Danish RCT of cognitive behavior therapy for whatever ails your physician about you

Posted on 12/10/2016 by wames

PLOS blog post by James Coyne PhD, 7 December 2016: Danish RCT of cognitive behavior therapy for whatever ails your physician about you

I was asked by a Danish journalist to examine a randomized controlled trial (RCT) of cognitive behavior therapy (CBT) for functional somatic symptoms. I had not previously given the study a close look.

I was dismayed by how highly problematic the study was in so many ways.

I doubted that the results of the study showed any benefits to the patients or have any relevance to healthcare.

I then searched and found the website for the senior author’s clinical offerings.  I suspected that the study was a mere experimercial or marketing effort of the services he offered.

Overall, I think what I found hiding in plain sight has broader relevance to scrutinizing other studies claiming to evaluate the efficacy of CBT for what are primarily physical illnesses, not psychiatric disorders. Look at the other RCTs. I am confident you will find similar problems. But then there is the bigger picture…

[A controversial assessment ahead? You can stop here and read the full text of the RCT  of the study and its trial registration before continuing with my analysis.]

Schröder A, Rehfeld E, Ørnbøl E, Sharpe M, Licht RW, Fink P. Cognitive–behavioural group treatment for a range of functional somatic syndromes: randomised trial. The British Journal of Psychiatry. 2012 Apr 13:bjp-p.

A summary overview of what I found:
The RCT:

  • Was unblinded to patients, interventionists, and to the physicians continuing to provide routine care.
  • Had a grossly unmatched, inadequate control/comparison group that leads to any benefit from nonspecific (placebo) factors in the trial counting toward the estimated efficacy of the intervention.
  • Relied on subjective self-report measures for primary outcomes.
    With such a familiar trio of design flaws, even an inert homeopathic treatment would be found effective, if it were provided with the same positive expectations and support as the CBT in this RCT. [This may seem a flippant comment that reflects on my credibility, not the study. But please keep reading to my detailed analysis where I back it up.]
  • The study showed an inexplicably high rate of deterioration in both treatment and control group. Apparent improvement in the treatment group might only reflect less deterioration than in the control group.

The study is focused on unvalidated psychiatric diagnoses being applied to patients with multiple somatic complaints, some of whom may not yet have a medical diagnosis, but most clearly had confirmed physical illnesses.
But wait, there is more!

It’s not CBT that was evaluated, but a complex multicomponent intervention in which what was called CBT is embedded in a way that its contribution cannot be evaluated.
The “CBT” did not map well on international understandings of the assumptions and delivery of CBT. The complex intervention included weeks of indoctrination of the patient with an understanding of their physical problems that incorporated simplistic pseudoscience before any CBT was delivered. We focused on goals imposed by a psychiatrist that didn’t necessarily fit with patients’ sense of their most pressing problems and the solutions.

And the kicker.

The authors switched primary outcomes – reconfiguring the scoring of their subjective self-report measures years into the trial, based on a peeking at the results with the original scoring.

Investigators have a website which is marketing services. Rather than a quality contribution to the literature, this study can be seen as an experimercial doomed to bad science and questionable results from before the first patient was enrolled. An undeclared conflict of interest in play? There is another serious undeclared conflict of interest for one of the authors.

For the uninformed and gullible, the study handsomely succeeds as an advertisement for the investigators’ services to professionals and patients.

Personally, I would be indignant if a primary care physician tried to refer me or friend or family member to this trial. In the absence of overwhelming evidence to the contrary, I assume that people around me who complain of physical symptoms have legitimate physical concerns. If they do not yet have a confirmed diagnosis, it serves little purpose to stop the probing and refer them to psychiatrists. This trial operates with an anachronistic Victorian definition of psychosomatic condition.

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Exercise exposes new types of POTS

Posted on 12/09/2016 by wames

Health rising blog post, by Cort Johnson, 6 December: Exercise Exposes New Types of Postural Orthostatic Tachycardia Syndrome (POTS)

Extracts:

Exercise has been used in many studies to understand chronic fatigue syndrome (ME/CFS), but nobody until recently has used exercise to try to understand POTS.  Exercise is a particularly interesting tool in the case of POTS because exercise intolerance is often present, and because like with fibromyalgia, exercise has become a kind of go-to therapy for POTS.

