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PACE study and oxford criteria

anniekim

Senior Member
Messages
779
Location
U.K
A poster wrote the following about the Oxford criteria and the Pace trial, 'They selected first using the Oxford Definition but ME patients are actively excluded at that point as they often have neurological signs so they cannot be selected afterwards'.

Sorry have I been misunderstanding this? I thought the Oxford Criteria meant that neurological symptoms, pem etc.are not required to get a diagnosis of CFS, just fatigue (which could be due to depression, anxiety, burn out and so on these are not exclusions in the Oxford criteria), but neurological symptoms and PEM alongside fatigue does not mean you are excluded from a diagnosis of CFS (in UK often interchanged wih M.E) under the Oxford criteria?

Would really appreciate an answer to this as the assertion that people with the classic symptoms of M.E/CFS such as neurological and post exertional malaise would be excluded from a diagnosis under the Oxford criteria - and if true would not be even studied under the Pace trial - has really confused and thrown me. Many thanks in advance.
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
A poster wrote the following about the Oxford criteria and the Pace trial, 'They selected first using the Oxford Definition but ME patients are actively excluded at that point as they often have neurological signs so they cannot be selected afterwards'.

Sorry have I been misunderstanding this? I thought the Oxford Criteria meant that neurological symptoms, pem etc.are not required to get a diagnosis of CFS, just fatigue (which could be due to depression, anxiety, burn out and so on these are not exclusions in the Oxford criteria), but neurological symptoms and PEM alongside fatigue does not mean you are excluded from a diagnosis of CFS (in UK often interchanged wih M.E) under the Oxford criteria?

Would really appreciate an answer to this as the assertion that people with the classic symptoms of M.E/CFS such as neurological and post exertional malaise would be excluded from a diagnosis under the Oxford criteria - and if true would not be even studied under the Pace trial - has really confused and thrown me. Many thanks in advance.

Well - the Oxford Criteria are an exercise in semantics and linguistic and conceptual gymnastics, a common problem with CFS criteria. The devil is in the detail - but the important thing to remember is that Oxford ALLOWS EXCLUSION of signs and symptoms of organic disease in order to select sufferers OUT of RESEARCH cohorts.

Around the time these were published, Anthony David, referring to these, commented:

"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.” David, A.S. ‘Postviral syndrome and psychiatry‘ British Medical Bulletin: 1991: 47: 4: 966-988

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.

CFS (and I would argue, some ME, including the London) criteria allow a Humpty Dumpty approach (from Through the Looking Glass):

“it means just what I choose it to mean—neither more nor less.”
“The question is,” said Alice, “whether you can make words mean so many different things.”
“The question is,” said Humpty Dumpty, “which is to be master, that’s all.”
 

oceanblue

Guest
Messages
1,383
Location
UK
A poster wrote the following about the Oxford criteria and the Pace trial, 'They selected first using the Oxford Definition but ME patients are actively excluded at that point as they often have neurological signs so they cannot be selected afterwards'.

Sorry have I been misunderstanding this? I thought the Oxford Criteria meant that neurological symptoms, pem etc.are not required to get a diagnosis of CFS, just fatigue (which could be due to depression, anxiety, burn out and so on these are not exclusions in the Oxford criteria), but neurological symptoms and PEM alongside fatigue does not mean you are excluded from a diagnosis of CFS (in UK often interchanged wih M.E) under the Oxford criteria?

Would really appreciate an answer to this as the assertion that people with the classic symptoms of M.E/CFS such as neurological and post exertional malaise would be excluded from a diagnosis under the Oxford criteria - and if true would not be even studied under the Pace trial - has really confused and thrown me. Many thanks in advance.

You can find the exclusions for the Oxford Criteria used by PACE here
http://forums.aboutmecfs.org/showth...l-and-PACE-Trial-Protocol&p=154121#post154121. There's nothing that i can see that would actively exclude ME patients so I'm confused too.
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
You can find the exclusions for the Oxford Criteria used by PACE here
http://forums.aboutmecfs.org/showth...l-and-PACE-Trial-Protocol&p=154121#post154121. There's nothing that i can see that would actively exclude ME patients so I'm confused too.

I can't find that post with those OXFORD exclusions Oceanblue- any chance you could cut and paste for me please?

