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CO-CURE Medical & Research Posts Only Digest - 23 Oct 2006 to 30 Oct 2006 (#2006-49)

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Date:    Tue, 24 Oct 2006 13:29:38 -0400
From:    "Bernice A. Melsky" <bernicemelsky@VERIZON.NET>
Subject: RES: Daily fatigue in women with osteoarthritis, rheumatoid  arthritis, and fibromyalgia

Daily fatigue in women with osteoarthritis, rheumatoid arthritis, and

Pain. 2006 Oct 19; [Epub ahead of print]

Zautra AJ, Fasman R, Parish BP, Davis MC.

Department of Psychology, Arizona State University, Tempe, AZ 85287-1104, USA.

PMID: 17055648

We examined between and within-person variability, affective correlates,
and diagnostic differences in daily fatigue in women with rheumatoid
arthritis (RA),
osteoarthritis (OA), and fibromyalgia syndrome (FMS). Two hundred and
fifty-five female patients recruited from the community served as
participants for this project. The patients had a physician-confirmed
diagnosis of RA (n=89), OA (n=76), or FMS (n=90). Individuals completed an
initial questionnaire and up to 32 daily diaries assessing illness symptoms
and psychosocial variables (i.e., fatigue, pain, sleep problems,
depression, and affect). The primary outcome for the current project was
variability in fatigue. We examined affective, pain, and sleep correlates
of fatigue, and tested whether these relations varied by diagnosis.

Results indicated that FMS patients had higher overall levels of and
greater daily variability in fatigue compared with the other pain groups.
For all patients, fatigue correlated highly with lower positive affect
(PA). Moreover, day-to-day increases in fatigue were associated with
decreases in PA, particularly among FMS patients, and with increases in
negative affect (NA). Daily pain was associated with increased fatigue in
all groups, although OA patients showed less pain reactivity than either
FMS or RA patients.

These findings indicate that fatigue is a common feature of rheumatologic
conditions. Nonetheless, there are important differences between RA, OA,
and FM patients in both the everyday manifestations and the biopsychosocial
correlates of fatigue.

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Date:    Tue, 24 Oct 2006 15:37:34 -0400
From:    "Dr. Charles Shepherd <charlesbshepherd @lineone.net> Co-Cure
         Moderator" <co-cure-mod@LISTSERV.NODAK.EDU>
Subject: ACT,MED: Comprehensive MEA response to NICE Guideline on ME/CFS (draft 2) [UK]

[Note: This message is being resent because the original was
inadvertently truncated.]

Monday, October 23, 2006
Comprehensive MEA response to NICE Guideline on ME/CFS (draft 2)


This second draft takes account of the very helpful comments and feedback
that has been sent in by people with ME/CFS over the past week.

Further comments to the MEA are most welcome - see notes at the end.

A further draft will be prepared next week.


Following on from our previous statements on the September draft of the
NICE guideline on ME/CFS, and our summary of the meeting held at NICE on
Thursday 5 October, the MEA has now produced a second draft of the
comprehensive response that we intend to send to NICE at the end of this
stage in the consultation process.

This response takes account of all the feedback that the MEA has received
so far and the discussion that took place at NICE on 5 October. Thank you
to everyone who has sent in comments.

As a stakeholder in the guideline development process the MEA has a duty to
consult with its members and produce a response that reflects their views.

So we want to know if you feel that our response is appropriate and
constructive. We want to know if there are any omissions or areas where we
have been too critical, or not critical enough. We also want to know if
there are any areas where we should be praising the guideline.

In April 2007 NICE will publish a final version of a guideline on ME/CFS.
This will have a major effect on how your illness is going to be managed
for years to come.

The MEA believes that the current attempt is seriously flawed and is not
therefore fit for purpose.

Over the coming weeks and months we need to do all we can to make changes
while there is still an opportunity to do so.



The ME Association (MEA) has carefully considered the contents of this draft.

As a stakeholder in the guideline development process we have actively
sought the views of our members over the past few weeks as well.

We have also taken note of the responses to our criticisms that were made
at the meeting with NICE on Thursday 5 October.

The comments below represent the outcome of this extensive consultation


The MEA fully supports the view that a guideline on the assessment and
management of ME/CFS should be prepared by NICE and made available to all
health professionals in the UK.

Such a guideline must reflect the wide variety of clinical presentations
and pathophysiological mechanisms that come under the ME/CFS umbrella.

Above all, it must be acceptable to people who have this illness.

Overall, we feel that the current (ie September 2006) version of the
guideline that has been prepared by NICE is unfit for purpose and we would
not be willing to endorse it.

We have five major disagreements.

a.. First involves the unbalanced coverage of CBT and GET.

a.. Second is the failure to provide any meaningful advice on management
during the acute and very early stages of the illness before a firm
diagnosis of ME/CFS has been made.

a.. Third is the failure to provide any meaningful advice on symptomatic
management as the illness enters a more chronic stage.

a.. Fourth is the way in which it deals with issues affecting the severely

a.. Fifth is the failure to acknowledge the WHO classification of ME/CFS
(and PVFS) as being neurological disorders (in section G93.3 of ICD 10) - a
position that the Department of Health also accepts - and instead adopts a
new and much wider clinical definition of ME/CFS that includes almost
anyone with chronic unexplained fatigue.

We will first elaborate on these five objections in more detail:


Our principal disagreement involves the way in which almost all of the
management section is devoted to a manual-like approach that sets out how
the authors believe that cognitive behaviour therapy (CBT) and graded
exercise therapy (GET) should be used as an automatic first line treatment
for almost everyone who has mild to moderate ME/CFS.

The sections on CBT and GET contain numerous recommendations on how to deal
with specific management problems - most of which are based on opinion
rather than the type of evidence based medicine that normally dominates a
NICE guideline.

Some of the advice on non-pharmacological management contains sensible and
common sense suggestions. We already recommend some of these coping
strategies in our own self-help literature. But there is no reason why this
type of advice has to be given by specially trained behaviour therapists in
hospital. Where the advice is sensible, and not based purely on the
psychosocial model of abnormal illness beliefs and behaviour, it should
form part of a self-help or Expert Patient management programme. This sort
of advice could easily be given out in a primary care setting - where most
people with ME/CFS are, and will continue to be managed.

However, much of the coverage here is seriously flawed because the opinions
of those who are obviously very enthusiastic about the overall value of
hospital-based CBT and GET are given undue emphasis whereas any form of
critical opinion from people who have been treated with these approaches is
simply ignored. The Chief Medical Officer's report adopted a trident
approach to deal with this difficult issue whereby it took note of opinion
from clinicians and patients, as well as the results from published
research studies, when it came to dealing with CBT and GET.

This is crucial because patient opinion submitted to the CMO report
indicated that the results for CBT were not at all impressive with around
65% saying that this approach had not been helpful. And around 50% of
people who had been placed on a graded exercise regime reported that this
had made their condition 'worse'.

NICE has clearly not grasped the fact that the treatment trials being
quoted to support the use of CBT and GET have only used relatively small
numbers of carefully selected patients, have generally been carried out in
tertiary care centres that support the psychosocial model of ME/CFS
causation, and in some cases have had quite high drop-out rates (37% in one
GET trial). Our feedback in relation to GET dropouts is that some of these
people have gone on to relapse as a result of the exercise programme - but
this is never made clear in published results.

While preparing this response we have received feedback from someone who
has recently been treated at an internationally recognised centre where
this type of behavioural research is carried out. This person has stated
that when someone cannot build up the exercises in the speed that the
centre require, they are then told that they are not motivated enough to
follow the programme and have to leave We would be willing to forward the
complete response to NICE if requested.


With regard to CBT (sections, we believe it is completely
unacceptable to imply that everyone with mild to moderate ME/CFS needs to
take part in a hospital-based CBT programme that includes an underlying
assumption that symptoms are maintained by factors such as abnormal illness
beliefs and behaviour. While there are some people who come under the
diagnostic umbrella of CFS who do fit the psychosocial model of illness
perpetuation, there are many others who do not, have no psychiatric
co-morbidity, are well motivated, and are doing everything they can to try
and get better. They would, quite rightly, object to such an approach to
their management.

The Guideline Development Group (GDG) should also take note of the most
recent research study on CBT. This found that CBT did not offer any
significant overall benefit when compared to education and support and
standard medical care (reference: Cognitive behaviour therapy in chronic
fatigue syndrome: a randomised controlled trial of an outpatient group
programme. Health Technology Assessment. 2006 Oct; 10: number 37 -
available on-line at: http://www.hta.ac.uk/fullmono/mon1037.pdf).

Neither does NICE appear to appreciate that counselling may well be just as
effective as CBT in some instances. Two relevant references are:

Chronic fatigue in general practice: economic evaluation of counselling
versus cognitive behaviour therapy. British Journal of General Practice
2001; 51: 15-18.
Chronic fatigue in general practice: is counselling as good as cognitive
behaviour therapy? A UK randomised trial. British Journal of General
Practice 2001; 51: 19-24.


We have a number of major concerns about the information being given on GET
(sections - 18).

Our first concern relates to the word exercise. Exercise is, of course, a
completely misleading term for energy management in the severely affected
group. It is also inappropriate for most people in the moderately affected
group. It may or may not be appropriate in mild cases.

The unqualified and frequent use of the term exercise clearly implies that
exercise is the key to recovery and that rest/relaxation is generally harmful.

NICE only have to look at the press coverage of the York systematic review
in the Journal of the Royal Society of Medicine to see that this is how the
media is already interpreting this type of advice. The same sort of
over-simplistic interpretation will be made by most doctors who have no
special interest in ME/CFS. What is required is a name and a practical
approach that advises people with ME/CFS on how to achieve a sensible and
flexible balance between activity or energy management (not exercise) and
rest. This will depend on the stage, severity and variability of their
condition - as we point out in some detail in our own information
literature. Some people may need to increase their activity levels whereas
others may actually need to reduce them, especially in the early weeks and
months following an acute onset - this is not what graded exercise implies.

Our second concern relates to the way in which the guideline appears to
have dealt with energy/activity management during the very early stages of
this illness (ie first few weeks and months) before a firm diagnosis of
ME/CFS has been made. At this stage we believe that a period of appropriate
rest and convalescence is essential (we are not advocating that people go
to bed and stay there) and that inappropriate exercise could well produce a
further deterioration. Is NICE really advocating graded exercise during the
very early stages of ME/CFS? This appears to be the case in section

Our third concern relates to what is commonly referred to as the 'glass
ceiling' effect whereby people with ME/CFS often make a degree of
improvement over the prolonged course of time, but then reach a point at
which they are unable to increase their physical activity - despite high
levels of motivation. The guideline does not even acknowledge this
situation - presumably on the assumption that graded exercise will
eventually return almost everyone to normal health.

Our fourth concern relates to the advice that activity levels should
largely be maintained during a period of relapse or setback (section We believe this advice is over simplistic and potentially
dangerous, and is once again based on opinion rather than any sound
evidence. We do not believe that spending a few days resting in bed during
a significant relapse of symptoms, certainly one caused by an infection, is
going to be harmful or result in deconditioning. This is the way in which
many people with ME/CFS successfully cope with a relapse and we believe it
would be irresponsible to ignore the views of patients yet again. We also
believe that NICE has not taken appropriate note of several research
studies which refute the role of deconditioning in the perpetuation of

The section covering relapse or setback is curious in that while it
provides advice on how to cope with a relapse/setback it fails to include a
list of very common causes of relapse (ie infection, over-exertion, trauma,
surgery and general anaesthetics, some types of vaccination). This is
important information that doctors ought to be aware of and passing to
their patients.


The sections on CBT and GET are unbalanced and contain advice that is
potentially harmful for a significant proportion of people who come under
the ME/CFS umbrella. We cannot therefore endorse them.

Instead, we would like to see a guideline that advocates the type of common
sense, self-help strategies (ie pacing their activities according to stage
and severity) that have been repeatedly endorsed by people with ME/CFS.
This is an approach that could be incorporated into primary care management
and/or an Expert Patient programme, and we find it strange that the Expert
Patient Programme in relation to ME/CFS is not even mentioned in the
shortened version, which will presumably form the basis for what is sent
out to health professionals.

We also wonder whether NICE is living in the real world. The clear
implication being given in this guideline (key priorities section on p6/48)
is that if people with mild to moderate ME/CFS want to improve then they
need to be referred by their GP to a multidisciplinary hospital-based
ME/CFS service that has expertise in CBT and GET. NICE acknowledges that
these services cannot be delivered by general practitioners.

But where is the money going to come from to assess and treat around
180,000 people with ME/CFS in the mild to moderate category? If an
assessment and course of CBT and/or GET costs around £1,000, the total cost
to the NHS would be around £180 million.

And where are all the cognitive behaviour therapists going to come from?
CBT services are already in a position where they cannot cope with a
rapidly increasing referral rate for common psychiatric conditions such as
anxiety and depression - a steadily worsening situation that NICE has been
well aware of for some time.


Our second major disagreement concerns the way in which the guideline has
almost completely ignored (apart from section 1.2.10) what happens in the
first four months before a diagnosis of ME/CFS is confirmed. Whilst we
agree that a period of time needs to elapse before the diagnostic label of
ME/CFS is used, there are a number of crucial points that need to be
discussed in relation to how these patients should be managed during the
very early stages (ie the first few weeks and months).

On the question of labelling, the 2005 ME Alliance report into early
diagnosis suggested that there are appropriate names that could be used
while the diagnosis of ME/CFS is being considered - one example being a
post-viral fatigue syndrome.

But what is far more important is the fact that advice on aspects such as
sleep disturbance and energy management is likely to quite differ quite
significantly from that offered once the illness enters a more chronic
stage. In regard to sleep, excessive sleep (hypersomnia) is very common at
this stage and may well form a crucial part of a natural recovery process.
We know of no evidence to suggest that people who are needing to sleep for
a long period of time at night following an acute infection should be
coerced into adopting a more normal pattern of sleeping (as in

Anecdotal evidence is overwhelmingly in favour of a period of carefully
monitored rest during the very early stages, something that may include a
period of bed rest, followed by convalescence. Exercise in the normal sense
of the word usually has little or no role to play during this very early
stage. In fact, an inappropriate exercise programme is very likely to make
the illness worse.

MANAGEMENT (mainly section 1.3.4)

Our third major disagreement is that having spent most of the guideline
recommending CBT and GET, the remainder contains a totally inadequate
review of all the other aspects of management - many of which are extremely
important to patients, and are likely to be dealt with in primary care
rather than hospital-based services.

In particular, the almost non-existent coverage of pain, which for some
people is the most disabling aspect of their illness, is very poor -
especially when this is compared to the vast amount of space given to sleep

In other words, there is very little of practical value in this guideline
for general practitioners and members of the primary healthcare team - who
are likely to remain the main source of information, advice and support for
people with ME/CFS.


Although the guideline acknowledges that its recommendations regarding CBT
and GET do not apply to the severely affected, we feel that the information
that has been supplied does not take account of the enormous difficulties
currently being experienced by many people in this group when it comes to
accessing either hospital-based or domiciliary-delivered medical care,
obtaining practical support, and being refused one or more component of the
disability living allowance because both lay and medically qualified
assessors have received misinformation about the nature of this illness.

The description of severe ME/CFS (pp 4 - 5 of the short version) needs to
include the type of more severe neurological symptoms - ie blackouts,
atypical convulsions, loss of speech and swallowing necessitating tube
feeding - that are prominently referred to in section of the CMO


We are very concerned at the way in which the guideline has modified the
current Fukuda research criteria for CFS (section to produce a new
clinical criteria that extends the boundaries of what currently constitutes
ME/CFS (ie chronic unexplained fatigue + one other symptom). Many
clinicians and researchers believe that the existing research criteria are
already far too wide and as a result CFS has become a dustbin diagnosis for
anyone with unexplained chronic fatigue. The diagnostic criteria proposed
by NICE means that almost anyone with unexplained chronic fatigue, or
feeling 'tired all the time' will now be diagnosed as having ME/CFS.

The practical result is that hospital-based services, which are still
virtually non-existent in some parts of the UK, or are struggling to cope
with their existing workload in others - will be flooded with referrals for
people with unexplained chronic fatigue.

It makes no sense whatsoever to advocate what is basically a 'one treatment
fits all' approach to the extremely heterogeneous range of illness
presentations that comes under the existing ME/CFS umbrella. To try and do
this to everyone with unexplained chronic fatigue indicates a very serious
lack of judgement.

And while we appreciate that the aetiology and pathogenesis of ME/CFS falls
outside the NICE guideline remit, the situation regarding ME/CFS is unique
in that a significant proportion of doctors still do not even accept that
this illness exists as a distinct clinical entity (reference: Primary
healthcare provision and Chronic Fatigue Syndrome: a survey of patients'
and General Practitioner's beliefs. BMC Family Practice 2005; 6: 49;
epublication: http://www.biomedcentral.com/content/6/1/49). So there must
be reference to some of the important neuroradiological, neuroendocrine and
neuroimmunological research findings that support the World Health
Organisation classification of ME/CFS as a neurological disorder.

