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CO-CURE Medical & Research Posts Only Digest - 27 Nov 2006 to 2 Dec 2006 (#2006-54)
 
  
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Date:    Tue, 28 Nov 2006 11:28:25 -0500
From:    "Dr. Marc-Alexander Fluks <fluks@xxx.xx>" (via Co Cure Moderators)
Subject: RES,NOT: CFS Science Classification System: determine scientific, value of CFS research

Think like a scientist, act like your doctor: you can now determine
the scientific value of CFS research yourself.

Surf to,
   http://www.me-net.dds.nl/meweb/web4.13.html

The classification process is simple: determine which characteristic
topics are present in a CFS research project, find the corresponding
number of points, add the numbers and then find the scientific value
of a research project.

It is the first version - so please send your comments to <me-net@dds.nl>
for future updates.

[Return to top]            

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Date:    Tue, 28 Nov 2006 11:32:40 -0500
From:    "Blake Graham <blanket@xxx.xxx.xx>" [via Co-Cure Moderators]
Subject: MED:Correcting disordered sleep in CFS

Dear Co-Cure readers,

I have recently written a detailed (3000+ words) article on treating sleep disorders in CFS patients. It is available online at:

http://www.nutritional-healing.com.au/content/articles-content.php?heading=Correcting%20disordered%20sleep%20in%20CFS
Best regards,

Blake Graham, B.Sc (Honours)
Clinical Nutritionist

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Date:    Tue, 28 Nov 2006 11:25:31 -0000
From:    Stephen Ralph <stephen.e.ralph@xxxxx.xxx>
Subject: ACT,NOT,RES: Digest of Gibson Report on CFS/ME - By Horace Reid

Permission to Repost

http://www.meactionuk.org.uk/Gibson_Inquiry_-_Digest_Format.htm

Digest of Gibson Report on CFS/ME.

Horace Reid.

On 26th November an all-party group of parliamentarians launched an
explosive report on the lack of British research into CFS/ME. They said:

·        Although there is no compelling evidence that CFS/ME is
psychological, there is persistent psychiatric bias in the UK.
·        The UK is lagging in biological research; important international
research is ignored.
·        The Medical Research Council is funding only psychological research
into CFS/ME.
·        The ME patient community is "extremely hostile" to certain
psychiatrists.
·        Current treatments amount only to symptom management, not cure.
·        There should be a government inquiry into ongoing research failure.
·        Some senior doctors have a "blatant conflict of interest", and
should be investigated.

The group was chaired by Dr. Ian Gibson, past chairman of the Commons
Science and Technology Select Committee. Other members included veteran
Labour MPs Ann Cryer and Michael Meacher, Dr. Des Turner, chairman of the
All Party Parliamentary Group on ME, Lords deputy Speaker the Countess of
Mar, and Lord Turnberg former President of the Royal College of Physicians.

£3.5 Billion Annual Cost.

CFS/ME is one of the most contentious illnesses in modern medicine, say the
MPs. In Britain it affects more than 200,000 patients. It can be a severely
incapacitating illness; many who suffer from it have their lives completely
ruined. There is no effective method of diagnosis, treatment or cure.
Current NHS provision leaves much to be desired. CFS/ME costs the UK about
£3.5b annually in medical services, social benefits and lost incomes.

Some Doctors Stigmatize ME Patients.

The MPs say they "heard a number of extremely disturbing testimonials from
patients dismissed by their GPs as 'attention seeking'." The inability of
some in the medical profession to identify genuine patients with CFS/ME
"enhances the view that all patients with CFS/ME are neurotic or not
genuinely ill".

They were also "concerned to receive written submissions from parents of
children with CFS/ME " who were disbelieved by social services and GPs. As a
result "their children were put on the at risk register, or even made wards
of court and removed from the family home." The MPs said CFS/ME "should not
be confused with Munchausen by Proxy".

Psychiatric Bias.

ME and CFS have been defined as neurological illnesses by the World Health
Organisation. "There is no compelling evidence it is purely psychosocial",
say the MPs. But in Britain there has been a clear historical bias towards
research into the psychosocial explanations of CFS/ME, they found. "The UK
has not been a major player in the global progress of biomedical research
into CFS/ME".

The effects of this psychiatric bias can be seen in some major British
textbooks for doctors. The 2004 edition of Kumar & Clark's "Clinical
Medicine" relegated CFS/ME to the chapter on psychiatric medicine. "While
CFS/ME remains only in the Psychological section of medical discourse, there
can be little chance of progress", the MPs conclude.

Professor Wessely of King's College Hospital is considered by many to be the
leading expert on treating CFS/ME. But many patient groups believe Dr.
Wessely and his colleagues are responsible for the perception that ME is a
psychosocial illness. "It is clear the CFS/ME community is extremely hostile
to the psychiatrists involved". "The Group invited Wesseley to speak at an
Oral Hearing, however he declined the offer", says the report. "The Group
were disappointed not to have the opportunity to discuss this important
issue with such a key figure".

No medical witness who appeared at the Oral Hearings proposed that CFS/ME
was entirely psychosocial. "So why has this model taken such a prominent
role in the UK?" the committee asked.

International Research Ignored.

The committee preferred the Canadian diagnostic protocol to existing British
criteria, and reproduced it in full in their report. "The Canadian Clinical
Criteria were much more detailed, including many more symptoms of CFS/ME
compared with the Oxford Criteria". They also admired new American
guidelines issued by the US Centers for Disease Control: "The CDC provides
very patient focused criteria".

The MPs wondered why British doctors had not made use of valuable
international research: "The Group was very interested in the international
evidence submitted and concerned as to why this evidence has not been
seriously examined in the UK".

Biomedical research needed.

"The underlying theme in all of our hearings was the paucity of research
into causes", said the Group. The origins and causes of CFS/ME will only be
found through scientific research. Provision of resources for biomedical
research is urgently needed. But there has been no massive investment.
Research areas defined by the Chief Medical Officer's 2002 Report on CFS/ME
have not been addressed.

The MPs called for a government Inquiry into the Scientific Evidence for
ME/CFS, undertaken by independent scientific and medical experts, (including
virologists, immunologists, biochemists) to objectively assess the relevance
of international scientific data.

They called for a crash programme of research investment, similar to the
AIDS project funded previously by the MRC.

Treatments.

Existing treatments consist of psychotherapy and exercise (CBT & GET). These
treatments "should be regarded as symptomatic treatments, not as cures", say
the MPs. CBT is at best only a partial answer. "It is most effective in
those with less severe forms of CFS/ME and appears to be much less effective
in those with severe disease".

"GET is an area for particular concern", they continued. "Some of our
evidence suggests that GET carries some risk". Some patients claim they are
harmed by this treatment, and as a result, there can be "serious antipathy
to the doctors offering it", the MPs found.

Treatment guidelines for CFS/ME will be released by the National Institute
for Clinical Excellence next April, and will likely recommend CBT and GET.
"The Group is concerned that NICE guidelines are recommending these
treatments without caveats", says the report. NICE guidelines should accept
that, as the causes and pathogenesis of ME/CFS remain poorly researched,
treatments are empirical and of only marginal symptomatic help in some
cases. "NICE will certainly benefit from listening to international
experts", they say.

Depression caused by medical neglect.

The committee noted a "close link with depression in many ME cases." However
many cases of depression were made worse by medical neglect.  There are
"professionals who do not believe" CFS/ME patients, and subject them to
"social stigma." Often CFS/ME is not accepted as a legitimate condition;
there is "lack of classification". Unlike other illnesses, there is less
"possibility of a cure." All of these factors "leave the CFS/ME sufferer
more disillusioned than those with other chronically disabling diseases, and
thus more prone to depression".

MRC Bias.

The Medical Research Council confirmed that from Apr. 2003 to Nov. 2006, it
has turned down 10 biomedical applications relating to ME/CFS. Over the same
period it has funded five applications relating to CFS/ME, mostly in the
psychiatric/psychosocial domain. These amounted to £11m. Biomedical
applications rejected include those by Professor Jill Belch (herself a
Principal Fellow of the MRC) and Dr Vance Spence of Dundee, as well as Dr
Jonathan Kerr of St Georges, London.

"The group were concerned by the MRC CFS/ME Research Advisory Group paper",
which concentrated "research effort on case management and 'potential
interventions' ", and "diverted attention away from the need for more
research into causation and diagnosis". "The MRC should be more open-minded
in their evaluation of proposals for biomedical research into CFS/ME". "They
should assign at least an equivalent amount of funding (£11 million) to
biomedical research as they have done to psychosocial research".

Social Security Benefits.

People with ME/CFS, like others, often experience great difficulty in
obtaining state sickness and disability benefits. CFS/ME patients are at a
massive disadvantage because of the controversy surrounding the cause of
their illness and suggestion that it may be psychosomatic. At present ME/CFS
is defined as a psychosocial illness by the Department for Work and Pensions
(DWP) and medical insurance companies. This classification is in the
financial interest of both the DWP and the insurance companies.

"The sooner there is a biomedical model of assessment for this illness the
better", say the MPs.

"The Group feels that patients with CFS/ ME, which is often an extremely
long term condition, should be entitled to the higher rate DLA. Until
medical opinion is better informed as to the nature of this illness ME
sufferers will have to live with the double burden of fighting for their
health and their benefits".

"Blatant" Medical Conflict of Interest.

"There have been numerous cases where advisors to the DWP have also had
consultancy roles in medical insurance companies. Given the vested interest
private medical insurance companies have in ensuring CFS/ME remain
classified as a psychosocial illnesses, there is blatant conflict of
interest here. The Group find this to be an area for serious concern and
recommends a full investigation of this possibility by the appropriate
standards body".

Conclusion.

The MPs say they will not be "distracted by debates centring on semantics in
this difficult and contentious field. The principal actuality remains, that
there exists a serious disease, which causes much suffering for patients,
and which may be severe and incapacitating."

"Our aim is to build consensus from this point forward', and to "ensure that
the voice of the patient is heard".

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Date:    Tue, 28 Nov 2006 16:15:54 +0100
From:    Jan van Roijen <j.van.roijen@xxxxx.xxx>
Subject: act,med: MERUK NICE Stakeholder Comments

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>> 28 November 2006     <<<<
Editorship : j.van.roijen@xxxxx.xx
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:

From:  "Neil Abbot" <Neil.Abbot@xxxxx.xxx.xx>

National Institute for Health and Clinical Excellence
CHRONIC FATIGUE SYNDROME / MYALGIC
ENCEPHALOMYELITIS (CFS/ME) GUIDELINE
Stakeholder Comments; 23rd November 2006


Organisation: ME Research UK

Address: The Gateway, North Methven St, Perth PH1 5PP, UK;
http://www.meresearch.org.uk/


Author of comments: Dr Neil Abbot, Director of Operations


The draft produced by the Guideline Development Group (GDG)
is unsafe and unsatisfactory ("unfit for purpose") because it does
not engage with key issues involved in the diagnosis and
management of ME/CFS. These comments briefly outline the
areas where core difficulties arise, and then present a line-by-
line critique of the main limitations. These core areas of difficulty
can be divided into the following:

