concerns about how far it will probe industry’s role in the disease outbreak. The CDC states it will provide “technical assistance and subject matter expertise,” for the studies, with the foundation serving as the “grant administrator overseeing the donor funding and facilitating the research activities.”

Researchers think that the epidemic, which has killed over 20 000 mostly young men,12 is most likely to be caused by “two interdependent factors: the misuse of agrochemicals and the working conditions of the labor force.”13 The men are exposed to banned and dangerous pesticides, some of which are known to be nephrotoxic, and the working conditions cited include “regular exposure to very hot temperatures and extreme physical effort, lead[ing] to heat stress and dehydration.”13

Daniel Brooks, associate professor of epidemiology at the Boston University School of Public Health, will lead the CDC research, which includes several observational studies examining genetics and biomarkers in children and a longitudinal study of the sugarcane workers and their families for an as yet undetermined time period. He defends the CDC’s involvement, saying it provides two main benefits, creating a “firewall between donors and researchers” and enlisting the expertise of the CDC.

The sugar industry has trumpeted Brooks’ earlier research into the epidemic as proof that conditions in the fields are not the cause of the men’s deaths; Mario Amador, general manager of Nicaragua’s National Committee of Sugar Producers, dismissed the idea that the disease has an occupational origin, telling a reporter with the International Consortium of Investigative Journalists, “We are fully convinced that there is no direct relationship between [chronic kidney disease] and the activities conducted in the sugarcane industry.”5

The Pan American Health Organization has called the outbreak, “a serious public health problem that requires urgent, effective, and concerted multisectoral action.”

Jerome R Hoffman, a methodologist and emeritus professor of medicine at UCLA, told The BMJ, the study was asking the wrong questions. “Epidemiologic studies can of course be tremendously useful in cases like this, but given the human suffering involved, we need to devise and test interventions that have a chance to prevent or ameliorate this substantial harm, as quickly as possible. It’s inappropriate to focus on things that cannot protect these workers, such as identifying an unusual genetic predisposition to kidney failure, or evaluating a biomarker to follow the disease, while ignoring modifiable factors.”

Not just the carrot—but the stick

Corporations have not only been offering gifts to the CDC; they have also used a heavy stick—with consequences that continue to hobble critical research. In 1996, the National Rifle Association, which is underwritten in large part by gun manufacturers, mounted an offensive against CDC’s research into gun violence. The association lobbied Congress, and pro-gun representatives slashed $2.6m from the CDC budget—the exact amount the agency had spent in the previous year on firearm injury research. The funding was later restored, but the bill prohibited any of the restored funds from being used to “advocate or promote gun control.”

Frederick Rivara, one of the team members who conducted gun research for the CDC before the cuts, told The BMJ that firearms research has “plummeted dramatically,” and that gun violence remains a major public health concern in the US, where nearly half a million people have died from gunshot wounds since the funding cuts.

After multiple mass murders, including the shooting of 20 first grade children at the Sandy Hook Elementary School in Newton, Connecticut in 2012, President Obama asked Congress for $10m to fund research into preventing gun violence; however, Congress has not approved the funds to date. The president renewed this request for the 2016 budget.

Professional reaction

Neil Calman, president and chief executive of the Institute for Family Health in New York, a large community health center network in 31 locations with over half a million patient visits a year, says the institute has relied on CDC guidance largely because of its prestige as an independent agency, free of industry relationships. Calman told The BMJ, “Industry funding undermines trust and introduces a bias in the presentation of results and treatment recommendations that is deplorable for a government agency. If the allegations of industry funding and influence are true, we will have to look very carefully at recommendations we are following now and those made in the future by the CDC.”

Calman said, “Industry claims their scientific methodology ensures their studies are unbiased—just as the CDC claims money doesn’t affect their recommendations. Yet multiple studies clearly—and repeatedly—show that who sponsors a study, or issues a guideline, makes a difference.”

Hoffman said, “Most of us were shocked to learn the CDC takes funding from industry. Of course it is outrageous that industry apparently is allowed to punish the CDC if the agency conducts research that has the potential to cut into profits. But it was our government that made this very bad arrangement, so the way to fix it is not to ask the CDC to ‘pretty please be more ethical, and avoid conflicts of interest’; rather, as a society, we have to get the government to reject this devil’s bargain, by changing the rules so this can no longer happen.”

John Mandrola, a cardiologist in Louisville, Kentucky, reacted to the news of industry funding, saying that the CDC “must have the highest of moral ground. For if we are to believe them about public health matters, there can be no conflicts of interest. The public good, pure evidence, that is all.”14

Monday, May 11, 2015

Dr. Kerr Rebuts Assertion That GET and CBT Are Legitimate Treatments for ME/CFS

Unfortunately, PACE isn't admitting anything. 
In a recent editorial published in the British Medical Journal Andrew Lloyd states: "The evidence for graded exercise and cognitive behavioural therapy is already clear, so this treatment should be made widely available."

Dr. Lloyd, an immunologist associated with the University of South Wales, Australia, is a long-time proponent of exercise as the "cornerstone" of treatment for ME/CFS.

The reply by Dr. Jonathan Kerr, who is regarded as one of Britain’s foremost ME/CFS  researchers and an expert in microbiology, inflammation and genetics, lays out the errors in Dr. Lloyd's endorsement of GET and CBT, not the least of which is that Lloyd's "evidence" is based entirely on a study so flawed that it should never have been published. 

In the wake of the Columbia studies documenting progressive immune abnormalities in ME/CFS, and the IOM's unequivocal statement supporting the biogenesis of ME/CFS, it is clear that the proponents of psychological interventions and exercise as legitimate treatments have only one leg to stand on.

And that leg is increasingly in need of a crutch.
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The biological pathogenesis of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis

By Jonathan Kerr

This editorial (1) comes from authors from two of three CFS/ME centres whose prolific academic production in CFS/ME provides almost the sole support for a supposed psychiatric basis for the disease; these centres are Kings College London, Nijmegen Medical Centre in the Netherlands, and the University of New South Wales, Sydney, Australia. However, the scientific basis on which the treatments, Cognitive Behavioural Therapy (CBT) and Graded Exercise Therapy (GET), are offered is critically flawed. The original PACE trial conducted by Kings College London, enrolled patients using the 1991 Oxford criteria (2), which allows inclusion of patients with affective disorders. This is in direct conflict with the internationally accepted 1994 CDC criteria which specifically excludes patients with affective disorders. This means that this study was performed using patients whose exact diagnoses are unknown. However, despite this flaw, global insurance companies do not pay sickness benefit to CFS/ME patients on the basis that effective treatments are available. Yet these interventions are not effective in CFS/ME.