The cohort used for the negative XMRV study (Erlwein et al) and Wessely and Cleare's further descriptions do shed some more light on the matter. Here is my response to them (I looked at the references they gave in their PlosOne post):


http://www.plosone.org/annotation/l...notation/13ea20d1-91e6-49c3-bc4b-8fd1ca18f150


The authors’ reply to the concerns about patients selection for research for this paper raises more problems in addition to those of the original paper. My comments here should be read in addition to other problems raised by authors on this forum.

Firstly, 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/tabid/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.
 

oceanblue

Guest
Messages
1,383
Location
UK
Here's the key part from that post:

Medical Exclusions

1. Organ failure (eg emphysemia)
2. Chronic infection (eg Hepatitis B, not XMRV!)
3. Rheumatic & chronic inflammatory diseases
4. Major neurological diseases eg MS
5. Diseases requiring systematic treatment eg chemotherapy
6. Major endocrine diseases eg hypopituitarism

Full details here (paragraph 2 under Results).

Don't suppose you could summarise the key points in the post you just made? I don't have the energy to read it all. thanks
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
Here's the key part from that post:

Medical Exclusions

1. Organ failure (eg emphysemia)
2. Chronic infection (eg Hepatitis B, not XMRV!)
3. Rheumatic & chronic inflammatory diseases
4. Major neurological diseases eg MS
5. Diseases requiring systematic treatment eg chemotherapy
6. Major endocrine diseases eg hypopituitarism

Full details here (paragraph 2 under Results).

But that paragraph show this is about Fukuda, not Oxford.

Don't suppose you could summarise the key points in the post you just made? I don't have the energy to read it all. thanks

I'll bold key points - they may still be long though!
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
Bolded most (I hope) relevant points:

The authors’ reply to the concerns about patients selection for research for this paper raises more problems in addition to those of the original paper. My comments here should be read in addition to other problems raised by authors on this forum.

Firstly, 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:[/B]"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/A...3/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.
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
I still don't see how, in practice, any ME patients are excluded by the PACE definition. Which tests of organic abnormality do you think they are using to exclude patients?

The key is that any reporting of symptoms that might show neurological damage (say, for example, blurred vision, POTS, as just two examples) or even certain neurological signs that a GP can test in their surgery would allow exclusion under Oxford (and Fukuda, for that matter). These are present in ME patients, as Ramsay's definition, Canadian criteria demonstrate.
 

oceanblue

Guest
Messages
1,383
Location
UK
The key is that any reporting of symptoms that might show neurological damage (say, for example, blurred vision, POTS, as just two examples) or even certain neurological signs that a GP can test in their surgery would allow exclusion under Oxford (and Fukuda, for that matter). These are present in ME patients, as Ramsay's definition, Canadian criteria demonstrate.

1. Those exclusion say "major neurologic diseases (e.g., multiple sclerosis, neuromuscular diseases, epilepsy or other diseases requiring ongoing medication that could cause fatigue, stroke, head injury with residual neurologic deficits)", which doesn't really include blurred vision or POTS. In fact, a friend of mine is a patient at Bart's and her POTs didn't get in the way of a CFS diagnosis.
2. Could you say which neurological tests done by GPs exclude ME?

So far at least, I can't see how this excludes all or even many ME patients from the PACE version of the Oxford Criteria.
 

Angela Kennedy

Senior Member
Messages
1,026
Location
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1. Those exclusion say "major neurologic diseases (e.g., multiple sclerosis, neuromuscular diseases, epilepsy or other diseases requiring ongoing medication that could cause fatigue, stroke, head injury with residual neurologic deficits)", which doesn't really include blurred vision or POTS. In fact, a friend of mine is a patient at Bart's and her POTs didn't get in the way of a CFS diagnosis.
2. Could you say which neurological tests done by GPs exclude ME?

So far at least, I can't see how this excludes all or even many ME patients from the PACE version of the Oxford Criteria.

1.Can you cite where that quote's come from Oceanblue? Secondly, ME is a neurological disease! It is accepted as such by the World Health Organisation (since 1969). People with ME (not chronic fatigue) have signs and symptoms of neurological dysfunction, as demonstrated in, as I've already said, Ramsay and the CC. By the rubric of the Oxford criteria (even though these are often quoted in diverse terms) they should be (and can be- the conceptual mechanism is there) excluded from a RESEARCH cohort.

Also -you do understand that neurologic deficits INCLUDE blurred vision and POTS?

