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Studies on Cognitive Behavioral Therapy and Graded Exercise Therapy for ME/CFS are misleading

  • Proximion AB, Kista, Sweden


There have been a number of studies on Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS based on a treatment model where the disease is perpetuated by cognitive processes. Although the studies are flawed and the model lacks scientific support, the treatments are described as evidence based. The studies are non-blinded and rely on subjective outcomes. There are no objective measures of adherence. The diagnostic criteria vary, and the participating patients often have one or several psychiatric diagnoses apart from suffering from chronic fatigue. The underlying model has no theoretical foundation and is at odds with physiological findings. Surveys suggest that the efficacy of CBT is no better than placebo and that GET is harmful. Therefore, cognitive behavioral therapy and graded exercise therapy for ME/CFS are not evidence based.
Studies on Cognitive Behavioral Therapy and Graded
Exercise Therapy for ME/CFS are misleading
Sten Helmfrid
Assoc. Prof. of Physics, Member of the Swedish ME Association
This is a translation of an article published in Socialmedicinsk tidskrift, Stockholm,
Sweden, on September 28
, 2016.
Link to the original article in Swedish (vol. 93, issue 4, pp. 433–44):
Citation: Helmfrid S. Studier av kognitiv beteendeterapi och gradvis ökad träning vid
ME/CFS är missvisande. Soc Med Tidskr. 2016;93(4):433–44.
There have been a number of studies on Cognitive Behavioral Therapy (CBT) and
Graded Exercise Therapy (GET) for ME/CFS based on a treatment model where the
disease is perpetuated by cognitive processes. Although the studies are flawed and
the model lacks scientific support, the treatments are described as evidence based.
The studies are non-blinded and rely on subjective outcomes. There are no objective
measures of adherence. The diagnostic criteria vary, and the participating patients
often have one or several psychiatric diagnoses apart from suffering from chronic
fatigue. The underlying model has no theoretical foundation and is at odds with
physiological findings. Surveys suggest that the efficacy of CBT is no better than
placebo and that GET is harmful. Therefore, cognitive behavioral therapy and graded
exercise therapy for ME/CFS are not evidence based.
Keywords: myalgic encephalomyelitis, chronic fatigue syndrome, treatment,
biopsychosocial, PACE
— 1 —
ME/CFS—sometimes also referred to as chronic fatigue syndrome—is a severely de-
bilitating disease [1]. It is classified since 1969 as a neurological disease by the World
Health Organization (WHO) [2]. Although ME/CFS has unknown etiology and patho-
genesis, a number of abnormalities have been observed in patients, including immu-
ne and autonomic dysfunction, neuroendocrine abnormalities, brain and mitochond-
rial dysfunction, and neurocognitive defects [3].
In the late 1980s, a group of British psychiatrists—the so-called Oxford school—
introduced a biopsychosocial treatment model for ME/CFS. They claimed that the
disease is perpetuated by avoidance behavior and deconditioning and that this
pattern can be reversed by cognitive behavioral therapy (CBT) [4]. The cognitive
therapy is often combined with graded exercise therapy (GET), which means that the
patients gradually increase their activity level to agreed targets in order to reverse
the deconditioning. The psychiatrists created their own criteria for chronic fatigue
syndrome, which only requires prolonged fatigue and therefore selects a larger and
more heterogeneous group of patients than what is normally understood by ME/CFS
There have been numerous studies published on cognitive behavioral therapy and
graded exercise therapy for ME/CFS, for example the British PACE study [6]. It was
published in the Lancet in 2011, and attracted a lot of media attention. The studies
have serious methodological flaws, and evidence that contradicts the model has been
neglected. Negative results have been played down. Despite criticism from research-
ers, doctors, journalists, and patients’ organizations, which often has been harsh [7–
15], the proponents continue to claim positive outcomes for the treatments. This
article provides an overview of the methodological flaws of the studies and of the
evidence that contradicts the underlying model. Cognitive behavioral therapy and
graded exercise therapy according to the Oxford model has no positive effect in
patients with ME/CFS, but on the contrary often leads to deterioration.