CBT helps only a fraction of patients and GET has been shown to exacerbate the symptoms of patients with CFS/ME, which is logical as one of the cardinal symptoms of CFS/ME is post-exertional malaise, and so GET should not be used for CFS/ME patients. Furthermore, the Institute of Medicine in the USA has recently recommended that the name, CFS/ME, should be changed to Systemic Exercise Intolerance Disease (SEID) (3), which again reinforces the truth that exercise therapy should not be used for CFS/ME.

We know that CFS/ME can be triggered by a variety of infections, vaccines, exposure to organophosphate chemicals, and that the pathogenesis involves prolonged immune activation, which results in a flu-like illness that persists for months to years, and we all know how we feel during a flu-like illness, and there is no dispute that flu-like illnesses are caused by viruses. Several infection models have been presented which illustrate very well this progression in patients followed from the time of acute infection to development of CFS/ME. Parvovirus B19 triggers CFS/ME and this is predisposed to by carriage of HLA-DRB1*01, *04 and *07 alleles, is characterised by raised levels of circulating TNF-α and IFN-γ, and CFS/ME triggered by B19 has been cured with intravenous immunoglobulin (IVIG) which is the specific treatment for B19 infection (4). Coxiella burneti also triggers CFS/ME and this is predisposed to by carriage of HLA-DRB1*11 and certain IFN-γ polymorphisms, is associated with chronic immune activation and Q fever-associated CFS/ME is treated successfully with tetracyclines which are the specific treatment for Q fever (5). Epstein-Barr virus triggers CFS/ME, and patients with EBV-triggered CFS/ME have been successfully treated with valacyclovir (6), which is a specific treatment for EBV infection. In all of these models, the infectious agent persists long-term with chronic genomic persistence and antigen presentation, which appears to be important. The diversity of infectious triggers and individual responses likely account for the heterogeneity observed in CFS/ME, and the existence of subtypes, which are recognised to be important for the optimal management of patients.

Maybe the big breakthrough in CFS/ME comes when we are free to apply our significant existing knowledge of CFS/ME towards the best investigation and treatment of INDIVIDUAL patients, whom we know have different pathogenetic processes which account for the existence of disease subtypes. Disease subtypes are a feature of multiple chronic inflammatory autoimmune diseases and are taken into account in their management, and therefore CFS/ME is typical of such a biological disease.

References

1. Lloyd AR, Meer JW. The long wait for a breakthrough in chronic fatigue syndrome. BMJ. 2015;350:h2087. doi: 10.1136/bmj.h2087.

2. Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ, et al. A report--chronic fatigue syndrome: guidelines for research. J R Soc Med.1991 Feb;84(2):118-21.

3. Institute of Medicine. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Washington, DC: National Academies Pr; 2015

4. Kerr JR, Cunniffe VS, Kelleher P, Bernstein RM, Bruce IN. Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome. Clin Infect Dis. 2003;36(9):e100-6.

5. Sukocheva OA, Marmion BP, Storm PA, Lockhart M, Turra M, Graves S. Long-term persistence after acute Q fever of non-infective Coxiella burnetii cell components, including antigens. QJM. 2010;103(11):847-63.

6. Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up. In Vivo. 2007;21(5):707-13.


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Editorial

The long wait for a breakthrough in chronic fatigue syndrome

BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h2087 (Published 05 May 2015) Cite this as: BMJ 2015;350:h2087

Andrew R Lloyd, professor,
Jos W M van der Meer, professor

Author affiliations

Correspondence to: A R Lloyd a.lloyd@unsw.edu.au

There hasn’t been much good news for patients with the prevalent but enigmatic disorder chronic fatigue syndrome (also referred to as myalgic encephalomyelitis). Over decades, research into the pathophysiology has failed to find convincing evidence of either persistent infection or immunological, endocrine, or metabolic change, and has rejected simplistic notions of depression (typical or atypical) or primary sleep disorder. Several notable “breakthroughs” have failed independent replication. The most noteworthy is the recent rise and fall of xenotropic murine leukaemia virus related virus (XMRV) as the cause, which was ultimately established as a murine DNA laboratory contaminant.1 Similarly, an exhaustive array of randomised controlled trials seeking curative outcomes from antiviral, immunological, hormonal, antidepressant, and many other therapies have failed to show any benefit over placebo, or failed the replication test.

Where then is the progress? Firstly, there is reproducible evidence implicating certain infections as a trigger—notably, infectious mononucleosis caused by Epstein-Barr virus, but also infection with other pathogens.2 Secondly, there is clear evidence that a substantial proportion of patients have a coexisting mood disorder, and sometimes a sleep-wake disorder, and that these conditions may exacerbate or perpetuate the illness.3 Thirdly, independent studies using both structural and functional imaging techniques have identified alterations in the brains of patients with chronic fatigue syndrome, implicating the central nervous system as the site of pathophysiology.4 Fourthly, there is solid evidence from multiple controlled studies that patients can gain control of symptoms and functional improvement through multidisciplinary interventions incorporating graded exercise therapy and cognitive behavioural therapy. These interventions have clearly positive outcomes in systematic reviews and meta-analyses.5 6 7 For instance, the recent Cochrane review of graded exercise therapy5 states that “patients with CFS [chronic fatigue syndrome] may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed.”

How therapy works

Plausibly, graded exercise may reverse a perpetuator in the form of physical deconditioning.