ALso- the devil is in the detail - 'other diseases' means an ME sufferer can be excluded from a RESEARCH cohort.

It's very interesting- your anecdote about your friend. When the negative XMRV study came out- Wessely and Cleare brought something to my attention (they didn't intend to). They select their RESEARCH cohorts FROM clinic attendees. This is done ad hoc, because SOME people attending the clinics WILL HAVE 'neurological deficits' (for example POTS). But the psychs do not admit 'consecutive' clinic attendees to their RESEARCH cohorts (This is a vital piece of information). They only admit people for whom they've EXCLUDED evidence of organic disease! So some (probably most) clinic attendees are left out of the research because they have evidence of organic disease.

In this way, CLINICAL attendees can still be (sometimes extremely) ill with signs and symptoms of neurological dysfunction (such as POTS) but still get a 'CFS' diagnosis, told it's medically unexplained (with the minimum of investigations I might add), be subjected to psychogenic dismissal and only offered CBT/GET by the clinics.

2. Romberg's sign, Babinski's sign, nystagmus are just 3 of a battery of signs that can be elucidated by a GP. These can be found in ME sufferers, as can other neurological deficits at both sign and symptom levels of detection.

I'm sorry that you cannot see how these criteria have the capacity to be used to exclude ME patients from the Oxford Criteria. It's actually there in my answer to Wessely and Cleare (and indeed in their response that led me to make my response).

As for the 'PACE version of the Oxford Criteria'. You need to clarify what you mean there. I can actually quote the text from the PACE article here (all from page 2, my bolding):

"We recruited 641 participants from consecutive new out patients attending six specialist chronic fatigue syndrome clinics in the UK National Health Service..."

Obviously this supports the point about patients not being SELECTED for research cohorts just by being a patient.

"We selected participants in accordance with Oxford criteria for chronic fatigue syndrome.These criteria require fatigue to be the main symptom, accompanied by significant disability, in the absence of an exclusionary medical or psychiatric diagnosis (psychosis, bipolar disorder, substance misuse, an organic brain disorder, or an eating disorder). All participants were medically assessed by the specialist clinic doctors to exclude alternative diagnoses."

Ok, Oxford is the first line selction (and exclusion) criteria for this research cohort. Interestingly, the 2003 Reeves et al article is given as reference here (as is NICE). But 2003 isn’t the criteria as such- but an article arguing identification of ambiguities in Fukuda! The actual criteria article was produced in 2005:

Reeves, W. C. Wagner, D. Nisenbaum, R. Jones, J. F. Gurbaxani, B. Solomon, L. Papanicolaou, D. A. Unger, E. R. Vernon, S. D. Heim, C. 'Chronic Fatigue Syndrome - a clinically empirical approach to its definition and study' BMC medicine 2005 3: 19. Also available via open access: http://www.biomedcentral.com/1741-7015/3/19

So they weren’t necessarily using Fukuda at all!!! This needs further investigation.

They go on:

"We excluded patients who...had medical needs that made participation inappropriate"

Well - ME sufferers (particularly the seriously affected) have those (those with cardiovascular and mitochondrial failure, for example?). So this provides yet another means of excluding ME sufferers from the research cohort (just in case any slipped through the net- which I accept is possible, although the chances of this happening have been deliberately lessened, from the evidence available).

"Participants were also assessed by international criteria for chronic fatigue syndrome, requiring four or more accompanying symptoms and the London criteria for myalgic encephalomyelitis (version 2), requiring postexertional fatigue, poor memory and concentration, symptoms that fluctuate, and no primary depressive or anxiety disorder (interpreted as an absence of any such disorder)"

Again, the 2003 Reeves paper is given (I suspect incorrectly) here - NOT Fukuda! Note the interesting use of 'version 2 of the London criteria'. So we know there IS more than one version of the so-called 'London' criteria doing the rounds on the internet! As far as I know- only one version was given in the National Task Force report?

So to summarise- Oxford, Reeves, Fukuda, NICE etc. allow EXCLUSION of ME sufferers for RESEARCH purposes, even if those sufferers are called 'CFS' as CLINICAL attendees (whether at special clinic or GP). It relates to the fallacious concept of 'medically unexplained' where people are not given the investigations they need by GPs or the clinics, UNLESS it's to exclude organic illness (of which ME is one- not because I want it to be, but because of the clinical descriptions such as Ramsay, Carruthers et al, even Nightingale, that show that). PACE have been tinkering with ad hoc methodology I suspect, and we should be scrutinising this very closely (not just outcome measures- though these are very useful).