There should also be some reference to the important new research into gene
expression that is being carried out in both the UK and the USA. This has
already identified abnormalities in gene expression which may be
characteristic of ME/CFS - a finding that could, of course, lead to a
diagnostic test and specific forms of treatment.

We are disappointed to find that the Guideline Development Group (GDG)
appear to have totally rejected the way in which the Canadian Guidelines
have, quite sensibly, moved towards a much tighter clinical definition that
clearly recognises the importance of sub-grouping under the ME/CFS umbella,
and recommends that individual differences in symptoms and signs should
play an important role in how an individual patient should be managed.

If NICE fails to take note of these crucial points relating to causation
and subgrouping in formulating a new clinical criteria, ME/CFS will
continue to be trivialised as a dustbin diagnosis with patients being
incorrectly labelled as having some sort of psychosomatic or somatiform

As a result, people with ME/CFS will not receive the individual approach to
management that they deserve and this will add to, rather than alleviate,
the cost of health and social service provision.

We now move on to comment on some of the other conclusions and recommendations:


The is the one and only area where we find the content to be generally
balanced, helpful and sensible - as it sets out the common sense protocols
that should govern the management of any chronic disabling illness. We are
particularly pleased to see that information regarding the issue of
informed consent has been included here.

However, the value of the advice in this section is obviously dependent on
the quality of the advice that is contained elsewhere in the guideline.


The failure to include a compehensive list of illnesses that ought to be
considered before the diagnosis is confirmed is a serious omission - as is
the failure to point out that there are important clinical and research
findings that differentiate ME/CFS from depression.

Where symptoms are being discussed in relation to disease severity (eg on
page 5 of the shortened version) it should be pointed out, as was done in
section of the CMO report, that some people with more severe ME/CFS
may have neurological symptoms and signs such as those already referred to.

With regard to the investigation of people with a possible diagnosis of ME/CFS:

Some of the recommendations regarding the investigation of people with a
possible diagnosis of ME/CFS in section 1.2.2 suggest that the authors are
not in touch with the sort of information that patients are taking to their
doctors regarding diagnostic tests. For example, having funded research
into the value of investigations involving RNaseL (for antiviral activity)
and chronic fatigue syndrome urinary markers (CSFUMs), the ME Association
is surprised to find no mention of these tests.

We are also concerned at the lack of emphasis regarding the need to further
investigate people who, while they fit the diagnosis of ME/CFS, still have
a symptom or symptoms, which is/are more prominent than is normally found
in this illness. For example, the need to exclude sarcoidosis in someone
who also has respiratory symptoms. Or systemic lupus and parvovirus
infection in someone with joint pains. Or multiple sclerosis where
neurological symptoms and signs are difficult to differentiate between the
two - as does sometimes happen. Or an assessment for possible sleep apnoea,
with an Epworth sleepiness score, where daytime sleepiness is excessive or
comes on sudddenly.

There also needs to be far more information on where extended investigation
is required from points that are gathered during the routine history taking
(eg a positive response to a past history of blood transfusion prior to
1991 indicates the need to check hepatitis C status).

And why is the estimation of creatine kinase (section only
recommended in children when it may be a marker of a muscle disease in adults?

With regard to the physical examination:

We are perplexed as to why there is no mention of clinical examination in
the diagnostic assessment - in particular the assessment of problems such
as dysequilibrium where a Romberg test or Fukuda test (for vestibular
function) may demonstrate abnormal findings. Equally, people with symptoms
suggesting postural hypotension should have their blood pressure checked
lying and standing, and may in some circumstances require hospital based
investigations. The various fibromyalgia trigger points need to be checked
in those patients who have a fibromyalgic component.


The very short sections on prognosis ( and are inadequate
and fail to provide an accurate overall picture of current research
evidence on prognosis. While we accept that an approach of cautious
optimism, especially early on, should be adopted, the overall impression
being given of a generally good prognosis is not consistent with published
evidence. We suggest that the Guideline Development Group refer to the
information on prognosis that is provided in section 1.4.3 of the CMO report.


This section is hopelessly inadequate because, for many people with ME/CFS,
providing effective management for one or more of their symptoms can be far
more imprtant than the contribution of lifestyle management..

People with ME/CFS have a number of symptoms - pain, sleep disturbance,
gastric symptoms - where a combination of self-help strategies and
medication can often be very helpful. We do not understand why the
guideline cannot provide more detailed information on the sort of
approaches that can and should be given to patients. We have already
referred to pain control, which for some is the most disabling aspect of
having ME/CFS, but there are numerous other symptoms where symptomatic
relief plays an important role in any management programme.

We enclose some examples of MEA self-help literature on pain relief and our
ABC of symptomatic management to illustrate what could actually be done here.

DIET AND NUTRITION (section 1.3.5)

Again, this is hopelessly inadequate - especially in view of the fact that
people with ME/CFS are very interested in dietary approaches and are going
to ask questions about what may or may not be helpful. They clearly need
straightforward and sensible advice that covers a wide area of dietary
management, along with advice on the vitamins, minerals and supplements
that are extensively used and recommended to people with ME/CFS.

Why, for example, is there no information about the reasons why some people
(especially those with self-imposed dietary restrictions) with ME/CFS could
be at increased risk of developing osteoporosis and how diet may be
relevant here. Why is there no mention about the value of complex
carbohydrates in helping to stabilise blood sugar levels? Why is there no
mention of the importance of a good fluid intake? - especially in relation
to those who have postural hypotension or orthostatic intolerance. Why is
there no mention of simple self-help approaches that can help in the
management of nausea (eg use of ginger) or the use of drugs such as
ondansetron if this is more severe.

Why is is there no mention of EPA supplements, which are probably the most
popular supplement currently being used by people with ME/CFS. While we
accept that there have been no randomised controlled trials to support the
use of EPA, it is untrue to say that there is 'no evidence' in relation to
this supplement (reference: The use of eicosapentaenoic acid in the
treatment of chronic fatigue syndrome. Prostaglandins, Leukotrines and
Essential Fatty Acids 2004; 70: 399 - 401).

It is also unhelpful to simply state that 'Exclusion diets are not
generally recommended for the management of CFS/ME' when irritable bowel
symptomatology is quite common in this illness and there is good evidence
to show that exclusion diets can be helpful in identifying food
intolerances - where these occur in IBS. This section should also include
advice about not going on a gluten free diet before a screening test for
coeliac disease has been carried out. We could go on.


Again, this section is hopelessly inadequate and appears from the first
sentence - 'There are no complementary therapies that treat CFS/ME for
adults and children and their use is not recommended' - to be very
dismissive about any aspect of alternative medicine. With the lack of
recognition, or limited management input from many NHS practitioners,
people with ME/CFS have been spending large amounts of time and money in
the alternative health sector.

The pros and cons of the popular alternative treatments - eg anticandida
regimes; dubious allergy tests and treatments, Reverse therapy - commonly
aimed at people with ME/CFS must be properly reviewed, and where necessary
discredited. Approaches such as acupuncture for pain relief, which can be
supported by some degree of clinical evidence, need to be included in a
fair and balanced discussion.


As the CMO report acknowledged, the management of ME/CFS crosses many
boundaries. It is not just dealing with a wide range of symptoms. The NICE
guideline, while acknowledging that other management issues exist, almost
completely ignores what could and should be done in these areas.

State sickness and disability benefits, for example, are a major source of
worry for people with ME/CFS with many currently have to go to appeal in
order to obtain benefits to which they should be entitled. Any guideline on
management must, therefore, contain a section on state benefits, and make
it clear that where ME/CFS is concerned people should be entitled to
Incapacity Benefit and Disability Living Allowance where there is a genuine
need. It also needs to be pointed out that ME/CFS has been recognised as a
disease that can be covered by the Disability Discrimination Act, and that
this can be very useful in relation to employment and education.


The medical defence organisations have repeatedly warned doctors that
prescriptions for exercise must be given with exactly the same care as with
a prescription drug. Failure to do so is likely to result in litigation if
harm occurs as a result of inappropriate advice. The MEA continues to
receive reports from people with ME/CFS whose condition has relapsed
following inappropriate advice about exercise and as a result we believe
that the guideline must include this warning if it continues to use the
term exercise - even when what is being referred to is activity or energy


Section 1:3:1:3 'Where the adult or child's main goal is to return to
normal activities....' Many people will find this offensive as it implies
that there is a substantial proportion of people who do not want to return
to normal activities. The statement thereforet reinforces the prejudices
about sick role behaviour held by some health professionals.


1 We welcome the inclusion of information about informed consent but feel
that the guidance needs to make it clear, as did the CMO report in section
4.4.2, that benefit provision must not be made conditional on agreeing to
participate in a particular form of treatment.

2 The guidance, certainly in the shortened version, repeats itself at times
to no added effect.


In sending in this response as a stakeholder in the guideline development
process, the MEA has consulted widely with its members and reflected their
very strong views on the composition of the current draft.

We find it hard to imagine another situation where a group of people, many
of whom have little or no direct experience in the clinical care of an
illness they are advising on, have produced such a poor quality guideline.

We cannot understand why the views of people with ME/CFS and their charity
representatives are not being listened to.

Unless NICE takes on board what the stakeholders representing patient
opinion have to say, they will have failed the stakeholder principle -
something that government continually tells us is at the heart of the
consulting and listening process.

If this draft guidance becomes definitive guidance for health professionals
in April 2007, it will be a very sad day for people with ME/CFS.


If you wish to send in your views on the current NICE draft, or this second
draft of the MEA response, this can be done by clicking on following link
to email The MEA

More details on the MEA response so far, and a summary of the meeting held
at NICE on 5 October, can be found elsewhere on this blog.

The MEA blog also contains a link to the shortened version of the NICE
guideline and all other NICE documents relating to the September draft.


[Return to top]


Date:    Tue, 24 Oct 2006 14:27:53 +0200
From:    "Dr. Marc-Alexander Fluks" <fluks@DDS.NL>
Subject: RES,NOT: Pain in CFS

Source: European Journal of Pain
Date:   July 2006
URL:    http://www.sciencedirect.com/science/journal/10903801


Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: A 
systematic review
Mira Meeus(*), Jo Nijs, Kenny De Meirleir
Division of Musculoskeletal Physiotherapy, Higher Institute of Physiotherapy,
Department of Health Care Sciences, Hogeschool Antwerpen (HA), Van Aertselaer-
straat 31, 2170 Merksem, Belgium
Department of Human Physiology, Faculty of Physical Education and
Physiotherapy, Vrije Universiteit Brussel (VUB), Belgium
* Corresponding author. Tel.: +32 3 641 82 05.
   E-mail address: Mira.Meeus@vub.ac.be

Received 19 February 2006; received in revised form 7 June 2006; accepted
7 June 2006


In addition to debilitating fatigue the majority of patients with chronic
fatigue syndrome (CFS) experience chronic widespread pain.

Conducting a systematic review to critically assess the existing knowledge
on chronic pain in CFS. We focussed on the definition, the prevalence and
incidence, the aetiology, the relevance and the therapy strategy for
chronic musculoskeletal pain and post-exertional pain in CFS.

To identify relevant articles, we searched eight medical search engines.
The search terms 'chronic fatigue syndrome' AND 'pain', 'nociception',
'arthralgia' and 'myalgia', were used to identify articles concerning pain
in CFS. Included articles were reviewed by two blinded researchers.
Results: Twenty-five articles and two abstract were identified and selected
for further appraisal. Only 11 search results focussed on musculoskeletal
pain in CFS patients. Regarding the standardized review of the articles, a
96% agreement between the researchers was observed. There is no consensus
in defining chronic widespread pain in CFS, and although there is little or
no strong proof for the exact prevalence, chronic pain is strongly
disabling in CFS. Aetiological theories are proposed (sleep abnormalities,
tryptophan, parovirus-B, hormonal and brain abnormalities and central
sensitisation) and a reduction of pain threshold after exercise has been
shown. Furthermore depression seemed not related to pain in CFS and a
staphylococcus toxoid vaccine caused no significant pain reduction.

The results from the systematic review highlight the clinical importance of
chronic pain in CFS, but only few studies addressing the aetiology or
treatment of chronic pain in CFS are currently available.

Chronic fatigue syndrome (CFS); Musculoskeletal pain; Epidemiology; Aetiology;
Treatment; Review

1. Introduction

Chronic fatigue syndrome (CFS) is a debilitating condition that is
characterised by persistent and relapsing fatigue, lasting at least six
months, not resolved by rest, causing a marked reduction of working activity,
and exacerbated by minimal physical exercise. Fatigue is accompanied by
secondary symptoms including sore throat, memory and concentration
impairments, headache, sleep disorders, but most often muscle and joint pain.
The diagnosis of CFS is performed according to standardized clinical criteria
established by the 'Centre of Disease Control and Prevention' (CDC) in 1994
(Fukuda et al., 1994).

In addition to debilitating fatigue the majority of chronic fatigue syndrome
(CFS) patients experience chronic widespread persistent pain, such as
arthralgias and myalgias (Goldenberg et al., 1990; Goldenberg, 1991;
Buchwald, 1996; Jason et al., 1999). A population-based study revealed that
94% of the persons diagnosed with CFS report muscle aches and pain, and 84%
report joint pain (Jason et al., 1999). Nishikai et al. (2001) reported
muscle pain in 85 CFS-patients of 114 patients (74.6%). Seventy-four patients
(64.9%) complained of arthralgia. In another study 24 of 44 patients suffered
from chronic widespread pain (Nijs et al., 2004a). Furthermore clinic-based
investigations suggest that 35­70% of persons with CFS meet criteria for
fibromyalgia (FM) and 20­70% of individuals with FM also suffer from CFS
(Goldenberg et al., 1990; Wysenbeek et al., 1991; Norregard et al., 1993;
Buchwald and Garrity, 1994; Buchwald, 1996). Following the criteria of the
American College of Rheumatology (ACR) individuals with FM present with a
history of widespread pain and pain in at least 11 of 18 tender point sites
on digital palpation (with an appropriate force of 4 kg). Pain is considered
to be 'widespread' when all of the following are present: pain in the left
side of the body, pain in the right side of the body, pain above the waist
and pain below the waist. In addition, axial skeletal pain (cervical spine or
anterior chest or thoracic spine or lower back) must be present. Pain
complaints are present for at least three months (Wolfe et al., 1990).
Chronic fatigue accompanied by chronic musculoskeletal impairments, such as
myalgias and arthralgias, could be considered as an important subclass of CFS
(Tan et al., 2002). However it should be considered that the high frequency
of pain in persons with CFS may be due, in part, to the inclusion of myalgias
and arthralgias as two of the minor symptoms in the diagnostic criteria
following the CDC (Fukuda et al., 1994). Besides the persistent
musculoskeletal pain, CFS patients typically experience an exacerbation of
their symptoms, after previously well-tolerated levels of exercise (Fukuda et
al., 1994; Clapp et al., 1999). They experience muscle pain after a level of
exertion that does not cause any tissue damage. The worsening of symptoms is
considered to be an important reason for low compliance with graded exercise
therapy (Chaudhuri, 2002).

Musculoskeletal pain complaints appeared to be more disabling than chronic
fatigue in patients with CFS. Evidence supportive of the clinical importance
of widespread pain in CFS has been provided: correlation coefficients between
pain intensity and self-reported activity limitations and participation
restrictions (r varying between 0.51 and 0.58) were stronger than those
between fatigue and the functional status (r=0.50) (Nijs et al., 2003,
2004c). Interpreting these correlation coefficients chronic pain accounts for
26­33% of the CFS patients' self-reported activity limitations and
participation restrictions (Nijs, 2005). In general, pain complaints strongly
compromise the physical (Crook et al., 1984; Becker et al., 1997), the social
(Latham and Davis, 1994), psychological (Magni et al., 1993; Becker et al.,
1997; Gureje et al., 1998), and the financial integrity (Kemler and Furnee,
2002) of the individual and his environment. Furthermore the professional and
the socio-economic consequences should be considered. A large body of
literature concerning pain complaints in patients with FM is available, since
musculoskeletal pain is the main concern in these patients. In CFS however,
fatigue is rather emphasized. Therefore, we would like to make an inventory
about what exactly is yet known about chronic musculoskeletal pain in CFS.
This might be important to identify lacunas for future research. After all,
amassing knowledge about chronic pain in CFS is essential, given the high
prevalence and the relevance of this symptom.

The aim of this study was to systematically review the existing knowledge on
chronic musculoskeletal pain in CFS. A systematic review is defined as 'a
review of the evidence on a clearly formulated question that uses systematic
and explicit methods to identify, select and critically appraise relevant
primary research, and to extract and analyse data from the studies that are
included in the review.' (NHS Centre for Reviews and Dissemination, 2001).
The systematic review thus aims to identify all valid answers from existing
research to such focused questions Explicit methods are used to judge the
quality of the literature and (crucially) the same criteria are applied to
all studies (Griffiths et al., 2005).