However, there is little evidence for loss of aerobic fitness in patients with chronic fatigue syndrome, and limited evidence for improved physical performance after successful graded exercise therapy.8
Instead, graded exercise has been proposed to act by desensitising an exaggerated central nervous system response to the physiological signals associated with exercise.9 In psychological terms, patients may avoid activity because of the prolonged exacerbation of symptoms that follows minor physical activity; this leads to an understandable conclusion that exercise is harmful or to a conditioned fear of such activity.10 In this respect, the recent mediation analysis of the outcomes of the PACE trial is of interest.11 This trial compared standard medical care, cognitive behavioural therapy, graded exercise, and adaptive pacing therapy, concluding that both cognitive behavioural and graded exercise therapy were more effective at reducing fatigue and improving physical disability than standard care or adaptive pacing.12 The mediation analysis suggested that both cognitive behavioural therapy and graded exercise worked by reducing avoidance of activity. This is broadly consistent with findings by others,13 although whether the effect simply relates to the behavioural change itself (that is, exercise) or reconditioning of the associated fear of activity remains unclear. In addition, a substantial proportion of patients do not avoid activity but have repeated boom-bust cycles of overactivity when feeling relatively well (the boom) followed by reduced activity when symptoms are exacerbated thereafter (the bust). These data argue for a personalised approach to both therapies.

Cognitive behavioural therapy for patients with chronic fatigue syndrome is based on the premise that inappropriate cognitive attributions (thinking patterns) and behaviours help perpetuate symptoms. It seeks to alter these attributions and modify the associated behaviour, targeting activity patterns and sleep-wake behaviours. For example, although primary sleep disorders do not explain chronic fatigue syndrome,14 patients typically report that their night-time sleep is unrefreshing, and as fatigue is the dominant symptom, patients may consider that increased sleep will relieve symptoms and aid recovery. This idea commonly leads to frequent daytime naps and a delayed sleep-wake cycle.

Prospects for cure

There has been recent contention about the possibility of cure after graded exercise and cognitive behavioural therapy. An analysis of the PACE trial suggested cure was possible, but recovery outcomes were defined post hoc using population norms with generous thresholds (such as the population mean plus one standard deviation for self reported fatigue).15 This analysis was criticised because of the limited assessments and less than full restoration of health,16 leading to a recommendation that trials use more accurate outcomes (such as clinically relevant improvement) defined in advance and capturing a broad based return to health with assessments of fatigue and function. Trialists must also consider patients’ perceptions of their recovery.17 In this context, the increase in volume of grey matter associated with clinical response to cognitive behavioural therapy, as reported in one study, needs further investigation.18 Even with the unduly liberal designation of recovery, less than one quarter of patients “recovered” in the PACE trial.

What then of the long awaited breakthrough? As is often the case in medical research, progress is predominantly made in modest increments not breakthroughs. The evidence for graded exercise and cognitive behavioural therapy is already clear, so this treatment should be made widely available. The next increments are to find ways to increase the symptom relief and functional improvement achieved by these treatments and to identify factors predicting clinically relevant improvement and non-response in order to increase the proportion of patients who benefit.


Notes
Cite this as: BMJ 2015;350:h2087

Footnotes
Competing interests: We have read and understood BMJ policy on
declaration of interests and have no relevant interests to declare.

Provenance and peer review: Commissioned; not externally peer reviewed.

References

1. Van Kuppeveld FJ, van der Meer JW. XMRV and CFS—the sad end of a story. Lancet2012;379:e27-8.
2. Hickie I, Davenport T, Wakefield D, et al. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ2006;333:575.
3. Prins JB, van der Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet2006;367:346-55.
4. Tanaka M, Ishii A, Watanabe Y. Neural mechanisms underlying chronic fatigue. Rev Neurosci2013;24:617-28.
5. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev2015;2:CD003200.
6. Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue syndrome. BMJ 2000;320:292-6.
7. Knight SJ, Scheinberg A, Harvey AR. Interventions in pediatric chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. J Adolesc Health2013;53:154-65.
8. Moss-Morriss R, Sharon C, Tobin R, Baldi JC. A randomized controlled graded exercise trial for chronic fatigue syndrome: outcomes and mechanisms of change. J Health Psychol2005;10:245-59.
9. Nijs J, Meeus M, Van Oosterwijck J, et al. In the mind or the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome. Eur J Clin Invest2011;42:203-11.
10. Clark LV, White PD. The role of deconditioning and therapeutic exercise in chronic fatigue syndrome (CFS). J Mental Health2005;14:237-52.
11. Chalder T, Goldsmith KA, White PD, Sharpe M, Pickles AR. Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. Lancet Psychiatry2015;2:141-52.
12. White PD, Goldsmith KA, Johnson AL, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet2011;377:823-36.
13. Wiborg JF, Knoop H, Prins JB, Bleijenberg G. Does a decrease in avoidance behavior and focusing on fatigue mediate the effect of cognitive behavior therapy for chronic fatigue syndrome? J Psychosom Res2011;70:306-10.
14. Jackson ML, Bruck D. Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review. J Clin Sleep Med2012;8:719-28.
15. White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med2013;43:2227-35.
16. Kindlon T, Baldwin A. Response to: reports of recovery in chronic fatigue syndrome may present less than meets the eye. Evid Based Mental Health2014. doi:10.1136/eb-2014-101961.
17. Adamowicz JL, Caikauskaite I, Friedberg F. Defining recovery in chronic fatigue syndrome: a critical review. Qual Life Res2014;23:2407-16.
18. De Lange FP, Koers A, Kalkman JS, et al. Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. Brain2008;131:2172-80.

Friday, May 8, 2015

Unite for Equal Funding at NIH!

By Robert and Courtney Miller

Two scientific reports in two months by experts independent of the ME/CFS field say the same thing: "The committee stresses that more research is urgently needed." To change our disease, we must work together to push the National Institutes of Health to increase funding for research. Join us by emailing the Secretary of Health and Director of NIH for equal funding for ME/CFS research!