There is no improvement in objective outcomes
In treatment studies, the group or groups receiving the experimental treatment are
always compared with a control group. To avoid systematic errors in the comparison
due to the placebo effect or reporting bias, the study must either be blinded or use
objective outcomes [16]. Several factors contribute to the systematic error, for exam-
ple the attitude of the therapists. It is therefore expected that the errors are large in
studies of cognitive behavioral therapy and graded exercise therapy, as it is part of
the treatment model to convince patients that the method works.
The studies of CBT and GET according to the Oxford model have almost exclusively
relied on subjective self-reports [6], which makes it impossible to determine the real
efficacy of the treatment. In the few cases where objective outcomes have been re-
ported, the results have been disappointing. One way of obtaining an objective mea-
sure of fatigue is to register the activity level of the patient by a so-called accelero-
meter, a device roughly the size of a watch that is attached to the wrist or the ankle.
A Dutch group reviewed three earlier studies in which activity data were recorded by
accelerometers, but no analysis was carried out. Their post-analysis showed that
— 2 —
there was no increase in the objective activity levels of the patients, in spite of re-
ported improvement in the subjective fatigue [17]. In two other uncontrolled studies
of CBT with accelerometers, subjective improvement did not result in any increase in
the objective activity level [18,19]. In a study that compared neuropsychological test
results before and after intervention with cognitive behavioral therapy, the self-
reported cognitive impairment improved, but the objective test scores remained un-
changed [20].
The PACE study included a test of how far the patients were able to walk in six
minutes. All treatment groups improved slightly during the study, but the group that
followed the graded exercise program improved more than the others [6]. This was
portrayed as objective support for GET by the authors. However, the walking test is a
rough measure of improvement, as it is not possible to control what effort the parti-
cipants are making. In the complementary fitness test that was carried out during
the study, but was published only four years later, there was no improvement for any
of the groups—including the one that followed the graded exercise program [21]. This
suggests that the attitude of the patients changed, but that there was no improve-
ment in physical functioning [22]. It should be pointed out that the result of the GET
group in the walking test, 379 m, was very modest. A result of 400 m corresponds to
severe functional impairment and has been suggested as a marker when lung pati-
ents should be listed for transplantation [23]. The normal result for healthy adults is
about 640 m [24].
Other objective measures of improvement are return to productive work or studies.
A follow-up of PACE showed that the treatment did not result in fewer sick days, nor
in a reduction in levels of benefits or payments from insurance companies. The same
picture emerged in an audit of four Belgian rehabilitation centers. There was no im-
provement in the physical fitness of the patients after 6–12 months of treatment, and
the number of hours in employment decreased [26].
When activity is used as an objective measure in studies of ME/CFS, it is important
to register the overall activity for a period of time. Patients are often compensating
for increased activity by cutting back on other commitments. Children with ME/CFS,
for example, usually abandon leisure activities in order to keep up at school [27]. In a
Dutch study of internet-based cognitive behavioral therapy for adolescents (FIT-
NET), school attendance increased alongside with improvements in subjective out-
comes, which was interpreted as a big success by the authors [28]. The fact that nei-
ther activities out of school nor performance in school were monitored makes it im-
possible to determine if there was any improvement in the physical or cognitive capa-
city of the patients. The results of FITNET are at odds with previous experiences of
objective outcomes and must therefore be interpreted with caution.
The risks are underestimated because there are no objective measures of
Patients’ organizations have often pointed out that graded exercise therapy may lead
to deterioration in ME/CFS. Reports of adverse events in published studies have not
always been easy to interpret, but treatment risks are usually dismissed by propo-
nents of the Oxford model. In the PACE study, more cases of severe deterioration
— 3 —
were reported in the GET group than in other groups. However, the authors thought
that the difference was negligible and concluded that graded exercise therapy is a
safe intervention [6].
When the risks of a treatment are assessed, it is important to know how the patients
adhere to the protocol. The lack of objective measures of the activity level in most
studies of graded exercise therapy means that there are also no objective measures of
adherence. Studies in which accelerometers were used show that self-reported acti-
vity levels are unreliable [19]. In a case study of graded exercise therapy, the patient
was unable to follow the training program and reduced the activity level [29]. Similar
results were obtained in another study where patients should walk a certain distance
every day [30]. The authors of the PACE study claim that the adherence to the exer-
cise protocol was good, but the poor results in the fitness test suggest otherwise. The
relatively low number of adverse events that has been reported in published studies
therefore does not mean that graded exercise therapy according to the protocol is
The inclusion criteria are not consistent
Another problem is that the inclusion criteria in the studies have been inconsistent.