In these two studies researchers at the Mayo Clinic in Rochester, New York exercised adolescent POTS and ME/CFS patients (in one of the studies)  to exhaustion while measuring their heart rates, oxygen usage, anaerobic threshold, ventilation, gas exchange, etc. The hypothesis – POTS is a heterogeneous condition that is caused in several ways.  The goal – to elucidate different subsets.

POTS is characterized by high heart rates upon standing which attempt to compensate for blood pooling in the lower body

  • Exercise stress tests exposed types of POTS that tilt tests failed to reveal
  • The high cardiac outputs and blood flows in hyperkinetic POTS patients attempt to compensate for a failure to vasoconstrict or tighten down their blood vessels when they stand.
  • The overly vasoconstricted blood vessels in hypokinetic POTS patients attempt to compensate for reduced blood volume, low venous capacity and reduced blood flows to the heart
  • The study suggested that deconditioning adds another burden to both adolescent POTS and ME/CFS patients.

Neuropathic POTS – caused by decreased vasoconstriction of the blood vessels in the legs and/or abdomen causing blood to pool in the lower body upon standing. Not associated with autoimmune issues according to a 2014 review. Treatment is focused on improving circulation with exercise and vasoconstricting drugs such as Midodrine, droxidropa and Mestinon (pyridostigmine)

Hyperadrenergic POTS – associated with increased sympathetic nervous system activity which can be caused in multiple ways. Treatment includes exercise, beta blockers and possibly angiotensin receptor blockers and droxidopa.

Hyperkinetic – The high cardiac output seen in the “hyperkinetic” POTS group attempts to compensate for problems constricting their blood vessels. During exercise our blood vessels should narrow in order to develop enough pressure (perfusion pressure) to force more blood into our tissues. In the hyperkinetic group, however, their blood vessels remain open; instead the group kicks their heart output up in order to produce the needed perfusion pressure.

That compensatory effort – like so many compensatory efforts in the body – is not entirely successful. These patients get lots of blood flowing through their systems but still get reduced oxygen extraction at the muscles. The authors noted that the reduced oxygen extraction  could be due to metabolic issues but they believe is probably simply a blood flow problem. They characterized these patients’ muscles as starving in the land of plenty – and becoming fatigued because of it.

Unlike the hypokinetic group, these patients do not have problems with  blood volume or preload.

The Hypokinetic Group – Hypokinetic POTS  patients have the opposite problem; their low blood volume and decreased blood vessel capacity means they can’t increase their cardiac output. Instead, they tighten down their blood vessels in order to apply pressure.

In 2004 Stewart called this group of patients the “low-flow” group. Low blood volume clearly plays a major role. These patients’ low calf blood volumes, reduced venous capacitance and tightened down blood vessels left Stewart describing them as being “chronically vasoconstricted”.  The “muscle pump” that’s supposed to kick in to keep their blood from draining into their lower body when they stood isn’t working either.

This study indicates that this group of POTS patients also has reduced stroke volume (cardiac output) due to reduced preload. Reduced preload  – or the inability to fill the heart with enough blood to pump it out in normal amounts – is same problem that Systrom uncovered in his large exercise study of patients with unexplained exercise problems.

The only thing the body can do to combat a problem like this is to clamp down on the blood vessels in an attempt to build up enough pressure to get the blood to the tissues (e.g. perfusion pressure again).

Read the full article

 

 

 

 

 

 

Exercise Exposes New Types of Postural Orthostatic Tachycardia Syndrome (POTS)

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High-frequency rTMS for the treatment of CFS

Posted on 12/08/2016 by wames

Research abstract:

Structural and functional abnormalities of the prefrontal cortex seem to correlate with fatigue in patients with chronic fatigue syndrome (CFS).

We consecutively applied facilitatory high-frequency repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) of seven CFS patients over three days. Five patients completed the 3-day protocol without any adverse events.

For the other two patients, we had to reduce the stimulation intensity in response to mild adverse reactions. In most of the patients, treatment resulted in an improvement of fatigue symptoms. High-frequency rTMS applied over the DLPFC can therefore be a potentially useful therapy for CFS patients.

High-frequency rTMS for the Treatment of Chronic Fatigue Syndrome: A Case Series. by W Kakuda, R Momosaki, N Yamada, M Abo in Intern Med. 2016;55(23):3515-3519. [Epub 2016 Dec 1.]