Concretely we aimed at answering following questions: (1) How do researchers
define chronic musculoskeletal pain, (2) What is the prevalence and incidence
of chronic musculoskeletal pain, (3) What is known about post-exertional
pain, (4) What is known about the aetiology of (post-exertional) pain, (5) Is
there evidence for the clinical relevance, and finally (6) Are there effective
treatment strategies for chronic musculoskeletal pain in CFS patients?

2. Methods

2.1. Systematic literature search

We sought to identify all studies concerning chronic musculoskeletal pain in
individuals with CFS.
To identify relevant articles, we searched Science Direct,
Biomed Central,
Article Database of the Vrije Universiteit Brussel,
Cochrane Central Register of Controlled Trials,
Cochrane Database of Systematic Reviews,
and Web of Science,
covering the period 1972 to December 2004. The combination of the search
terms 'chronic fatigue syndrome' AND pain, nociception, arthralgia and
myalgia, was used to identify articles concerning pain in CFS. These key
words are not really specific, because we anticipated that there would not be
a large body of literature concerning pain in CFS.

To be included in the review an article had to meet the following criteria:
(1) subjects of the study had to be individuals diagnosed with CFS; (2) the
author(s) studied the concept of musculoskeletal pain in these individuals;
(3) both the words 'pain', 'nociception', 'arthralgia' or 'myalgia'
together with the phrase 'chronic fatigue syndrome' must be presented in
the title; and (4) the studies were presented in English written full texts.
If any of the four inclusion were not fulfilled, then the article was
excluded from the literature review.

Afterwards we focussed on the search results that fulfilled these four
criteria. Two independent, blinded researchers (MM and JN) reviewed the
selected manuscripts, i.e., they were not acquainted with each others
evaluation of the search results. Both reviewers achieved the degree of
Master of Science and concentrated on research regarding CFS for respectively
three and six years. JN already obtained the degree of PhD on this matter.
Articles were categorised by the reviewers following study design (clinical
and study aim (aetiology/prevalence/incidence/treatment/case report/diagnosis).
In case of clinical trials, the reviewers were expected to specify the used
diagnostic criteria for CFS and widespread pain, and to assess the
methodological quality of the trial. In order to make a clear separation
between clinical trial and cross-sectional studies, following definitions
were used. The US National Library of Medicine (NLM) defines a clinical trial
in the Medical Subject Headings (MeSH) as a preplanned study of the safety,
efficacy, or optimum dosage schedule (if appropriate) of one or more
diagnostic, therapeutic, or prophylactic drugs, devices, or techniques
selected according to predetermined criteria of eligibility and observed for
predefined evidence of favourable and unfavourable effects. A cross-sectional
study is defined as a study in which the presence or absence of disease or
other health-related variables are determined in each member of the study
population or in a representative sample at one particular time (NLM, 2002).

Methodological quality factors were derived from a general knowledge of the
literature on bias (for example, importance of comparable groups). The
'check-list', used to categorise and to assess the search results, is shown
in Table 1. After reviewing the selected articles, the results of both
researchers were compared and differences were analysed. In case of
disagreement, the reviewers screened the manuscript a second time and the
point of difference was discussed. Both reviewers got the opportunity to
argue and to convince the other in order to obtain a consensus. A consensus
means the same answers since the possible answers were rather limited as
mentioned in an earlier paragraph (study design and study aim) and as shown
in Table 2 (yes, no, not applicable). When a consensus was impossible, both
views were recorded.

Finally the results were analysed and the existing knowledge off chronic pain
in CFS was summarised.

3. Results

3.1. Study selection

Twenty-five articles and two abstracts were identified by the literature
search and selected for further appraisal. Eleven of the 27 search results
were considered after screening following the already mentioned selection
criteria. Afterwards the 11 manuscripts were screened and reviewed by the two
independent researchers. In most cases (96% or 184 of the 192 items) the two
researchers agreed. After a second review and a comparison of the eight
differences, the reviewers reached a consensus for six items. Only twice, the
two assessors could not agree. The properties of the 11 studies that
fulfilled the four inclusion criteria are presented in Table 2.

3.2. Study characteristics

Two of the 11 remaining articles were case reports. One manuscript was a
hypothetical article. Furthermore the remainders included one clinical trial
and one review, and finally one prospective and five cross-sectional studies.

Focussing on the study aim of the manuscripts, 10 of them concerned the
aetiology of pain, of which the review also described the prevalence and two
other articles were completed by the incidence and by diagnostic
considerations. Besides those 10 articles, one focussed on a possible
treatment and the last one targeted the prevalence and epidemiology of pain
in CFS.

Another point of interest were the diagnostic criteria used to define CFS
patients and widespread pain. In four cases the 1994 CDC criteria (Fukuda et
al., 1994) were used (see Section 1). In two articles the older 1988 CDC
criteria were applied (Holmes et al., 1988). Morriss et al. (1999) used the
Oxford criteria (Sharpe et al., 1991). In the review, the hypothetical
article and the case report by Van Houdenhove (2003), diagnostic criteria
were not applicable. Only three research groups defined widespread pain,
following the American College of Rheumatology (ACR) classification (Wolfe et
al., 1990). Andersson et al. (1998) and Morriss et al. (1999) did not only
use the criteria for widespread pain, as defined by ACR. Patients included in
their investigations had to meet the criteria for FM (see Section 1:
widespread pain and 11 of the 18 tender point), described by ACR (Wolfe et
al., 1990). Study criteria are thus even more strict, because in order to
fulfil the FM criteria tender point have to be controlled.

3.3. Methodological quality

The evaluation of the methodological quality was not applicable for all the
manuscripts (i.e., the review and the hypothetical article). The two case
reports included three and four subjects. The number of subjects included in
the prospective study, the cross-sectional studies, and the clinical trial
varied between 13 and 145. Evaluation points one to five of Table 2 (1:
comparable control group?; 2: accounted for gender as a potential
confounder?; 3: blind assessment?; 4: outcome measurements defined?; 5:
statistical methods clearly described?) could be applied to the
cross-sectional and the prospective study. The clinical trial could be
subjected to the entire assessment. A score, dependent on the applicable
evaluation points, was given to these studies. The results are shown in Table
3. Only one study (Kerr et al., 2002) was given a maximum score (4/4).

Besides listing the different search results and their characteristics, this
review attempts to answer, as presented below, the six key questions asked in
Section 1. Table 4 will clarify the current findings concerning these six
questions, based on the included manuscripts.

3.4. How do researchers define chronic musculoskeletal pain?

As already mentioned only three research applied the ACR criteria for
widespread pain (Wolfe et al., 1990). In the other investigations the term
'chronic musculoskeletal pain' is not used or not defined, as for example
in the review, the case report of Van Houdenhove (2003), the hypothetical
article and the study of Lindal et al. (1996), Whelton et al. (1992) and
Whiteside et al. (2004). They talk about (musculoskeletal) pain complaints in
general. Others simply talk about arthralgias (Kerr et al., 2002) and
myalgias (Priori et al., 1994).

3.5. Prevalence

The review of Bradley et al. (2000) mentions that widespread pain is indeed
quite common in patients with CFS and refers even so to the study of Jason et
al. (1999), in which 94% of the CFS patients reported muscle aches and 84%
reported joint pain. Also the overlap between CFS and FM is described in the
review. Arthralgias, myalgias, and other pain complaints show the greatest
overlap between sufferers with FM and CFS (Bradley et al., 2000). Van
Houdenhove (2003) even concluded that there is preliminary evidence for a
relationship between CFS/FM and complex regional pain syndrome type I, based
on many clinical features similar with CFS and FM, such as a predominance in
women, frequent traumatic onset and allodynia or hyperalgesia.

Most frequent experiences of pain in CFS, reported in the study of Lindal et
al. (1996) were localised in the neck and right buttock (11 out of 23
patients, or 44%), upper parts of the chest, left calf and lower back (10 out
of 23 patients, or 40%). The investigators used a picture of a human body,
divided into grids, as described by Lindal (1993). Patients had to mark the
grids where they experienced pain.

3.6. Clinical relevance

Nijs et al. (2005) describe the high disabling character of the chronic
musculoskeletal pain in patients with CFS. Chronic pain accounts for up to
33.6% of the CFS patients' self-reported activity limitations and
participation restrictions. Chronic pain would even be more disabling than
chronic fatigue.

3.7. Post-exertional pain

Following the 1994 CDC criteria patients with CFS typically experience
worsening of symptoms after previously well-tolerated levels of exercise
(Fukuda et al., 1994). Whiteside et al. (2004) reported that healthy
volunteers presented with a mean increase of the pressure pain threshold
(PPT) of 2.7 Newton, measured on the skin fold between thumb and the second
finger. CFS patients, in contrary, showed a mean reduction of the PPT of 4.7
Newton. Increased perception of pain/fatigue after exercise may be indicative
of a dysfunction associated with the central anti-nociceptive mechanism.
Post-exertional myalgia and chronic muscle pain have implications for
successful rehabilitation programmes in CFS. However Nijs et al. (2004b)
found no associations between pain-related fear of movement, measured with
the Tampa Scale for Kinesiophobia-Dutch version, and exercise capacity and
activities limitations and participation restrictions in CFS patients
experiencing widespread pain.

3.8. Possible causes

Bradley et al. (2000) list several possible causes for the pain complaints
seen in CFS. They suggest that abnormally low hypothalamic levels of CRH may
disrupt the function of several biologic systems involved in pain modulation.

Secondly, brain abnormalities are put forward. Pain experiences of patients
with CFS may be related to low resting state levels of functional activity in
the brain stem (Bradley et al., 2000).

The high prevalence of psychiatric comorbidity, and in particular depression,
often leads to suggestions that CFS is merely a somatic presentation of
depression. Morriss et al. (1999) found that CFS-patients with depressive
disorder and CFS-patients without depressive disorder did not differ from
each other, but experienced significantly more widespread bodily pain
(defined by the ACR criteria), self-rated pain, tension headaches and
lifetime medically unexplained symptoms than the patients with only a primary
unipolar depressive illness. In contrary, CFS patients scoring 11 or more on
the anxiety subscale of the HAD (Hospital Anxiety and Depression Scale) had
significantly more tender points on examination than CFS patients scoring
below 11 on this scale (Morriss et al., 1999).

Sleep patterns in patients with CFS has been studied by Whelton et al.
(1992). They showed greater difficulty falling asleep, reduced sleep
efficiency and rapid eye movement (REM) sleep in patients with CFS, compared
to healthy subjects. Patients showed also more alpha electroencephalographic
(EEG) activity during non-REM sleep. Their altered sleep physiology and
symptoms are similar to those observed in FM (Whelton et al., 1992).

Priori et al. (1994) described four adolescents who developed a syndrome
indistinguishable from CFS as defined by Holmes et al. (1988) after
therapeutic ingestion of L-tryptophan and subsequent to the development of a
transient rise in eosinophil count and severe myalgia. Following parovirus B
19 infection, 13% (5 of the 39 cases) of the patients developed CFS, as
defined by Fukuda et al. (1994) associated with severe arthralgia (80% or 4
of the 5 patients) (Kerr et al., 2002).

Finally, it is hypothesised by Nijs et al. (2005) that sensitisation of
central pain processing pathways explains chronic widespread pain in patients
with CFS and that nitric oxide (NO)-levels are related to central pain
processing in subjects with CFS experiencing chronic widespread pain. Their
hypothetical explanation is based on the current understanding of the
pathoimmunity of CFS, together with the observations by Vikman et al. (2003),
concerning the NO-dependent reduction of inhibitory activity of the central
nervous system and consequent central sensitisation. In addition to the
immunological contribution, behavioural changes, such as somatisation,
catastrophising and activity-avoidance may induce central sensitisation (Nijs
et al., 2005). This link is founded on the findings that these cognitive
styles and personality traits may result in sensitisation of dorsal horn
spinal cord neurons (through inhibition of descending tracks in the central
nervous system) (Zusman, 2002).

3.9. Possible treatment

The current knowledge about possible treatment strategies for pain
complaints in CFS, is scarce. Treatment of depression per se is likely to
make little clinical impact on reported pain, psychophysiological disorders
such as tension headache and irritable bowel syndrome or other medically
unexplained symptoms in CFS patients but may improve their perception of
their health and social function (Morriss et al., 1999).

One study addressed to the effect of staphylococcus toxoid vaccine on pain
(Andersson et al., 1998). The same research group performed further studies
on this matter (Zachrisson et al., 2002). This approach is based on the
potential link between infectious illnesses and CFS (Wilson et al., 1994) and
on the personal experiences of the authors that prolonged Staphylococcus
vaccination, aiming at stimulating the immune system, resulted in clinical
improvement. The randomised and double-blind study included 28 women,
fulfilling the criteria for FM established by the ACR and the CDC-criteria
for CFS. They were randomly allocated to the placebo treatment (injection of
sterile water) or to the vaccination treatment (injection of Staphylococcus
toxoid). The vaccine group showed a significant overall clinical improvement,
compared with the pre-treatment results and compared to the improvement in
the placebo group. Pain severity was reduced, without intergroup differences.
The intergroup differences concerning Comprehensive Psychopathological Rating
Scale 'pain' bordered on significance (p>0.1). The increase in PPT, both
in placebo group and in treatment group, bordered on significance in the
vaccine group (p>0.1).

4. Discussion

Summarising the actual knowledge concerning chronic musculoskeletal pain in
CFS is difficult given the dearth of appropriate studies of good
methodological quality. In practicing Evidence Based Medicine (EBM),
physicians require relevant studies, with appropriate strength. Several
rankings of the strength of evidence generated by different types of clinical
research designs have been presented. In addressing a particular clinical
issue, clinicians or policy-makers can base their decision making on the
types of clinical reports that have been published along with an assessment
of the strengths and weaknesses of each study. Table 5 presents the hierarchy
of scientific evidence following Sackett (1989). Interpreting this table in
relation to the present search results, we still have a lot of work on hand.
Search results of this literature study are chiefly situated in the lowest
levels of the hierarchy. However, as interpreted by Green and Byar (1984),
proceeding down the list, there is a broader and broader base on which to
establish one's conclusions. All of the types of studies have played a role
in the development of medical science. All of them are useful, and they all
have a role in EBM. However, the basic issue is which type of evidence one
should rely on the most. Thus, a foundation towards research on
musculoskeletal pain in patients with CFS has been laid, but more
investigations of good quality are indispensable, aspiring to EBM in CFS. In
addition, although reviews are quite high classified in Table 5, it is not
always appropriate to include reviews (and even meta-analyses) in a new
review. In the current systematic review we included the review of Bradley et
al. (2000), but one must be careful in using Bradley's findings and in
drawing conclusions, given the different search methods and the different
selection criteria. We focussed on conduction a systematic review, in order
to supervise the sources and in order to execute a reproducible
investigation, therefore information extracted [in the current review, e.g.,
the prevalence and possible aetiological theories traced in the review of
Bradley et al. (2000)] from other reviews should be handled with caution.

Furthermore, the number of investigations about a certain aspect of the
chronic pain is too small to give a useful overview about incidence,
consequences, possible causes or treatment strategies for musculoskeletal
pain complaints in CFS patients. Anno 2005 it is known that an important
subgroup of patients diagnosed with CFS suffers from chronic widespread pain,
especially myalgias and arthralgias. Furthermore studies provided preliminary
evidence for the huge impact of pain complaints. Despite these facts, neither
an appropriate explanation nor an appropriate therapy is yet available. The
current literature has led to the development of a small number of models of
the development of pain in CFS. However, relatively little work has been
performed to test hypotheses based on these models. Consequently, possible
therapies are withheld.

The methodological problems associated with the study of this disorder may
account for the lack of experimental proofs. The literature reviewed
previously shows that the recruitment of the patients is the first point of
discussion. It is required to recruit only patients who meet criteria for
CFS. The 1994 CDC criteria for CFS are most often frequented. Unfortunately
not all investigators used these criteria. In the study of Lindal et al.
(1996) for example, the subject were diagnosed with an illness like CFS in an
epidemic nearly 50 years ago in Iceland. Morriss et al. (1999) included
patients with CFS defined by operationalised Oxford consensus research
criteria (Sharpe et al., 1991). Secondly, subjects of different studies must
be comparable and representative for the population of CFS patients. That is
not the case in the investigation where pain complaints were localised
(Lindal et al., 1996). The mean age of the 23 women included, was 62.9 years
(SD=9.1) and all had symptoms for more than 50 years. Given the
non-representative sample such results can not be generalised to the CFS
population. In addition, when studying pain results should be accounted for
gender as a potential confounder. Females often have lower thresholds,
greater ability to discriminate, higher pain ratings, and less tolerance of
noxious stimuli than males (Berkley, 1997). Women report also greater levels
of pain catastrophising (Edwards et al., 2004). Finally studying CFS patients
with generalised pain complaints, it is proposed that researchers around the
world utilise the criteria for widespread pain of the American College of
Rheumatology (Wolfe et al., 1990). This definition was used in only three
investigations. The varying results for prevalence, as outlined in Section 1,
are likely due to the different definitions of musculoskeletal pain used in
the different investigations. Several investigators reported the quantity of
patients that simply suffer from muscle pain or joint pain. Therefore these
frequencies are higher. To talk about chronic widespread pain, it is
considered to use the ACR criteria of 1990. In addition, several study
protocols require a washout of psychoactive and pain-modulating medications
(Bradley et al., 2000).