Centers for Disease Control and Prevention (CDC) published the first criteria for the
disease in 1988 after an epidemic in Lake Tahoe, and introduced the term Chronic
Fatigue Syndrome (CFS) [31]. CDC singled out persistent fatigue as the cardinal
symptom, although experienced physicians that were involved in several earlier
epidemics had suggested that muscle fatigability is the most characteristic symptom
[32,33]. The criteria were revised in 1994, the so-called Fukuda criteria [34]. The
patients must experience severe fatigue over a period of six months and have addi-
tionally four of eight specified neurological and immunological symptoms. Criteria of
this kind—where some of the symptoms from a larger pool of symptoms should be
present—are called polythetic and have the disadvantage that the selected group of
patients becomes more heterogeneous.
The Oxford school emphasized the symptom fatigue and suggested that the other
symptoms and the etiology were of secondary importance. They published criteria of
their own in 1991, which only required persistent, severe fatigue [5]. They used the
name CFS, although it was already used in the CDC construct with a slightly diffe-
rent meaning, and despite the word syndrome usually referring to a combination of
symptoms rather than a single symptom. This has caused a lot of confusion in the
scientific literature. CFS according to the Oxford criteria selects a larger and more
heterogeneous group than the Fukuda criteria and includes many patients with
psychiatric diagnoses. Studies of exercise programs are difficult to interpret, as pati-
ents with ME/CFS often feel worse after exercise, whereas fatigued patients with
major depressive disorder (MDD) often feel better [35].
In 2003, an expert panel selected by Health Canada published a consensus document
on chronic fatigue syndrome. They revived the earlier term ME for the disease and
introduced the compromise term ME/CFS. They also proposed a new and more
restrictive set of criteria for the disease, the Canadian Consensus Criteria (CCC)
[36]. The objective was to select a more homogeneous group of patients. Post exer-
— 4 —
tional malaise became mandatory for diagnosis. In addition, the patients should have
a number of neurological, immunological and endocrine symptoms. These criteria are
used by the International Association for CFS/ME (IACFS/ME) [3] and are recom-
mended by most biomedical researchers in the field.
The evaluation and the comparison of treatment studies on ME/CFS have been comp-
licated not only by different inclusion criteria, but also because the criteria have been
incorrectly operationalized by some investigators. To operationalize usually means
that abstract formulations are interpreted, so that they can be applied in a practical
situation. In many treatment studies of CBT and GET, the investigators have pushed
the boundaries and changed or removed some of the conditions that should be met. In
some cases, this has caused uncertainty whether the patients in the study really re-
flect the group selected by the inclusion criteria. For example, a Dutch group claimed
that the Fukuda criteria were used in a study, but they "operationalized" the criteria
by removing the four additional symptoms [37].
Most of the early studies of cognitive behavioral therapy and graded exercise therapy
used the Oxford criteria [38], but in more recent studies the Fukuda criteria have
also been used [39]. It is unclear if the results from a heterogeneous group of patients
may be particularized to a more strictly defined group, for example patients who
meet the Canadian consensus criteria. A study of patients with chronic fatigue in the
UK primary care suggested that a strong predictor for poor outcome of cognitive
behavioral therapy and graded exercise therapy is that the patients meet the Fukuda
criteria for ME/CFS [40].
The Oxford criteria were used in the PACE study, but the study included a sub-group
analysis that compared the results for the main group with the results for patients
who met the so-called London criteria [41] and CDC's revised criteria from 2003 (in
practice the same as the Fukuda criteria) [42]. The conclusion was that there were no
significant differences between the compared diagnostic criteria. Unfortunately, the
sub-groups in the comparison were biased. Patients who were recruited to PACE met
the Oxford criteria, which require fatigue to be the predominant symptom [5]. From
this group, patients who fulfilled the other diagnostic criteria were then selected. The
process excludes patients who fulfill the London criteria or CDC criteria, but who
have predominantly neurological or immunological symptoms. The correct procedure
would be to recruit the patients with different diagnostic criteria separately, not from
the group of Oxford patients. On top of this, a follow-up publication two years after
the original study revealed that the Fukuda criteria were operationalized in PACE.