Extract from the full text:

The present study has certain limitations.

First, this is a case-series pilot study with only a small number of patients that lacked a control group. Comparative studies, such as randomized controlled design studies that include a large number of patients, are needed to confirm the efficacy of rTMS in CFS patients.

Second, although all patients met the inclusion criteria for rTMS application, they were a heterogeneous group based on the wide variability of age, duration of illness and severity of the fatigue symptoms. The identification of the clinical factors that correlate with the efficacy of rTMS can help in the selection of patients who will best benefit from the treatment.

Third, although it is difficult to stimulate deep brain lesions using the currently available technology, the stimulation of other brain areas with functional or structural  abnormalities in CFS, such as the cingulate cortex and brainstem, may produce a better clinical improvement.

Furthermore, for one left-handed patient, we applied high-frequency rTMS to the right hemisphere unlike the other six patients. The appropriateness of this therapeutic strategy of rTMS depending on whether patients were righthanded or left-handed should be also confirmed.

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TV interview with Dr Nancy Klimas

Posted on 12/07/2016 by wames

US TV news report [NBVDFW Dallas], December 1, 2016

Dr Nancy Klimas of the Institute for Neuro Immune Medicine and ex marine Paula Bushman are interviewed.

dr-klimas

Researchers helping those tired of chronic fatigue [2 mins 4 sec]

Now Dr. Klimas and her team are on the verge of a breakthrough identifying a specific gene which will allow them to predict the best medications.

 

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NICE investigates if there’s a need to update CFS/ME guideline

Posted on 12/07/2016 by wames

As a stakeholder WAMES has been informed about NICE plans regarding the 2007 CFS/ME guideline and will be participating fully:

I am writing to advise you that NICE has commenced its formal check of the need to update the clinical guideline CG53 Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management.

In 2014 this guideline was added to the clinical guidelines static list as no quality standard had been commissioned for this topic and no major ongoing studies completing within the next 3-5 years were identified. Guidelines on the static list remain in existence and will be considered for new evidence at 5-year intervals. In the case of CG53 the static list review was due in 2019. However, if important new evidence is notified we can remove the guideline from the static list and carry out a full guideline surveillance review.

In 2015 we were advised of 3 US reports that indicated there are likely to be changes in the diagnostic criteria in this field that will have implications for the guideline in the future, but not until after the proposed 2 year validation of the diagnostic criteria is completed.  In view of these reports we have decided to commence a formal check of the need to update the guideline earlier than the 5 year interval.  We have since been made aware of new information about the 2011 PACE trial, and we will also consider that in the review.

The guideline surveillance review has been scheduled for review at the beginning of 2017 and a decision is expected to be published by summer 2017. A surveillance report will be developed to communicate the update decision and provide a commentary on approximately 3 articles felt to be of particular interest within this topic.  The exact publication date will depend on the progress of the review and the proposed update decision.  We will email stakeholders when the report has been published.

There will be a 2-week consultation with registered stakeholders if information summarised indicates that a ‘no update’ decision should be considered.  There is no consultation if the decision is to update the guideline because it has been based on the availability of new evidence, and is usually supported by stakeholders. It is important to note that if the decision is to update the guideline then the update will be developed in accordance with NICE processes for updating guidelines.  The timescales for any update of the guideline will depend on the size and extent of the required update and available capacity.

Consultation dates and times are posted in advance on the guideline page on the NICE website, and stakeholders are reminded by email.

Administrator Surveillance Reviews

NICE Centre for Guidelines

National Institute for Health and Care Excellence Level 1A, City Tower, Piccadilly Plaza, Manchester M1 4BT     www.nice.org.uk

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Epistemic injustice in healthcare encounters: evidence from CFS/ME

Posted on 12/06/2016 by wames

Research abstract:

Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) remains a controversial illness category. This paper surveys the state of knowledge and attitudes about this illness and proposes that epistemic concerns about the testimonial credibility of patients can be articulated using Miranda Fricker’s concept of epistemic injustice.

While there is consensus within mainstream medical guidelines that there is no known cause of CFS/ME, there is continued debate about how best to conceive of CFS/ME, including disagreement about how to interpret clinical studies of treatments. Against this background, robust qualitative and quantitative research from a range of countries has found that many doctors (and medical students) display uncertainty about whether CFS/ME is real, which may result in delays in diagnosis and treatment for patients. Strikingly, qualitative research evinces that patients with CFS/ME often experience suspicion by healthcare professionals, and many patients vocally oppose the effectiveness, and the conceptualisation, of their illness as psychologically treatable.