In contrary, a large body of scientific literature regarding the etiology of
chronic pain complaints in fibromyalgia (FM) is currently available. This may
be surprising given the similarities in both diseases. Is there even any good
evidence that chronic pain mechanism are different between FM and CFS?
However, there is evidence for other abnormalities in CFS, like immunological
abnormalities, the dysregulation of RNase L (Suhadolnik et al., 1994, 1999),
and autonomic abnormalities (Naschitz et al., 2001) typically seen in
patients with CFS and not in patients with FM. Also on pain processing there
is evidence for differences between the two syndromes, e.g., the brain
abnormalities. Patterns of functional brain activity in patients with FM are
quite different from those in patients with CFS. Patients with CFS, relative
to controls, showed significantly lower blood perfusion in the brain stem
(Costa et al., 1995; Tirelli et al., 1998). Patients with FM exhibited
significant lower rCBF levels, during rest, in the thalamus and the caudate
nucleus (Mountz et al., 1995). Furthermore Substance P has found to be
elevated in CSF of FM patients (Russell et al., 1994) and not in patients
with CFS (Evengard et al., 1998). Furthermore, some peculiarities has been
proofed in FM and not yet in CFS; such as increased temporal summation
(Sorensen et al., 1998; Staud et al., 2001; Price et al., 2002) and spatial
summation, dysregulated descending pain inhibitory control (Kosek and
Hansson, 1997; Lautenbacher and Rollman, 1997; Vierck et al., 2001; Julien et
al., 2005), hypersensitization of spinal cord neurons (Banic et al., 2004),
etc. Thus, as well differences as similarities between the two diseases has
been shown. In order to distinguish between FM and CFS, investigations should
only include patients who only fulfill the criteria of one syndrome and that
would be, clinically, rather unimportant, knowing that the majority of
patients present with a combination of the diseases. In future research it
would be more interesting, in our opinion, to apply protocols similar to
those used for FM patients on CFS patients, for example the protocols
addressing spatial and temporal summation or inhibitory pain control as
described by the previous mentioned investigators. Those more advanced
protocols, could be preceded by more basic research, given the lack of
elementary knowledge on chronic pain in CFS. For example, until now there is
not much information on specific pain characteristics in CFS (intensity,
variation, course, etc.). In addition, we do not know if this widespread pain
was preceded by more localized pain and there is not really certainty about
the existence of hyperalgesia or allodynia in CFS. Is the chronic pain in CFS
accompanied by other symptoms or complaints, like a dysregulated
stress-system or decreased muscle endurance as the result of muscle pain?
Based on those elementary findings in order to describe or classify the pain
in CFS, further research could even so focus on the different hypothetical
causes of pain in CFS and the possible treatment strategies for these
complaints. For example, to test the hypothesis of the central sensitisation
(as a cause of the pain) in an indirect manner, by comparing PPT of healthy
controls and CFS patients in relation to painful spots indicated by the
subjects on a picture of the human body. Normally, PPT on pain free spots
should be similar in controls and in patients, if not the results would
provide preliminary and indirect evidence for central sensitisation in
patients with CFS.

To conclude, the preceding review shows that progress has been made towards
understanding chronic widespread pain in patients diagnosed with CFS. Several
hypotheses have been proposed, but until the present they are not yet
experimentally tested. The proposed models should be used to further research
focussed on possible causes and treatment strategies of pain complaints in
CFS, in order to produce sustained improvements in these patients' pain


Table 1. Evaluation criteria methodological quality
  1. Comparable control group?
  2. Accounted for gender as a potential confounder?
  3. Blind assessment (in case of comparison of CFS patients with
  4. Outcome measurements clearly described?
  5. Statistical methods clearly described?
  6. Co-interventions avoided?
  7. Intention to treat analysis?
  8. Randomisation?
  9. Randomisation procedure described?
10. Drop outs and reasons mentioned?
11. Double blind? Procedure?
12. Follow-up?

Table 2. Assessment of the included articles
                          Diagnostic criteria    Aim             Design N   1 2 
3 4 5   6 7 8 9 10 11 12
Van Houdenhove (2003)                           Aetiology,      Case report 3 / 
/ / / /   / / / /  /  /  /
                                                 case report
Kerr et al. (2002)       Fukuda et al. (1994)   Aetiology,      Prospective 101 
+ + / + +   / / / /  /  /  /
Priori et al. (1994)     Holmes et al. (1988)   Aetiology,      Case report 4 / 
/ / + /   / / / /  /  /  /
                                                 case report
Bradley et al. (2000)    /                      Aetiology,      Review / / / / 
/ -*  / / / /  /  /  /
Morriss et al. (1999)    Oxford 1991, ACR 1990  Aetiology       Cross-sectional 
145 + - + + +   / / / /  /  /  /
Nijs et al. (2005)       /                      Aetiology       Hypothetical / 
/ / / / /   / / / /  /  /  /
Andersson et al. (1998)  Fukuda et al. (1994),  Treatment       Clinical trial 
28 + + + + +   - - - -  +  +  +/-
                          ACR 1990
Lindal et al. (1996)     Iceland disease        Prevalence      Cross-sectional 
23 - + / + -   / / / /  /  /  /
Whiteside et al. (2004)  Fukuda et al. (1994)   Aetiology       Cross-sectional 
10 + + / + +/- / / / /  /  /  /
Nijs et al. (2004a)      Fukuda et al. (1994)   Aetiology       Cross-sectional 
64 - - / + +   / / / /  /  /  /
                          ACR 1990
Whelton et al. (1992)    Holmes et al. (1988)   Aetiology       Cross-sectional 
26 + - / + +   / / / /  /  /  /
1: comparable control group?; 2: accounted for gender as a potential 
confounder?; 3: blind assessment?; 4: outcome
measurements defined?; 5: statistical methods clearly described?; 6: 
co-interventions?; 7: intention to treat?; 8:
randomised?; 9: randomisation procedure described?; 10: drop-out mentioned?; 
11: double-blind?; 12: follow-up?; +:
clearly described; : not mentioned; /: not applicable; *: literature search not 

Table 3. Score obtained following the methodological evaluation
                                 N      Score    Lacuna
Kerr et al. (2002)              101    4/4      /
Morriss et al. (1999)           145    4/5      female/male
Andersson et al. (1998)          28    7/12     Co-interventions?,
                                                 intention to treat?,
                                                 no randomisation,
Lindal et al. (1996)            23     2/4      Controls, statistics?
Whiteside et al. (2004)         26     3/4      female/male
Nijs et al. (2004a)             64     2/4      Controls, female/male
Female/male: not accounted for gender as a potential confounder.

Table 4. Present knowledge based on search results
                          Define pain         Prevalence-incidence 
Post-exertional  Aetiology              Relevance            Treatment
Van Houdenhove (2003)    Pain                /                     / / 
/                    /
Kerr et al. (2002)       Arthralgia          /                     / Parovirus 
B19          /                    /
Priori et al. (1994)     Myalgia             /                     / 
L-tryptophan           /                    /
Bradley et al. (2000)    Pain                84% arthralgia and    / flCRH, 
brainstem       /                    /
                                              94% myalgia (Jason activity
                                              et al., 1999)
Morriss et al. (1999)    ACR 1990            /                     / No 
relation with       /                    Depression no influence
but                             on pain, but + for
tender                             perception of health
and social functioning
Nijs et al. (2004a)      ACR 1990            /                     / / 
/                    /
Andersson et al. (1998)  ACR 1990            /                     / / 
/                    Staphylococcus toxoid
-> overall
trend for | pain
Lindal et al. (1996)     Pain                Localisation: neck    / / 
/                    /
                                              and right buttock,
                                              upper chest, left
                                              calf and lower back
Whiteside et al. (2004)  (Post-exertional)   /                     Reduction 
pain   /                      /                    /
                          pain                                      threshold 
Nijs et al. (2005)       Chronic widespread  /                     / Central 
sensitisation  Pain 33.6% variance  /
                          pain by NO and by           of functioning
Whelton et al. (1992)    Musculoskeletal     /                     / Sleep 
abnormalities    /                    /
Overview of the answers found in the included articles on the six key question.

Table 5. Hierarchy of evidence (Sackett, 1989)
Level 1  (1a) RCTs that are sufficiently large to be either: positive,
          with a small risk of being falsely positive or negative, with a
          small risk of being falsely negative
          (1b) Meta-analyses of individual patient data (ie, analyses of
          raw, unprocessed data on individual patients enrolled in
          previously conducted RCT s)
Level 2  (2a) RCTs that are not sufficiently large to confidently detect
          (or rule out) a treatment effect
          (2b) Meta-analyses of the literature (i.e,, systematic reviews
          integrating the processed findings of previously published RCTs)
Level 3  Cohort observational studies comparing treated patients with
          concurrent, nonrandomised controls
Level 4  Cohort observational studies comparing treated patients with
          historical controls
Level 5  (5a) Case-series describing the experience of treated patients
          and using no controls
          (5b) Expert opinion


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Kosek E, Hansson P. Modulatory influence on somatosensory
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Lindal E, Bergman S, Thorlacius S, Stefansson JG. The localization of
    pain in chronic fatigue syndrome on a pain drawing according to
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Magni G, Marchetti M, Moreschi C, Merskey H, Luchini SR. Chronic
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Morriss RK, Ahmed M, Wearden AJ, Mullis R, Strickland P, Appleby
    L, et al. The role of depression in pain, psychophysiological
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Mountz JM, Bradley LA, Modell JG, Alexander RW, Triana-Alexander M,
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    cerebral blood flow in the thalamus and the caudate nucleus are
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Nijs J, Vanherbergen K, Duquet K, De Meirleir K. Chronic fatigue
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Nishikai M, Tomomatsu S, Hankins RW, Takagi S, Miyachi K, Kosaka
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    chronic fatigue syndrome. Rheumatol Int 1991;10:227-9.
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[Return to top]     

Date:    Tue, 24 Oct 2006 16:32:42 +0200
From:    Jan van Roijen <j.van.roijen@CHELLO.NL>
Subject: res: Picornavirus Kills Brain Cells


Send an Email for free membership
       >>>> Help ME Circle  <<<<
 >>>>    24 October 2006      <<<<
Editorship : j.van.roijen@chello.nl
Outgoing mail scanned by Norton AV

From:  Vogel_frau <vogel_frau@yahoo.com>

Polio Virus Family Causes Brain Infection,
Injuries, Memory Loss and Cognitive Impairment

New MAYO research implicating Polio's family of virus will be of
interest to Myalgic Encephalomyelitis patients and researchers:

*...We think picornavirus family members cross into the
brain and cause a variety of brain injuries...*
(see article below)

To read about the relation of Polio and ME (per Dr Bruno's work)
see The Committee for Justice and Recognition of ME
(TCJRME) link: Poliomyelitis relation to Myalgic

Those interested in vaccine safety, autism, Gulf War Illnesses,
and Alzheimer's Disease may also find the MAYO findings




Virus may affect memory decades later, study finds

Mon Oct 23, 12:09 PM ET


Forget where you left your glasses? Did those keys go missing
again? Now you do not have to blame your spouse -- a virus may
be to blame.

A family of viruses that cause a range of ills from the common
cold to polio may be able to infect the brain and cause steady
damage, a team at the Mayo Clinic in Minnesota reported on

"Our study suggests that virus-induced memory loss could
accumulate over the lifetime of an individual and eventually lead
to clinical cognitive memory deficits," said Charles Howe, who
reported the findings in the journal Neurobiology of Disease.

The viruses are called picornaviruses and infect more than 1
billion people worldwide each year. They include the virus that
causes polio, as well as colds and diarrhea. People contract two
or three such infections a year on average.

"We think picornavirus family members cross into the brain and
cause a variety of brain injuries. For example, the polio virus can
cause paralysis," Howe said.

"It can injure the spinal cord and different parts of the brain
responsible for motor function. In the murine (mouse) virus we
studied, it did the same thing and also injured parts of the brain
responsible for memory."

The Mayo Clinic infected mice with a virus called Theiler's
murine encephalomyelitis virus, which is similar to human

Infected mice later had difficulty learning to navigate a maze.
Some were barely affected, while others were completely unable
to manage, and when the mice were killed and their brains
examined, a correlating amount of damage was seen in the
hippocampus region, related to learning and memory.

One virus particularly likely to cause brain damage is enterovirus
71, which is common in Asia, the researchers said. It can cross
over into the brain and cause encephalitis, a brain inflammation
that can lead to coma and death.

"Our findings suggest that picornavirus infections throughout the
lifetime of an individual may chip away at the cognitive reserve,
increasing the likelihood of detectable cognitive impairment as
the individual ages," the researchers wrote in their report.

"We hypothesize that mild memory and cognitive impairments of
unknown etiology may, in fact, be due to accumulative loss of
hippocampus function caused by repeated infection with
common and widespread neurovirulent picornaviruses."

Other viruses are known to kill brain cells, including the herpes
virus and human immunodeficiency virus or  HIV.

[Return to top]


Date:    Tue, 24 Oct 2006 20:44:58 -0400
From:    "CF-Alliance <cf_alliance@YAHOO.COM> (via Co-Cure Moderators
         <co-cure-mod@listserv.nodak.edu>)" <auntiem6@PTD.NET>
Subject: RES:Molecule Discovered To Be Key To Pain Sensitivity

Source:  Massachusetts General Hospital    Date:  October 23, 2006

Molecule Discovered To Be Key To Pain Sensitivity

[Return to top]


Date:    Tue, 24 Oct 2006 21:45:46 -0400
From:    "Bernice A. Melsky" <bernicemelsky@VERIZON.NET>
Subject: RES: Individuals' descriptions of living with fibromyalgia

Individuals' descriptions of living with fibromyalgia.

Clin Nurs Res. 2006 Nov;15(4):258-273.

Cunningham MM, Jillings C.

University of British Columbia, Vancouver, Canada.

PMID: 17056769

Fibromyalgia (FM) is a chronic pain syndrome with no known etiology, cure,
prognosis, or clear diagnostic criteria. This interpretive descriptive
study was focused on the experience of living with FM.

Using a constant comparative inductive analytic method, the researcher
collected and analyzed data from in-depth, semistructured interviews with
eight participants.

This study's findings offer insights into the experience of living with and
managing FM and identify social, policy, and health care issues that
profoundly affect those suffering from it. Participants believe that people
with FM would benefit if more health care professionals, as well as family
and friends, would validate their condition and provide them with better

More research could clarify ways in which health care providers may provide
more effective interventions, appropriate care, and ongoing support for
those affected with FM.

[Return to top]


Date:    Wed, 25 Oct 2006 10:17:58 -0400
From:    "Bernice A. Melsky" <bernicemelsky@VERIZON.NET>
Subject: RES: Cultural adaptation and validation of the "Fibromyalgia  Impact Questionnaire"--Portuguese version

[Cultural adaptation and validation of the "Fibromyalgia Impact
Questionnaire"--Portuguese version]
[Article in Portuguese]

Acta Reumatol Port. 2006 Apr-Jun;31(2):157-65.

Rosado Mda L, Pereira JP, da Fonseca JP, Branco JC.

Unidade de Fisioterapia, Centro de Medicina de Reabilitacao de Alcoitao,
Fisioterapia. maria.rosado.4@netvisao.pt

PMID: 17058362

The aim of this study was to translate the Fibromyalgia Impact
Questionnaire (FIQ) into Portuguese (Portugal) and to evaluate its
reliability and validity by use with Portuguese--speaking patients with
Fibromyalgia. After translating the FIQ into Portuguese we administered it
to 68 patients with Fibromyalgia together with an informed consent, a
Portuguese version of the Health Assessment Questionnaire (HAQ) and a
formulary with the socio-demographic characteristics and duration of the

The content validity was assessed with a panel of experts, with high
consensus. In the concurrent validity, we obtained significant correlations
between the FIQ first item and the HAQ [r = 0,531 (p = 0,001)]. Cronbach's
alpha was 0,814, indicating an acceptable level of internal consistency.

In conclusion, the Portuguese version of the FIQ is a reliable and valid
instrument for measuring health status and physical functioning in
Portuguese patients with Fibromyalgia. This instrument is available for use
in the clinical practice.