The four additional symptoms needed to be present only for a week, rather than for
six months [43]. The six-month limit is important to rule out other conditions [44],
and it is therefore unclear which type of patients were actually included in the com-
parative analysis of PACE.
There is no scientific support for the underlying “theory”
There is no scientific support for the treatment model used by the Oxford school, and
its proponents have caused confusion by using inaccurate terms in the scientific lite-
rature and by presenting exaggerated claims. In science, a theory or a model is a de-
scription of the mechanisms behind a phenomenon [45]. (A model should not be con-
— 5 —
fused with a treatment model, which is merely a flow chart for the therapeutic
efforts.) If a theory, model or other scientific proposition does not yet have empirical
support, it is called a hypothesis [46]. The interventions with cognitive behavioral
therapy and graded exercise therapy are based on a hypothesis that the disease is
perpetuated by avoidance behavior and that symptoms are caused by a lack of fit-
ness. Although the Oxford school have not described any underlying mechanisms, nor
presented any evidence for the presumed causation, they refer to their hypotheses
either as theories [6] or models [47]. This gives the impression of scientific support,
which in fact does not exist.
When the hypotheses of the Oxford school first were introduced, the authors descri-
bed their ideas with an analogy. They accepted that infections often are triggers for
ME/CFS, but they pointed out that for example in a hit-and-run accident, pursuing
the guilty party is not necessary in order to get started with the rehabilitation of the
victim [4]. Similarly, it is not necessary to know what triggered ME/CFS in the first
place. The analogy misses an important point. When victims of a traffic accident are
rehabilitated, doctors must know what injuries they have sustained—fractures requi-
re different therapies than burns—and when ME/CFS is treated, the rehabilitation
strategy must resonate with the true perpetuating factors. The hit-and-run traffic
analogy gives no hint as to whether the proposed strategy really works.
The hypotheses of the Oxford school are implausible given what we know about ME/
CFS. The activity level of patients often follows a push–crash pattern [48]. Patients
push themselves to their limit, which leads to a deterioration (“crash”), and eventual-
ly to a recovery and to a new push period. This is inconsistent with the assumption of
avoidance behavior. Another problem is that post-infective fatigue only has been rep-
orted after a limited number of infections [49,50]. The hypotheses do not explain why
some pathogens do not trigger ME/CFS. The same perpetuating cognitive factors
should be present after any infection. It is also unlikely that lack of fitness could
cause ME/CFS symptoms. In this case similar symptoms should be observed in
people who are inactive for other reasons, such as people in plaster for a long time or
prisoners in isolation cells.
There have been several attempts to provide a theoretical basis for a biopsychosocial
understanding of ME/CFS. Vercoulen et al. published a structural equation model for
ME/CFS and concluded that behavioral and cognitive factors are involved in the per-
petuation of the symptoms [51]. However, this is a misinterpretation of the results.
Structural equation models can be used to test assumptions on how different factors
are related to each other, but the causal relations are always ambiguous [52]. It is
impossible to determine which of the biological, behavioral and cognitive factors are
antecedents and which are consequents without first having an understanding of the
underlying mechanisms, and this is not provided by the article. Moreover, Vercoulen
used a heterogeneous group of patients. When other researchers tried to replicate the
results, they obtained poor agreement for patients with ME/CFS, but good agreement
for patients with psychiatric conditions [53].
— 6 —
Physiological abnormalities verify that patients deteriorate after exercise
In graded exercise therapy, patients should gradually increase their level of activity
according to a predetermined plan. This treatment strategy has often been criticized,
as exertion may trigger a relapse in patients. Today there is strong evidence that
post-exertional malaise—which is regarded as a cardinal symptom of ME/CFS—has a
biomedical basis. Several independent studies show that patients cannot reproduce
their test parameters on day two in a repeated cardiopulmonary exercise test (CPET)
[54–56]. ME/CFS patients have reduced capacity to recover from acidosis as com-
pared to healthy controls [57]. Immunological changes [58] and cognitive impairment
[59] after exertion have also been demonstrated.
The principal investigator from the PACE trial, Peter White, has dismissed the criti-
cism of graded exercise therapy and claims that the activity level is below the level
that triggers physiological changes [60]. However, he admits that the graded-exercise
programs have been adapted so that patients may abstain from an increase in the
activity level or if necessary return to a previous lower level of activity. His defense is
thus an indirect confirmation that post-exertional deterioration does occur and that
the Oxford model does not describe the disease correctly.