1. The problem of the diagnostic rubric and the need for
research-based subsets.

2. The skewing of the RCT evidence-base examined by the
GDG, and the devaluation of evidence from scientific studies
and surveys. 3. The limitations of the evidence base for
non-specific management and coping strategies.


``````````````````````

1. Problem of diagnosis and the need for research-based
subsets

As the draft guidelines point out, ME/CFS is a diagnosis of
exclusion based on a collection of vaguely defined symptoms
that it shares with other illnesses. While the GDG has tried in
good faith to fulfill its remit – to suggest guidelines for "diagnosis
and management" – it has failed to ask what the diagnosis"
means and which patients or groups of patients it contains.
Without addressing these issues, the guidance is no more than
the blind leading the blind round in circles.

Terminology is the 'hot' issue in ME/CFS: it energises the
debate between patients and healthcare professionals, and it
impacts on patient management, clinical practice, and the
results of clinical trials (which are heavily dependent on the
entrance criteria used to recruit subjects). The issue can be
simply put. The original case description of the illness, myalgic
encephalomyelitis (ME) - Acheson, 1959; Dowsett et al, 1990 -
referred to a condition, commonly of infectious onset,
characterised by:

a) Exercise-induced myalgia and fatigue precipitated by trivial
exertion (physical or mental).`

b) Neurological disturbance, especially of cognitive, autonomic,
and sensory systems. This could include impairment of
short-term memory and loss of powers of concentration, usually
coupled with emotional lability, nominal dysphasia, disturbed
sleep patterns, dysequilibrium and/or tinnitus.

c) An extended and relapsing course with fluctuation of
symptoms, usually precipitated by either physical or mental
exercise; typically, the symptoms vary capriciously from
hour-to-hour and day-to-day with varying involvement of the
cardiac, gastro-intestinal, and lymphoid systems.

Since the late 1980s, however, the medical profession has been
urged by a small subset of its members to adopt the term
Chronic Fatigue Syndrome (CFS), a more wide-ranging
diagnostic category which includes patients whose dominant
symptom is medically unexplained, on-going, or chronic fatigue
(in conjunction with several other physical or psychological
symptoms) who would not necessarily fulfil the original criteria for
ME.

There are now several definitions of CFS, all still unvalidated in
2006; the Guideline Development Group (GDG) has mentioned
these (FULL Guideline, page 111- 2), but has not grasped their
significance. In the USA, the 1994 CDC case- definition of CFS
is currently utilised (Fukuda et al, 1994), supplanting its
predecessor, the 1988 CDC criteria. However, in the UK, a
frequently-used case definition is the 'Oxford criteria' (Sharpe
1991) which can include patients with no physical signs and
inadvertently selects subgroups of patients with high levels of
psychological diagnoses (Katon & Russo 1992; Freiberg 1999).
Since the adoption of a particular case-definition of CFS will
greatly influence the outcome of particular studies, it is perhaps
no surprise that groups researching biopsychosocial
management and coping strategies have tended to use the
broader Oxford criteria, whereas groups outside the UK (mainly
in the USA) have tended to use the Fukuda et al 1994 definition
for their biomedical research.

Today – whichever definition is used – the term ME/CFS (or
CFS/ME which the GDG prefers) is an impossibly wide
"umbrella term", based on a collection of vague non-specific
symptoms shared with other illnesses, that contains different
patient groups. The issues surrounding the establishment of
CFS as a diagnostic category, and the inaccurate and biased
characterisations of CFS that have subsequently arisen, were
well-reviewed a decade ago by Jason et al (1997), and their key
points are still valid:

...A significant complicating factor in understanding the
dynamics of this illness is that there are probably different types
of illnesses now contained within the CFS construct... We
believe that it is crucial for CFS research to move beyond fuzzy
recapitulations of the neurasthenia concept and clearly delineate
precise criteria for diagnosing pure CFS and CFS that is
comorbid with psychiatric disorders. It is also necessary to
better differentiate CFS from other disorders which share some
CFS symptoms but are not true CFS cases."

Importantly, many people with ME/CFS across the world point
out a key fact, namely that though they are "diagnosed" and
placed under the ME/CFS umbrella:

a) Fatigue is not their primary problem: musculoskeletal pain
and post- exertional myalgia along with other physical signs are
far more prominent, corresponding more closely to the classical
definition of ME. b) The World Health Organisation International
Classification of Diseases (ICD) has, since 1969, classified ME
separately as a neurological problem (ICD 10 93.3), with 'CFS'
incorporated into the current ICD as a sometime synonym for
ME. The chronic fatigue states per se are listed under mental
and behavioural disorders (F 48.0), a category which specifically
excludes ME/PVFS/CFS.

It is now recognised by clinical champions – and by most
charities representing patients in the UK and overseas – that
there is a strong, perhaps overwhelming, case for unpacking the
term 'ME/CFS' and reclassifying and renaming in accordance
with more specific clinical criteria (e.g., De Becker et al 2001;
Tan et al 2002). Indeed, the further categorisation or
substratification on the research-based subsets, or the need for
it, is so often alluded to in the scientific literature on ME/CFS
(vide http://www.cfids-cab.org/MESA/subsets.html) that it is now
a commonplace (though this body of literature has eluded the
GDG).

Examples in the past two years alone include: Jason,
Neuropsychology Review 2005; Natelson, Clinical and
Diagnostic Immunology 2005; de Lange FP, Neuroimage 2005;
Baraniuk, BMC Neurology 2005; Kaushik N, J Clin Pathol 2005;
Nijs J, Med Sci Sports Exerc 2005; Chia J, Journal of Clinical
Pathology 2005; Lange G, Neuroimage 2005; Reeves, BMC
Med 2005).


Alongside this groundswell for change, there have been
attempts to revise the CDC-1994 criteria directly (e.g., Reeves
2005), including suggestions for subclassification by mode of
onset – rapid post-viral onset versus gradual onset – given that
there appears to be a genetic basis for this distinction. In
addition, the recent Canadian Consensus Document produced
by the Expert Medical Consensus Panel in Canada (Carruthers
2003) was a valiant first attempt at arriving at an
evidence-based yet historically consistent system of
subgrouping patients based on their specific symptoms and
signs. As these authors say, "The CDC [1994] definition, by
singling out severe, prolonged fatigue as the sole major
(compulsory) criterion, de-emphasized the importance of other
cardinal symptoms, including post-exertional malaise, pain,
sleep disturbances, and cognitive dysfunction. This makes it
more difficult for the clinician to distinguish the pathological
fatigue of ME/CFS from ordinary fatigue or other fatiguing
illnesses". The lack of any substantive allusion to this Canadian
Consensus Document (2003) in the current GDG guidelines is a
serious omission, and one which diminishes the authority of the
GDG.

Our key point is that CFS/ME or ME/CFS is a wide umbrella
term recognised by clinical champions, patient charities, leaders
of ME/CFS support groups, and scientific researchers to
contains many different patient groups. Without addressing this
core issue, the efforts of the GDG to give diagnostic and
management guidance that goes beyond the recommendation
of anodyne, non- specific interventions will be inadequate and
probably constitute misguidance.


````````````````````````

2. The skewing of the RCT evidence-base examined by the
GDG, and the devaluation of evidence from scientific studies
and surveys.

While RCTs are the best evidence of "efficacy", there is a
particular problem in the case of the diagnostic rubric ME/CFS.
The large majority of "good quality" RCTs have examined the
use of the non-specific management and coping strategies
cognitive behavioural therapy (CBT) and graded exercise
therapy (GET). Such trials are very expensive to conduct, and
their authors have had the impetus - and been able to access
the resources - to conduct them. This means that systematic
reviews, such as that conducted by the GDG and ancillary staff –
building on Whiting 2001, Mulrow 2001 and Chambers 2006 –
find that the most prominent RCT evidence is for these
non-specific management and coping strategies which (by their
very non-specificity, with inadequate blinding and in the absence
of a truly indistinguishable control intervention) are prone to
result in mildly positive outcomes. The fact that these trials of
CBT and GET have had relatively unspectacular results is less
important to reviewers than the fact that they are "positive".

In short, the accepted strategy of looking at formal "evidence" is
flawed in ME/CFS because the evidence-base is skewed
towards the small group of mildly positive RCTs. It is not a case
of finding the "best" evidence garnered from the work of a range
of biomedical and biopsychosocial scientists working on a level
playing field, but rather finding quite modest evidence in a
forgotten field put there by proponents of one model of the illness
– the biopsychosocial model – a construct which contrasts with
the biomedical model which implies that a primary disease
entity exists and that biopsychosocial aspects are secondary
(the two models discussed in the report to the UK Chief Medical
Officer in 2002). Contrast this situation with, say, breast cancer
which has been well supplied with funding for biomedical trials,
and in which meta- analysis can arrive at a best estimate of
treatment effects from a large number of different studies,
including replicate investigations on different populations by
different research groups (vide NICE Guidance on Cancer
Services Improving Outcomes in Breast Cancer, 2002). Breast
cancer with the formal evidence-base that currently exists for
ME/CFS would be no less a physical illness, and the
non-specific management and coping strategies would be no
more specifically effective for the underlying disease. Our point
is that a NICE guideline on the diagnosis and treatment of
breast cancer in the face of such an evidence-based would not
be meaningful, or fair to the patients.

A corollary of this is that the importance of evidence from
non-RCT scientific studies is diminished or discounted. There is
no need for us to list here the range of biomedical investigations
already conducted on people with ME/CFS – these have already
been flagged for the attention of the GDG, and a full database of
over 3000 abstracts exists at http://www.meresearch.org.uk/.
Most are not RCTs or controlled trials, and come lower in the
hierarchy of research evidence, but given the paucity of clinical
trials in ME/CFS (a function of lack of the basic funding needed
to test hypotheses) and the skewing of the small RCT
evidence-base that exists, they do, in fact, represent a
considerable body of evidence that biomedical investigation can
uncover, within a subgroups of people with ME/CFS, biological
anomalies that might well help to explain many of the clinical
features associated with the illness and indicate areas for
therapeutic treatment.

Similarly, patient survey evidence is largely discounted because,
in the GDG's words (FULL guideline, page 43/269, line 22),
"surveys from self selected respondents are subject to bias and
not necessarily representative of the wider population of people
with CFS/ME". Of course, surveys come low in the hierarchy of
research designs, since they are not deemed valuable for
determining causation or the true effect of treatment, and tend to
come from apparently self-selecting" group of people with
self-reported symptoms. However, there are two things to be
said. First, the evidence for the effectiveness of non- specific
management and coping strategies is itself gathered by
self-selecting professionals promoting their areas of expertise
with access to central funding, and who also have difficulty
ascribing causation or determining the true treatment effects.
Second, such soft survey data contains real, hard experience –
the experience of thousands of patients who have no access to
funding for trials, and no way to publish their experience in the
scientific literature. And while they are limited as formal
evidence yet they are surely not meaningless or valueless. When
they say –as in one large survey (CMO report 2002, page 49) –
that only 7% of respondents found CBT "helpful", compared with
26% who believed it made them "worse", the remaining 67%
reporting "no change", they are not joking, and nor are the 79%
of patients in the same survey who answered that they had
severe pain sometimes, much of the time, or all of the time.
Clearly, community-based surveys can be very useful for
describing the experiences of people with severe and less
severe ME/CFS and can help uncover widespread areas of
concern (such as the lack of community care provision), or
highlight areas where new research is needed (such as the
urgent need for pain relief). In short, they can provide a
systematic record of individual suffering, and point to ways to
alleviate it. In this regard, they should be taken seriously by the
GDG.