[Return to top]


Date:    Wed, 25 Oct 2006 10:24:35 -0400
From:    "Bernice A. Melsky" <bernicemelsky@VERIZON.NET>
Subject: RES: Botulinum toxin for the treatment of pain syndromes

[Botulinum toxin for the treatment of pain syndromes]
[Article in Portuguese]

Acta Reumatol Port. 2006 Jan-Mar;31(1):49-62.

Ferreira JJ, Couto M, Costa J, Coelho M, Rosa MM, Sampaio C.

Unidade Neurologica de Investigacao Clinica, Instituto de Medicina
Molecular, Lisboa. joaquimjferreira@net.sapo.pt

PMID: 17058384

Although botulinum toxin (BoNT) is being used for therapeutic purposes for
more than 20 years, the list of potential new indications continues to
increase and includes various pain syndromes.

The pain relief experienced by patients with dystonia and spasticity from
intramuscular BoNT injections suggested that other chronic skeletal-muscles
pain conditions may also benefit. BoNT inhibits the release of
acetylcholine at the neuromuscular junction thereby reducing striatal
muscle contractions and the proposed analgesic property was initially
attributed to muscular relaxation. A specific analgesic BoNT effect is
difficult to conclude from studies where pain is conditioned by other
associated symptoms like dystonia, muscle contraction or spasticity.

One alternative is to critically appraise clinical trials where BoNT was
studied as the active intervention and pain evaluated as an outcome. From
this analysis there is convincing evidence for the effectiveness of BoNT in
the treatment of pain associated with cervical dystonia. For all other pain
syndromes there have been relatively few, small sized, placebo-controlled
studies (myofascial pain syndrome, chronic neck and low back pain,
piriformis syndrome and fibromyalgia) and the results of these studies have
been contradictory or non conclusive.

To establish the analgesic properties of BoNT there is a need for
appropriately designed, exploratory randomized controlled studies in well
accepted human models of nociceptive or neuropathic pain. This does not
exclude the subsequent need to conduct pragmatic trials to evaluate the
effectiveness of BoNT in conditions where the improvement of pain or any
associated clinical sign or symptom may be of clinical relevance.

[Return to top]


Date:    Wed, 25 Oct 2006 12:04:42 -0700
From:    "Jacqui Footman.....................via Co-Cure moderators"
Subject: ACT, MED: NHS specialist CFS/ME services (UK)

This may be reposted, but only in its entirety, so that specific comments are
not taken out of context.

Over the past few months a number of postings have appeared on Co-Cure
criticising the UK's NHS new specialist CFS/ME services and suggesting that
their funding should be withdrawn, saying that the money could be better spent
on biomedical research into ME.  For reference, examples of such include



Some of these postings have included derogatory, defaming statements about
Devon's ME Support groups.  We therefore write now on behalf of one of Devon's
three ME support groups, South Molton ME Support Group, email contact with
which can be made via jacquiftmn@ukonline.co.uk .

Our purpose is to provide Co-Cure readers with some factual information about
what is happening in one of these new services.  It may be generalisable to
other local services; we don't know - we have heard mixed reports and
anecdotes.  Our purpose is to present things we are quite sure about only.

We list here FACTS, where we are aware about what is happening specifically
within our local area (North, East & Mid Devon & Exeter) as a direct result of
our local multidisciplinary team CFS/ME service.

1. General background.  Our local service has now been seeing patients for one
year, having been established as part of the second wave of government
funding - for 2005/6.  It is led by a consultant liaison psychiatrist and
comprises 3 part-time occupational therapists, a secretary, and is supported
by a Service Development Manager from the local PCT.  There has also been
input and some clinics from a consultant endocrinologist and from a
psychologist who is also involved with the South and West Devon team.  Our
team is currently looking to recruit further medical input, probably from a
consultant neurologist.  The paediatric part of the service is just about to
start seeing patients.  Things have been quite slow to get going.  Resourcing
is minimal and does not reflect what the team thought was necessary when they
first submitted their bid.  Referrals are made by GPs.  There is currently a
waiting list of 9-12 months.

2.  The service works closely with the 3 patient reps.  We have been listened
to, we have been thanked for our input and made to feel valued, we have been
asked to contribute beyond just attending steering group meetings, by acting
as speakers at launch events or training events for other health
professionals.  Where our service has offered or been asked for input to
training events, we provide the patient perspective part of the event and
again are publicly acknowledged and valued.  Patient reps are also asked to
participate in procedures for the appointment of staff to the service.

3.  The service has appointed a part-time secretary who is also a carer
because (apart of course from her secretarial skills) of the understanding of
ME she can bring to her contact with patients, not to mention the general
input to the service.

4.  The service linked with us on an ME Awareness Week project to send a
jointly headed letter to every GP practice in our area together with a copy of
the MERGE DVD on research and of the Canadian guidelines short version.  The
letter was also signed jointly on behalf of the support groups and on behalf
of the service/PCT by the doctor who chairs of the PCT's professional
executive committee - a senior signatory within the PCT was chosen
deliberately so that the materials would be seen as important by recipients.

5.  Our service offers domiciliary visits from both the consultant and the
Occupational Therapists and apportions time and resources such that about 25%
goes to this part of the service, which provides what it can for the severely
affected.  The team are looking into local inpatient provision such as would
be appropriate for the severely affected when needed for emergencies or
respite care.

6.  They are raising the profile of ME/CFS within the wider health community
and involving many other health professionals and social services.  Members of
our group have reported having more helpful encounters with other services as
a result of this.

7.  A member of our group who for a number of years had suffered stresses and
problems with benefits (DLA and IB) found this was instantly resolved with a
letter from the consultant once she had been referred to the service and seen
him.  (Aside - as support group officers we are still frustrated having to
help people with benefits and adaptations/equipment issues etc because they
are still on the waiting list - we are frustrated knowing that were these
people able to access the local CFS/ME service more quickly they would not be
having such problems)

8.  A member of our group reports getting very sympathetic and useful help on
an insurance issue from the consultant.

9.  The service has a policy of copying all letters/reports about patients to

10.  If patients have any problem getting a referral from their GP, they can
self refer by contacting the service, who then write to the GP, asking the GP
to confirm the referral.  We had one instance where even this didn't work, but
it was quickly resolved with a phone call complaining to the practice manager
following up on the letter from the service.

11.  Some patients report an improved relationship with their GP following
formal (ie consultant-level) diagnosis from the service, others have reported
comments from the GP such as the GP being impressed with the number and depth
of blood tests that are requested before the referral can go through, etc and
how carefully other conditions and chronic fatigue that is not CFS are

12.  The service runs a CBT-based group intervention for mild-moderately
affected covering topics such as graded activity/activity management, keeping
positive, relaxation techniques.  These group programmes have been well
received as far as I have heard and have provided opportunities for patients
to create their own friendship/support networks within the group, some of
which persists after the end of the programme.  There is emphasis on a branch
of CBT known as 'mindfulness' (for example info on this approach see

13.  Referral to group or individual CBT/GA programmes is not automatic -
patients are individually assessed; if it is clear they are already managing
the illness as effectively as they can they are told that the treatment
offered by the service would not be suitable for them and referred back to GP.
This might seem disappointing or negative, but it is an acknowledgement that
the programmes are not thought to be curative and can only achieve so much -
as much as some patients achieve alone or with social support or support from
self-help material, counsellors or complementary therapists.   These new
services do not profess to cure pwme, but to provide helpful management
strategies and practical support.  Our service falls administratively within
the physical disabilities and long-term conditions section of our Primary Care
Trust (PCT).

14.  All patients with ME/CFS who are referred have the experience of their
illness being validated since this is a proper NHS specialist service.  They
also get a compassionate listening ear, signposting and useful practical
advice.  What is particularly important about this is that it provides better
access to benefits and disability services, and also official 'permission' to
take it easy for those very many who are clinging onto the cliff-face by their
fingertips, trying to do as much as they can to keep going, but well above a
suitable baseline.  The guilt is taken out of not-doing things, they get help
to find a more sensible baseline and get the opportunity to feel ok about
taking time for themselves.  Where necessary people are signposted to
help/equipment/benefits they need eg from social services.

We probably could go on with this list, but we hope this is enough for you to
see how valuable this CFS/ME service is to the people with ME/CFS (Canadian
diagnosis) in our area.  Things may never be perfect, but people are working
hard together to do the best they can to help relieve the suffering of others;
we want and need it and we take exception to others who presume to write or
speak to MPs and government meetings on our behalf, generalising about all the
new CFS/ME services and hence including ours, suggesting that we don't need it
and funding should be withdrawn.  We can't speak for others outside our area
but we have a fairly good idea that patients in South and West Devon and
Cornwall derive help and benefit from their local teams too.  We have heard
anecdotally of problems with the services in one or two other areas, but
equally we have heard anecdotally of services going well and trialling
innovative approaches including offering complementary therapies such as
acupuncture and homeopathy.  A whole range of health disciplines have become
involved with the new CFS/ME services.  Two of the 13 national clinical
champions have endorsed the Canadian Clinical Guidelines; indeed we feel it is
likely that this helped our service decide to send copies out to help inform
local GPs.

Regarding CBT in our new service, there are insufficient resources to provide
every pwme with programmes of CBT, but principals of CBT underpin group
programmes, which are otherwise run on eclectic and practical principles in
response to the situation of the individual participants.  This use of CBT and
approach used by our, and I presume most other, new services is comparable to
the 'SHS' or Self Help Strategies recommended in the shorter version of the
Canadian Clinical guidelines.  There is no suggestion whatsoever in our
service of CBT being used to treat misguided illness beliefs etc.  It is used
to help people adjust and cope and is not seen as curative.  Such use is also
described by the draft NICE guidelines (see page 202/3 of the long version -
pdf downloadable at http://www.nice.org.uk/page.aspx?o=368958).

We request that anyone considering writing to their MP to request the
withdrawal of the new services, or registering their support of organisations
such as RiME (who will use the comments of people who have written to them or
use the numbers of people registering their support of them in their campaign
against the new services) first consider the benefits described above that are
available through the new services, and consider which doors have been opened
to pwme.

Those campaigning for biomedical research have our fullest support, but NOT if
biomedical research has to be at the expense of these new services that are
providing so much practical help to pwme.  We need the help and support NOW -
a cure could be years down the line of further painstaking research.  And we
need the biomedical researchers AS WELL - more of them, and better funded.

Specialist services ARE needed by pwme.  They must be allowed to develop and
health professionals be allowed to learn (sadly, learning can sometimes also
involve making mistakes).  The services can't instantly be as we want them
overnight.  We need to trust in people's (health professionals') capacity to
listen to other people (patients), hear what they are saying and respond.  The
services provide a conduit for this listening to take place.  The rest is a
leap of faith.  Without faith we are so much the poorer.

Ann Dixon, Chair of South Molton ME Support Group, North Devon (founded 1992)
and carer of daughter with ME for 17 years, 8 of which severe

Jacqui Footman, Publicity and Information Officer for South Molton ME Support
Group and person with ME (diagnosed 3 years)

[Return to top]


Date:    Thu, 26 Oct 2006 19:30:12 +0200
From:    Jan van Roijen <j.van.roijen@CHELLO.NL>
Subject: res: Journal of CFS -Volume 13


Send an Email for free membership
       >>>> Help ME Circle  <<<<
 >>>>    26 October 2006      <<<<
Editorship : j.van.roijen@chello.nl
Outgoing mail scanned by Norton AV

The Haworth Press Inc.

Journal of Chronic Fatgigue Syndrome
Volume 13, Number 4, 2006

Conservation of Resources and Quality of Life in
Individuals with Chronic Fatigue Syndrome

Renée R. Taylor, Supriya Kulkarni, Yukiko Shiraishi.


To examine the relationship between resources and quality of
life in individuals with chronic fatigue syndrome (CFS).

Participants and Study Design:

A cross-sectional design was used to describe associations
between resource loss and gain and quality of life for 47
individuals diagnosed with CFS.

Main Outcome Measures:

The Conservation of Resources Evaluation was used to
measure resources in terms of perceived loss and gain.
Health-related quality of life was assessed with the Quality of
Life Index.


Total resource loss and total resource gain were significant
correlates of overall quality of life. Gains in self-esteem, energy,
and work resources were associated with higher-perceived
quality of life. Material loss and energy loss were associated
with lower-perceived quality of life.


Findings for the relationships between perceived resources of
self-esteem, work, material items, and energy and perceived
quality of life can be used inform future rehabilitation efforts.
These relationships appear to occur independently of illness
severity among individuals CFS.

Conservation of resources theory, quality of life, chronic fatigue


Antiviral Pathway Deregulation of Chronic Fatigue
Syndrome Induces Nitric Oxide Production in Immune
Cells that Precludes a Resolution of the Inflammatory

Marc Frémont, Freya Vaeyens, C. Vincent Herst, Kenny De
Meirleir, Patrick Englebienne.

Chronic fatigue syndrome (CFS) is a poorly defined medical
condition diagnosed by exclusion, which, besides severe
chronic fatigue as the hallmark symptom, involves inflammatory
and immune activation stigma. Although viral infections are not
systematically found in CFS patients, the type I interferon
antiviral pathway has been repeatedly shown to be activated in
peripheral blood mononuclear cells (PBMC) of the most afflicted
patients. An abnormal truncated form of ribonuclease L (37-kDa
RNase L) is also found in the PBMC of CFS patients and this
protein has been proposed as a biological marker for CFS.

Recently, the levels of this abnormal protein have been
significantly correlated to the extent of inflammatory symptoms
displayed by CFS patients. We report here that active
double-stranded RNA-dependent kinase (PKR) is expressed
and activated in parallel to the presence of the 37-kDa RNase L
and to an increase in nitric oxide production by immune cells.
However, PKR upregulation results also in a significant increase
followed by a decrease in caspase 3 activity for the samples
containing the highest levels of 37-kDa RNase L. This caspase
3 downregulation does not result from increased expression of
the anti-apoptotic proteins Bcl-2 and Bcl-XL.

These results therefore suggest that chronic inflammation due to
excess nitric oxide production plays a role in CFS and that the
normal resolution of the inflammatory process by NF-KB
activation and apoptotic induction is impaired.

These observations draw new directions for the therapeutic
approach of CFS.

RNase L pathway, nitric oxide, PKR, chronic inflammation.


Long-Term Treatment with a Staphylococcus Toxoid
Vaccine in Patients with Fibromyalgia and Chronic Fatigue

Carl-Gerhard Gottfries, Ove Häger, Björn Regland, Olof

One hundred and sixty patients with fibromyalgia and chronic
fatigue syndrome, who were on a continuous treatment with a
Staphylococcus vaccine, were followed during one year with
repeated consultation visits. The patients had participated in
controlled studies and been on continuous treatment with the
vaccine for 22_10 months before inclusion into this follow-up
study. They were treated with 1 mL of the vaccine
subcutaneously every third to fourth week. Adverse events were
few. The adherence to the treatment was very good. Over a
period of one year, 8% withdrew, and in only 5%, the withdrawal
was due to insufficient clinical effect. Only in two cases where
the patients were allergic to the preservative of the vaccine, the
side effects caused the withdrawal of the treatment. Ratings with
scales (CPRS-15 and FibroFatigue) showed improvement from
start of treatment and also further improvement during the
follow-up year. In view of the natural history for these disorders
the result is of interest.

Fibromyalgia, chronic fatigue syndrome, Staphylococcus
vaccine, long-term treatment


Reliability of a Chronic Fatigue Syndrome Questionnaire

Caroline Hawk, Leonard A. Jason, Susan Torres-Harding.


A diagnostic instrument, the CFS Questionnaire, was developed
for clinicians and researchers to administer to their patients as a
screening instrument for CFS. The CFS Questionnaire is
comprehensive, covering the inclusionary and exclusionary
self-report criteria of the current U.S. case definition (Fukuda et
al. 1994). The instrument also assesses past and current activity
levels, and symptoms of post-exertional malaise to ensure these
items are adequately assessed.


The goal of the present study was to evaluate the diagnostic
reliability of an experimental measure for assessing chronic
fatigue syndrome (CFS).


This instrument was administered to 15 persons with CFS, 15
persons with major depressive disorder (MDD), and 15 controls.
Using the Fukuda et al. (1994) diagnostic criteria, raters
independently reviewed  participants' CFS Questionnaire
responses and rated whether each study participant met criteria
for chronic fatigue syndrome.


This instrument demonstrated good inter-rater reliability. Further,
this instrument demonstrated adequate classification accuracy,
with a 9.3 positive likelihood ratio and a .08 negative likelihood
ratio. Overall, the CFS Questionnaire demonstrated good
test-retest reliability, with intra-class correlation coefficients
and kappa coefficients at .70 or higher for most items. Lower
test-retest reliability coefficients were found for some items
assessing temporal symptoms or items requiring an estimate of


The present study suggests that the CFS Questionnaire is a
reliable diagnostic tool. Use of the CFS Questionnaire should
promote higher levels of diagnostic reliability because it allows
for accurate classification of individuals with CFS.