Surveys suggest that CBT and GET are of no benefit
Patients’ organizations have for a long time used surveys to evaluate the efficacy of
different therapies. Data is available from eleven independent surveys conducted in
four different countries with replies from more than 15,000 patients [61–64]. The
results give a completely different picture than the published studies of the Oxford
model. The surveys suggest that graded exercise therapy carries a high risk of dete-
rioration. More than 4,700 patients have tried this treatment, and 53% reported that
they felt worse.
One of the largest surveys was conducted by the ME Association in the UK. In a
comparison between different therapies, graded exercise therapy had the second low-
est proportion of patients who reported an improvement, and the highest proportion
who reported deterioration [63]. More than 56% of the patients felt worse, and 33%
said they became much worse. The proportion of patients who improved was smaller
both for graded exercise therapy and cognitive behavior therapy than for homeopa-
thy—that is, in practice placebo. The same pattern appeared in a Norwegian patient
survey [62].
In the late 1980s, British psychiatrists introduced a treatment model for ME/CFS,
which has been tested in a number of non-blinded studies. A moderate improvement
in subjective parameters has been demonstrated in some cases, but the results have
been negative when objective parameters have been assessed. Patients have not been
able to return to productive work after treatment. Even though there are no objective
measures of adherence, the treatments are described as safe. Most studies have been
carried out on patients with chronic fatigue, but it has been assumed that the results
apply to more strictly defined ME/CFS. There is no scientific support for the hypo-
— 7 —
thesis that cognitive processes perpetuate the disease. A treatment where psycho-
therapy is used to convince the patients about the validity of an unproven hypothesis
can hardly be regarded as evidence based.
Both the treatment model and the results of the studies are contradicted by other
evidence. There are many reports that suggest a biomedical basis for post-exertional
malaise. This is inconsistent with the assumption that there is pathological avoidan-
ce of exertion in ME/CFS, and makes it difficult to believe that exercise leads to im-
provement. Patient surveys suggest that the efficacy of cognitive behavioral therapy
according to the Oxford model is no better than placebo, and that more than half of
the patients are made worse by graded exercise therapy.
PACE is so far the largest study on cognitive behavioral therapy and graded exercise
therapy. Even though it does not nearly meet the requirements for pharmacological
studies, it is described as a randomized controlled trial [47]. It is astonishing that so
many voices in the debate have been completely uncritical. The problems became
known to a wider audience in 2015, when an American health reporter demolished
the PACE study on the popular website Virology blog [15]. The initial article was
followed by several other critical blog posts [65]. Eventually, six prominent scientists
wrote an open letter to the editor-in-chief of the Lancet and demanded an indepen-
dent review of PACE [66]. The letter was ignored, but was followed by another letter
with forty two signatories [67]. More criticism has come from the 2013 Bill Silverman
prize winner, Professor James Coyne [68], and from the Director of, Profes-
sor Rebecca Goldin [69].
It is ultimately up to healthcare providers to critically assess the quality of treatment
studies. This article shows that there is no evidence for benefits of CBT according to
the Oxford model in ME/CFS and that graded exercise therapy often leads to deterio-
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... It is worth noting that the GET model is at odds with the physiological findings (Helmfrid, 2016). Physical deconditioning does not seem to be a perpetuating factor in CFS (Bazelmans et al., 2001) and CFS patients without a comorbid psychiatric disorder do not have an exercise phobia (Gallagher et al., 2005). ...
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The analysis of the 2017 Cochrane review reveals flaws, which means that contrary to its findings, there is no evidence that graded exercise therapy is effective. Because of the failure to report harms adequately in the trials covered by the review, it cannot be said that graded exercise therapy is safe. The analysis of the objective outcomes in the trials provides sufficient evidence to conclude that graded exercise therapy is an ineffective treatment for myalgic encephalomyelitis/chronic fatigue syndrome.