ME Research UK and the wider ME/CFS community are not
alone in pointing out such concerns. The central point was well
put in recent letter (The Guardian, Oct 26 2006) by Dr Stilgoe of
Demos, and Prof Irwin and Dr Jones; "The experiences of
patients and the professional judgments of doctors are
important. It is not a simple battle between evidence and
anecdote....NICE needs to do more than just look at published
science. It needs to start listening to people, patients and
doctors".


````````````````````

3. The limitations of the evidence base for non-specific
management and coping strategies.

As the recent review by Chambers et al (2006) – which informs
and is informed by the deliberations of the GDG – shows, there
have been only 5 trials of CBT which have a validity score >10,
one of which is negative for the intervention; and only 3 RCTs of
GET with a validity score >10. The total number of available
trials is small; numbers are relatively low; no trial contains a
"control" intervention adequate to determine specific "efficacy";
and their results are relatively modest (for example, one of the
flagship trials [Prins 2001] described as having "cure of chronic
fatigue syndrome as its explicit goal of therapy", reported no
improvement on the fatigue severity endpoint in 56/83 patients
after 8 months and in 38/58 after 14 months. The result was
significantly better than in the control groups, but was modest
nevertheless). In addition, some of the studies (particularly those
on GET) have used the Oxford criteria (Sharpe 1991) for
diagnosis, a rubric which allows selection of patients with
chronic fatigue states, raising the question of the applicability of
their results to patients with specific symptoms and signs. Again,
the heterogeneity of the trials, the potential effect of publication
or funding bias for which there is some evidence, and
professional doubts about the evidence base for some
behavioural therapies themselves give grounds for caution as
regards the usefulness of this evidence-base to direct the
management of people with ME/CFS. A commentary in the
British Medical Journal (Bolsover 2002) is particularly relevant to
the deliberations of the GDG: Until the limitations of the evidence
base for cognitive behavioural therapy are recognised, there is a
risk that psychological treatments in the NHS will be guided by
research that is not relevant to actual clinical practice and is less
robust than is claimed."

These concerns have been echoed by reviews in the past, which
have recommend caution in interpretation of the evidence-base:
Whiting et al. 2001 stated, "all conclusions about effectiveness
should be considered together with the methodological
inadequacies of the studies. Interventions that have shown
promising results include CBT and GET"; and Mulrow et al. 2001
stated, "….it is unlikely that the beneficial effects of such general
treatments are specific or limited only to patients with CFS. In
other words, although these therapies may help some people
with CFS, their effectiveness does not help establish an
underlying aetiology or cause of CFS". Indeed, a large body of
both professional and lay opinion considers that these
essentially adjunctive techniques have little more to offer than
good medical care alone, and questions what specific additional
therapeutic value they bring. As Carruthers et al (2003) have
pointed point out: "The question arises whether a formal CBT or
GET program adds anything to what is available in the ordinary
medical setting. A well informed physician empowers the patient
by respecting their experiences, counsels the patients in coping
strategies, and helps them achieve optimal exercise and activity
levels within their limits in a common sense, non- ideological
manner, which is not tied to deadlines or other hidden agenda."

It would be referable for NICE and the GDG to recognise that
specific, rigorous, evidence-based recommendations for
treatment cannot be made at present than to incorporate an
inadequate evidence-base into established guidelines which
feed into clinical care and government policy to the detriment of
people with ME/CFS.

``````````````````

SPECIFIC COMMENTS ON THE DRAFT (line references
omitted for clarity)


````````````````````````

"...like other chronic illnesses with no certain disease
process...."

This leaves open the possibility that there might not be a
disease process at all, when there are thousands of people with
a physical illness.

REPLACE WITH "like other chronic illnesses whose causes
have yet to be discovered and disease processes elucidated...


``````````````````


"... Communication should be supported by the provision of
evidence-based information....."


Given the particular problems with the meaning and relevance of
the RCT evidence in ME/CFS, evidence-based information
should have a wider scope.

REPLACE WITH "Communication should be supported by the
provision of evidence- based biomedical and scientific
information from the international literature, as well as
evidence-based suggestions for coping with symptoms...

``````````````````````

"... CBT is an evidence based treatment for CFS/ME...."

It is not. The evidence base consists of only 5 trials which have a
validity score >10, one of which is negative for the intervention
(vide Chambers 2006). Again, "treatment" is too strong a word
for the relatively modest (and probably non-specific) effects seen
in these trials. As proponents of the biopsychosocial model of
ME/CFS (CMO report 2002, page 24) themselves make clear: it
is "not a cure" (Deale 2001); it is "modestly effective" and not
remotely curative" and "not the answer to CFS" (Wessely 2001);
and "...it should be kept in mind that evidence from randomized
trials bears no guarantee for treatment success in routine
practice. In fact, many CFS patients, in specialized treatment
centres and the wider world, do not benefit from these
interventions. When it comes to the management and treatment
of CFS patients, there is still a lot to be learned." (Huibers and
Wessely 2006). We note that the most recently published RCT
on CBT (O'Dowd 2006) states, "...there was, however, no
evidence that the treatment restored normal levels of function for
the majority of patients."

Furthermore, the methodological problems with these trials have
been well- described by Carruthers et al (2003): "The complexity
of CBT studies, their varied inclusion and exclusion criteria, the
very limited portions that can be properly blinded, and the
subjective means used for most evaluations, puts in question the
validity of their results. In addition, the numerous variables
between the CBT studies, the CBTs and control programs, the
different comparison therapies, and the varied frequency and
duration of therapy, make it very challenging to determine which
parts are responsible for any perceived improvement. Are any
effects due to the shift in cognitive beliefs, the exercise involved,
the amount and quality of the attention and counseling, the
discontinuance of other medical therapies during the test period,
etc? Thus the Powell et al [2001] study found GET alone to be as
effective as CBT, and the Ridsdale et al [2001] study found CBT
to be no more effective than counseling."

REPLACE WITH: .... While cognitive behavioural therapy most
likely has some role in helping patients with all illnesses,
including cancer and MS, to better cope with their symptoms
until a cure is found, this role is limited and essentially
non-curative...

````````````````````````


"... CBT or psychological approaches to CFS/ME do not imply
that symptoms are psychological, 'made up' or in the patient's
head. It is used in many health settings including cardiac,
cancer, diabetes and chronic pain as well as with mood
disorders such as anxiety and depression...."

This is a disingenuous paragraph. The British Association for
Behavioural and Cognitive Psychotherapies website
(http://www.babcp.org.uk/) states that "CBT is an approach to
help people experiencing a wide range of mental health
difficulties. The basis of CBT is that what people think affects
how they feel emotionally and also alters what they do....CBT
practitioners... aim to work jointly with the person to help them
begin to identify and then change their extreme thinking and
unhelpful behaviour...." CBT is universally recognised to be a
form of psychotherapy used to treat a variety of psychological
impairments, but also used as a therapeutic adjunct for symptom
management and coping in illnesses such as cardiac, cancer,
diabetes and chronic pain. Indeed, we note that when references
to CBT appear in the document, "Multiple Sclerosis: National
Clinical Guideline for Diagnosis and Management in Primary
and Secondary Care" (2004), it is in the context that that
psychological management strategies be employed IF the
patient is depressed or anxious, but not otherwise.

Interestingly, the rationale for using CBT in ME/CFS is that
inaccurate beliefs/ineffective coping maintain and perpetuate
the illness, but it has never been proven that these illness beliefs
have caused or maintain the illness, and correlations (where they
exist) might just as well have arisen from the valid belief that
illness DOES have a physical cause, and that activity avoidance
IS the correct course of action.

The GDG guidelines could follow the NICE Guidelines for
Multiple Sclerosis, and reinforce the adjunctive, supportive role
of CBT in ME/CFS by stating the below:

REPLACE WITH: .... CBT or psychological approaches to
CFS/ME do not imply that symptoms are psychological, 'made
up' or in the patient's head. Rather, they can be thought of as
essentially adjunctive management and coping strategies which
might be useful for some people some of the time.....


``````````````````

"... GET is an evidence-based self-management approach to
CFS/ME...."

It is not. The evidence base consists of only 3 RCTs with a
validity score >10, one of which concludes, "...graded exercise
produces small but clinically significant improvements in case
level fatigue and functional work capacity in CFS patients...."
(Wearden 1998). Given that all three trials recruited patients on
the basis of the Oxford criteria which selects an over-broad
groups of patients including those with idiopathic chronic fatigue;
that there is a strong likelihood of significant non-specific effects
given the design of the studies; and the likelihood that
self-pacing or good quality clinical care would produce similar
small effects much more cheaply (free, in fact), this management
approach cannot be called properly evidence-based or
cost-effective in ME/CFS at present.

THIS SHOULD BE DELETED


````````````````````````````````

"...Severity...These definitions were agreed by the GDG and
have been derived from definitions in the Royal College of
Paediatrics and Child Health Guidelines and the CMO report...."

These three severity levels are not evidence-based. Levels
should be based on clinical observation of clusters of symptoms,
each scored according to severity, to allow accurate ascription
of a patient to a category of severity. The simple but effective
"Symptom Severity Chart" of the Canadian Consensus
Document (Carruthers 2003) – which allows for scoring – would
be a good starting point.

REPLACE WITH: .... Severity...These definitions are ad hoc and
essentially based on mobility, and efforts are underway to derive
a symptom-based scale.

``````````````````


"...they have usually stopped work...."

REPLACE WITH: ...they have usually been forced by illness to
stop working...


````````````````

"... When the adult or child's main goal is to return to normal
activities..."

There is a suspicion that this would not be written of patients with
other illnesses, and that it is included to suggest that some
people with ME/CFS could be malingerers.

THIS CLAUSE SHOULD BE DELETED


``````````````````

"... then the therapies of first choice should be CBT or GET
because there is good evidence of benefit for this condition in
mild to moderately affected adults and some evidence in mild to
moderately affected children."

This is not true for adults (as discussed above). As regards
children, the updated systematic review which informs the GDG
(Chambers 2006) says: "The recommendations for children and
young people were largely developed by consensus because of
a lack of specific evidence for this age group. GET and CBT
were recommended for consideration based on extrapolation
from studies in adults. The effectiveness of CBT for adolescents
is supported by a recent high- quality RCT [Stulemeijer 2005]
although this had only 69 participants" (It is also the only positive
RCT on children with a validity score >10.) And the GDG s draft
guidelines subsequently say, in section 4.1, "There is no
evidence for the use or effectiveness of these strategies in these
two patient groups [young people and the severely affected]".


THIS RECOMMENDATION SHOULD BE DELETED


``````````````

"... When an acute infection is followed by excessive fatigue, the
adult or child should receive advice on how to promote
recovery...."

REPLACE WITH: ... When an acute infection has characteristic
sequelae of ME/CFS, then the adult or child should receive
advice on how to receive treatment and promote recovery.......

````````````````

"... Healthcare professionals should be proactive in advising
about fitness for work and education..."

This is not a standard phrase used in NICE Guidelines for other
chronic conditions. The GDG should show why it is necessary to
use this phrase here since there is a suspicion that this phrase
would not be written of patients with other illnesses. What
evidence is there – to inform evidence-based guidelines – that
people with ME/CFS need unusual prompting from healthcare
professionals to return to their pre-illness lives and jobs?


THIS SHOULD BE DELETED


``````````````````````

"... A documented, individualised management plan should be
developed with the adult or child with CFS/ME, and the carer,
where appropriate to include...... education or employment
plans..."

As above, this seems to imply that people with ME/CFS need a
healthcare professional to prompt them into education or
employment.

THIS SHOULD BE AMENDED


````````````````

"... CFS/ME is recognised on clinical grounds alone...."

The reasons for this, and its implications for the validity of any
guidelines produced by NICE, have been discussed in the long
preamble to these specific comments. However, the
clinical-basedness of the rubric ME/CFS does not mean that
widening it further (as proposed by the GDG – see below) is
sensible. Nor does it mean that other supportive evidence of
illness need be absent. For example:

a) The paper by Devanur and Kerr (2006) expresses the
biomedical evidence well – and there is a range of reviews in a
similar vein: "Studies of pathogenesis have revealed immune
system abnormalities and chronic immune activation,
dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis,
brain abnormalities, evidence of emotional stress (comprising
host aspects) and evidence of exogenous insults, for example,
various microbial infections (Epstein-Barr virus, enteroviruses,
parvovirus B19, Coxiella burnetii and Chlamydia pneumoniae),
vaccinations and exposure to organophosphate chemicals and
other toxins (comprising environmental aspects)."

b) The Canadian Consensus Document (Carruthers 2003) is a
diagnostic guideline distilled from the panel's collective
extensive clinical experience of diagnosing and/or treating more
than twenty thousand ME/CFS patients. The clinical definition
derived "encompasses the broad cluster of symptoms and signs
that give ME/CFS its distinctive character. Diagnosis is based
on these characteristic symptom patterns, which reflect specific
areas of pathogenesis". This is a superb 108-page document
which should inform the deliberations of the GDG.

c) There is clinical evidence, and some research evidence, that
frank signs can be found if clinicians look for them. For example,
of the quadriceps muscle, To our surprise, the patients with CFS
were physically weaker than both the depressed patients and
sedentary subjects" (Fulcher & White 2002), and more generally,
"In all three groups, a majority of patients exhibited muscle
weakness in the lower limbs, and significant numbers of patients
had absent or abnormal reflexes." (Kennedy et al 2004).

NICE has a great opportunity to look beyond the significantly
rudimentary and skewed RCT evidence-base towards a fresh
assessment of the biomedical evidence in ME/CFS, and the
revision of the symptoms and signs in people with the illness. A
full examination of the Canadian Consensus Document (2003)
would be a good starting point.