Christine Hunter of the Alison Hunter Foundation had something very interesting to say today which I think also sums up my point earlier:

In 2011 the overwhelming strength of biological evidence is determinedly ignored and semantics (not science) based medicine prevails in "the treacherous swamp of confusion that is ME".
 

Angela Kennedy

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From my PloSone letter, just to reiterate my point about the issue of CLINICAL attendees versus RESEARCH cohorts and how they are treated differently:

‘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.
 

alex3619

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I think this is a very unclear issue, the use of neurological symptoms to exclude a CFS diagnosis under the Oxford criteria. It would not surprise me if the general lack of knowledge of the fine details mean some patients are excluded, and some are not, with the same symptoms. It would also not surprise me if this were used as an exploit by some researchers. Bye, Alex
 

Angela Kennedy

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I think this is a very unclear issue, the use of neurological symptoms to exclude a CFS diagnosis under the Oxford criteria. It would not surprise me if the general lack of knowledge of the fine details mean some patients are excluded, and some are not, with the same symptoms. It would also not surprise me if this were used as an exploit by some researchers. Bye, Alex

Well what was interesting on the PloSone responses were patients who were saying (to paraphrase) "we've attended the clinics and get no suitable investigations like the ones Wessely et al claim their cohort had". This pointed to there being a complete difference in the way RESEARCH and CLINICAL cohorts are treated.

Oxford is NOT used in CLINICAL diagnosis as such - so investigations are limited for patients NOT in a research cohort. You'll find plenty of CLINICAL patients at the clinic with neurological symptoms and signs. But NOT in the RESEARCH cohorts. They can't be, by the very rubric of the researcher's tools themselves.

I used to believe the researchers were letting in neurological deficit sufferers into their research cohorts because I couldn't get my head around what was happening. It wasn't until the negative XMRV study, ironically, and us all calling for CC to be used like in Lombardi et al, and then this belligerent attempt by Wessely and Cleare to bully people into guilty submission ('how dare you say these patients aren't suffering' sort of accusation) that they unwittingly gave information that showed what they do with research cohorts that they dont' do to clinical patients (investigations to exclude things) AND EXCLUDE people from the research cohorts with evidence of organic disease (which neurological symptoms would not do- let alone signs).

Now 'neuros' may still get under the net- but the chances of that are very slim. With PACE- they were required to find new patients for RESEARCH and we know there were problems in achieving that. What that means in terms of cohort is uncertain- but we should be aware that the vast majority of people in the trial may not have had any neuro signs and symptoms associated with the ME criteria such as Ramsay and Carruthers et al (the cc).

Understanding that does not mean that CBT/GET is 'efficacious and safe' even for 'fatigue' sufferers. We don't know exactly the various types of patient in the PACE trial really. But it is highly unlikely that there were sufficient numbers of actual neuro symptoms/signs 'ME' sufferers to make any assertion about efficacy and safety for actual ME or related neurological illness sufferers (Lyme). It means there are further major confounders in this trial to make the results unsafe.
 

Angela Kennedy

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The other thing I would say is this is a very important issue that the community (and doctors) need to get their heads around, because the psychs have been relying on the bounded rationality of others (myself included) in trying to understand this over the years, in order to present this facade of 'neuro' ME sufferers being included in their research (even though Wessely and gang 'don't believe in ME).

It's comically ironic that the desperate attempt to do a quick and dirty negative XMRV study led to this issue with the research cohorts revealing itself.
 

oceanblue

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Hi Angela

Just one comment:

ME is a neurological disease! It is accepted as such by the World Health Organisation (since 1969)

I think this goes to the heart of it. If YOU were applying the PACE criteria you would exclude ME patients as having a neurological or other organic diseases. But those running the trial don't accept the WHO classification or see ME as an organic disease, so they won't exclude patients on that basis. That's what I meant when I said that 'in practice' the PACE criteria won't exclude ME patients.

plus a few clarifications:

Can you cite where that quote's come from Oceanblue?
Yes, it's that 2003 Ambiguities paper, the source for the exclusions used by PACE, as cited by the Protocol and as referenced by me earlier in this thread.