Chronic fatigue syndrome, depression, symptomatology,
diagnostic criteria.


Lyme Disease Presenting as Chronic Fatigue Syndrome

Samuel Shor.


Chronic Fatigue Syndrome (CFS) by definition represents a
diagnosis of exclusion. Late stage or "Chronic Lyme" infection
with or without "co-infections" is a difficult diagnosis to establish.
The symptom complex of both conditions can be very similar.
This case study represents an attempt to support serious
consideration for a subpopulation of patients otherwise
diagnosed with "CFS," as actually representing chronic Lyme


A case study is presented of a 33-year-old man, who for two
years, was being managed as having CFS. However, after ~2
years of utilizing multiple modalities of management with limited
success, the diagnosis of Lyme was reconsidered. Historical
exposure risks to Lyme in this individual were high. He had
prolonged exposure in the highly tick-infested mountains of North
Carolina for 18 months, several years prior to becoming ill. More
aggressive investigation confirmed the diagnosis of Lyme.
Appropriate changes in management were associated with an
improved level of functioning that was far in excess of what
maximal management of CFS was able to achieve. The features
of CFS and chronic Lyme can be very similar and include the
following: Profound fatigue often associated with cognitive
impairment. Other common symptoms related to both of these
conditions include sleep disturbances, fibromyalgia, and
dysautonomias. In pursuing clarification of this  diagnosis, the
author was exposed to a contrast in medical opinion regarding
diagnostic tools and criteria that were perceived as creating
potential barriers to the management of patients presenting with
these symptoms.


Acceptance and awareness of the possibility that Lyme disease
can present as CFS has important therapeutic and prognostic

Lyme disease, chronic Lyme, chronic fatigue syndrome, CFS,


Depression, Chronic Fatigue Syndrome, and
Fibromyalgia: An Update

Kenneth R. Kaufman, Paul J. Goodnick.

Centers for Disease Control criteria for chronic fatigue
syndrome (CFS) specifically recognize that patients can have
both CFS and depression. The clinician's challenge is to judge
for each individual patient whether the complaint of fatigue is
primarily depression, physical illness, such as CFS, or a
combination of both.This review differentiates CFS and
fibromyalgia, discussed as "chronic fatigue syndrome and
related immune deficiency syndromes" (CFIDS), from
depression in terms of physical signs, symptoms, biological
parameters, brain imaging, immunology, and treatment. The
review focuses on practical applications of research findings
with a further focus on future ability to show clear biologic
separation and specific treatment.

When depressive symptoms exist with those of CFS, accurate
differentiation can usually be accomplished by focusing on
diagnostic criteria. Presence of multiple physical signs and
symptoms of CFIDS may be of great value. In terms of
laboratory testing, a single helpful test may be measuring the
plasma cortisol, which is usually high in depression and low in
CFS. Future research should focus on the combination of
plasma cortisol with an index of serotonin function, which is high
in CFIDS and low in depression. Additional research should
focus on neuroimaging and immune differentiation. Combination
of multiple tests should result in a significant and clinically useful
separation between CFIDS and major depressive disorder

In treating patients with significant depression or MDD with
CFIDS, one should think of the noradrenergic approach using
bupropion or low-dose tricyclic antidepressants in combination
with a selective serotonin reuptake inhibitor, especially
sertraline, to aid improvement of global, pain, and immunologic
parameters. Alternatively,serotonin norepinephrine reuptake
inhibitors (venlafaxine and duloxetine) should be considered.
Future treatment research should focus on larger
placebocontrolled, double-blind trials of these and other
antidepressants as well as the evaluation of psychostimulants,
electroconvulsive therapy (ECT) and repetitivetranscranial
magnetic stimulation (rTMS).

Chronic fatigue syndrome, fibromyalgia, depression, treatment,
neurobiology, endocrine, cortisol, 5HIAA, fludrocortisone, P300,
immune modulation, neuro-imaging, antidepressant, serotonin,
psychostimulant, atypical antipsychotic, ECT, rTMS.

[Return to top]


Date:    Thu, 26 Oct 2006 14:23:02 -0400
From:    Co-Cure Moderators <mods@CO-CURE.ORG>
Subject: ALL: Co-Cure Celebrates Its Tenth Anniversary

Co-Cure is 10 years old today.

We want to thank everyone who's been involved as founders,
moderators, and members for making the project worthwhile.

Here's hoping Co-Cure is unnecessary 10 years from now!

The Co-Cure Moderators

[Return to top]


Date:    Thu, 26 Oct 2006 20:08:11 -0400
From:    "Bernice A. Melsky" <bernicemelsky@VERIZON.NET>
Subject: RES: Atrophic Autoimmune Pangastritis: A Distinctive Form of  Antral and Fundic Gastritis Associated With Systemic Autoimmune Disease

Atrophic Autoimmune Pangastritis: A Distinctive Form of Antral and Fundic
Gastritis Associated With Systemic Autoimmune Disease.

Am J Surg Pathol. 2006 Nov;30(11):1412-1419.

Jevremovic D, Torbenson M, Murray JA, Burgart LJ, Abraham SC.

Departments of Pathology, Gastroenterology and Hepatology, Mayo Clinic,
Rochester, MN; Department of Pathology, The Johns Hopkins Hospital,
Baltimore; Hospital Pathology Associates, P.A., Abbott NW Hospital,
Minneapolis, MN.

PMID: 17063082

The 2 major recognized forms of atrophic gastritis are autoimmune and
environmental atrophic gastritis. These differ in their topographical
distribution in the stomach, histologic features, and etiology. Autoimmune
atrophic gastritis results from immune-mediated destruction of specialized
oxyntic glands, is restricted to the body and fundus, and shows
characteristic neuroendocrine hyperplasia. Environmental atrophic gastritis
is associated with long-standing Helicobacter pylori infection and
preferentially involves antrum and transition zone mucosa.

In this study, we describe a distinctive form of atrophic gastritis that
differs markedly from both of these classic variants. This gastritis is
characterized by: (1) intense mucosal inflammatory infiltrates, persisting
even into the phase of severe glandular atrophy, (2) pangastric
distribution with diffuse involvement of both body and antrum, (3) lack of
association with H. pylori, and (4) lack of neuroendocrine hyperplasia. The
8 patients presented ranged from 1 to 75 years and showed a slight female
predominance (5F:3M). All had systemic autoimmune and/or connective tissue
diseases including autoimmune enterocolitis (4 cases), systemic lupus
erythematosus, refractory sprue, autoimmune hemolytic anemia, and disabling

Positive serum autoimmune markers were documented in 7 of 8 (87%) patients,
but serologies for antiparietal cell and anti-intrinsic factor antibodies
were undertaken in only 1 patient each and were negative.

We propose that the distinctive histology of this form of atrophic
pangastritis and its association with systemic autoimmune disease suggests
an autoimmune process directed against multiple cell lineages in the
stomach. The development of multifocal low-grade dysplasia in 1 patient, a
19-year-old woman, suggests that this condition might have neoplastic potential.

[Return to top]


Date:    Thu, 26 Oct 2006 20:12:35 -0400
From:    "Bernice A. Melsky" <bernicemelsky@VERIZON.NET>
Subject: RES: Evaluation of psychophysiological asymmetry in patients  with fibromyalgia syndrome

Evaluation of psychophysiological asymmetry in patients with fibromyalgia

Appl Psychophysiol Biofeedback. 2006 Sep;31(3):217-25. Epub 2006 Aug 3.

Mitani Y, Fukunaga M, Kanbara K, Takebayashi N, Ishino S, Nakai Y.

Department of Psychosomatic Medicine, Kansai Medical University,
Moriguchi-shi, Osaka, Japan.

PMID: 17063406

Fibromyalgia syndrome (FMS) is characterized by systemic pain of unknown
etiology, and is often accompanied by various psychological symptoms. In
the present study, differences in surface electromyographic (SEMG) levels
of the trapezius muscle, skin temperature (TEMP) and skin conductance level
(SCL) were compared between the right and left side of the body in 31 FMS
and 47 control subjects (Control Group).

We observed significant asymmetries of SEMG level, TEMP and SCL in the FMS
Group. These asymmetries might be related to central, peripheral and
autonomic nervous system dysfunctions. Marked increase of SEMG levels, and
a decrease of TEMP and SCL were observed at the dominant side in the FMS
Group, and a negative correlation of SEMG levels with TEMP and SCL was found.

These results suggest that continued antalgic postures in response to pain
at the dominant side in FMS patients might lead to asymmetries of SEMG
level, TEMP and SCL. Thus, a focus on pain related behaviors and muscle
asymmetry might be a useful therapeutic approach.

[Return to top]


Date:    Thu, 26 Oct 2006 21:03:10 -0700
From:    Co-Cure moderators <cocuremoderator@QWEST.NET>
Subject: MED, ACT: CBT, GET And Human Rights: A Response To The NICE Draft Clinical Guidelines ON CFS/ME

CBT, GET And Human Rights: A Response To The NICE Draft Clinical Guidelines ON

The NICE CFS/ME: full guideline DRAFT was published in September 2006 and
recommends CBT or GET as the therapies of first choice for CFS/ME. (1)
Detailed critiques of the draft are appearing on the internet (2) and already
the guideline has been declared unfit for purpose (3). This paper seeks to
show that failures and omissions in the draft guidelines highlight a human
rights issue with regard to the application of psychological therapies, with
implications for society as a whole.

The failures this paper examines are: the failure to explain the
biopsychosocial theory on which NICE recommendations for treatment are based;
the failure to address the scientific and medical dispute with regard to the
safety and appropriateness of the use of the biopsychosocial theory and the
use of CBT and GET in ME/CFS; the failure to address the moral, ethical and
safety issues arising from its recommended therapies.

By ignoring these serious issues with regard to CBT and GET, we believe that
as currently drafted the NICE Guidelines violate the right of clinicians and
patients to the highest, safest standards of Medical practice and care,
amounting to a violation of their Human Rights.

Turning first to the issues of the failure to explain the biopsychosocial
theory and the scientific and medical dispute with regard to the safety and
appropriateness of the use of the theory and CBT and GET in CFS/ME:

Carruthers and van de Sand in an Overview of the Canadian Consensus Document
on CFS/ME state:

'A hypothesis underlying the use of Cognitive Behaviour Therapy (CBT) for
ME/CFS is based on the premise that the patient's impairments are learned due
to wrong thinking and "considers the pathophysiology of CFS to be entirely
reversible and perpetuated only by the interaction of cognition, behaviour,
and emotional processes. The patient merely has to change their thinking and
their symptoms will be gone. According to this model, CBT should not only
improve the quality of the patient's life, but could be potentially curative".'
' Proponents ignore the documented pathophysiology of ME/CFS, disregard the
reality of the patients' symptoms, blame them for their illness, and withhold
medical treatment. Their studies have often included patients who have chronic
fatigue but excluded more severe cases as well as those who have other
symptoms that are part of the clinical criteria of ME/CFS. Further, their
studies fail to cure or improve physiological impairments such as OI, sore
throat, IBS, etc. Dr. A. Komaroff, a Harvard based world authority, stated
that the evidence of biological process "is inconsistent with the hypothesis
that (the syndrome) involves symptoms that are only imagined or amplified
because of underlying psychiatric distress. It is time to put that hypothesis
to rest." ' (4)

 Hooper (2006) writing in the August Journal Of Clinical Pathology states:

'The challenge of these syndromes to modern medicine is in accord with the
growing understanding of the neuroendocrineimmune (NEI) paradigm, sometimes
referred to as the psychoneuroimmune (PNI) paradigm. This has emerged as a
result of the identification of complex biological messenger molecules that
serve to communicate between these NEI systems.'

'This understanding, supported by extensive human and animal studies, provides
an extensive intellectual foundation for the biological approach to
investigating these complex and challenging syndromes of uncertain origin.'

'In contrast, the alternative and controversial claims of some psychiatrists
that all these syndromes are expressions of somatisation or covered by the
biopsychosocial (BPS) theory lack any sound intellectual basis and spell the
failure and possible imminent extinction of modern psychiatry.'

'Undoubtedly the perverse use of chronic fatigue syndrome, to impose a
psychiatric  definition for ME/CFS by allying it to fatigue syndromes, has
delayed research, the discovery of effective treatment(s), and care and
support for those suffering from this illness '

'Any activities associated with increased free radical production should not
be recommended to sick ME/CFS patients as this will intensify the damage. This
is why GET is so damaging for many ME patients since exercising muscle is
known to generate increased oxidative stress.' (5)

Hooper and Reid (2006) published a critique exposing the inadequacy of the
evidence base of RCTs relied upon by NICE, which include inter alia the

'There is no objective evidence that CBT & GET are effective, nor that claimed
improvements are sustained long term. These treatments are not tolerated by a
large minority of patients. Internationally, a number of prominent researchers
have strong reservations about GET. '(6)

In a presentation to the Group on Scientific Research into Myalgic
Encephalomyelitis (Gibson Parliamentary Inquiry) ME Research UK Chairman Dr
Vance Spence (2006) said:

'The evidential basis of the CBT model for ME/CFS, consists of 8 discrete
RCTs, 3 "negative" for the intervention and 5 "positive". While there are
arguments for and against each of these trials, I think we can agree that this
constitutes a far-from-impressive evidence base, particularly when set beside
other evidence bases and beside patients' reports and surveys.' (7)

Marshall, Williams, Hooper (2001), give the opinion of an eminent Leading
Counsel (a member of the House of Lords) which states:

'On the document you have sent me there is an overwhelming case for the
setting up of an immediate independent investigation as to whether the nature,
cause and treatment of ME (biopsychosocial theory and the use of CBT and GET)
as considered by the Wessely School is acceptable or consistent with good and
safe medical practice.

 There is substantial doubt as to whether such could be the case in view of
the clear division of medical opinion.' (8)

There are therefore serious concerns within the scientific and medical
community as to the safety of both CBT and GET with regard to CFS/ME and the
theoretical basis on which they are founded. The draft maintains a deafening
silence on these issues.

Turning to the moral and ethical issues with regard to the safety and
appropriateness of the use of CBT and GET in CFS/ME:

Marshall And Williams (2006) draw attention to studies that show Psychological
therapy brings about physical changes in the brain comparable to those brought
about by drug therapy. They quote Friedman (2002) who describes three brain
imaging studies, one looking at obsessive-compulsive disorder and the other
two at depression, all of which showed that when patients improved, the
changes in their brain, as shown on PET scans, 'looked the same regardless of
whether they had received antidepressants or CBT.'

They also draw attention to "The MRC Neuroethics Report, April 2005: Session 2
("Altering the brain") in which Psychiatrists explain 'a growing understanding
of neurotransmission at a molecular level has allowed the design of
interventions to alter specific brain functions, one such intervention being
CBT: Psychological therapies such as CBT have now been shown to alter brain
function.  These developments may alter our view of individuality.' The MRC
Report also asks; 'What are the risks of changing personality? Is cognitive
enhancement acceptable to society? Psychological treatments also raise a
number of issues about consent and coercion.  How much information should
patients be given about the possible effects of therapy on their brain?' and
concludes that 'further research is needed to determine whether such therapies
are reversible, or if there are persistent adverse effects', noting: 'There is
already evidence that in certain situations psychotherapy can do harm.' (9)

There are therefore serious ethical concerns about whether this type of
therapy is 'acceptable to Society', as well as outstanding safety issues.
Where are the safeguards for this form of treatment? The draft again maintains
a deafening silence on these issues.

Drugs undergo exhaustive testing over an extended period of time overseen by
an independent body thus ensuring their safety and efficacy. Comprehensive
information on the intellectual foundation of the treatment, its effects and
counter effects are provided to clinicians and patients. In the US, according
to a Report By. Wierenga and Eaton  'It takes 12 years on average for an
experimental drug to travel from lab to medicine chest. Only five in 5,000
compounds that enter preclinical testing make it to human testing. One of
these five tested in people is approved.' (10)

Similar rigorous testing processes apply to the UK under European Community
regulations. The MHRA UK Regulatory Authority website states:

'Safety, quality and efficacy are the only criteria on which legislation to
control human medicines is founded.  It is the responsibility of the MHRA and
the expert advisory bodies set up by the Medicines Act to ensure that the
sometimes difficult balance between safety and effectiveness is achieved.
MHRA experts assess all applications for new medicines to ensure they meet the
required standards.  This is followed up by a system of inspection and testing
which continues throughout the lifetime of the medicine.  Safety monitoring is
also continuous and the MHRA also ensures that doctors and patients receive
up-to-date and accurate information about their medicines.  This is achieved
by ensuring that product labels, leaflets, prescribing information and
advertising meets the required standards laid down by the Regulations.' (11)

Contrast the intellectual and scientific rigour applied in the approval
process for the licensing of drugs for clinical use, with the lack of
scientific and intellectual rigour applied in the NICE draft with regard to
the recommendations for the use of Psychological Therapy in CFS/ME. When
compared with the extensive clinical trialling over many years and the
independent scrutiny a drug therapy is subjected to, the small and heavily
criticised evidence base used to justify the recommendation of CBT and GET for
CFS/ME in the NICE draft is seen to be totally inadequate.