````````````````

"...CFS/ME should be considered if an adult or child has fatigue
that is all of the following:..."

This section introduces a novel – and entirely unvalidated –
method of diagnosing" CFS clinically. The criticism of the most
widely used "research" definition – the CDC (Fukuda) 1994 – is
that it is impossibly broad, being based on "fatigue" plus 4/8
concurrent "minor criteria" symptoms, thereby lacking specificity
since it does not, in practice, completely exclude patients with
other biomedical conditions or, indeed, those with a primary
psychiatric basis for their fatigue.

This attempt by the GDG in section 1.2.1.2 to define a clinical
definition – on a basis other than systematised clinical
experience – makes the situation far worse. It introduces a
diagnosis based on "fatigue" plus ONE or more of 9 vague,
ill-defined symptoms shared with many other illnesses. To be
clear, if (as many believe on the basis of evidence) the current
CDC-1994 research definition is an "umbrella term" covering
diverse groups of patients, then NICE is proposing to replace it
with a marquis similar to a circus tent. The widened diagnosis
would include many thousands of patients currently diagnosed
with idiopathic fatigue (most of whom could report at least one of
nine common concurrent symptoms); it would lead to
significantly increased heterogeneity within the diagnostic
category (which could contain a still-working person with a sore
throat alongside a bed-bound person with all 9 symptoms to a
severe degree; yes, they might have the same illness at a
different stage of development, but NICE has no evidence of
that); and it would not be taken seriously since it flies in the face
of other expert opinion. For example, even the CFS Working
Group at the CDC has recommended that symptom severity be
taken into consideration, and standardised outcome measures
be used to improve its specificity (Reeves 2005). Furthermore,
the experts devising the Canadian Consensus Document
(Carruthers 2003) derived a diagnostic rubric based on
characteristic symptom patterns, which reflect specific areas of
pathogenesis.

The central issue has been put very nicely by Dr Charles
Shepherd of the ME Association in a letter to the BMJ
(December 2004; 329: 1405): "The medical profession has only
itself to blame for the awful mess that currently surrounds
ME/CFS. It has created an illness that covers a wide variety of
fatigue state clinical presentations, with or without psychiatric
co-morbidity, and almost certainly an equally diverse range of
possible pathological and physiological explanations. Doctors
who deal with patients suffering from unexplained abdominal
pain, arthralgia or headaches do not work on the basis that they
all have the same pathoaetiology and will therefore respond to
the same form of treatment. So why apply this form of flawed
logic to ME/CFS?"

The "clinical" revision proposed by the GDG in these guidelines
can only worsen the pre-existing mess.

THE ATTEMPT TO ARRIVE AT A CLINICAL DEFINITION
SHOULD BE POSTPONED UNTIL INTERNATIONAL
EXPERTS ON ME/CFS HAVE BEEN CONSULTED AND
EXISTING CLINICAL EVIDENCE EVALUATED


``````````````````

...physical or mental exertion making symptoms worse..."

This "symptom" is almost synonymous with "characterised by
post-exertion malaise and/or fatigue" of the major fatigue
criteria. Is this an indication that the novel revision of the clinical
criteria by the GDG needs revising?

THE ATTEMPT TO ARRIVE AT A CLINICAL DEFINITION
SHOULD BE POSTPONED UNTIL INTERNATIONAL
EXPERTS IN ME/CFS HAVE BEEN CONSULTED AND
EXISTING CLINICAL EVIDENCE EVALUATED


``````````````````

"...Some serious underlying diseases might present with similar
symptoms and signs as CFS/ME. The following should be
regarded as 'red flags', indicating a higher index of suspicion of
serious underlying pathology.`

Abnormal neurological signs. Features of cardiovascular
problems. Weight loss. Features of sleep apnoea. Features of
anxiety and depression...."

Most patients currently diagnosed with ME/CFS – including the
20,000 members of ME/CFS self-help groups – have arrived
there after some minor clinical investigations by their GPs that
have had negative results. They remain ill, however, and – in the
absence of investigations for clinical signs, or in the face of
disbelief – lose faith in clinical services. However, the umbrella
diagnosis certainly contains seriously people who could benefit
from full and comprehensive clinical examinations, and in whom
alternative diagnoses (e.g. Lyme disease; frank sleep apnoea;
Addison's disease – just some of the re- diagnoses that have
come to our attention) could be found if healthcare professionals
and researchers were motivated to find them.

````````````````

"...the following tests should not be done routinely....The head-up
tilt test...

...Serology testing for chronic bacterial infections (for example,
borelliosis) in the absence of any indicative history.

.. Serology for chronic virus infections: HIV, hepatitis B and C, in
the absence of any indicative history. ..

..Serology for general viruses (for example, heterophile antibody
tests for infectious mononucleosis) in the absence of any
indicative history.

...Serology testing for latent infections: toxoplasma, EBV
(Epstein Barr virus), CMV (cytomegalovirus) in the absence of
any indicative history."

These recommendations are in direct contrast to those forming
the basis of the Canadian Consensus Document (Carruthers
2003) which have been distilled from the panel's collective
extensive clinical experience diagnosing and/or treating more
than twenty thousand ME/CFS patients. Examples of their
recommendations include the below:

"Autonomic Manifestations

...Orthostatic intolerance is commonly seen in ME/CFS patients
and Includes neurally mediated hypotension (NMH); postural
orthostatic tachycardia syndrome (POTS); and delayed postural
hypotension...`

Laboratory and Investigative Protocol

...a) Further Laboratory Testing: diurnal cortisol levels, 24 hour
urine free cortisol; hormones including free testosterone, B 12
and folate levels, DHEA sulphate, 5-HIAA screen, abdominal
ultrasound, stool for ova and parasites, NK cell activity, flow
cytometry for lymphocyte activity, Western blot test for Lyme
disease, hepatitis B and C, chest x-ray, TB skin test and HIV
testing. Do the 37-kDa 2-5A RNase L immunoassay when it
becomes available.

b) Differential Brain Function and Static Testing: MRI: those with
significant neurological finding should be considered for a MRI
to rule out multiple sclerosis (MS), and cervical stenosis.
Quantitative EEG, SPECT and PET Scans and Spectography:
qEEG analysis of brain waves, SPECT estimation of dynamic
brain blood flow and PET analysis of brain metabolism show
diagnostic promise and will become more important as these
techniques are refined and research confirms their diagnostic
value.

c) Tilt Table Test d). Sleep Study; e) 24-Hour Holter Monitoring:
if a significant arrhythmia is suspected. f) Neuropsychological
Testing: can be utilized to identify cognitive dysfunction and/or
confirm diagnosis. If done, it should focus on the abnormalities
known to differentiate ME/CFS from other causes of organic
brain dysfunctions etc......."

There is a clear mismatch between the truncated
recommendations of the GDG, and the routine examinations
recommended by ME/CFS clinicians across the world.


THIS RECOMMENDATION SHOULD BE REVISED AND
RE-EXAMINED IN LIGHT OF BEST PRACTICE AND
CURRENT RESEARCH


````````````````````````````

"... When a diagnosis is made, a prognosis of cautious
optimism should be conveyed. With appropriate management,
most children and adults, but not all, will have some improvement
and some will recover fully...."

This is not true (and again the problem involves  "what"
diagnosis and using "which" definition). Two separate recent
reviews have concluded that, "… patients exhibit severe,
long-term functional impairment. Substantial improvement is
uncommon and is less than 6%" (Andersen 2004); and, "Full
recovery... is rare" (Cairns and Hotopf 2005).

REPLACE WITH: .... When a precise diagnosis is made, a
prognosis of cautious optimism should be conveyed. With
appropriate management, most children and some adults can
improve or even recover fully, though the patient must be left in
no doubt that long-tern morbidity can be high....


````````````````````


"....When the adult or child's main goal is to return to normal
activities..."

There is a suspicion that this phrase would not be written of
patients with other illnesses, and that it is included to suggest
that some people with ME/CFS could be malingerers.

THIS SHOULD BE DELETED

````````````


General Global Comments on Guidelines section 1.3
(Management)
This section consists of recommendations for management that
include: Cognitive behavioural therapy Graded exercise therapy

Neither cognitive behavioural therapy (a form of psychotherapy
designed to manage dysfunctional illness beliefs) nor graded
exercise therapy (which is used as part of a biopsychosocial
programme predicated on a model of physical deconditioning)
are evidence-based to a level that would allow NICE to
recommend that these management strategies be rolled out to
the 120,000–240,000 people with ME/CFS in the UK. In
addition, in the few good quality RCTs which exist, the effect is
modest and non-curative, and there is more than a strong
suspicion that much of the apparent treatment outcome relates
to the non- specific effects, i.e., that good quality usual clinical
care (in the case of CBT) and self-pacing (in the case of GET)
would produce similar results.

Also, the evidence from formal RCTs is opposed by evidence
from patient surveys which overwhelmingly find against the
usefulness of these strategies. As the FULL guideline (56/269,
line 2) states "Graded exercise was felt to be the treatment that
made more people worse than any other. 39% were made
worse by this whereas, in contrast, only 2% were made worse by
diet. Graded exercise was also considered to be the least
helpful treatment or management schedule; only 13% said that it
helped a lot and 26% said that it helped a little [n=347]". Again,
as regards cognitive behavioural therapy, the FULL guideline
(pages, 56 and 58, Table ) states that only "7% reported to be
helped by CBT whereas 67% were unaffected and 26% made
worse."

Accordingly, the emphasis on these strategies in the NICE
guideline draft is misplaced, as described in the preamble
above.

THE ENTIRE SECTION 1.3 (PAGES 17–24) SHOULD BE
REMOVED, OR TRUNCATED TO A PASSAGE SUCH AS
THE BELOW:

...Cognitive behavioural therapy (CBT) and graded exercise
therapy (GET) are comparatively expensive symptom
management strategies which some patients might want to try
until the cause(s) of ME/CFS are unravelled and a cure
identified....


``````````````


"…Cognitive behaviour therapy (CBT) …A programme of CBT
should include: … explanation of the CBT model for CFS/ME…"

There is no CBT model for ME/CFS per se. Rather there is
CBT, a form of psychotherapy, which can be applied to all
illnesses though the supposed biopsychosocial model. Even
though CBT has its critics – such as Holmes (2002), "...the
foundations on which [CBT] rests are not as secure as some of
its proponents would have us believe." – there is some evidence
that it can be used as a tool to help some patients cope with
some symptoms. Its application for people with ME/CFS would
therefore be as a management tool, and not as an overarching
model for the pathophysiology of illness.

REPLACE WITH: ……Cognitive behaviour therapy (CBT) …A
programme of CBT should include: … explanation of how CBT,
a form of psychotherapy, might be a useful as part of a
management strategy for coping with symptoms.


````````````````


"…discussion of the patient's attitudes and expectations…
…developing awareness of thoughts or expectations, or beliefs
and defining fatigue-related cognitions and behaviour…
…challenging cognitions which may adversely affect
rehabilitation and/or symptom management, for example, fear of
activity and perfectionist beliefs… …decreasing somatic
attributions and addressing symptom overvigilance... …problem
solving using activity management and homework tasks to test
out alternative thoughts or beliefs…"

Such sentences, characteristic of proponents of the pure
generalist biopsychosocial model, have been given undue
prominence by the GDG. There is a suspicion that they would
not be so prominently displayed in NICE guidelines for other
illnesses; indeed, we note that they do not appear in the
document, Multiple Sclerosis: National Clinical Guideline for
Diagnosis and Management in Primary and Secondary Care
2004" (despite the fact that fatigue is one of the dominant
symptoms of most people with MS) which recommends (on the
basis of three positive trials of CBT for MS) that psychological
management strategies be employed IF the patient is
depressed or anxious, but not otherwise.