There seems to be some confusion over this paper. It was first-authored by Reeves but on behalf of the International Working Group on CFS that included Lenny Jason and Nancy Klimas. All it does is try to tidy up Fukuda a bit. The 2005 paper is completely different, solely the work of Reeves and the CDC, which launched the batty 'empirical defintion': PACE doesn't mention or use this definition. Here's what the 2003 paper said:
The 1994 CFS case definition [5] recommends that patients with severe chronic fatigue undergo a clinical evaluation to identify underlying, contributing, and comorbid conditions that require treatment. The lists of exclusionary diagnoses used to screen subjects for enrollment into CFS studies provided by the 1994 case definition were not exhaustive, but rather were examples to guide investigators in their decisions. To increase the uniformity of decisions about exclusionary conditions, we have further clarified exclusionary criteria and give more exhaustive recommendations of conditions that should be excluded.
----
Also -you do understand that neurologic deficits INCLUDE blurred vision and POTS?
The relevant quote was "head injury with residual neurologic deficits", which doesn't apply here.

As for the 'PACE version of the Oxford Criteria'. You need to clarify what you mean there.
I've posted my understanding of this here (post #19), it's based on both the published Protocol and the full 200-page unpublished protocol that Dolphin has posted somewhere.
 

Angela Kennedy

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Hi Angela

Just one comment:



I think this goes to the heart of it. If YOU were applying the PACE criteria you would exclude ME patients as having a neurological or other organic diseases. But those running the trial don't accept the WHO classification or see ME as an organic disease, so they won't exclude patients on that basis. That's what I meant when I said that 'in practice' the PACE criteria won't exclude ME patients.

It doesn't work like that. It is in the interests of the psychs (and it's evident BY THEIR OWN WORDS) that they exclude from their research cohorts any people with signs and symptoms of neurological disorder (or indeed ANY organic dysfunction they can find). It's all there in the evidence I've presented. ME sufferers by definition HAVE at least symptoms, and often signs, of neurological disorder. That's not my belief- that's by Ramsay and Canadian authors - doctors.


Yes, it's that 2003 Ambiguities paper, the source for the exclusions used by PACE, as cited by the Protocol and as referenced by me earlier in this thread.

There seems to be some confusion over this paper. It was first-authored by Reeves but on behalf of the International Working Group on CFS that included Lenny Jason and Nancy Klimas. All it does is try to tidy up Fukuda a bit. The 2005 paper is completely different, solely the work of Reeves and the CDC, which launched the batty 'empirical defintion': PACE doesn't mention or use this definition.

No, you're right, they don't mention this. But, by them referencing the 2003 paper, you've assumed they've used Fukuda- but that might not be the case at all. I think what may have happened is that they used Reeves 2005, but erroneously referenced Reeves 2003. IN ANY CASE- this needs further investigation and a call for clarification from the authors- because we just can't assume that they were using this paper's DISCUSSION of Fukuda. Otherwise- they would (should) have referenced Fukuda! They also referenced NICE- but which part of NICE??? That's a whole other can of worms there...

Here's what the 2003 paper said:
----

The relevant quote was "head injury with residual neurologic deficits", which doesn't apply here.

No- but neurological deficits per se do.

I've posted my understanding of this here (post #19), it's based on both the published Protocol and the full 200-page unpublished protocol that Dolphin has posted somewhere.

Well- if you think it is relevant, perhaps you could reproduce it here because this is a thread dedicated to the problems people have with understanding why Oxford allows exclusion of neurological signs.

Also- have you noticed the Anthony David comment, made at the time of the production of the Oxford Criteria (of which he is a co-author) which quite clearly says neurological signs are EXCLUDED in Oxford.

Or are you having trouble with the fact that Myalgic Encephalomyelitis is a neurological condition, and that if people don't have the neurological symptoms shown in Ramsay or CC, they may not have ME, but something else? People do seem to have trouble with that, and This appears to be a legacy of the special pleading of the psychs with regard to people presenting with ME symptoms (and signs).
 

Angela Kennedy

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OK! to confuse matters even more, Here is the Oxford and Fukuda exclusions according to the RCPCH. I have lost my access to both Fukuda and Oxford original articles, unfortunately. But we need to compare them here, because they are different to the 'exclusions' Reeves et al discuss in 2003, indicating Fukuda was not being used by PACE. So I'm using the RCPCH ones for the time being, will use NICE as well later, and when I have the original articles again, I'll show them in comparison.