The Institute of Medicine, an arm of the widely-respected National Academy of Sciences, and National Institute of Health's own Pathways to Prevention Program have issued urgent calls to federal health agencies and the NIH to conduct more medical research into the causes and treatments for ME/CFS, also known as Systemic Exertion Intolerance Disease.
"Remarkably little research funding has been made available to study the cause of ME/CFS, mechanisms associated with the development and progression of the disease, or effective treatment, especially given the number of people affected." Institute of Medicine
"Unfortunately, ME/CFS is an area where the research and medical community has frustrated its constituents, by failing to assess and treat the disease and by allowing patients to be stigmatized....Over the last 20 years, minimal progress has been made to improve the state of the science for patients with ME/CFS.... Innovative biomedical research is urgently needed to identify risk and therapeutic targets, and for translation efforts." NIH Pathways to Prevention Report

The power of the P2P report and the IOM report is in the common conclusions that the need for evidence-based research is urgent and that ME/CFS is a complex, serious physiological disease. And the P2P and IOM recommendations are more powerful because they came from independent scientists.

Best Opportunity in Decades to UNITE for Equal Funding!

We have powerful ammunition from prestigious institutions to press for equal research funding from the NIH. The need isn't new, but having demands from well-respected institutions outside of our illness is.

Please take positive action to raise the pressure for #EqualFunding for ME/CFS. We can make this opportunity bigger by organizing our community to speak with one voice on the need for more research funding.

EMAIL CAMPAIGN

Help us reach a goal of 1,000 emails to Secretary of Health Burwell and NIH Director Collins!

Copy and paste the email addresses below into the “To” section of your email. Then copy and paste the template email text. Feel free to add your own personal story. Family members or supporters may have to change a few phrases, since we drafted the letter from the perspective of patients.

We ask you to cc the White House and Courtney, so that we can know how many emails are sent.

Thank you!!

Robert and Courtney Miller

___________________________

TEMPLATE

Email addresses:

To: sylvia.burwell@hhs.gov, scheduling@hhs.gov, francis.collins@nih.gov, collinsf@od.nih.gov, brewera@od.nih.gov

Cc: jarrettpublic@who.eop.gov, courtneymiller999@gmail.com

Subject Line: Equal Funding for Chronic Fatigue Syndrome (ME/CFS) Research

Dear Secretary Burwell and Dr. Collins:

I am disabled with ME/CFS, and I am writing to ask you to raise research funding for my disease to a level of $100 million annually, equal to illnesses like Multiple Sclerosis and Systemic Lupus.

I want to highlight two scientific reports commissioned by HHS that were released in the last two months by independent experts. They say the same thing: "The committee stresses that more research is urgently needed."

The Institute of Medicine, an arm of the widely respected National Academy of Sciences, and National Institutes of Health's own Pathways to Prevention Program have issued urgent calls to federal health agencies and the NIH to conduct more medical research into the causes of and treatments for ME/CFS.

"Remarkably little research funding has been made available to study the cause of ME/CFS, mechanisms associated with the development and progression of the disease, or effective treatment, especially given the number of people affected." Institute of Medicine

"Unfortunately, ME/CFS is an area where the research and medical community has frustrated its constituents, by failing to assess and treat the disease and by allowing patients to be stigmatized....Over the last 20 years, minimal progress has been made to improve the state of the science for patients with ME/CFS.... Innovative biomedical research is urgently needed to identify risk and therapeutic targets, and for translation efforts." NIH Pathways to Prevention Report

NIH currently funds only $5 million annually for CFS research, despite the fact that 1-2.5 million Americans suffer with the disease. That is not enough funding to spur breakthrough science, much less FDA-approved treatments. By contrast, illnesses such as Multiple Sclerosis and Systemic Lupus receive more than $100 million annually in NIH research funding, although fewer patients are ill. Those diseases now boast diagnostic tests and many FDA-approved treatments because of the high quality research NIH has funded in those fields. That is what patients like me so desperately need, and I believe that is what it takes to fulfill President Obama’s 2012 commitment to elevate CFS at the NIH.

I have no treatments and I am very ill. The FDA has rejected the only medication that has undergone clinical trials. Please help me by funding medical research into ME/CFS equally and urgently, so I can get well and return to work and live my life.

Patient Name:

Years Ill:

State:

Friday, May 1, 2015

May 12 - International ME/CFS, Lyme, and FM Awareness Day Events

This post first appeared on ProHealth.

International ME/CFS Awareness Day was originated by Tom Hennessy, an ME patient and staunch advocate who testified at numerous national and international ME/CFS conferences and meetings.

Tom chose May 12th as ME/CFS Awareness Day to commemorate the birth of the famous nurse, Florence Nightingale, who suffered from an ME/CFS-like illness. May 12 is also International Nurses Day.

Over the years May 12 has been expanded to include other neuro-immune illnesses that share many of the features of ME/CFS. At present May 12 includes Fibromyalgia (FM), Lyme disease, and Multiple Chemical Sensitivity (MCS). All of these illnesses employ May 12 as an opportunity to raise public awareness, to contact representatives for more research, and to promote fund-raising activities.

Although it is not formally recognized in the US, International ME/CFS and FM Awareness Day is observed worldwide.

Simple things you can do:

  • Wear a blue ribbon for ME/CFS, a purple ribbon for FM, or a green ribbon for Lyme disease and MCS.
  • Tweet on May 12. Add #may12 to your tweet.
  • If you have a blog or a Facebook page, post something. It can be as simple as an awareness image.
  • If you have some spare cash, donate to research efforts. Big Sleep in the UK is raising money for research to find a cure.

EVENTS

Here are some of the activities scheduled for the week of May 12-18, 2015. (Some events are scheduled for the days prior.)

You can see a full list of events (worldwide) HERE.

You can view an updated roster of events HERE.

INTERNATIONAL


Light Up the Night Challenge. “The challenge is to get as many buildings as possible in your country to light up with one of the 3 colours used on May 12th – blue (ME/CFS), purple (FM) or green (Lyme and MCS). We want public buildings/places like City Halls, Niagara Falls and we want individual homes lit up too!” To see all the places that are lighting up May 12th go HERE.

#May12BlogBomb. May 12th is Awareness Day for ME, Fibromyalgia, Lyme Disease, Chronic Fatigue Syndrome and Multiple Chemical Sensitivity. Every year bloggers use this opportunity to express their views and to raise the profile of these much misunderstood and often maligned conditions. Blog bomb information is HERE.

Google – Create a Doodle. Every year the doodlers ask Google to create a doodle. They’ll ask until Google caves in and does it. Please go to the Facebook page

FIBRO FLARE: “Aunty Acid has agreed to promote International Fibromyalgia Awareness Day on May the 12th!