A quote from the Canadian Consensus Document (Carruthers
2003) expresses well how many ME/CFS patients and charities
feel when they see such statement so prominently displayed:
"…there is much that is objectionable in the very value-
laden…hypothesis, with its implied primary causal role of
cognitive, behavioural and emotional processes in the genesis
of ME/CFS. This hypothesis is far from being confirmed, either
on the basis of research findings or from its empirical results.
Nevertheless, the assumption of its truth by some has been used
to influence attitudes and decisions within the medical
community and the general cultural and social milieu of ME/CFS.
To ignore the demonstrated biological pathology of this illness,
to disregard the patient's autonomy and experience and tell
them to ignore their symptoms, all too often leads to blaming
patients for their illness and withholding medical support and
treatment…Crucially, there is a serious question mark over
whether a program of formal CBT or GET program adds
anything to what is available in the ordinary medical setting".

THE GUIDELINE SHOULD REMOVE THESE AND
SUGGEST THAT – LIKE THE NICE GUIDELINES FOR
MULTIPLE SCLEROSIS – PSYCHOLOGICAL STRATEGIES
MIGHT BE USEFUL FOR ANXIETY AND DEPRESSION.


````````````````````````````

"...Health professionals should be aware that there is no
evidence for the following strategies: ....those which encourage
complete rest (cognitive, physical and emotional) during
significant increases in symptoms..."

There is well-founded support from patient surveys and from
established ME/CFS clinicians that during periods of
stabilisation of illness (as well as in the very early post-infectious
phases) periods of rest are very important (vide Shepherd and
Chaudhuri 2001).

````````````````````````


"..Adults with mild or moderate CFS/ME should be offered a
programme that includes planned increases in duration of
physical activity/exercise followed by increases in intensity
leading to aerobic exercise (that is, exercise which increases
the pulse rate) such as GET...."

Much of the current thinking about ME/CFS is driven by models
of deconditioning, predicated on the belief that deconditioning is
a factor in the perpetuation of the illness. However, there is good
evidence that deconditioning is not a significant factor
(Brazelmans 2001; Van der Werf 2000) and that it cannot
account for delayed post-exertional symptoms or the
documented changes in muscle metabolism (Lane 1998 and
2000). Historically, Myalgic Encephalomyelitis is characterised
by a delay in muscle recovery after exercise (with pain and
fatigue 24 or 48 hours after exertion), a phenomenon which few
have studied and which the deconditioning hypothesis does not
address.

In modern ME/CFS patients, there is both clinical and anecdotal
evidence that exercise can exacerbate symptoms and cause
relapse, particularly the some 50% of the patient group whose
illness had a post-infectious onset. One study, however, has
confirmed patient's experience by demonstrating that CFS
patients fail to recover properly from a fatiguing exercise
protocol and that the failure was more pronounced after 24 hours
(Paul 1999). Further, the new "CFS Toolkit for Health Care
Professionals: Managing Activity" (2006) produced by the CDC
in Atlanta (vide http://www.cdc.gov/cfs/toolkit.htm) is clear that
"Advising patients who have chronic fatigue syndrome to
engage in aerobic exercise... can be detrimental. Most CFS
patients cannot tolerate traditional exercise routines aimed at
optimizing aerobic capacity. Instead of helping patients, such
vigorous exercise can cause postexertional malaise, a hallmark
of CFS that is defined as exacerbation of fatigue and other
symptoms following physical or mental exertion. Even worse, this
kind of exercise can precipitate a full-scale relapse that lasts for
days or weeks. A different way of defining exercise and
managing activity is needed for CFS patients and their health
care team." And a similar view is expressed in the Canadian
Consensus Document (Carruthers 2003) "Exercise
programmes must be entered cautiously as clinical studies have
indicated that symptoms worsened in approximately half of the
ME/CFS patients". And again, Dr Charles Lapp re-emphasised
at the American Association for Chronic Fatigue Syndrome
(AACFS) 6th International Conference in 2003, "....although may
clinicians have heard that graded exercise can be helpful,
patients should not embark on an exercise regime which
increases the severity of illness, a phenomenon occurs, as many
experienced clinicians recognise, when patients push
themselves too much". Finally, people with ME/CFS themselves
consistently report the phenomenon of post-exercise worsening
of symptoms: in one report of 1,214 patients graded exercise
therapy was reported to make 50% of patients worse (CMO
report 2002) - the greatest number of 'worse' reports of any
therapy; and the survey of the severely affected (25% ME Group,
2004) found 82% of ME patients reporting that exercise therapy
worsened their condition, with only 5% finding it useful.

There may be sound physiological reasons for the specific
post-exercise malaise encountered. First, post-viral fatigue
(which is not related to the muscle disuse and deconditioning
that can result from the initial period of illness; Lane 2003) might
result in a long-term smouldering infection involving glutathione
depletion (Pierce and Pierce 2006), and be exacerbated by
exercise; or there might be an exercise-induced
physiologically-significant delivery of free radicals, not because
of disuse of muscle and deconditioning, but because there is
something organically wrong with muscle metabolism and/or
vascular endothelial function. Whatever the reason, it is
important to remember that the current evidence for
deconditioning from the psychosocial literature is not based on
scientific investigations of muscle but on suppositions about
patients with "fatigue".

Thus, issues regarding the role of rest and exercise (whether in
the form of GET or not) for people with ME/CFS is not as
clear-cut as the GDG suggests. And, as Shepherd (2001) has
pointed out, physicians must take as much care in prescribing
appropriate exercise as in prescribing medications to ME/CFS
patients. And physicians should only approve of exercise
programs in which the patient's autonomy is respected,
appropriate pacing is encouraged, fluctuations in severity of
symptoms are taken into account, and adequate rest periods
are incorporated (Carruthers 2003).

THE GDG SHOULD TAKE ACCOUNT OF THESE POINTS
IN SUBSEQUENT REVISIONS TO ITS DRAFT

````````````````````


"...Management of Setbacks.. People with CFS/ME have
variations in the severity of their symptoms and will experience
setbacks or transient increases in fatigue and other symptoms.."

The usual term used in the ME/CFS literature is "crash" (e.g.,
Carruthers 2003) or "relapse" (e.g., CDC, "CFS Toolkit for
Health Care Professionals: Managing Activity" 2006). Relapses
are reported to occur frequently in people with ME/CFS, and can
be long-lasting and affect all areas of life, and be much more
than transient.


THE WORD RELAPSE SHOULD BE REINSTATED AND
ROLE OF RELAPSES EXAMINED


``````````````````````


"1.4 Key principles of care for people with severe CFS/ME...."

It is generally agreed that severely affected people could make
up 25% of the total number of ME/CFS patients, though some
estimates put the figure higher; the late Dr Melvin Ramsay, the
doyen of ME patients in the UK, stated that one third of patients
experience "a severe and debilitating downhill course", and one
Members Survey of November 2000 reported some 34%
classifying themselves as severely affected. It is surprising then
that the care and management of people with severe illness
takes up only 1.5 pages in the guideline draft produced by the
GDG.

For the benefit of the Guideline Development Group, the article
by Crowhurst (2005) is an excellent starting point for the
development of meaningful and patient-specific principles of
care; indeed the tabled section, "impact and service response"
would do credit to NICE guidelines, and we hope NICE will
consider their incorporation in its final document. `


````````````````````

"....GET may be an appropriate addition to help patients to
develop their physical capacity and functioning.... "...Activity
management should be the core therapeutic strategy but
elements of CBT may be suitable for some adults and
children...."

This is disingenuous. As regards activity, a survey by The 25%
Severe ME Group (2004), 82 per cent of patients with severe
ME/CFS stated that their condition was exacerbated by graded
exercise therapy, of which activity management is a satellite in
this context (as stated in section 1.3.1.4 on the NICE Guideline
draft). Also, the statement that follows this section (NICE
Guideline draft Section 4.1) states: "There is no evidence for the
use or effectiveness of these strategies in these two patient
groups [children and the severely affected].... Patient experience
suggests that some of these interventions may be harmful and/or
not effective....."

The support for the statement of the possible usefulness of CBT
for the most severely ill patients is a single report in the scientific
literature (Powell et al, 1999) which describes two
wheelchair-bound patients who had dramatic improvements in
health following a the "pragmatic rehabilitation regimen". Two
other seemingly relevant reports in the scientific literature are, in
fact, small pilot studies that refer to inpatient treatments within
psychiatric wards (vide Chalder et al 1996 and Essame et al
1998). `

``````````````````````````

General Comment on section 1.3.4 "Pharmacological
interventions"

There is now much clinical experience to inform this section –
which comprises only 1.5 pages in the NICE guideline. For
example, recent reviews (Carruthers 2003; Shepherd and
Chaudhuri 2001; and Spotilla 2005) have much to say, and
revisions to this guideline should reflect these.


``````````````````````````````````

General Comment on section "Research recommendations" -
page 258 Full Guidelines

The research recommendations consist of refining existing
biopsychosocial coping strategies, assessing their
cost-effectiveness, looking at rates of prevalence, and tinkering
with outcome measures. Crucially no research
recommendations are given for strategies to uncover the
cause(s) of the illness or find a cure.

While the GDG were asked to produce a guideline on
"Diagnosis and Management", the very remit begs the
questions: Diagnose what, and manage what? ME/CFS is a
diagnosis of exclusion – albeit one that the NICE guideline draft
would widen impossibly (see above) – containing patients who
apparently do not fit squarely into any other category. The human
beings inside it are a heterogeneous group who might all have
the same illness at varying degrees of severity, but might not -
the GDG doesn't know where the truth lies, but fills the gap with
general non-specific management and coping strategies which
might help some in a modest way but solve nothing for most.

A programme of research is indeed urgently required, but to
boost and extend physiological and biochemical abnormalities
found in groups of patients meeting the broad criteria for
ME/CFS. Examples of anomalies that can be found include:
Oxidative stress (e.g. Kennedy 2005); Dysregulation of anti-viral
pathways (e. g., De Meirleir 2000); Endothelial dysregulation
(e.g., Khan 2004); Altered brain perfusion (e.g., Tirelli et al.,
1998); Orthostatic hypotension (e.g., Spence and Stewart
2004); Brain metabolic abnormalities (e.g., Chaudhuri et al.,
2003); and Cardiac anomalies (e.g., Lerner 2004); Altered
muscle metabolism (e.g., Fulle et al., 2003); Abnormal response
to exercise ((e.g., McCully et al., 2004); Enteroviral sequences in
muscle (e.g., Lane et al., 2003) ....and so on........

THESE RESEARCH RECOMMENDATIONS SHOULD BE
REMOVED FOR RENOVATION

``````````````````````````````

Comparisons between the FULL guideline and the NICE
Guideline

Since the shorter NICE guideline is the one read by 99% of
interested parties, including healthcare professionals, it is
important that the caveats of the FULL version be reproduced in
the NICE version. These include:

a) …The GDG did not regard CBT or other behavioural
treatments as curative or directed at the underlying disease
process, which remains unknown. Rather, such treatments can
help some patients cope with the condition and consequently
experience a improved quality of life….

b) ...substantial number of patients will pursue a fluctuating
course with periods of relative remission and relapse, and a
significant minority become severely, and perhaps, permanently
disabled.... .... recovery rates of 8% to 63% (median 40%), with
full recovery being rare (5– 10% achieving total remission)...

c) ...the GDG considered that patients should take the lead on
any behavioural approaches to manage their CFS/ME. The
objectives of any programme must be agreed with the patient
who must understand the aims and objectives and must be
willing to take part.....

````````````````````````````

OMISSIONS

1. The Analysis Report (2004) by the 25% ME Group for Severe
Sufferers which was submitted to the Guideline Development
Group previously, is not mentioned in either the FULL or the
NICE guidance. This reported that 93% of respondents found
CBT unhelpful and that GET was found to be unhelpful by 95%. It
may be, as the FULL guideline says (page 43/269, line 22),
"surveys from self selected respondents are subject to bias and
not necessarily  representative of the wider population of people
with CFS/ME". But this report is still valuable and full of meaning,
coming from a group representing over 1000 house- and
bedbound people with ME/CFS, and does not deserve to drop
off the edge of the evidential world.

2. There is a need for clear criteria for referral to
psychology/psychiatry services. The guideline draft is vague
regarding the circumstances under which a patient can be
referred for cognitive behavioural/graded exercise and other
similar interventions, and for psychiatric/psychological
assessment. We understand this to be an area of great concern
for some people with ME/CFS, and so we feel that precise
criteria for such referrals should be published as part of the final
guidelines. Openness is a key element of modern NHS reform,
and the publication of clearly-defined criteria would be both a
major step towards reassuring  parents and carers, and a
signpost for professionals working in this area. The concern of
some people with ME/CFS is that unless this is done, most
cases will be referred for psychology/psychiatry services
routinely. Given some of the statements in the current draft  -
which can read as thinly-veiled invitations to uncover
psychological dysfunction - these concerns may, in fact, be valid.

3. The GDG fails to make a positive statement about the
entitlement of people with ME/CFS to Disability Living
Allowance/Incapacity Benefit. This is a perplexing issue for the
many thousands of people with this illness who rely on disability
benefits.