OXFORD EXCLUSIONS according to RCPCH guidelines (page 113 of PDF)
http://www.rcpch.ac.uk/Research/ce/RCPCH-guidelines

A Patients with established medical conditions known to
produce chronic fatigue
B. Patients with a current diagnosis of schizophrenia, substance
abuse, manic depressive illness, eating disorders and organic
brain syndrome.

Fukuda exclusions according to RCPCH

*Active or unresolved medical conditions that may explain fatigue.
*Current or past diagnosis of major depressive disorder with
psychotic or melancholic features; bipolar affective disorder;
schizophrenia; delusional disorder; dementia; anorexia nervosa;
bulimia nervosa.
*Substance abuse within 2 years before onset or any time afterward.
*Severe obesity

Now Reeves 2003 write this:

The 1994 CFS case definition [5] recommends that patients with severe chronic fatigue undergo a clinical evaluation to identify underlying, contributing, and comorbid conditions that require treatment. The lists of exclusionary diagnoses used to screen subjects for enrollment into CFS studies provided by the 1994 case definition were not exhaustive, but rather were examples to guide investigators in their decisions. To increase the uniformity of decisions about exclusionary conditions, we have further clarified exclusionary criteria and give more exhaustive recommendations of conditions that should be excluded.

Examples of permanent medical exclusions include the following: 1) organ failure (e.g., emphysema, cirrhosis, cardiac failure, chronic renal failure); 2) chronic infections (e.g., AIDS, hepatitis B or C); 3) rheumatic and chronic inflammatory diseases (e.g., systemic lupus erythematosis, Sjogren's syndrome, rheumatoid arthritis, inflammatory bowel disease, chronic pancreatitis); 4) major neurologic diseases (e.g., multiple sclerosis, neuromuscular diseases, epilepsy or other diseases requiring ongoing medication that could cause fatigue, stroke, head injury with residual neurologic deficits); 5) diseases requiring systemic treatment (e.g., organ or bone marrow transplantation, systemic chemotherapy, radiation of brain, thorax, abdomen, or pelvis); 6) major endocrine diseases (e.g., hypopituitarism, adrenal insufficiency); 7) primary sleep disorders (e.g., sleep apnea, narcolepsy).

Temporary medical exclusions include treatable conditions that require evaluation over time to determine the extent to which they contribute to the fatiguing illness. These encompass four general categories: 1) conditions discovered at onset or initial evaluation (e.g., effects of medications, sleep deprivation, untreated hypothyroidism, untreated or unstable diabetes mellitus, active infection); 2) conditions that resolve (e.g., pregnancy until 3 months post-partum, breast feeding, major surgeries until 6 months post-operation, minor surgery until 3 months post-operation, and major infections such as sepsis or pneumonia until 3 months post-resolution; sleep disorders such as restless leg syndrome and periodic limb movement should be considered temporary exclusions for research criteria, if they are severe, but not if the degree of the sleep problem is insufficient to explain the severity of the fatigue); 3) major conditions whose resolution may be unclear for at least 5 years (e.g., myocardial infarction, heart failure); and 4) morbid obesity (body mass index [BMI] > 40). The 1994 CFS case definition specified a BMI > 45. While both cut-off values are arbitrary, a BMI > 40 defines morbid obesity and is a more inclusive contributing factor to explain chronic fatigue.

This looks like Reeves' 'exclusions', NOT Fukuda's which were not exhaustive, according to Reeves et al here.

Another thing to remember is that the ad hoc nature of clinical diagnosis is put to good use here (in all the CFS-only research criteria) to allow a RESEARCH doctor to say "This person in front of me has some signs of organic dysfunction. I don't really know why- but as I'm trying to weed out organic dysfunction from my research cohort, this person is excluded".

Another problem is that use of Oxford correctly (and in the way that suits the psychs) renders both London and Fukuda superfluous, one of the key objections some of us made right at the beginning of the PACE trial. We've also already seen that the way London was used could allow people to be designated 'London ME' even if they were very similar to Oxford, and neurological symptoms and signs are not necessary to get a London designation (remember London were also supposed to be 'research' and not 'clinical' criteria). If you put London against Ramsay or CC, for example, this becomes obvious.