For anyone who may not be aware of Auntie Acid, visit her page https://www.facebook.com/auntyacid


Please also notice it has 7.1 million likes worldwide.

This is a huge victory for Fibro awareness as it reaches so many people.

They have also been a huge supporter of Autism awareness!

We at the Fibro Team are incredibly excited about this! Thank you Auntie Acid!”

USA

The National FM and Chronic Pain Association lists events in 20 states across the US. Click HERE for a complete list. (Each state has a drop-down menu.)

Haines City, Florida has proclaimed May 12th Fibromyalgia and Chronic Fatigue Syndrome Awareness Day.

Newark, NJ mayor Ras Baraka has proclaimed May 12 “Fibromyalgia Awareness Day.”


New York City. The Caterpillar Walk program is a fundraising campaign designed to raise awareness and support for Fibromyalgia and Chronic Pain. 100% of proceeds raised will support education, advocacy and research efforts. While many walks have taken place across the country to support our work, this is the 1st annual walk in NYC. Our goal is to help bring the Fibromyalgia and Chronic Pain community together. The NYC Caterpillar Walk will take place on Saturday May 9th. Registration: 9:00 am. Where: Hudson River Park (on the river by 23rd Street & West Side Highway). Welcome, Announcements & Awards: 9:45 am. Walk Start: 10:00 am followed by finish line photos, entertainment and an afterparty. Every Walker will receive a T-Shirt and Medal. Due to the generous support of Branded in Brooklyn we can waive the registration for up to 50 walkers. You can find them on facebook or visit their crowd funding page to register HERE.

Danbury, CT. Lyme Conference and Health Fair. Tuesday, May 12, 2015 1:00 pm - 9:30 pm. Location:Western CT State University, West Side Campus Student Center, Danbury, CT. Lyme disease specialist and author Dr. Richard Horowitz is the keynote speaker for our ninth annual Lyme disease patient conference entitled " Lyme Disease: Why Can't We Get Better? From Symptoms to Solutions" This event is free. No registration required.

Ridgefield, CT. 9th Annual Lyme Connection Patient Seminar and Health Fair at WestConn on Tuesday, May 12, 2015. “Lyme Disease: Why Can't We Get Better? From Symptoms to Solutions.” Free and open to the public, the event includes an afternoon integrative medicine workshop from 1 to 4 p.m. with Dr. William Lee Cowden and Eva Sapi, PhD; a Lyme-focused health fair beginning at 6 p.m. and an evening presentation spotlighting the work of Lyme-treating physician and bestselling author Dr. Richard Horowitz at 7 p.m. Lyme Disease Association president Pat Smith will receive the first “Courage in Advocacy Award." The program concludes at 9:30 with questions and answers.

AUSTRALIA

The Do Something for ME project is designed to raise awareness in the general community about ME/CFS and to raise funds to support Emerge Australia to continue its work advocating for, educating about and providing information on the condition.


CANADA

Nanaima, BC has proclaimed May 12th Fibromyalgia and Chronic Fatigue Syndrome Awareness Day.

Send an email to your MP. A template can be found here.

Charlottetown, Prince Edward Island City Hall will be lit with all three colors on May 12th.

ME/FM Society of BC. In collaboration with the National ME/FM Action Network and the BC Complex Chronic Diseases Program ME/FM Society of BC will present talks by Dr. Daniel Peterson and Staci Stevens. When: Sunday May 24th, 2015 1:00 pm - 5:00 pm. Doors Open 12:30 pm. Where: Paetzold Lecture Theatre, Jim Pattison Pavillion, Vancouver General Hospital, 799 West 12th Ave, Vancouver. Entry for Members: $10 / Non-Members: $20. Memberships ($25) are available at the door. Space is limited, so please RSVP: 604-878-7707/1-888-353-6322. Please leave a message with your name, phone number and # of tickets.

Langevan Bridge in Calgary, Alberta will light up on May 12th. along with many other places, buildings and spots like the Niagara Falls (will light up blue on May 12th at 10pm It can be watched on either of these 2 webcams HERE or HERE) and the city halls of Mississauga, Ontario; Brampton, Ontario; Ottawa, Ontario; Halifax, Nova Scotia and Toronto, Ontario. The Montreal Olympic Stadium in Quebec will be lit with all colours and the Ontario’s CN Tower in Toronto will be lit with all 3 colours (blue for ME, green for Lyme and purple for fibromyalgia).

Vancouver. Opera Mariposa is bringing audiences a night of musical theatre showstoppers in support of chronic neuro-immune disease awareness. On Saturday, May 16th, sopranos Jacqueline Ko and Robin Eder-Warren, baritenor Kyle Preston Oliver and pianist Chris Feige will present 'Tour de Force,' a Broadway benefit show at Marpole United Church. The performance will honour the International Awareness Week for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia (ME/CFS & FM), and a portion of every ticket sale will go to the National ME/FM Action Network. Tickets start at $15 and are available at operamariposa.com or from Brown Paper Tickets at 1-800-838-3006.

GERMANY

Join Germany’s May 12 Thunderclap.

HOLLAND

ME/cvs Vereniging is making an appeal to all readers of its facebook and site. Which song or poem or book or film helps you somewhat in hard times? You may explain in a few words why, but it’s not obligated. Sending the link to it suffices. If you are on twitter, please send them a DM, but you can also respond by email: contact@me-cvsvereniging.nl. On May 12 they will publish all tweets using ?#‎12MEi and your first name. They do hope a lot of people will join them again so that they will create a lot of attention for ME!

IRELAND

Newlands Cross. On May 12, at Bewleys’ Hotel, Newlands Cross from 10 AM-12PM, and 1PM-2PM at Leinster House, there will be coffee with guest speakers.

