...the authors express some resentment towards those legitimately have
questioned this research cohort and the criteria over the years, which is rather
surprising. Contrary to the insinuation by the authors, no person on the Plosone
responses forum has insinuated that the research cohort they use are somehow
'less deserving' than say, the WPI cohort, purely that they are a different type
of patient, using different criteria that select a different population, and
that this may cause problems with the findings, and claims made based on those
findings, with regard to the British 'CFS' population. This is a reasonable
concern to express, and such a deduction can be made based on the evidence the
authors provide themselves in their paper, citations, and their response. For
example, their paper states:
"Patients in our CFS cohort had undergone medical screening to exclude
detectable organic illness".
In the authors' response here, they also write:
"Thus patients in our service have also co operated in studies of PET and fMRI
neuroimaging, autonomic dysfunction, neurochemistry, respiratory function,
vitamin status, anti nuclear antibodies, immune function, neuroendocrine
function and genetics "
While patients being processed for a research cohort may well, indeed are
likely, to have co-operated and had such tests done, this does not necessarily
mean that patients with positive results are part of the research cohort.
Indeed, positive results, which would indicate organic abnormality, would surely
be likely to prevent a patient being selected for a cohort, by the very logic
described in the author's paper here, by their own response (the additional
tests are considered `not clinically necessary'?) and in at least one of their
citations (Quarmby et al)? In the Quarmby et al paper, the cohort is described,
in which the criteria used (in addition to 'Fukuda/CDC') is 'Oxford'. The Oxford
criteria (Sharpe et al 1991) in particular actually do allow for patients who
fulfil organic abnormality to be selected out of a research cohort. Indeed,
Anthony David, referring to these, commented at the time:
"British Investigators have put forward an alternative, less strict, operational
definition which is essentially chronic (6 months or more) severe disabling
fatigue in the absence of neurological signs with myalgia, psychiatric symptoms
and previous viral infections as common associated features."Here special attention needs to be paid to the term `previous viral infections'
and `absence of neurological signs', in order to contextualise the cohort
selection process applied using the Oxford Criteria.
It is therefore quite reasonable to presume that patients in the cohort
described in the Erlwein et al paper are less likely to be suffering from
organic abnormalities associated with 'CFS' populations than in other research
cohorts. It is also rational to be concerned that the cohort described here may
not be representative of many people diagnosed with 'CFS' in Britain. NICE
guidelines for example, acknowledge that very little research has been done on
`severely affected' patients, who comprise, possibly at least 25% of the
population of people given a `CFS' diagnosis (though so little research has been
done on `severely affected` in Britain, the true number is not yet clear). While
patients potentially destined for a research cohort which weeds out `detectable
organic abnormality' may be subjected to a rigorous amount of investigations,
those not undergoing this process do not undergo such testing, at least not in
the NHS. Indeed, such investigations of clinical patients are severely
proscribed in the majority of `guidelines': NICE, and the RCPCH guidelines as
just two examples.
Ironically, Fukuda guidelines also make the following
comment:
"The use of tests to diagnose the chronic fatigue syndrome should be done only
in the setting of protocol-based research.
In clinical practice, no additional tests, including laboratory tests and
neuro-imaging studies, can be recommended. Examples of specific tests (which
should not be done) include serologic tests for enteroviruses; tests of
immunologic function, and imaging studies, including magnetic resonance imaging
scans and radionuclide scans (such as single photon emission computed
tomography
(SPECT) and positron emission tomography (PET) of the head.
We consider a mental status examination to be the minimal acceptable level of
assessment." (1994
That clinical populations are not to be afforded the types of investigations
given to research populations makes the whole idea of `medically unexplained' or
`unexplained by disease', or 'functional' (as synonymous with 'non-organic' or
not discernibly organic`) as common characterisations of CFS (including by at
least one of the authors themselves in previous publications, for just one
example, Page et al, 2003) highly problematic at best.