We address the intersection of these issues and healthcare ethics, and claim that this state of affairs can be explained as a case of epistemic injustice (2007). We find evidence that healthcare consultations are fora where patients with CFS/ME may be particularly vulnerable to epistemic injustice. We argue that the (often unintentional) marginalisation of many patients is a professional failure that may lead to further ethical and practical consequences both for progressive research into CFS/ME, and for ethical care and delivery of current treatments among individuals suffering from this debilitating illness.

Epistemic injustice in healthcare encounters: evidence from chronic fatigue syndrome by Charlotte Blease, Havi Carel, Keith Geraghty in J Med Ethics [Published Online 5 December 2016]

Comment on this article:

BMJ blogs: Mind the Gap: Ethical Failures in the Treatment of Chronic Fatigue Syndrome. Guest Post: Charlotte Blease & Keith Geraghty, 6 Dec 2016

Some illnesses are uncool.

That might sound like an inflammatory comment – especially for a medical journal, yet perhaps the biggest concealed fact in medicine is that hierarchies of diseases exist among patients and healthcare professionals. A caste system of illness influences how patients perceive their health complaints, whilst health professionals also hold biases that influence how they treat and rank patients in the medical pecking order.

When it comes to hierarchies of illness, evidence shows that chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME), features at the bottommost end of the medical “favoured” list.   read more

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Newcastle University experts in hunt for “smoking gun” of CFS/ME

Posted on 11/30/2016 by wames

Northern echo news article, by Tony Kearney, 29 Nov 2016: Newcastle University experts in hunt for “smoking gun” of chronic fatigue syndrome ME

UNIVERSITY scientists are leading research to develop a simple blood test for the chronic fatigue syndrome ME.

Researchers from Newcastle and Oxford Universities have been awarded £50,000 funding from the ME Association to spend 12 months analysing nearly 300 blood samples, looking at metabolomics – chemical clues that are left behind after changes in cells.

Finding similarities in the cells of patients diagnosed with ME could help identify a test for the condition – and ultimately a cure.

Dr Charles Shepherd, medical adviser for the ME Association, said: “Put simply, this is the hunt for a smoking gun.

“This could be a major breakthrough.

He added: “Once and for all, we would be able to dispel the myth that ME should be treated as a psychological illness which is primarily in the mind.”

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Podcast about CFS/ME research with Melbourne researcher Chris Armstrong

Posted on 11/30/2016 by wames

insidestory.com.au, 24 Nov 2016: In Melbourne, progress on chronic fatigue

Peter Clarke talks to Bio21 researcher Chris Armstrong about new research that challenges popular views of this enigmatic illness

With its debiliating symptoms – fatigue, “brain fog,” pain, gastrointestinal disorders – and its elusive causes, chronic fatigue syndrome has been one of the great unsolved medical mysteries. Now, a growing number of research teams around the world are tackling the challenge of diagnosing and treating the illness using new medical research techniques.

By looking at patients’ genetics and the changing pattern of their metabolites – the molecules produced by their individual metabolisms – these researchers have made enormous progress in uncovering patterns exclusive to the condition and countering once-popular psychological explanations.

Among the research centres working on CFS (also known as myalgic encephalomyoletis) is the Bio21 Institute at the University of Melbourne. Earlier this month, amid the centrifuges, mass spectrometers and NMR cylinders used to identify shifts in biological material, Peter Clarke spoke to Bio21 researcher Chris Armstrong.

The Institute’s work is supported by the Mason Foundation, with assistance for NMR equipment from the Australian Research Council.

Read more and listen to podcast. Duration: 24 mins 11 secs

PETER CLARKE
Peter Clarke is a Melbourne-based broadcaster, writer and educator who pioneered national talkback on Australian radio as the inaugural presenter of Offspring (now Life Matters) on ABC Radio National.