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An increasing number of studies have examined how the immune system of patients with Chronic Fatigue Syndrome (CFS), or myalgic encephalomyelitis, responds to exercise. The objective of the present study was to systematically review the scientific literature addressing exercise-induced immunological changes in CFS patients compared to healthy control subjects. A systematic literature search was conducted in the PubMed and Web of science databases using different keyword combinations. We included 23 case control studies that examined whether CFS patients, compared to healthy sedentary controls, have a different immune response to exercise. The included articles were evaluated on their methodological quality. Compared to the normal response of the immune system to exercise as seen in healthy subjects, patients with CFS have a more pronounced response in the complement system (i.e. C4a split product levels), oxidative stress system (i.e. enhanced oxidative stress combined with a delayed and reduced anti-oxidant response), and an alteration in the immune cells' gene expression profile (increases in post-exercise interleukin-10 and toll-like receptor 4 gene expression), but not in circulating pro- or anti-inflammatory cytokines. Many of these immune changes relate to post-exertional malaise in CFS, a major characteristic of the illness. The literature review provides level B evidence for an altered immune response to exercise in patients with CFS.
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Recent years have brought growing recognition of the need for clinical criteria for myalgic encephalomyelitis (ME), which is also called chronic fatigue syndrome (CFS). An Expert Subcommittee of Health Canada established the Terms of Reference, and selected an Expert Medical Consensus Panel representing treating physicians, teaching faculty and researchers. A Consensus Workshop was held on March 30 to April 1,2001 to culminate the review process and establish consensus for a clinical working case definition, diagnostic protocols and treatment protocols. We present a systematic clinical working case definition that encourages a diagnosis based on characteristic patterns of symptom clusters, which reflect specific areas of pathogenesis. Diagnostic and treatment protocols, and a short overview of research are given to facilitate a comprehensive and integrated approach to this illness. Throughout this paper, “myalgic encephalomyelitis” and “chronic fatigue syndrome” are used interchangeably and this illness is referred to as “ME/CFS.”
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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multi-system illness characterized, in part, by increased fatigue following minimal exertion, cognitive impairment, poor recovery to physical and other stressors, in addition to other symptoms. Unlike healthy subjects and other diseased populations who reproduce objective physiological measures during repeat cardiopulmonary exercise tests (CPETs), ME/CFS patients have been reported to fail to reproduce results in a second CPET performed one day after an initial CPET. If confirmed, a disparity between a first and second CPET could serve to identify individuals with ME/CFS, would be able to document their extent of disability, and could also provide a physiological basis for prescribing physical activity as well as a metric of functional impairment. 22 subjects diagnosed with ME/CFS completed two repeat CPETs separated by 24 h. Measures of oxygen consumption (VO2), heart rate (HR), minute ventilation (Ve), workload (Work), and respiratory exchange ratio (RER) were made at maximal (peak) and ventilatory threshold (VT) intensities. Data were analyzed using ANOVA and Wilcoxon's Signed-Rank Test (for RER). ME/CFS patients showed significant decreases from CPET1 to CPET2 in VO2peak (13.8%), HRpeak (9 bpm), Ve peak (14.7%), and Work@peak (12.5%). Decreases in VT measures included VO2@VT (15.8%), Ve@VT (7.4%), and Work@VT (21.3%). Peak RER was high (>=1.1) and did not differ between tests, indicating maximum effort by participants during both CPETs. If data from only a single CPET test is used, a standard classification of functional impairment based on VO2peak or VO2@VT results in over-estimation of functional ability for 50% of ME/CFS participants in this study. ME/CFS participants were unable to reproduce most physiological measures at both maximal and ventilatory threshold intensities during a CPET performed 24 hours after a prior maximal exercise test. Our work confirms that repeated CPETs warrant consideration as a clinical indicator for diagnosing ME/CFS. Furthermore, if based on only one CPET, functional impairment classification will be mis-identified in many ME/CFS participants.
This chapter presents various aspects of different theories and models in medicine. Bolie's model of Insulin-Glucose Regulation assumes only three entities — glucose, insulin, and extracellular fluid — and identifies nine variables. The menstrual cycle is not restricted to humans but medical science has provided the most in-depth and physiologically embedded advances in understanding the cycle — its hormonal, biochemical, physiological, and evolutionary dynamics. An example of a unifying model in medicine is the construction of models of self-regulating systems (homeostatic systems) which, in endocrinology for example, subsumes the insulin–glucose system as well as the menstrual cycle and many other hormonal systems such as the TSH–thyroxin system. An example of a unifying model in medicine is the construction of models of self-regulating systems (homeostatic systems) which, in endocrinology, for example, subsumes the insulin–glucose system as well as the menstrual cycle and many other hormonal systems such as the TSH–thyroxin system. It is suggested that the vast majority of medical science is deeply connected to the rest of science and shares the theoretical depth, sophistication, and explanatory power of those sciences.