It is also significant that `CFS' is so often described as a `diagnosis of
exclusion' (see, for example, the Centre for Disease Control CFS information
website (Footnote:
http://www.cdc.gov/cfs/cfsdiagnosis.htm) . Certain research
case definitions comply with this assumption, such as the Oxford Criteria
(Sharpe et al, 1991) and CDC Criteria (Fukuda et al, 1994) Here, `diagnosis of
exclusion' also functions as a euphemism of `medically unexplained'. The key
problem within this recurring theme in the literature, which most frequently
remains un-addressed, is how a clinical patient's condition can all too easily
become `medically unexplained' because of the practice of encouraging doctors to
severely limit investigations in the first place: except, it would appear,
ironically, in research populations in which `organic' illness is being weeded
out to provide the type of cohort that might fulfil `not organically ill'
definitions.
The issue of `disability' also needs to be clarified. The references cited in
the Erlwein paper to support the statement that the patient cohort was of 'high
levels of disability' refer only to 'disability' in psycho-social terms or
feelings of `fatigue`, and not in terms of physical impairment, a key omission.
Mundt et al's paper in particular focuses on specific mental health problems and
the social exclusionary effects of living with these. While in no way
invalidating or trivialising the disability caused by mental health problems, it
must be pointed out that both Mundt et al and Chalder Scales nevertheless fail
to elucidate a high level of physical or physiological (say, for example,
neurological, mitochondrial and/or cardiovascular) impairment, key problems
present in people given a clinical diagnosis of `CFS', usually related to
specific organic abnormalities that can be found, if they are tested for in the
first place.
With regard to the Canadian criteria (Carruthers et al), in fact they have
undergone some `validation'. Jason et al found:
"…Canadian criteria selecting cases with less psychiatric co-morbidity, more
physical functional impairment, and more fatigue/weakness, neuropsychiatric, and
neurologic symptoms. The overall findings suggest that the Canadian clinical
criteria appear to select a more symptomatic group of individuals than the CFS
criteria, and these individuals do demonstrate less current and lifetime
psychiatric impairment than those selected according to the CFS criteria. In
contrast, the CFS group was not significantly different from the Chronic
fatigue-psychiatric group in psychiatric impairment. Predictably, the Chronic
fatigue-psychiatric group evidenced the highest frequency of current and
lifetime psychiatric disorders… Overall, there were 17 significant symptom
differences between the Canadian and Chronic fatigue-psychiatric group, but only
7 significant symptom differences between the CFS and Chronic
fatigue-psychiatric group. Findings suggest that the Canadian criteria select a
group of patients with more symptoms, and the Canadian criteria identify a group
with higher levels of physical functional impairment and less psychiatric
comorbidity. Findings from the present study indicate that the Canadian criteria
does capture many of these cardiopulmonary and neurological abnormalities, which
are not currently assessed by the current CFS case definition (Fukuda et al.,
1994). However, it is worth noting that when the Fukuda et al. (1994) CFS case
definition was conceived, the research had not yet been done investigating these
abnormalities. In combination with symptom patterns, it is possible to conclude
that the Canadian group does select individuals with greater impairment,
particularly given the physical composite score, fatigue/weakness, neurologic
and neuropsychiatric symptoms, as these symptoms can interfere with daily living
and occupational performance. Results from this present investigation highlight
the importance of contrasting different diagnostic criteria in order to gain a
greater understanding of the syndrome now known as CFS. The findings do suggest
that the Canadian criteria point to the potential utility in designating
post-exertional malaise and fatigue, sleep dysfunction, pain, clinical
neurocognitive, and clinical autonomic/ neuroimmunoendocrine symptoms as major
criteria for future attempts to define this syndrome..."
(
http://www.mefmaction.net/Patients/Articles/Diagnosis/ComparingDefinitionsJL/ta\
bid/223/Default.aspx)
In addition to using the Carruthers et al criteria (or `Canadian Criteria`), the
WPI give this information about their patient cohort in their supporting online
material:
"Their diagnosis of CFS is based upon prolonged disabling fatigue and the
presence of cognitive deficits and reproducible immunological abnormalities.