The Irish ME/CFS Association is pleased to announce the following two talks as part of its ME Awareness Month activities in May by Dr. Abhijit Chaudhuri from the UK. The talks will include questions-and-answers sessions. Admission is E5, on the door, to help towards the costs of organising these two meetings, and Dr. Chaudhuri's trip.
  • Saturday, May 30: 2:45 pm, Connacht Hotel (formerly Carlton Hotel), Dublin Road, Renmore, Galway City. Hotel tel: 091 381 200. http://theconnacht.ie/ Free parking.
  • Sunday, May 31: 11 am, Carlton Hotel Dublin Airport, Old Airport Road,Cloghran (Santry), Dublin Airport, Co. Dublin. Hotel tel: (01) 8667500. E-mail: info.dublin@carlton.ie . Free parking.
Celbridge Co Kildare. From Trisha in Ireland: For International awareness Day May 12th I am having a Tea/Coffee Morning From 9.30 to 12.30 at my home in Celbridge Co Kildare with the kind help of Fionnuala Kelly Monahan. It will be a pop in at a time that suits you feel free bring a cake or buns there will be a cover charge of €5 all money will go directly awareness fund. Everyone will be asked to wear something purple as we will be taking lots of photos.You will be given a Raffle ticket on arrival as my son’s girlfriend Rebecca has kindly Donated a Pandora Jewellery Box as prize to be raffled at 12.30. Please bring a friend neighbour your mum daughter all will be so welcome let's make it the best we can. I will be adding extra boxes of tea and coffee to my shop over next few weeks to make sure everything on the day donated goes to our cause as every cent will make a difference. Why don't you try do the same in your area?

ITALY

AISF ONLUS (the Italian Association for Fibro and CFS) is organizing an event on the 10th of May in Verona.

JAPAN

Thunderclap from Japan

SWEDEN

In Sweden, wear something blue on May 12.

RME's different Facebook pages and groups will be observing 12th May by using a Remember ME header from the 10th of May to the 13th. For more information click HERE.

UK

Walk for ME UK is arranging an international Walk for ME. The idea behind Walk for ME is that friends and family of an ME sufferer do a sponsored walk, run or swim on their behalf, hence the name Walk for ME or Walk for me. Walk for ME has had walkers, runners and swimmers across England, Scotland, Wales, Ireland, the Isle of Man as well as in Spain, New Zealand and both coasts of America and in total has raised over £28,000 including gift aid. Wherever you are, we hope you'll become involved this year! It is hoped that as many friends and loved ones as possible will do a sponsored walk or other sponsored event during ME Awareness week which runs from 11th May to 17th May 2015. See event details HERE.

Afternoon Tea: An afternoon tea will be held in the Tyme Trust's home county of Essex. The event takes place in ME Awareness Week, in the Summer Parlour at Ingatestone Hall, on Monday 11th May, from 2.30-4.30pm. Ingatestone Hall is the ancestral home of Lord Petre, Lord Lieutenant of Essex, who will be addressing our guests. We will be presenting our new ME Awareness publication. You can find out all about the Hall at www.ingatestonehall.com If you would like to attend, please email us as soon as possible on the Contact Us form at www.tymestrust.org. There will be an opportunity to meet our Trustees and volunteers.

Big Sleep for ME: Raising funds for a cure.

Tuesday, April 28, 2015

Guts, Bugs and "Slow Sepsis" in ME/CFS

Last fall, Invest in ME announced an update in its research into the microbiome of ME/CFS patients. The study is based on the hypothesis that exposure to gut microbes through increased intestinal permeability (aka "leaky gut") initiates microbe-driven inflammatory reactions in ME/CFS. The researchers hope to detect increases in serum antibodies towards specific intestinal bacteria.

The goal of the study is "to determine if alterations in intestinal barrier function and/or microbiota firstly, exists in ME/CFS patients and secondly, whether there is an interaction between microbe-driven inflammatory responses and neuronal proteins."

As a hypothesis, this study has a firm foundation. 

Antibodies produced by the infiltration of gut bacteria into the bloodstream can initiate, among other things, a cascade of potentially lethal inflammatory responses. In 2014, researchers at the University of Chicago found that patients in the Intensive Care Unit had only limited kinds of gut flora left in their intestines after multiple rounds of antibiotics. Not surprisingly, these were flora that were pathogenic (Candida, a yeast, and antibiotic-resistant Staph). What was more, once the normal flora had been killed off, these pathogens became deadly. Three of the ICU patients died - not from injuries or from infections - but from pathogenic gut flora.

Slow Sepsis

Dr. David Bell proposed that patients with ME/CFS have what he called "slow sepsis." In his monograph, Cellular Hypoxia and Neuro-Immune Fatigue, he suggests that ME/CFS is a slow, chronic form of septic shock. The sequence of events in septic shock is: 1) a serious infection, 2) production of cytokines, 3) increased nitric oxide, and 4) interference with the production of cellular energy. In severe cases of septic shock, the loss of cellular energy is so profound that it can be fatal.

Dr. Bell suggests that a similar sequence takes place in ME/CFS, but more gradually. In ME/CFS there is: 1) an initiating infection or toxic exposure, which 2) leads to immune activation, increasing the production of cytokines, 3) the increase in cytokines leads to the production of increased nitric oxide (NO), 4) NO increases peroxynitrite and superoxide, which leads oxidative stress, and interferes with mitochondrial function, 5) the cell becomes hypoxic (oxygen-starved), and 6) vasculopathies, neuropathies, and autoimmune processes develop.

While Dr. Bell does not propose that this sequence of events can be initiated by leaky gut, there is absolutely no reason to assume that it can't. The destruction of the tight juncture between the cells of the intestinal lining has a host of causes. Any infection in the intestines (e.g. enteroviruses, parasites), drugs (e.g. NSAIDs. steroids), viral infections, radiation therapy for cancer, nutrient deficiencies (e.g. zinc), inflammatory conditions, toxins, and antibiotics can lead to the production of excess NO (oxidative stress), compromising the integrity of the gut lining (Wu et al, 2002). Given the high level of oxidative stress found in people ME/CFS it is likely that the majority of patients will develop leaky gut.

Evidence of gut dysbiosis in ME/CFS

The involvement of intestinal flora in the perpetuation of ME/CFS is one that is backed by solid research.