In respect of informed consent, it cannot arise. There simply cannot be
informed consent since there are important ethical, safety and regulatory
questions arising from these treatments, to be addressed.

Ethical and safety questions such as those raised in the MRC Neuroethics
Report 2005 should be paramount. It is hard to envisage any Independent
authority clearing a drug for Human testing or use without ethical and safety
issues, like those surrounding Psychological Therapy, being resolved.

By ignoring these serious issues with regard to Psychological Therapy, we
believe that, as drafted, the Guidelines violate the right of clinicians and
patients to the highest, safest standards of Medical practice and care,
amounting to a violation of their Human Rights.

This is a Human Rights issue. Without an answer to whether this type of
therapy is 'acceptable to Society' and if it is, without an effective
Regulatory framework governing its development and use, there is the serious
risk that sick and vulnerable people everywhere will be vulnerable to
exploitation and abuse at the hands of the vagaries of power, politics and

Following the consultation process, if NICE does not see the depth and breadth
of the failures and omissions in the draft guidelines then a judicial review
must be inevitable.

R Mitchell, V Mitchell.


1. NICE CFS/ME: full guideline DRAFT http://www.nice.org.uk/page.aspx?o=368933

2. Responses to NICE CFS/ME Guidelines  available at:

3. Comprehensive MEA response to NICE Guideline on ME/CFS (draft 2)
4. Carruthers and van de Sand : An Overview of the Canadian Consensus Document

5. Myalgic Encephalomyelitis (ME):a review with emphasis on key findings in
biomedical research. Malcolm Hooper University of Sunderland, JCP Online
First, published on August 25, 2006 as 10.1136/jcp.2006.042408"

6. Hooper and Reid (2006) (Inadequacy of the York (2005) Systematic Review of
the CFS/ME Medical Evidence Base, Comment on Section 3: the Diagnosis,
treatment and management of CFS/ME in adults and children: Work to support the
NICE Guidelines") available online at

7. Dr Vance Spence (2006). A presentation to the Group on Scientific Research
into Myalgic Encephalomyelitis (Gibson Parliamentary Inquiry) by ME Research
UK Chairman. http://www.meresearch.org.uk/archive/gibsonpres.html

8. Marshall, E.P. Williams, M. Hooper, M. 'What is ME? What is CFS?
Information for Clinicians and Lawyers' December 2001

9. Marshall And Williams in their paper CBT IN ME/CFS More Information dated
23 August 2006 http://www.meactionuk.org.uk/CBT_in_ME_More_Information.htm

10. Dale E. Wierenga, Ph.D. and C. Robert Eaton
Office of Research and Development
Pharmaceutical Manufacturers Association available at

11. MHRA UK Regulatory Authority website available at :

[Return to top]


Date:    Fri, 27 Oct 2006 10:11:55 -0400
From:    "Bernice A. Melsky" <bernicemelsky@VERIZON.NET>
Subject: RES: Asbestos as a possible major cause of malignant lung  tumors (including small cell carcinoma, adenocarcinoma &  mesothelioma), brain tumors (i.e. astrocytoma & glioblastoma  multiforme), many other malignant tumors, intractable pain including  fibromyalgia, & some cardio-vascular pathology: safe & effective  methods of reducing asbestos from normal & pathological areas

Asbestos as a possible major cause of malignant lung tumors (including
small cell carcinoma, adenocarcinoma & mesothelioma), brain tumors (i.e.
astrocytoma & glioblastoma multiforme), many other malignant tumors,
intractable pain including fibromyalgia, & some cardio-vascular pathology:
safe & effective methods of reducing asbestos from normal & pathological areas.

Acupunct Electrother Res. 2006;31(1-2):61-125.

Omura Y.

Heart Disease Research Foundation, USA.

PMID: 17063831

High incidences of Small Cell Carcinoma & Adenocarcinoma of the lung,
Astrocytoma & Glioblastoma Multiforme of the brain and Mesothelioma of the
lung were found in those who had a high accumulation of Asbestos in the
eyes and upper respiratory system (nose, larynx, trachea, etc.). When
measured non-invasively using the Bi-Digital O-Ring Test (BDORT), brain
tumors had the highest concentration of Asbestos (0.2 approximately 2.1 mg
BDORT units). Relatively high levels of Asbestos (0.2 approximately 0.6 mg
BDORT units) were found in: Squamous Cell Carcinoma of the lungs &
esophagus, Adenocarcinoma of the larynx & breast, myelogenic leukemia,
arteries of these cancers, left ventricle of failing heart, myocardial
infarction, some of the narrowed arteries, varicose veins, cataracts,
balding heads, hot flashes, Alzheimer's Disease and Autism. A small, round
or ellipsoidal area, with diameter of 5 mm or less, was found near the
center of every cancer tissue with a higher level of Asbestos (1
approximately 3 mg), As, Zn, Cr and Se, than in the rest of the tumor; this
small area may be where the cancer initiated. Among areas of intractable
pain with frequent recurrence and gradual worsening, about 0.2
approximately 0.5 mg BDORT units (or higher) of Asbestos were found. The
author found that in the Astrocytoma and many other cancer patients, the
optimal dose of DHEA produced very significant reductions of cancer cell
telomere from over 1400 ng in the brain tumors (and over 900 ng in other
cancers) to close to or less than 1 yg (=10(-24) g), with circulatory
improvement by reduction of TXB2. Unlike the standard, widely used
treatment with DHEA 25 approximately 50 mg daily, which is an overdose; we
only gave one optimal dose (1.5 approximately 12.5 mg) and the beneficial
effects usually lasted anywhere between 3-6 months, unless inhibiting
factors were introduced. In addition, once one optimal dose of DHEA was
given, the amount of Asbestos from these tumors decreased very
significantly (30 approximately 99% reduction) with marked increase in
urine Asbestos. One optimal dose of special Cilantro tablet reduced more
Asbestos than DHEA or (+) Qi Gong Energy Stored Paper. In addition, the
application of (+) Solar Energy Stored Paper often reduces 70 approximately
99% of the Asbestos, while (+) Qi Gong Energy Stored Paper reduces 50
approximately 99% of the Asbestos.

[Return to top]


Date:    Thu, 26 Oct 2006 11:48:22 +0200
From:    Manager ME-NET <me-net@DDS.NL>
Subject: RES,NOT: Mortality in CFS (Part 2)

Source: Health Care for Women International
         Vol. 27:615-626
Date:   Augustus 2006
URL:    http://www.tandf.co.uk/journals/titles/07399332.html
Ref:    For Part 1 (a paper by Smith et al.) see Co-Cure,

Causes of Death Among Patients With Chronic Fatigue Syndrome
Leonard A. Jason, Karina Corradi, Sara Gress, Sarah Williams, and Susan 
Torres-Harding, DePaul University, Chicago, Illinois, USA
Address correspondence to Leonard A. Jason, Center for Community Research,
   DePaul University, 990 W. Fullerton Ave., Suite 3100, Chicago, IL 60614,
   USA. E-mail: ljason@depaul.edu

Received 16 December 2004; accepted 16 March 2005.


Chronic fatigue syndrome (CFS) is a debilitating illness affecting thousands
of individuals. At the present time, there are few studies that have
investigated causes of death for those with this syndrome. The authors
analyzed a memorial list tabulated by the National CFIDS Foundation of 166
deceased individuals who had had CFS. There were approximately three times
more women than men on the list. The three most prevalent causes of death were
heart failure, suicide, and cancer, which accounted for 59.6% of all deaths.
The mean age of those who died from cancer and suicide was 47.8 and 39.3
years, respectively, which is considerably younger than those who died from
cancer and suicide in the general population. The implications of these
findings are discussed.


Chronic fatigue syndrome (CFS) is a severe illness, affecting a higher
proportion of women than men, and it can affect virtually every major system
of the body. Neurological, immunological, hormonal, gastrointestinal, and
musculoskeletal problems are all common among people with CFS (Friedberg &
Jason, 1998). Descriptions of symptom complexes similar to CFS have occurred
in the medical literature for centuries (Hyde, 2003), and it is a condition
that occurs throughout the world. Because it is one of the more prevalent
chronic health conditions (Jason et al., 1999), it is important to better
understand whether those with this condition have a higher risk of mortality.
Because few investigators have examined the issue of mortality and CFS,
databases that can provide estimates would be of particular importance to
public health officials and scientists from around the world.

Since the mid-1990s, the Fukuda and colleagues' (1994) case definition has
been used by most researchers and health care personnel to define this
syndrome. This CFS case definition stipulates that a person needs to
experience chronic fatigue of new or definite onset, that is not substantially
alleviated by rest, is not the result of ongoing exertion, and results in
substantial reductions in occupational, social, and personal activities. This
case definition also requires the concurrent occurrence of at least four to
eight other symptoms (i.e., impaired memory or concentration, sore throat,
tender lymph nodes, muscle pain, multiple joint pain, new headaches,
unrefreshing sleep, and postexertional malaise).

This case definition, however, has been criticized by several researchers. As
an example, Jason and Taylor (2002) used cluster analysis to define typologies
of chronic fatigue symptomatology. They found that a majority of individuals
with moderate to severe symptoms were accurately classified into two distinct
subgroups: one distinguished by severe postexertional fatigue and generalized
fatigue that is alleviated by rest; and one characterized by severe overall
symptomatology, severe postexertional fatigue, and generalized fatigue that is
not alleviated by rest. Markedly high severity of postexertional fatigue was a
key symptom that distinguished the two clusters that contained almost all
participants with CFS from a third cluster containing almost none of the CFS
participants. This symptom has been designated as a major criterion for the
London definition of myalgic encephalomyelitis (ME; Dowsett, Goudsmit,
Macintyre, & Shepherd, 1994), but as only one of eight possible symptoms
within the Fukuda et al. (1994) criteria. In other words, some individuals who
are diagnosed with CFS according to the Fukuda et al. case definition do not
have one of the central features of this illness.

Jason and colleagues (2003) investigated differences between CFS as defined by
Fukuda et al. (1994) and a set of criteria that has been stipulated for ME,
which requires postexertional malaise. The ME and the 1994 Fukuda et al.
criteria were compared with a group having chronic fatigue due to psychiatric
reasons (CF-psychiatric). There were 22 significant symptom differences
between the ME and CF-psychiatric group, but only eight significant symptom
differences between the CFS and CF-psychiatric group. Those meeting the ME
criteria were more symptomatic than those meeting only the 1994 criteria,
especially in the neurological and neuropsychiatric areas. Chronic fatigue
syndrome case definitions would be improved if more attention was devoted to
developing operationally explicit, objective criteria and standardized

In spite of the debate in some quarters over the most appropriate criteria for
CFS (Brimacombe, Zhang, Lange, & Natelson, 2002-2003; Linder, Dinser, Wagner,
Krueger, & Hoffmann, 2002), other investigations have been able to isolate CFS
as an illness distinct from other syndromes. For example, Taylor, Jason, and
Schoeny (2001) found diagnostic distinctions between CFS, fibromyalgia,
somatic depression, somatic anxiety, and irritable bowel syndrome when
employing a confirmatory factor analysis. In addition, Naschitz and colleagues
(2003) found a particular dysautonomia in CFS that differs significantly from
dysautonomia in patients with non-CFS fatigue, fibromyalgia, syncope, and
hypertensives, as well as healthy controls, but not generalized anxiety
disorder. In this study, the researchers computed blood pressure and heart
rate changes during a head-up tilt test, and processed the data by image
analysis methods.

Because other investigators have found cardiac and immunological dysfunction
in patients with CFS (Evengard, Schacterle, & Komaroff, 1999; Lerner et al.,
2003; Peckerman et al., 2003), it is possible that CFS might be associated
with the occurrence of other health conditions and, as a result, perhaps
decrease a patient's life expectancy. Macfarlane, McBeth, and Silman's (2001)
prospective follow-up study over eight years in England found that mortality
was higher in people with regional pain and widespread pain than in those who
reported no pain at baseline. The excess mortality was almost entirely related
to deaths from cancer, but there were also more deaths from causes other than
disease (e.g., accidents, suicide, violence) among people with widespread
pain. These findings may have implications for the long-term follow-up of
patients with CFS, who often report chronic pain syndromes.

In the CFS area, several investigators have explored links between CFS and
other diseases (Levine, 1994). Endicott (1998) found patients with CFS had
significantly poorer health up to the time of onset of CFS than a healthy
control group, and that parents of patients with CFS had an increased
prevalence of cancer and autoimmune disorders (Endicott, 1999). Grufferman and
colleagues (1988) reported an outbreak of CFS in the Raleigh, North Carolina
Symphony orchestra. Three of these members were later reported to have
developed cancer (Johnson, 1996). Levine, Atherton, Fears, and Hoover (1994)
reviewed data from the Nevada State Cancer Registry following an outbreak of a
CFS-like illness in Nevada. These investigators found an upward trend in the
incidence of brain/CNS tumors, although this could have been related to a
national upward trend for this disease. Levine, Fears, Cummings, and Hoover
(1998) also analyzed data from the Nevada Cancer Registry and found a higher
incidence of non-Hodgkin lymphoma and primary brain tumors in two northern
Nevada counties where an unexplained fatiguing illness was reported during
1984-1986. The higher incidence rate was in comparison with another county
where no such illness had been reported. Finally, Joyce, Hotopf, and Wessely
(1997) reported that among 2,075 people followed up in 19 published outcome
studies of prolonged fatigue and CFS, there was one death by suicide and two
unrelated deaths. In a more recent review, Cairns and Hotopf (2005) found
eight reported deaths in 12 studies. These mortality figures may underestimate
the true number of deaths because not all of these investigators had either
reported mortalities or had collected data on this topic.

The authors of a technical report issued by the Agency for Healthcare Research
and Quality (2001) concluded that estimates of recovery/improvement or relapse
from CFS are not possible because there are so few natural history studies and
those that are available have involved selected referral populations. The
authors recommended that studies need to be done to determine the long-term
natural history of CFS in longitudinal cohorts that included representative

Most CFS investigators believe that CFS can be a devastating and debilitating
illness, but not a fatal one. Despite this common belief, it is conceivable
that people with CFS might develop other serious secondary or cooccurring
health problems. In populations with poor health, we would expect to find an
increased susceptibility to many common diseases. Clearly, it is important to
establish if CFS leads to other illnesses or a shorter life expectancy. In the
present preliminary study, we reviewed the memorial list published by the
National CFIDS Foundation, and we used this as a source for examining reasons
for mortality in people with CFS. This database of information is limited due
to the nature of the informal collection and presentation of data, but it
still might provide intriguing data to warrant future scientific 



Participants in this sample included individuals who had been entered in the
memorial list compiled by the National CFIDS Foundation. This list included
individuals with ME Chronic fatigue immune dysfunction (CFIDS) who have died
up to the summer of 2003. There are several other memorial lists available on
the Internet, but the list from the National CIFDS Foundation was the most
comprehensive. We decided not to pool entries from more than one list as this
might have resulted in counting individuals twice. The National CFIDS
Foundation Memorial List included both individuals who had been members of the
National CFIDS Foundation as well nonmembers. Individual information for each
entry was submitted by family or friends of the deceased. The sample totaled
166, with 164 reporting the sex of the individual, 145 reporting the cause of
death of the individual, and 99 reporting the age of the individual.


Each individual report was entered into a database to record the entry, age,
sex, and cause of death. Many causes of death were listed. To enable
appropriate statistical analyses, cause of death was coded into categories.
The final categories included deaths caused by suicide, cancer (of all types),
heart failure (of all types), infections, complications due to CFS/ME, liver
or spleen or both failure, kidney failure, accidents and murder, other, and
unknown. The other conditions included entries where there was only one
individual in the category (i.e., ulceric gastritis, subdermal hematoma,
abcess on groin/sepsis, unrelated to ME/CFS, under anesthesia for minor
surgery, drug interaction/alcohol and medications, atypical pneumonia,
pneumonia, aneurysm, adult onset asthma attack, blood clot following fracture,
diabetes). The unknown condition referred to reports that specifically stated
that the cause of death was unknown.


Table 1 presents the reason for death among the 144 individuals where this
information was available. The three leading causes of death were heart
failure, suicide, and cancer, accounting for 59.6% of cases. In regard to
gender, 74.4% of this sample were female and 25.6% were male, and this
difference was significant at the p<.01 level using a binomial test. There
were also significant differences between males and females at the p<.01 level
for deaths due to suicide and cancer. Small sample sizes probably led to lack
of significance on other variables.