Chronic fatigue syndrome (CFS) and Gulf War Syndrome are diseases of unknown etiology which are accompanied by severe fatigue as a main complaint. Yet there may be some kind of "post-infectious fatigue syndrome" following any infection by a virus. Post-infectious fatigue, which is caused by many different viruses, includes chronic active Epstein-Barr virus (EBV) infection and it is thought that the onset of this disease is associated with latent EBV infection in a very unusual manner. As there may be an unusual latent infection with human herpesvirus 6 (HHV-6) which may be an etiology of CFS in the CFS patients, the study on latent infection is considered to be important for elucidating CFS and Gulf War Syndrome.
Background: Cognitive behaviour therapy (CBT) added to specialist medical care (SMC), or graded exercise therapy (GET) added to SMC, are more effective in reducing fatigue and improving physical function than both adaptive pacing therapy (APT) plus SMC and SMC alone for chronic fatigue syndrome. We investigate putative treatment mechanisms. Methods: We did a planned secondary mediation analysis of the PACE trial comparing SMC alone or SMC plus APT with SMC plus CBT and SMC plus GET for patients with chronic fatigue syndrome. 641 participants were recruited from six specialist chronic fatigue syndrome clinics in the UK National Health Service between March 18, 2005, and Nov 28, 2008. We assessed mediation using the product of coefficients method with the 12 week measure of the mediators and the 52 week measure of the outcomes. The primary outcomes were fatigue measured by the Chalder fatigue scale and physical function measured by the physical function subscale of the SF-36. We included confounder covariates and used treatment by mediator interaction terms to examine differences in mediator-outcome relations by treatment group. Findings: The largest mediated effect for both CBT and GET and both primary outcomes was through fear avoidance beliefs with an effect of larger magnitude for GET (standardised effects ×10, CBT vs APT, fatigue -1.22, 95% CI -0.52 to -1.97, physical function 1.54, 0.86 to 2.31; GET vs APT, fatigue -1.86, -0.80 to -2.89, physical function 2.35, 1.35 to 3.39). Increase in exercise tolerance (6 min walk distance) was a potent mediator of the effect of GET (vs APT, fatigue -1.37, 95% CI -0.76 to -2.21, physical function 1.90, 1.10 to 2.91), but not CBT. Interpretation: Our main finding was that fear avoidance beliefs were the strongest mediator for both CBT and GET. Changes in both beliefs and behaviour mediated the effects of both CBT and GET, but more so for GET. The results support a treatment model in which both beliefs and behaviour play a part in perpetuating fatigue and disability in chronic fatigue syndrome. Funding: UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions, National Institute for Health Research (NIHR), NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust, and Institute of Psychiatry, Psychology, and Neuroscience, King's College London.
Purpose: Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis (CFS/ME), has a significant impact upon daily functioning. Most recommended treatments aim to alter activity patterns based upon assumptions of activity avoidance. However, as there is limited research on the experience of activity and occupational beliefs in people with CFS/ME, this study took a qualitative approach to understand the meaning of activity in people with this disabling condition. Method: This study applied a social constructivist grounded theory methodology. Semi-structured interviews took place with 14 participants attending a Specialist CFS/ME Service in England. Findings: The emergent themes described a premorbid state of constant action with difficulty stopping an activity once it had commenced. When this pattern was interrupted by illness, participants attempted to maintain their previous level of occupational engagement. Negative associations and emotions were described in response to the concept of doing nothing or limited activity. A recurring cycle was reported of increasing activity levels when symptoms improved, followed by post exertional symptoms. Conclusions: Consequently, participants' beliefs about concepts of both activity and inactivity need to be considered within the application of rehabilitation programmes for CFS/ME that aim to modify activity related behaviours. Implications for rehabilitation: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is commonly treated in the UK using activity modification. In this small qualitative study, patients expressed negative feelings and beliefs towards the concept of doing nothing and therefore sought to push their activity levels when this was available, leading to recurring cycles of symptoms and activity. Rehabilitation programmes need to consider how people with CFS/ME engaged with activity and inactivity before the condition and how this may impact upon engagement with activity-based rehabilitation programmes.