``````````````````````````````

References

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Essame CS, et al. Pilot study of a multidisciplinary inpatient
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Modification of the functional capacity of sarcoplasmic reticulum
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Holmes J. All you need is cognitive behavioural therapy? British
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Jason LA et al. Politics, Science, and the Emergence of a New
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Psychologist 1997; 52(9): 973-83.

Jason LA et al. Chronic Fatigue Syndrome: The Need for
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Katon W, Russo J. Chronic fatigue syndrome criteria. A critique
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Kaushik N, Fear D, Richards SC, McDermott CR, Nuwaysir EF,
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Belch JJ. Oxidative stress levels are raised in chronic fatigue
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Kennedy G, Abbot NC, Spence V, Underwood C, Belch JJ. The
specificity of the CDC-1994 criteria for chronic fatigue
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Khan F, Kennedy G, Spence VA, Newton DJ, Belch JJ.
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Lane RJ et al. Muscle fibre characteristics and lactate
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Lane RJ. Chronic fatigue syndrome: is it physical? Journal of
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Lange G, Steffener J, Cook DB, Bly BM, Christodoulou C, Liu
WC, Deluca J, Natelson BH. "Objective evidence of cognitive
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Lerner AM, Dworkin HJ, Sayyed T, et al. Prevalence of abnormal
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McCully KK, Smith S, Rajaei S, Leigh JS Jr, Natelson BH.
Muscle metabolism with blood flow restriction in chronic fatigue
syndrome. J Appl Physiol 2004; 96(3): 871-8.

Mulrow CD, Ramirez G, Cornell JE, et al. Defining and
Managing Chronic Fatigue Syndrome. Evidence
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02- E001. Rockville (MD): Agency for Healthcare Research and
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Hoof E, De Meirleir K. Chronic fatigue syndrome: exercise
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O'Dowd H, Gladwell P, Rogers CA, Hollinghurst S, Gregory A.
Cognitive behavioural therapy in chronic fatigue syndrome: a
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Paul L, Wood L, Behan WM, Maclaren WM. Demonstration of
delayed recovery from fatiguing exercise in chronic fatigue
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Pierce S and Pierce PW. The physiology of exercise intolerance
in patients with myalgic encephalomyelitis (ME) and the utility of
graded exercise therapy. In Press. 2006.

Powell et al. The treatment of wheelchair-bound chronic fatigue
syndrome patients: two case studies of a pragmatic
rehabilitation approach. Behavioural and Cognitive
Psychotherapy 1999; 27: 249-60.

Powell P, Bentall RP, Nye FJ, Edwards RH. Randomised
controlled trial of patient education to encourage graded
exercise in chronic fatigue syndrome. BMJ 2001;322:387–90

Prins JB et al. Cognitive behaviour therapy for chronic fatigue
syndrome: a multicentre randomised controlled trial. Lancet
2001; 357: 841-7.

Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B,
Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C.
Chronic fatigue syndrome - a clinically empirical approach to its
definition and study. BMC Med 2005 15; 3: 19.

Ridsdale L, Godfrey E, Chalder T, Seed P, King M, et al.
Chronic fatigue in general practice: is counseling as good as
cognitive behaviour therapy? A UK randomised trial. Br J Gener
Pract, Jan. 2001;51:19-24.

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; 84(2): 118-21.
Shepherd C, Chaudhuri A. ME/CFS/PVFS - An exploraiton of
key clinical issues. ME Association 2001.

Shepherd C. Pacing and exercise in chronic fatigue syndrome.
Physiotherapy 2001; 87: 395-6.

Spence VA, Stewart JM. Standing up for ME. The Biologist
2004; 51(2): 65-70.

Spotila L. Pharmacotherapy for CFS. CFIDS Chronical: Special
Research Issue. 2005.

Stulemeijer M, de Jong LW, Fiselier TJ, Hoogveld SW,
Bleijenberg G. Cognitive behaviour therapy for adolescents with
chronic fatigue syndrome: randomised controlled trial. BMJ
2005; 330: 14-49

Tan EM et al. The case definition of chronic fatigue syndrome.
Journal of Clinical Immunology 2002; 22: 8-12.

Tirelli U, Chierichetti F, Tavio M, Simonelli C, Bianchin G, Zanco
P, Ferlin G. Brain positron emission tomography (PET) in
chronic fatigue syndrome: preliminary data. Am J Med 1998;
105(3A): 54S-58S.

Van der Werf et al. Identifying physical activity patterns in chronic
fatigue syndrome using actigraphic assessment. Journal of
Psychomotor Research 2000; 49: 373-9.

Wearden AJ, Morriss RK, Mullis R, Strickland PL, Pearson DJ,
Appleby L, Campbell IT, Morris JA. Randomised, double-blind,
placebo-controlled treatment trial of fluoxetine and graded
exercise for chronic fatigue syndrome. Br J Psychiatry 1998;
172: 485-90.

Wessely S. Chronic fatigue syndrome-trials and tribulations.
Journal of the American Medical Association 2001; 286: 1378.

Whiting P, Bagnall A-M, Sowden AJ, et al. Interventions for the
treatment and management of chronic fatigue syndrome: a
systematic review. Journal of the American Medical Association.
2001;286:1360-8.

[Return to top]

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

Date:    Wed, 29 Nov 2006 12:52:45 -0500
From:    "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx>
Subject: RES: Women's Health Issues with Fibromyalgia Syndrome

Women's Health Issues with Fibromyalgia Syndrome.

J Womens Health (Larchmt). 2006 Nov;15(9):1035-45.

Shaver JL, Wilbur J, Robinson FP, Wang E, Buntin MS.

University of Illinois at Chicago, College of Nursing, Chicago, Illinois.

PMID: 17125422


Background: Fibromyalgia syndrome (FMS) involves multiple sensory, somatic,
and cognitive symptoms that are bound to affect or be affected by physical
and mental health status and behavioral components of daily life.

Methods: From a telephone survey of 442 women with and 205 women without
FMS as volunteers, data were compared on (1) general health status, (2)
reproductive and sleep-related diagnoses, and (3) lifestyle health behaviors.

Results: All multiple or logistics regression analyses for group
differences were controlled for age, body mass index (BMI), race,
employment status, marital status, having a college degree, low household
income, and having ever been diagnosed with depression, with a Bonferroni p
value correction for multiple indicators. Accordingly, FMS negatively
impacted both perceived physical and mental health status, although
relatively more so for physical (p < 0.017). Women with FMS were more
likely to have had reproductive health or sleep-related diagnoses,
including premenstrual syndrome, dysmenorrhea, breast cysts, bladder
cystitis, sleep apnea, restless leg syndrome, and abnormal leg movements (p
< 0.0125). They were calculated to use less than half as many calories per
week as control women (689 ± 1293 vs. 1499 ± 1584 kcal/week, p < 0.05)
and had more sleep pattern difficulties (p < 0.0125), more negative changes
in sexual function (greater odds for 5 of 10 indicators at p < 0.005), and
lower alcohol use (odds ratio = 0.39, p < 0.05).

Conclusions: Patients with FMS deserve careful assessment for reproductive
conditions and sleep-related functional disorders. Besides more research
into mechanisms underlying symptoms, intervention testing specifically to
alleviate sleep problems, low physical activity levels, and sexual
dysfunction should be paramount.

[Return to top]

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

Date:    Wed, 29 Nov 2006 13:38:38 -0500
From:    Co-Cure Moderators <co-cure-mod@xxxxx.xxx.xxx>
Subject: NOT,MED: Dr. David Bell on "Intravenous Fluid as a Treatment for ME/CFS"

Dr. David Bell on "Intravenous Fluid as a Treatment for ME/CFS"
by Dr. David S. Bell, MD, FAAP

11-29-2006

Reproduced with permission from the November 1, 2006 issue of the
_Lyndonville News._ Dr. Bell is a widely published, internationally known
expert on adult and pediatric ME/CFS, practicing in Lyndonville, New York.

Introduction
The newsletter today is my first discussion of intravenous saline as a
treatment agent for ME/CFS. I have now been using this treatment for nearly
six years and wish to share my thoughts. While I plan to be open, honest
and even blunt about this treatment, I will not compromise the
confidentiality of the patients treated. I have nothing to sell, and I am
not encouraging this treatment, as it has not been rigorously tested.
However, I do not think I am witnessing a placebo response, and all things
considered, it is the most effective treatment for severe ME/CFS that I
have found in my 21 years of looking. But it has serious drawbacks and risks.

Read the complete article at
http://www.immunesupport.com/library/showarticle.cfm?ID=7552

[Return to top]

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

Date:    Wed, 29 Nov 2006 20:08:08 +0100
From:    Jan van Roijen <j.van.roijen@xxxxx,xx>
Subject: med: Therapeutic method for treating Epstein-Barr virus infection

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>> 27 November 2006     <<<<
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Outgoing mail scanned by Norton AV
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From:  DEnlander@xxx.xxx




Therapeutic method for treating Epstein-Barr virus infection
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~



Type and Number:
````````````````````````
United States Patent 5334395


Link to this page:
```````````````````````
http://www.freepatentsonline.com/5334395.html