Table 2 presents mean ages of death for individuals in the memorial list. Due
to small sample sizes, only the three largest categories were examined. For
heart failure, cancer, and suicide, employing an ANOVA, there was a
significant difference in ages (F(2,52)=7.88, p<.01). In addition, those who
died from suicide were significantly younger than those who died from heart


The authors examined causes of death in a sample of individuals that were
listed on a memorial list from the National CFIDS Foundation. Among those
listed, approximately 20% died from each of the following three causes: heart
failure, suicide, and cancer. The number deaths of women reported was
approximately three times the number deaths of men reported. Further, those
who died from suicide were significantly younger than those who died from
heart failure. Overall, at least among this group of individuals, there were
increased risks of death associated with heart failure, suicide, and cancer.

The fact that approximately 20% of the sample died of heart failure is of
importance given the growing evidence of cardiac problems among patients with
CFS. For example, Streeten and Bell (2000) found that the majority of patients
with CFS had striking decreases in circulating blood volume. The blood vessels
in patients with CFS were constricted dramatically, and efforts to restore
normal volume have met with limited success. Martinez-Lavin and colleagues
(1997) studied 19 fibromyalgia patients, of whom 10 had CFS. The patients were
asked to stand upright after they had been resting in a supine position, which
represents a stressful challenge to the body. The patients showed a decrease
in the intensity of the sympathetic transmission to the heart, and this
reduction was even more pronounced for the patients with comorbid CFS. By
comparison, controls evidenced increases in the intensity of sympathetic
transmission to the heart. When lying down, there was a trend among patients
for an elevated heart rate, whereas when standing up, there was a drop in
sympathetic output. The authors suggest that the sympathetic system might be
incapable of responding to a stressful challenge. Another line of research has
been pursued by the Natelson et al. research group at New Jersey Medical
School. They recently found that in response to postural stress, 81% of
patients with CFS, but none of controls, experienced ejection fraction
decreases (suggesting left ventricular dysfunction in the heart) and those
with more severe symptoms had greater decreases (Peckerman, Chemitiganti, et
al., 2003). Patients with CFS might have lower cardiac output, and the
resulting low flow circulatory state could make it difficult for patients to
meet the demands of everyday activity, and it could also lead to fatigue and
other symptoms (Peckerman, LaManca, et al., 2003).

The present study found that approximately 20% of the sample had died from
cancer, and this is of theoretical interest given the immune abnormalities
reported in patients. People with CFS appear to have two basic problems with
immune function: immune activitation as demonstrated by elevations of
activated T lymphocytes, including cytotoxic T cells and elevations of
circulating cytokines; and poor cellular function, with low natural killer
cell cytotoxicity and frequent immunoglobulin deficiencies (most often IgG1
and IgG3; Patarca-Montero, Mark, Fletcher, & Klimas, 2000). For example,
Antoni, Fletcher, Weiss, Maher, Siegel, and Klimas, (2003) found that patients
with low natural killer cell activity (NKCA) and a state of overactivation of
lymphocyte subsets (e.g., CD2+CD26+% activation markers) had the greatest
fatigue intensity and greatest fatigue-related impairments in emotional and
mental functioning. It seems that the Th2 cytokines are dominant over the Th1
cytokines. In addition, Suhadolnik and colleagues (1997) found a novel
low-molecular-weight (37 kDa) binding protein in a subset of individuals with
CFS who are severely disabled by their disease. A European team (De Meirleir
et al., 2000) has also found increased levels of 80 kDa and 37 kDa RNase L in
patients with CFS. The ratio of this 37 kDa protein to the normal 80 kDa
protein was high in 72% of patients with CFS but only in 1% of the healthy
controls and in none of the depression and fibromyalgia control patients.

Another 20% of patients died of suicide, possibly due to the losses that
patients with this illness experience from family, friends, coworkers, and
health care workers (Friedberg & Jason, 1998). Anderson and Ferrans (1997)
found that 77% of individuals with CFS reported past negative experiences with
health care providers, and 35% indicated that they no longer sought treatment
because of minimal benefits. David, Wessely, and Pelosi (1991) found that 57%
of respondents were treated badly or very badly by their doctors. Green,
Romei, and Natelson (1999) also found that 95% of individuals seeking medical
treatment for CFS reported feelings of estrangement, and 70% believed that
others wrongly attributed their CFS symptoms to psychological causes. Asbring
and Narvanen (2003) found that physicians regarded the illness as less serious
than the patients. The physicians characterized the patients with CFS and
fibromyalgia as illness focused, demanding, and medicalizing. Twemlow,
Bradshaw, Coyne, and Lerma (1997) found that 66% of individuals with CFS
stated that they were made worse by their doctors' care. Clearly, individuals
who are extremely sick with an illness will feel even more alienated and
demoralized if those who are responsible for helping them are insensitive to
their needs. Certainly, all of these factors, including demoralization,
estrangement from the medical establishment, and unsympathetic responses may
cause some individuals to develop depression as well. A sense of hopelessness
concerning the illness and comorbid depression may also increase the risk for
developing suicidal thoughts or behavior.

The fact that more women were reported to have died than men was not
unexpected, given that there is a higher percentage of women with CFS than
men. When examining individual cause of death categories, the authors found
significant gender differences were found only for suicide and cancer.
Analyses for gender differences in other causes of death, however, could not
be done due to low sample sizes. Of interest, the only category where men had
a higher reported percentage than women was with liver or spleen or both
problems; yet the very low number of individuals in this category requires
this finding to be viewed with caution.

When examining ages of death, we found that those dying of suicide were
significantly younger than those dying of heart failure. Another intriguing
finding was the overall ages of death for those dying of cancer, suicide, and
heart failure. If one examines national rates of death for these conditions,
the ages of death for these three conditions among the patients with CFS are
considerable earlier. The median age of death for cancer in the United States
is 72 (Reis et al., 2003, versus an average age of 47.8 for the CFS sample),
the average age of death for suicide in the United States is 48 (Centers for
Disease Control, 2003, versus an average age of 39.3 for the CFS sample), and
the average age of heart failure is 83.1 (CDC, 2003, versus an average age of
58.7 years for the CFS sample). What this suggests is that those from this
memorial list who did die of cancer, suicide, and heart failure were
considerable younger than what would have been expected from the general
population, which means that CFS might have increased the risk of death for at
least this sample.

CFS is a condition that affects individuals throughout the world (Hyde, 2003).
Most research on the epidemiology and pathophysiology of this syndrome,
however, has occurred in either the United States, Europe, or Japan (Jason,
Fennell, & Taylor, 2003). Given that CFS is one of the more common chronic
health conditions, affecting potentially .42% of the population (Jason et al.,
1999), it is imperative for international researchers and public health
officials throughout the world to seriously study potential factors that might
influence functioning and mortality of those with this condition.

The authors of the present study employed a sample from a self-help advocacy
organization in the United States. It is probably the case that most
individuals on this list were from the United States, but it is also likely
that there were individuals on this list from other countries. The authors,
before embarking on this investigation, did inspect lists that had been
generated from other self-help organizations in different locations, but the
authors felt that the list from the United States was the most comprehensive.
Unfortunately, the authors are not able to list the different countries where
mortalities occurred, but this is an important task for future investigations.
If mortality rates for CFS did differ by geographic location, this might have
implications for either service delivery issues or for the etiology of the

There are a number of methodological limitations in the present study. First,
there was no independent confirmation of cause of death, and self-report data
might have been inaccurate. It was not possible to interview the family
members or seek independent confirmation of cause of death. In addition, data
available from the memorial list often was not complete. Even when a cause of
death was provided, more specific information was frequently missing (e.g.,
what type of heart failure or cancer caused the death). It also was unclear
how representative the memorial list is and from what population it draws its
data. Clearly, it is not possible to generalize the data from this memorial
list to the overall population of patients with CFS.

We cannot underestimate this methodological flaw to the present study. In
other words, it is possible that some of the deaths were either misdiagnosed
or that the individuals did not even have CFS. We would urge future
investigators on this topic to place more attention on the diagnostic
criteria. Clearly, a study on causes of death related to a condition that may
have been unreliably diagnosed is a serious issue. There are so few published
findings in this area, however, that the current study could at minimum serve
to stimulate additional, better controlled studies.

In spite of the above limitations, among this sample of participants with CFS,
causes of death appear to cluster in three general domains: heart failure,
suicide, and cancer. For each of these areas, there is supportive evidence
that might help explain why heart failure, cancer, and suicide might be
associated with deaths among people with CFS in this sample. Longitudinal
prospective studies with community-based samples are needed in order to better
understand the unique health risks associated with having CFS.

The authors appreciate the assistance of Jill McLaughlin of the National CFIDS
Foundation in conducting this study. We also thank Connie Van der Eb, Gloria
Njoku, Amber Jurgens, Michael Fries, and Fred Friedberg for their editorial


Table 1. Causes of Death in Individuals With Chronic Fatigue Syndrome
Cause of death           n   Percent of     Percent    Percent   Significance
                              total sample   male       female
Suicide                  29     20.1        17.2        82.8      *
Heart failure            29     20.1        34.5        65.5
Cancer                   28     19.4        17.9        82.1      *
Complications of CFS/ME  16     11.1        31.3        68.8
Unknown                  14      9.7        28.6        71.4
Other                    12      8.3        25.0        75.0
Infections                5      3.5                   100.0
Accidents/murder          5      3.5        20.0        80.0
Liver and/or spleen       4      2.8        75.0        25.0
Kidney failure            2      1.4        50.0        50.0
Total                   144    100
^* Significant at <.01.

Table 2. Mean Age and Standard Deviation by Cause of Death
Cause of death           n         Age (mean)     Standard deviation
Suicide                  17           39.3              12.69
Heart failure            21           58.7              15.57
Cancer                   17           47.8              16.68
Complications of CFS/ME   7           35.6              13.73
Unknown                  10           46.6              13.70
Other                     9           44.4               3.84
Infections                3           48.3              17.62
Accidents/murder          4           46.2              20.76
Liver and/or spleen       1           69.0
Kidney failure            2           50.0               4.24


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(c) 2006 Taylor & Francis Group

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Date:    Sat, 28 Oct 2006 09:40:51 -0400
From:    "Adrienne G. <duckblossm@comcast.net> [via Co-Cure Moderators
         <co-cure-mod@listserv.nodak.edu>]" <auntiem6@PTD.NET>
Subject: NOT,RES: NIH Announces Awards in Chronic Fatigue Syndrome Research


NIH Announces Awards in Chronic Fatigue Syndrome Research
The Office of Research on Women's Health (ORWH) and the Trans-NIH
Working Group for Research in Chronic Fatigue Syndrome (CFSWG) of the
National Institutes of Health (NIH) are pleased to announce seven (7)
awards in Chronic Fatigue Syndrome (CFS) research. The proposed studies
will help researchers understand how the diverse symptoms in CFS are
related to the interactions between the immune and neurological
systems-an important step towards developing effective treatments for a
disabling condition.

The awards were funded by ORWH, Office of the Director, and four member
institutes: The National Institute on Alcohol Abuse and Alcoholism
(NIAAA), the National Institute of Environmental Health Sciences
(NIEHS), the National Institute of Arthritis Musculoskeletal and Skin
Diseases (NIAMS), and the National Institute of Neurological Disorders
and Stroke (NINDS).

Katherine Light, Ph.D., University of Utah, St. Lake City, Utah, plans
to first explore in humans the suggested mechanisms for the perception
of pain and fatigue in CFS by assessing repeated patterns in the immune
and neurological systems that are present before, during and immediately
after mental and physical exertion. There is a possibility that findings
will lead to the development of a biomarker for CFS. Her second pilot
study will focus on identifying family risk patterns in CFS using the
Utah Family Data Base (large genealogy data base) to explore the
familial/genetic component of CFS. Identifying a genetic predisposition
to CFS will assist in the development of more effective medications.

Theoharis Theoharides, M.D.,Ph.D., Tufts University, Boston,
Massachusetts, will explore the relationship of human mast cells
(molecules released in stress) in the brain, not only in explaining the
development of CFS but also in explaining the effects of antidepressants
in relieving symptoms in CFS patients. Dr. Theoharides will examine the
cellular changes that explain CFS symptoms using three different classes
of antidepressants: tricyclic, serotonin uptake inhibitors and
bupropion. Future studies will build on these findings to develop
clinical trials of select antidepressants or other molecules that
inhibit CFS.

Mary Ann Fletcher, Ph.D., University of Miami, Miami, Florida, plans to
study the role of specific peptides: neuropeptide Y (NPY) and
dipeptidyl-peptidase (CD26) in the development of CFS. These peptides,
formed from amino acids (the basic building blocks of the body that are
essential in combating illness), regulate many physiological and disease
processes in the cardiorespiratory, immune, nervous and endocrine
systems. This study will also examine aspects of the relationship
between different levels of peptides and the severity of CFS symptoms
and may lead to the development of biomarkers.

Dianne Lorton, Ph.D. at the Sun Health Research Institute in Sun City,
Arizona, will establish a tissue bank to make brain and spinal cord
tissue available to study CFS/FM (fibromyalga). She has gathered an
interdisciplinary research team that will determine the extent to which
chronic pain in these patients is associated with glial (support cells
of the nervous system) activation and resulting cytokine production
(compounds essential to engage the immune response). While studies in
rodents have shown this activation leads to inflammation and chronic
pain, Dr. Lorton will test the extent that this process is involved in
humans in order to target mechanisms to treat the chronic pain
associated with CFS.

James Baraniuk, M.D., Georgetown University, Washington D.C., has found
that despite its diverse clinical syndromes, the CFS proteome (the
entire group of proteins in an organism or system) is the same,
suggesting a strong relationship with malfunctioning of the central
nervous system. Dr. Baraniuk developed the first predictive model of CFS
based solely on objective data and he now proposes to recruit a new
group of CFS and Healthy Control subjects to determine if the proteins
in their cerebrospinal fluid will be a predictive marker of the spectrum
of CFS symptoms. There is a high probability that these methods and
markers will be of diagnostic value and will be useful for assessing
changes over time in disease severity and treatment effects.

Michael Antoni, Ph.D., at the University of Miami, Miami, Florida, has
demonstrated the positive effects of participation in group cognitive
behavioral stress management (CBSM) on quality of life, perceived
stress, fatigue, memory, muscle pain and post-exertional malaise for CFS
patients compared to those in a control condition. Many CFS patients are
too debilitated to attend regular therapy sessions. Therefore, in the
present study, he will test the physiological effects of a
telephone-based cognitive behavioral stress management intervention to
illuminate CFS patients' neuroimmune mechanisms in relation to stress
and stress management. The correlation of the neuroimmune parameters and
the behavioral components promises to identify a biologically useful
marker for CFS.

Italo Biaggioni, M.D. at Vanderbilt University in Nashville, Tennessee,
will explicate the role of the sympathetic nervous system (SNS) in the
cardiovascular and inflammatory abnormalities in the subset of patients
with postural tachycardia (POTS) -increase in heart rate and often
decrease in blood pressure on standing. Preliminary studies indicate a
relationship between the mechanisms underlying POTS and CFS symptoms.
Dr. Baggioni will test these hypotheses in a comprehensive set of
experiments with appropriate controls.

"These innovative, interdisciplinary studies to help us better
understand the role of the central nervous system in the origin and
development of CFS; represent efforts of the Trans-NIH Working Group for
Research on Chronic Fatigue Syndrome, chaired by the ORWH, to expand
interest in CFS research. I am excited that these efforts could lead to
major advances in understanding the disease processes of CFS and that
they may also provide diagnostic biomarkers that can be used to measure
treatment effects. These studies may also help us understand why some of
the known treatments are effective and lead to the development of newer
and more targeted remedies," stated Dr. Vivian W. Pinn, M.D., Director
of the ORWH.

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Date:    Sun, 29 Oct 2006 10:51:23 EST
From:    "Karen M. Campbell" <SacWriterEditor@AOL.COM>
Subject: Re: MED, ACT: CBT, GET And Human Rights: A Response To The NICE Draft

ProHealth has this quote from no less than Paul Cheney:

"Attitudes and beliefs about one's life and about chronic illness can be
impediments to treatment. ... A change in belief systems is essential; a change
from orientation from 'doing' as a definition of yourself, to 'being' as the
definition of yourself.  And to orient from recovery to healing."

Clearly, even Cheney recognizes that CBT as it relates to coping skills can
be a help.

I attended a seminar yesterday with Leonard Jason and Charles Lapp, and  they
also stressed the mind-body connection and the role of CBT in helping  to
adjust/de-stress to promote healing.

Which is far different from the notion that CBT is only used to  disabuse
emotionally-disturbed patients of the erroneous notion that they  are physically

Karen M.  Campbell
Sacramento, Calif.
Founder, _www.CFSFacts.org_ (http://www.cfsfacts.org/)  -- dispelling the
myths and  providing the facts


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End of CO-CURE Medical & Research Posts Only Digest - 23 Oct 2006 to 30 Oct 2006 (#2006-49)

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