Dr. Kenny De Meirleir found that gut dysbiosis correlates with cognitive dysfunction in people with ME/CFS. He discovered that in people with ME/CFS there are high levels of bacteria not normally found in gut flora, notably gram positive lactic acid bacteria. In addition, Dr. De Meirleir's team found active parvovirus B19 infections in the GI tracts of 40% of CFS/ME patients, as well as EBV and herpesvirus 6 in lesser amounts. Dr. John Chia has found a chronic form of enteroviral infection in the stomachs of ME/CFS patients, which he believes could lead to a variety of symptoms without causing direct organ damage.

In 2012, Michael Maes et al. published research indicating that translocation of bacteria due to increased intestinal permeability correlated with systemic inflammatory responses in ME/CFS patients. The researchers concluded that "translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients."

With the mounting evidence for GI infection, comprised gut lining, and translocation of gram-negative bacteria in patients with ME/CFS, it is imperative that research leading to treatment - such as the research conducted by Invest in ME - be supported.

Remedies for leaky gut

While research that helps explain the mechanisms of ME/CFS is important, people who have leaky gut and "slow sepsis" need to find ways of fixing the problem without delay. Poisoning, however slow, has immediate immune system consequences that cannot be ignored.

Although there is no drug to cure leaky gut, there are supplements that have been proven to help heal the mucosa of the gut lining;

Zinc carnosine: A 2007 study by A Mahmood et al, found that zinc carnosine stimulates gut repair processes. (You can read the full study here.)

Fiber: There is considerable debate about whether insoluble fiber (cellulose) is better for restoring the gut lining than soluble fiber. Research supports the idea that insoluble fiber is better for intestinal health, and that large amounts of soluble fiber may actually impair gut health (Shiao and Chang, 1986). In any case, diets that do not contain fiber increase intestinal permeability (G Spaeth, 1990).

Essential fatty acids (EFAs): Essential fatty acids, such as fish oil, flaxseed oil and borage oil, can help repair injury to the lining of the gut and restore gut mucosa. EFAs also limit the harmful effects created by the translocation of endotoxins (gram-negative bacteria found in the large intestine) (Vanderhoof et al. 1991).

Antioxidants: In 2008, M. Maes and J.C. Leunis found that leaky gut in patients with ME/CFS could be corrected with natural anti-inflammatories and antioxidants. Some of the antioxidants that have been reported as helpful for leaky gut are: NAC, Glutathione, and Gamma oryzanol.

Butyrates: Butyrates (also called butyric acid) are short-chain fatty acids produced in the colon by the fermentation of carbohydates through the action of intestinal flora. Butyrates enable your gut to function. Without them, the cells that line your intestines die by autophagy (they eat themselves). Butryrates are found naturally in butter. They can also be taken as a supplement (ButyrEn).
 

Friday, April 24, 2015

"Fear of Exercise" in Chronic Fatigue Syndrome

Therapy Today is the flagship professional journal published by British Association for Counselling and Psychotherapy (BACP), the largest membership organisation for counselors and psychotherapists in the UK with over 40,000 members.

In the News section of its February 2015 edition, the journal published this announcement:

"Fears that exercise or physical activity will make their symptoms worse is one of the main blocks to people with chronic fatigue syndrome (CFS) benefitting from effective treatment, a new study has found. Fears that exercise or activity would make their symptoms worse accounted for up to 60 per cent of the overall effect of CBT and graded exercise therapy (GET) on outcomes. Both have been shown to be beneficial to people with CFS."

The "new study, " published in the Lancet on January 13,  is actually a rehashing of the PACE trial, an old and very flawed study. The Lancet article simply repeats the conclusions of the trial: that CBT and graded exercise are effective treatments for ME/CFS and that "fear avoidance beliefs were the strongest mediator for both CBT and GET." In short, we fear exercise, and that is why we have CFS.

As Joan Crawford has pointed out, there are numerous reports of exercise causing harm to ME/CFS patients. But what also needs to be remembered is that the methodology of the PACE trial was fundamentally flawed, that the conclusions were not validated by any accepted scientific standards, and that full results of the PACE trial have been kept secret, which has allowed its proponents to endlessly repeat its unsubstantiated "findings." 

Nowhere else in the scientific community would a single unreplicated study - one that did not even follow the most fundamental requirements of study design -  be allowed to stand unchallenged, much less hold sway over government healthcare policies.

___________________________________________


Activity and chronic fatigue syndrome

By Joan Crawford, Therapy Today, February 2015
 
In the February 2015 edition of Therapy Today (News, p 6) there is a short report on exercise and CFS. Uncritically your report states, ‘Both [CBT aimed at increasing patients activity and GET (graded exercise therapy)] have been shown to be beneficial to people with CFS.’ The evidence base does not support this bold assertion.

In a recent Cochrane Review 1 of the eight clinical trials of GET (n=1518) 85 per cent of the patients (n=1287) were recruited into five of these trials based on one symptom – fatigue.2 This is a common symptom of many health problems, including major depression, making generalisation of the findings problematic. The high percentage of patients included in these trials with elevated levels of distress perhaps indicating a depressive state,1 which may be their primary condition, confounds the results.

Exercise, through behavioural activation programmes, has a moderately positive impact on patients with depression.3 It is unclear whether the modest improvement seen in some of these trials can be accounted for by an improvement in low mood caused by depression. Moreover, where there are data, there is a high usage of antidepressants in patients included in trials. Three further trials used the CDC4 CFS criteria (n=231). While these criteria purport to be more selective, they do not necessarily include patients whose primary difficulties include post-exertion weakness and debility beyond broadly defined fatigue and other general symptoms, that could be attributed to CFS or major depression.

There is also an issue with lack of evidence of patients’ fidelity to exercise programmes using objective measures. Without using monitoring devices such as actimeters or pedometers to track daily activity levels, we have no accurate way of assessing whether an increase in activity occurred and whether this helps. Black and McCully’s study5 demonstrates the difficulties CFS patients face when trying to increase activity and concluded that they were exercise intolerant, unable to sustain activity targets.