These included but were not limited to peturbations of the 2-5A synthetase/RNase
L antiviral pathway, low natural killer cell cytotoxicity (as measured by
standard diagnostic assyas) and elevated cytokines particularly interleukin-6
and interleukin-8. In addition to these immunological abnormalities, the
patients characteristically demonstrated impaired exercise performance with
extremely low VO2 max measured on stress testing..."
(
www.sciencemag.org/cgi/content/full/117905/DC1)
It is therefore highly unlikely, as the authors indeed acknowledge in their
reply here, that Erlwein et al were testing the same type of patient as those
tested by the WPI, which inevitably makes the Erlwein et al findings- and
perhaps some of the wilder claims that they have `cast serious doubt' on the
WPI`s findings, unfortunately made in some of the lay media- not scientifically
tenable. The failure of Erlwein et al to include such type of patient in their
cohort, however. does not mean that such patients do not exist in Britain.
Copious patient anecdotal experience, research reports, and charity surveys
indicate that they do exist. Whether XMRV is present or not is another matter,
but there are enough identifiable problems around patient selection alone with
the Erlwein et al paper to indicate this is not a definitive disproving of the
existence of the virus in Britain.
Ongoing neglect of the importance of establishing a possible `CFS' patient
population in Britain, clinically and in research settings, using the Canadian
Guidelines, is preventing the development of knowledge that might help extremely
ill and disabled people here in Britain.
The problems I have briefly outlined here do not fully express the range and
depths of problems with regard to: the identity of an accurate `CFS' population;
the instabilities of `CFS' criteria per se; the faulty concepts of `medically
unexplained' or `functional` and relation to `psychogenic` explanations for
somatic illness; the vagaries of criteria that claim to facilitate a `diagnosis
of exclusion'; and the psychogenic dismissal of serious organic dysfunction of
patients given a 'CFS' diagnosis, problems that have happened for many years.
These problems are relevant to the Erlwein et al paper. Furthermore, they are
highly relevant to all research that claim a psychological and/or behavioural
aetiology to the condition or conditions that get deemed as `CFS'.
REFERENCES
Carruthers, B. et al (2003) "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome:
Clinical Working Case Definition, Diagnostic and Treatment Protocols" Journal of
Chronic Fatigue Syndrome, Vol. 11(1), pp 7 - 115.
Chalder, T. Berelowitz, G. Pawlikowska, T. Watts, L. Wessely, S. Wright, D.
Wallace, E. P. 'Development of a fatigue scale' Journal of Psychosomatic
Research Vol 37: Issue 2: Feb 1993: 147-153.
David, A.S. `Postviral syndrome and psychiatry` British Medical Bulletin: 1991:
47: 4: 966-988
Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. 'The chronic
fatigue syndrome: a comprehensive approach to its definition and study' Ann
Intern Med. 1994 Dec 15;121(12):953-9.
Jason LA, Torres-Harding SR, Jurgens A, Helgerson J. "Comparing the Fukuda et
al. Criteria and the Canadian Case Definition for chronic Fatigue Syndrome".
Journal of Chronic Fatigue Syndrome 12(1):37-52, 2004
Mundt, J.C. Marks, I.MShear, K. Griest, J.H. 'The work and social adjustment
scale: a simple measurement of impairment in functioning' British Journal of
Psychiatry (2002) 180: 461-443
Page, L.A. Wessely, S. 'Medically unexplained symptoms: exacerbating factors in
the doctor–patient encounter' J R Soc Med 2003;96:223-227
Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards
RH, Hawton KE, Lambert HP, Lane RJ, et al ' Chronic fatigue syndrome: guidelines
for research' J R Soc Med. 1991 Feb;84(2):118-21.