Abstract:
````````````
A therapeutic method for treating Epstein-Barr virus infection.
The method comprises administering a therapeutically-effective
amount of a mammalian liver extract, the extract being
characterized by being heat stable, insoluble in acetone and
soluble in water, peptide or peptide fragment selected from the
groups consisting of Sequence Identification Numbers 1-9.

[Return to top]

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

Date:    Wed, 29 Nov 2006 21:12:23 +0100
From:    Jan van Roijen <j.van.roijen@xxxxx.xx>
Subject: res: ME/CFS -Ampligen -Phase III study

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>> 29 November 2006     <<<<
Editorship : j.van.roijen@xxxxx.xx
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~

http://immunesupport.com/



Major Late-Round Ampligen® Trial Recruits in Seven States
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~


by Editor ImmuneSupport.com

11-29-2006


An open label Phase III "intervention" study of the antiviral drug
Ampligen® 511 - the most recent step in Hemispherx
Biopharma's decade-long quest for FDA approval of the drug as
a CFS therapy - is recruiting subjects with "severely debilitating"
CFS/ME at centers in seven states, nationwide, according to
ClinicalTrials.gov:   http://clinicaltrials.gov/


Locations and Principal Investigators

The "chairs" or principal investigators of the trial, titled "An Open
Label Study of Ampligen® in Chronic Fatigue Syndrome,"
include three of the leading American names in CFS treatment:


      *   Daniel Peterson, MD, Sierra Internal Medicine,
      Incline Village, NV

      *   Lucinda Bateman, MD, Fatigue Consultation
      Clinic, Salt Lake City, UT

      *   Charles W. Lapp, MD, Hunter-Hopkins
      Center, Charlotte, NC



The other four listed trial locations include Los Altos, CA;
Springfield, NJ; Philadelphia, PA; and Reston, VA.


Trial Design and Purpose

Hemispherx noted recently that a previous, not-yet-published
Phase III (large) randomized placebo-controlled Ampligen® trial
enabled the group of CFS patients who received the drug for
twice weekly for 40 weeks to increase their exercise tolerance
by an average of 15 percent compared with another group of
CFS patients who were randomly selected to receive the
placebo (fake dose).


The current trial, officially titled An Open Label Study of
Ampligen® in Chronic Fatigue Syndrome (ClinicalTrials.gov
Identifier: NCT00215813) will be:



      *   An expanded access (large-population)
      interventional trial to study and analyze in more
      detail the drug's safety and effectiveness in
      affecting CFS symptoms among a large group
      of patients with "severely debilitating CFS/ME."

      *   Open label, non-randomized, and
      uncontrolled. All patients will knowingly be
      receiving the drug Ampligen® (Poly I: Poly
      C12U). None will receive placebo.

      *   And importantly, the FDA has "approved the
      study for cost recovery." This means patients
      enrolled in the study will be responsible for
      paying costs relating to the therapy – including
      the cost of the drug itself, and the cost of
      infusions, supplies, and diagnostic and other
      lab testing.


Though the trial-related costs are not specified, the drug is likely
to be quite expensive if and when the FDA's follow-up research
supports approval of Ampligen® as a CFS therapeutic. Some
project that the drug would cost $15,000 to $20,000 per patient
per year, according to a recent article in Science News. (The
co-inventor of Ampligen®, William A. Carter, MD, pioneered the
clinical development of the antiviral therapy interferon, which now
pulls down annual sales of $2 billion-plus.)


Eligibility and Inclusion Criteria:


Diagnosis

Diagnosis of Myalgic Encephalomyelitis (ME) as defined by the
1988 Centers for Disease Control and Prevention (CDC) case
definition for Chronic Fatigue Syndrome (CFS); ongoing for at
least 12 months. (Other clinical conditions which could present
with similar symptoms must be excluded.)

Age Range
Ages 18 through 65.

Males or non-pregnant, non-lactating females
Females must be of non-child bearing potential (either
post-menopausal for two years or surgically sterile including
tubal ligation), or using an effective means of contraception (birth
control pills, intrauterine device, diaphragm).

Females who are less than two (2) years post-menopausal,
those with tubal ligations, and those using contraception must
have a negative serum pregnancy test within the four (4) weeks
prior to the first study medication infusion.

Females of child bearing potential agree to use an effective
means of contraception from four (4) weeks prior to the baseline
pregnancy test until four (4) weeks after the last study medication
infusion.


Other

A reduced quality of life as determined by a Karnofsky
performance score (KPS) of from 20 to 60 at baseline. The KPS
must be rounded in increments of ten (10).

Ability to provide written informed consent indicating awareness
of the investigational nature of this study.


Documentation (during baseline or historically following onset of
CFS/ME) of:

      *   A negative antinuclear antibody test (ANA) or
      a negative anti-ds (double-stranded) DNA,

      *   A negative rheumatoid factor,

      *   And an erythrocyte sedimentation rate
      (ESR).



Documentation during baseline of a normal T4 (or other
laboratory evidence that the subject is euthyroid [normal thyroid])
is also required.

Contact Information


Please refer to this study by ClinicalTrials.gov identifier
NCT00215813

Sharon Conway 215-988-0080 sharon@hemispherx.net


Please contact Hemispherx Biopharma for additional
information regarding trial locations and site contacts:

By Fax: 215/988-1739

E-mail: trialinfo@hemispherx.net

Mail: Hemispherx Biopharma, Inc. One Penn Center
1617 JFK Blvd., 6th Floor
Philadelphia, PA 19103



More Information

Study ID Numbers: AMP 511 Last Updated: October 24, 2006


Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-10-27


[Return to top]

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

Date:    Thu, 30 Nov 2006 04:18:58 +0100
From:    Jan van Roijen <j.van.roijen@xxxxx.xx>
Subject: med: CDC: Chronic fatigue syndrome is real

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


Send an Email for free membership
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Outgoing mail scanned by Norton AV
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http://www.tulsaworld.com/NewsStory.asp?ID=061127_Ne_A9_CDCCh33407





CDC: Chronic fatigue syndrome is real
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~


By KIM ARCHER World Staff Writer

11/27/2006



A local medical director says the hardest part of getting help can
be finding a physician who believes you.

After years of ridicule and dismissal, chronic fatigue syndrome
sufferers may feel validated since the U.S. government has
declared the disease real.

In early November, the national Centers for Disease Control
launched an awareness and educational campaign called, "Get
Informed. Get Diagnosed. And Get Help." The campaign is
aimed at educating patients and doctors about the reality of
chronic fatigue syndrome, or CFS.

Eighty percent of an estimated 1 million Americans with the
disease do not know they have it, the CDC said.

"This is a disease that has been shrouded in a lot of mystery and
controversy. And sometimes people question if it's real or not
real," Centers for Disease Control Director Julie Gerberding
said earlier this month. "We are committed to improving the
awareness that this is a real illness and that people need real
medical care and they deserve the best possible help that we
can provide."

"It's very frustrating (to treat CFS patients)," said Robert Gray, a
medical doctor who once treated CFS patients but quit his Tulsa
practice to become medical director of OMNI Medical Group
sponsored by St. John Health System.

He said the CDC's step toward legitimizing the disease is a
good one in that it protects patients from "snake oil salesmen"
and provides doctors with evidence.

He said one of the biggest difficulties in diagnosing and treating
the disease is finding a doctor who believes it is a real illness.

"Most doctors have a strong bias that it's probably a psychiatric
syndrome," he said.

A recent study showed that doctors with loved ones or long-term
patients who suddenly fall ill with CFS are more likely to become
advocates for sufferers. "When they see this was not a needy
person, but an active, accomplished person who became
crippled, they probably can reconcile their preconceptions with
the facts," Gray said.

The CDC also announced $4 million in research grants for
studies.

After 20 years of research, the scientific community still does not
know what causes the disease or how to treat it. Scientists have
revealed the discovery of underlying biological abnormalities,
which could suggest a genetic link.