Many patient surveys from across the world report numerous instances of harm and worsening of symptoms from taking part in exercise programmes. For a summary of the difficulties and limitations of the reporting of harms, in and outside of clinical trials, and why these might be underestimated, please see Kindlon.6

Joan Crawford MA, MSc, CSci, MBPS, MBABCP
Chair, Chester ME self help (MESH);
Humanistic counsellor, CBT therapist and trainee counselling psychologist

References:
1. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Systematic Review 2015.http://www.ncbi.nlm.nih.gov/pubmed/25674924
2. Sharpe M, Archard L, Banatvala J et al. Chronic fatigue syndrome: guidelines for research. Journal of the Royal Society of Medicine 1991; 84(2):118–121.
3. Cooney GM, Dwan K, Greig CA et al. Exercise for depression. The Cochrane Library 2013.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004366.pub6/abstract
4. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Annals of Internal Medicine 1994; 121(12): 953–959.
5. Black CD, McCully KK. Time course of exercise induced alterations in daily activity in chronic fatigue syndrome. Dynamic Medicine 2005; 28(4):10.
6. Kindlon T. Reporting of harms associated with graded exercise therapy and cognitive behavioural therapy in Myalgic Encephalomyelitis/chronic fatigue syndrome. Bulletin of the IACFS/ME 2011; 19(2): 59–111.

Tuesday, April 21, 2015

Profound, Debilitating Fatigue in Autoimmune Disease Overlaps with ME/CFS

A number of researchers have proposed that ME/CFS eventually become an autoimmune disease. There is plenty of scientific evidence to support this theory.

Persistent viral infections, particularly infections with Epstein-Barr virus (EBV) can lead to systemic autoimmune disease. (See: Epstein-Barr Virus in Systemic Autoimmune Diseases)

Among other things, EBV inhibits natural killer cell (NK) function (a common immune system finding in ME/CFS patients) allowing EBV to proliferate and spread to many parts of the body. Each time EBV reactivates, the immune system responds by attacking increasing numbers of cells. Eventually, this process leads to organ degeneration. (Remember, CFS was originally thought to be a chronic EBV infection.)

Autoimmune activity has been documented in ME/CFS. (See: Is Chronic Fatigue Syndrome an Autoimmune Disease?) In an important study published in 2009, Hokama et al, found anti-cardiolipin antibodies in the sera of patients with CFS. Anti-cardiolipin antibodies (ACA) are formed when immune system cells attack mitochondria. ACA are found in lupus as well as other autoimmune diseases, which may account for the profound fatigue experienced by patients with autoimmune disease.

A number of physicians and researchers, including Dr. Kenny De Meirleir and Michael Maes, have pointed out that chronic infection eventually leads to autoimmunity. Recent research by Peterson et al. on cerebrospinal fluid in ME/CFS patients also indicates the development of autoimmunity in ME/CFS.

Given these strong overlaps, as well as the success of rituximab in treating Norwegian patients with ME, it makes perfect sense that patients with recognized autoimmune disease should share the defining symptom of CFS - fatigue.

Please see these related posts for additional information on autoimmunity and ME/CFS:

Immune Activation, Chronic Inflammation and Mitochondrial Dysfunction in Autoimmune Disease and ME/CFS


Is Chronic Fatigue Syndrome an Autoimmune Disease?

Fluge and Mella on Rituximab and Autoimmunity in ME

ME/CFS: From Infectious Disease to Autoimmune Disorder
___________________

Profound, debilitating fatigue found to be a major issue for autoimmune disease patients in new national survey

Press Release: American Autoimmune Related Diseases Association (AARDA), March 23, 2015. Fatigue described as "profound," "debilitating," and "preventing them from doing the simplest everyday tasks," is a major issue for autoimmune disease (AD) patients, impacting nearly every aspect of their lives. It affects their mental and emotional well-being and their ability to work. And while most AD patients have discussed their fatigue with their physicians, many have not been prescribed treatment for their fatigue.

Those are among the major findings of a new online survey of autoimmune disease patients conducted by the American Autoimmune Disease Related Diseases Association (AARDA), the nation's only not-for-profit autoimmune disease patient advocacy organization, to examine the connection between autoimmune disease and fatigue. AARDA released the findings of the survey of 7,838 AD patients at a national summit held to commemorate National Autoimmune Disease Awareness Month at the National Press Club in Washington, D.C.

Major findings include:
  • Almost all (98 percent) AD patients surveyed report they suffer from fatigue.
  • Nine-in-10 (89 percent) say it is a "major issue" for them and six-in-10 (59 percent) say it is "probably the most debilitating symptom of having an AD."
  • More than two-thirds (68 percent) say their "fatigue is anything but normal. It is profound and prevents [them] from doing the simplest everyday tasks."
  • While nearly nine-in-10 (87 percent) report they have discussed their fatigue with their doctor, six-in 10 (59 percent) say they have not been prescribed or suggested treatment by their doctors.
  • Seven-in-10 (70 percent) believe others judge them negatively because of their fatigue.
  • Three-quarters (75 percent) say their fatigue has impacted their ability to work; nearly four-in-10 (37 percent) say they are in financial distress because of it; one-in-five (21 percent) say it has caused them to lose their jobs; while the same number (21 percent) report they have filed for disability as a result of their fatigue.
Fatigue impacts nearly every aspect of AD patients' lives including overall quality of life (89 percent), career/ability to work (78 percent), romantic (78 percent), family (74 percent) and professional relationships (65 percent) and their self esteem (69 percent), among others.

"In this busy, busy world, it's normal to be tired, but the kind of fatigue autoimmune disease patients suffer from is anything but normal," said Virginia T. Ladd, President and Executive Director of AARDA.

"The overwhelming response AARDA received to this survey shows without a shadow of doubt that fatigue is not a 'fuzzy' symptom, it's real. Yet, for too long, it has been ignored and/or misunderstood by the medical community and the public at large. It's time we bring more research funding to this issue to advance understanding and effective treatments for fatigue."

The survey revealed that fatigue has a significant impact on AD patients' mental and emotional well-being. They say it has resulted in increased emotional distress (88 percent), a sense of isolation (76 percent), anxiety (72 percent) and depression (69 percent).

According to one AD patient, "It's difficult for other people to understand our ongoing fatigue when it can't be seen by them. It's so hard just trying to get others to really, really understand how very tired you are sometimes -- even our own doctors don't understand. One wonders if even our doctors may think we are for the most part just mental cases and/or whiners."
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