Article on Chris Armstrong by Cort Johnson

University of Melbourne blog post, by Florienne Loder, University of Melbourne: Chronic fatigue syndrome a kick in the guts,

Research suggests that chronic fatigue is linked to gut bacteria and how our bodies convert food into energy

 

 

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Experiences of GP continuity among women with CFS/ME in Norway

Posted on 11/29/2016 by wames

Research abstract:

Background:  Continuity of care is important for patients with chronic illness in need of coordinated healthcare services from multiple providers. Little is known about how patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) experience continuity of GP care.

This study explores how women with CFS/ME experience GP care across the three dimensions of continuity: informational, management, and relational continuity.

Methods:  This cross-sectional study uses questionnaire data collected from members of The Norwegian ME Association. Descriptive statistics and logistic regressions were used to estimate experiences of continuity, and associations with age, education, self-rated degree of CFS/ME, duration of the GP relation (GP duration), and number of GP visits for
CFS/ME-related issues during the previous year (GP frequency).

Results: Almost two-thirds of participants reported positive experiences across all three dimensions of GP continuity of care; 64.4% for informational, 64.1% for management, and 77.2% for relational continuity. Lower educational attainment was associated with more negative experiences of informational continuity (primary school only compared to university educated: odds ratio [OR] 0.12, confidence interval [CI] 0.03-0.49, p = 0.003).

Compared to participants aged 40-59 years, those aged 60+ years were significantly less likely to have experienced poor (negative) management continuity (OR 0.25, CI 0.09-0.76, p = 0.014). A GP relationship of three or more years was associated with positive
experiences of relational continuity (OR 2.32, CI 1.09-4.95, p = 0.030).

Compared to those with moderate CFS/ME, those who graded their CFS/ME as severe or very severe were significantly more likely to have negative experiences of relational continuity (OR 0.38, CI 0.14-0.99, p = 0.047).

Conclusions:  A large proportion of participants experienced all three aspects of
continuity of GP care (especially the relational dimension) positively. Informational and management continuity scores were moderately lower. Our results suggest greater emphasis on information giving, feedback, and better coordination of care to be good strategies for practice improvement for this patient group.

Experiences of general practitioner continuity among women with chronic fatigue syndrome/myalgic encephalomyelitis: a cross-sectional study, by Anne Helen Hansen, Olaug S. Lian in BMC Health Services Research Vol 16, #1, p 650, Published: 14 November 2016

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A targeted genome association study examining transient receptor potential ion channels, acetylcholine receptors, and adrenergic receptors

Posted on 11/28/2016 by wames

Research abstract:

BACKGROUND:
Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis (CFS/ME) is a debilitating condition of unknown aetiology. It is characterized by a range of physiological effects including neurological, sensory and motor disturbances. This study examined candidate genes for the above clinical manifestations to identify single nucleotide polymorphism (SNP) alleles associated with CFS/ME compared with healthy controls.

METHODS:
DNA was extracted and whole genome genotyping was performed using the HumanOmniExpress BeadChip array. Gene families for transient receptor potential ion channels, acetylcholine receptors, and adrenergic receptors, and acetylcholinesterase were targeted. The frequency of each SNP and their association between CFS/ME and healthy controls was examined using Fisher’s exact test, and to adjust for multiple testing, False Detection Rate (FDR) and Bonferroni corrections were applied (p < 0.05).

RESULTS:
The study included 172 participants, consisting of 95 Fukuda defined CFS/ME patients (45.8 ± 8.9; 69 % female) and 77 healthy controls (42.3 ± 10.3; 63 % female). A total of 950 SNPs were included for analysis. 60 significant SNPs were associated with CFS/ME compared with healthy controls. After applying FDR and Bonferroni corrections, SNP rs2322333 in adrenergic receptor α1 (ADRA1A) was higher in CFS/ME compared with healthy controls (45.3 % vs. 23.4 %; p = 0.059). The genotype class that was homozygous minor (AA) was substantially lower in CFS/ME compared with healthy controls (4.2 % vs. 24.7 %).

CONCLUSIONS:
This study reports for the first time the identification of ADRA1A and a possible association between CFS/ME and genotype classes. Further examination of the functional role of this class of adrenergic receptors may elucidate the cause of particular clinical manifestations observed in CFS/ME.

A targeted genome association study examining transient receptor potential ion channels, acetylcholine receptors, and adrenergic receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, by Johnston S, Staines D, Klein A, Marshall-Gradisnik S in BMC Med Genet. 2016 Nov 11;17(1):79.

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