````````````````````````````````````````````````````````````````
Kim Archer 581-8315
kim.archer@tulsaworld.com
````````````````````````````````````````````````````````````````


What is CFS?

Chronic fatigue syndrome is a debilitating, complex disorder
characterized by profound fatigue, and often accompanied by
weakness, muscle pain, memory impairment, insomnia and
post-exertional fatigue lasting longer than 24 hours.



~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~


http://www.contracostatimes.com/mld/cctimes/news/nation/16120395.htm


Posted on Wed, Nov. 29, 2006



Once dismissed as malingering,
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
chronic fatigue syndrome finally getting respect


By Nancy McVicar

South Florida Sun-Sentinel

(MCT)


FORT LAUDERDALE, Fla. - Marly Silverman had a high-energy
job as a financial consultant to a major U.S. bank, until she came
down with a viral infection that she couldn't seem to shake. She
was exhausted all the time, ran a low-grade fever and lost
weight, and then the neurological symptoms began.

"I would be driving on I-95 and forget where I was going - not a
good thing," said Silverman, 52.

It took several months, but eventually she was diagnosed with
chronic fatigue syndrome, the Rodney Dangerfield of diagnoses.

For years, people who complained of the symptoms -
exhaustion, joint pain, sleep problems, impaired memory,
inability to concentrate - were dismissed by some doctors as
malingerers or hypochondriacs.

This month, the federal Centers for Disease Control and
Prevention launched a campaign to change that by educating
patients and physicians that chronic fatigue syndrome, or CFS,
is a mysterious but serious disease sometimes triggered by a
viral infection but with other unknown factors.

It affects at least 1 million Americans, but many have not been
diagnosed because most doctors have not been trained to
recognize it, said Dr. William Reeves, chief of the chronic viral
diseases branch at the Centers for Disease Control. Women
are affected at about four times the rate as men, and non-white
women are affected at a rate greater than white women, Reeves
said. The age group most affected is 40 to 59.

Reeves, who leads a research group studying the syndrome,
said the illness follows a pattern of symptoms that can change
over time, and that sometimes disappear and then come back.
Spontaneous recovery is rare, he said.

Treatment plans typically involve doctors asking patients which
symptoms most affect their quality of life - such as
sleeplessness, joint pain, gastrointestinal complaints or
depression - and prescribing medications to ease those
symptoms.

Irwin Auster, who facilitates some of the meetings, said he
sought help from a dozen different doctors for his unexplained
physical pain, but none could figure out what was causing it or
give him anything strong enough to take it away.

"I was on the verge of ending my life, by sitting on the tracks and
waiting for the train," said Auster, 64.

Then he read an article about Dr. Nancy Klimas, a University of
Miami School of Medicine clinician-researcher, who treats
patients with symptoms like his.

"I do owe her my life," Auster said. "I really do."

Klimas, who was in Washington for the launch of the CDC
campaign, said research over the past 20 years is beginning to
figure out the biological underpinnings of the syndrome, which
she thinks is badly misnamed.

"If it were called chronic neuroinflammatory disease, then people
would get it," she said. "Up until now nobody's been willing to
change the name, but now there's proof (that inflammation
occurs in the brain.)

"There's evidence that the patients with this illness experience a
level of disability that's equal to that of patients with late-stage
AIDS, patients undergoing chemotherapy, patients with multiple
sclerosis."

Klimas is president of the International Association for Chronic
Fatigue Syndrome, an organization of medical professionals
and research scientists. Its next research conference will be in
January in Fort Lauderdale.

She and other investigators have shown that different types of
cells within the immune system are abnormal either in number or
their capacity to function in these patients.


University of Miami researchers, including Mary Ann Fletcher,
have just been awarded new grants from the National Institutes
of Health to continue their work. One goal is to come up with
tests to diagnose the disease in its different forms, Fletcher
said.

"We have fairly good reason to believe that CFS is not a
homogeneous syndrome. There may be several subsets, and it's
important to compare apples to apples. It's possible a treatment
that would work for subset A would not work for subset B,"
Fletcher said.

Klimas and Fletcher are recruiting 150 new patients for a study
that will assess them on days when they feel good and also
when they're feeling particularly bad, so they can compare their
blood samples for differences.

"And if on a bad day they are unable to come to the clinic, we will
send somebody to them to draw their blood," Fletcher said.

Klimas said even though researchers still don't have all the
answers, there are effective treatment strategies that do help
patients.

"There's no single treatment that fixes the illness, but there are
treatments that do help significantly - increasing the function of
the patient, and allowing them to engage in normal activities of
daily living," she said. "It's critical for patients and their health
care providers to know that there is hope and that we can help."

---

CHRONIC FATIGUE SYMPTOMS

Chronic fatigue syndrome can cause symptoms so severe that
people cannot function normally. There is no simple test to
diagnose the illness, but researchers, including a group at the
University of Miami, are working on that and on how best to treat
the syndrome.

The U.S. Centers for Disease Control and Prevention says
doctors should consider CFS in patients with six months or more
of unexplained fatigue accompanied by other characteristic
symptoms, including:


      *  Cognitive dysfunction, including impaired
      memory or concentration.

      *  Exhaustion lasting more than 24 hours after
      physical or mental exercise.

      *  Unrefreshing sleep, joint pain without
      redness or swelling, or persistent muscle pain.

      *  Headaches of a new type or severity.

      *  Tender lymph nodes or sore throat.




RESOURCES

The CDC has more information at www.cdc.gov/cfs. A local
patient group, PANDORA, or Patient Alliance for
Neuroendocrine-immune Disorders Organization for Research
and Advocacy, has a Web site: www.pandoranet.info.


[Return to top]

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

Date:    Thu, 30 Nov 2006 11:46:17 -0500
From:    "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx>
Subject: RES: Differential efficacy of a cognitive - behavioral  intervention versus pharmacological treatment in the management of  fibromyalgic syndrome

Differential efficacy of a cognitive - behavioral intervention versus
pharmacological treatment in the management of fibromyalgic syndrome.

Psychol Health Med. 2006 Nov;11(4):498-506.

Garcia J, Simon MA, Duran M, Canceller J, Aneiros FJ.

Department of Psychology, University of A Coruna, Spain.

PMID: 17129925


Given that studies about the differential efficacy of existing treatments
in fibromyalgia syndrome are scarce, the aim of this study was to compare
the differential efficacy of a cognitive - behavioral and a pharmacological
therapy on fibromyalgia.

Using a randomized controlled clinical trial, 28 fibromyalgic patients were
assigned to one of following experimental conditions: (a) pharmacological
treatment (i.e., cyclobenzaprine), (b) cognitive - behavioral intervention
(i.e., stress inoculation training), (c) combined pharmacological and
cognitive - behavioral treatment and (d) no treatment.

The results show the superiority of cognitive - behavioral intervention to
reduce the severity of fibromyalgia both at the end of the treatment and at
follow-up.

We conclude that cognitive - behavioral interventions must be considered a
primary treatment of fibromyalgia syndrome.

[Return to top]

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

Date:    Thu, 30 Nov 2006 11:49:43 -0500
From:    "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx>
Subject: RES: Mechanisms of Disease: genetics of fibromyalgia

Mechanisms of Disease: genetics of fibromyalgia.

Nat Clin Pract Rheumatol. 2006 Dec;2(12):671-8.

Ablin JN, Cohen H, Buskila D.

JN Ablin is a senior physician in the Department of Rheumatology, Tel-Aviv
Sourasky Medical Center and at the Sackler Faculty of Medicine, Tel-Aviv
University, Israel.

PMID: 17133252


Fibromyalgia is characterized by widespread pain and tenderness, and has a
significant familial component. The etiology of fibromyalgia remains
unclear, but genetic factors seem to have a significant role, and are
influenced by environmental factors.

Research over the past two decades has demonstrated that genetic
polymorphisms in the serotoninergic, dopaminergic and catecholaminergic
systems of pain transmission and processing are involved in the etiology of
fibromyalgia, but additional candidates continue to emerge.

Fibromyalgia is thought to belong to the group of affective spectrum
disorders, which include related psychiatric and medical disorders. As the
concept of affective spectrum disorders continues to evolve, progress in
the understanding of the genetic basis of related functional disorders,
such as irritable bowel syndrome and post-traumatic-stress disorder, is
aiding our understanding of the genetic basis of fibromyalgia.

[Return to top]

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

Date:    Thu, 30 Nov 2006 18:41:44 +0100
From:    Jan van Roijen <j.van.roijen@xxxxx.xx>
Subject: act,med: NICE Submission - Tymes Trust

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>> 30 November 2006     <<<<
Editorship : j.van.roijen@xxxxx.xx
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~

From:  "Ian McIlroy" <ian@xxxxx.xxx.xxx>


MAY BE REPOSTED



SUBMISSION TO NICE
by THE YOUNG ME SUFFERERS TRUST
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

We are now able to make public our submission to NICE.
Please note that we quote from a new publication - 'The
Nightingale Definition of Myalgic Encephalomyelitis (ME)' - with
which our Executive Director was asked to assist. This is now on
the publications page at www.tymestrust.org and at the
Nightingale Research Foundation's website. Our submission
aims to complement those of many other ME organisations and
add something new to the debate, rather than reiterate all the
points so excellently made already. We particularly concentrate
on:

a) the need to separate out ME from CFS and

b) the need to provide proper advice on children.


All comments are on the NICE version of the Guideline, the
version that would be the most read. Where comments refer to
specific page numbers we have inserted them in this
transcription. Other comments are 'general'.


OVERALL VIEW OF THE NICE GUIDELINE

The Trust believes that the present draft of the NICE guideline on
CFS/ME is unacceptable, and not fit for purpose for patients
suffering from ME.


ANALYSIS OF THE PROBLEM

The problem NICE faces is that it has attempted to put together
guidance on a medical condition that has been artificially
constructed. CFS is not a discrete disease, it is an arbitrary
grouping of symptoms, now with the profile even further widened
by NICE. By the very nature of the process by which 'CFS' was
created, different pathologies must be trapped within its remit;
descriptions of CFS always refer to it as a 'heterogeneous
condition' eg the Report of the Chief Medical Officer's Working
Group on CFS/ME published by the DOH in 2002.

Those who coined the term CFS were divided as to the
symptom profile they would research, rather than researching a
specific and recognisable disease. Government, physicians and
patients are all having to deal with the fall-out of this process.

In the Trust's opinion, this guideline as it stands would lead to an
unprecedented degree of iatrogenic injury to people with
genuine ME, particularly children, those in the early stages of
ME, and the severely ill. Those who are not yet severely ill risk
being made so, both by the treatments recommended, and by
the fact of relapses being trivialised by the term 'setbacks' and
patients being urged to continue with programmes despite these
setbacks. This is demonstrated in the many accounts we have
been given over the years, together with numerous patient
surveys such as that by the 25% Group. If a key symptom of a
disease is post-exertional malaise, it is illogical and
inappropriate to prescribe exercise as a treatment and the
damage done by such an approach is evident in patient
histories.

Before CFS was born (originally for research purposes only)
'ME' was the name for a well-defined, virally triggered, potentially
severe and chronic neurological disease. Incorporating it into a
collection of symptoms in which 'chronic fatigue' is the main
symptom masks its true nature. The fact that the CFS construct
has been taken into clinical use compounds the problem. This
has put NICE in the position of issuing guidance on an
unscientific basis, for a hopelessly mixed group of patients.

Consequently, if this guideline were published, physicians face
the stark choice of ignoring NICE when dealing with patients
who have ME rather than CFS, or risking actively causing harm
to this group of patients. They would also have no guidance on
how to distinguish this group.

Having seen and experienced what comes of trying to put
together guidance for 'CFS/ME', the Trust now believes that ME
and CFS should be the subject of separate guidelines. Despite
the step forward that the (recently updated) Canadian Criteria for
CFS/ME represented -criteria which the Trust was the first to
recommend in the UK - we believe that ME should now be
removed from the CFS bracket and steps taken to issue
guidance to doctors as to its true nature, using information from
appropriate ME specialists, who will not be those at present
advising the government on CFS. They should be drawn from
those who have the necessary knowledge, expertise and
experience of examining and investigating ME patients and who
can point to the infectious origin of ME, its known epidemiology,
history of epidemics, known biomedical research profile,
testable pathological changes, post mortem findings and other
robust scientific evidence.

We respectfully submit as evidence selected quotes from the
Nightingale Definition of ME by The Nightingale Research
Foundation, Ottawa, Canada, with which our Executive Director
Jane Colby was invited to assist. The Nightingale Definition will
shortly be available in full.

The expertise and knowledge that NICE needs on ME is
available. The Trust is dismayed that NICE has allowed such a
narrow perspective to inform such vital work and requests that it
reconsider the whole guideline in the light of our submission, our
new evidence, and that of other patient organisations.


QUOTES FROM THE NIGHTINGALE DEFINITION OF ME :

ME is a clearly defined disease process. CFS by definition has
always been a syndrome. At one of the meetings held to
determine the 1994 CDC definition of CFS [.] Dr. K Fukuda
stated that numerous ME epidemics  -* he cited the Los Angeles
County Hospital epidemic of 1934, the Akureyri outbreak of
1947-48 and the 1955-58 Royal Free Hospitals epidemics *-
were definitely not CFS epidemics. Dr. Fukuda was correct. [.]

Primary ME is an acute onset biphasic infectious disease
process, where there is always a measurable and persistent
diffuse vascular injury of the CNS in both the acute and chronic
phases. Primary ME is associated with immune and other
pathologies. [.]

Primary ME is a chronic disabling, acute onset biphasic
infectious disease process affecting both children and adults.
There are both central and peripheral aspects to this illness. [.]

Primary Infection Phase: The first phase is an epidemic or
endemic infectious disease generally with an incubation period
of 3 to 7 days; in most, but not all cases, an infection or
infectious process is evident. (See Clinical and Scientific Basis
of M.E./CFS, Hyde B, pps.124-126)

Secondary Chronic Phase: The second and chronic phase
follows closely on the first phase, usually within two to seven
days; it is characterized by a measurable diffuse change in the
function of the Central Nervous System. This second phase is
the persisting disease that most characterizes ME [.]


Extent of Injury

Type 1: One side of the cortex is involved. Those patients
labeled as 1A have the best chance of recovery.

Type 2: Both sides of the cortex are involved. These patients
have the least chance of spontaneous recovery.

Type 3: Both sides of the cortex, and either one or all of the
following: posterior chamber organs (the pons and cerebellum),
limbic system, the sub-cortical and brainstem structures are
involved. Type 3B are the most severely affected patients and
the most likely to be progressive or demonstrate little or no
improvement with time.


Degree of injury

Type A: Anatomical integrity is largely maintained in the Brain
SPECT scan.

Type B: Anatomical integrity is not visible in the CNS SPECT
scan.

Type 3B are some of the most severely and chronically injured
patients. [.]


What is new and different about the Nightingale ME Definition is
the following:

A Testable Definition: The definition is set out in both a clinical
diagnostic and scientifically testable fashion. This will allow the
physician both an early diagnostic bedside or office
understanding of the illness and a scientific and technological
method to investigate and confirm the diagnosis. [.]

END QUOTES



The Nightingale Definition lists the following:


      - Testable Neuropsychological Changes

      - Testable Major Sleep Dysfunction

      - Testable Muscle Dysfunction

      - Testable Vascular Dysfunction. POTS; Cardiac
      Irregularity; Raynaud's Disease; Circulating
      Blood Volume Decrease; Bowel Dysfunction;
      Ehlers-Danlos Syndromes Group; Persantine
      Effect in ME Patients; ME Associated Clotting
      Defects

      - Testable Endocrine Dysfunction: This feature
      is common and tends to be a late appearance. It
      is most obvious in: Pituitary-Thyroid Axis;
      Pituitary-Adrenal Axis Changes;
      Pituitary-Ovarian Axis Changes; Bladder
      Dysfunction Changes


In the Nightingale Definition of ME, more than 30 physicians are
listed who have to varying degrees also noted the historical and
the more recent investigational findings. We recommend this
definition to NICE.


FURTHER COMMENT

The Trust has been working co-operatively with the ME
Association regarding children with ME at their invitation. We
endorse the critique of the NICE guideline by the ME
Association in its submission.

The Trust agrees with the stance taken by the 25% Group on this
draft.

The Trust agrees with the view of the Edinburgh MESH group
and others that patient evidence has not been accorded
sufficient weight or respect. This is entirely at variance with the
government's own Expert Patient scheme and its aim to involve
the Patient Voice.

The Trust is in sympathy with virtually all comments that we have
read from ME Support Groups and group consortia around the
UK. Some responses have included a plethora of detail with
research references. We would emphasise that when virtually
every patient group and support organisation in the country
explains in a respectful and well-defined way that these
guidelines are not fit for purpose, NICE would be well advised to
take full cognisance of these views.

In the Trust's opinion there is a lack of information about
children's needs in the guideline and in some ways they are very
badly served by it; see our points below, which should be taken
to refer to children and young people with ME rather than the
broader chronic fatigue.

P4
NICE appears to suggest that young people aged 16-19 may
choose to remain under the care of a paediatrician rather than
transfer to adult services. It is unclear if NICE is suggesting an
increase in paediatricians' caseloads and a change in the usual
system of transfer at 16.

NICE has used the RCPCH guideline to inform this guideline
and so has perpetuated some of its mistakes rather than
re-considering the issues afresh with new advisers.

P34 1.4 1.3
On the severely affected, it is suggested that Graded Exercise
Therapy may be appropriate 'to help develop their physical
capacity and functioning'. This perception of exercise as being
able to 'do the recovery' to the person, is at variance with patient
experience, and the clinical experience of other physicians not
asked to advise NICE, who maintain that supporting the body's
natural recovery process, so that it is able to do more when
healing occurs (the same principle as applying a plaster to
broken bone) is safer and more effective than trying to force the
pace of healing. Capacity extends naturally as healing takes
place.

In the Trust's opinion, GET should only be considered as an
option when a person is sufficiently well into the recovery phase
and is much stronger and able to start increasing activity without
making themselves worse. Severely affected children are
commonly pressurised to increase activity inappropriately and
we have seen terrible relapses as a result, with memory loss,
paralysis, return to the stage of tube feeding due to inability to
swallow. Such relapses can be very long term. One young
person of 26 reported sti