MDDm should be resolved for more than 5 years before a CFS diagnosis can be given
Tom Kindlon, Irish ME/CFS Support Group
26 June 2007
In this paper, it says:
"Following recommendations of the International CFS Study Group, only current MDDm was considered exclusionary for CFS."
However, part of the specific recommendations of the International CFS Study Group [1] was that MDDm had to have been resolved for more than 5 years:
"The 1994 case definition stated that any past or current diagnosis of major depressive disorder with psychotic or melancholic features, anorexia nervosa, or bulimia permanently excluded a subject from the classification of CFS ... we now recommend that if these conditions have been resolved for more than 5 years before the onset of the current chronically fatiguing illness, they should not be considered exclusionary."
It might not be important to point this out for definitions for some illnesses: however if one looks at table 2, 6 of the 16 who are said to have CFS using the "current classification" of CFS, had been diagnosed with MDDm at a previous assessment which suggests it is important in this context.
Tom Kindlon
[1] Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER, International Chronic Fatigue Syndrome Study Group: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution.
How many SF-36 subscales were used for the "standardized clinically empirical criteria"?
Tom Kindlon, Irish ME/CFS Support Group
26 June 2007
I wonder whether the authors would confirm in a quick comment how many of the 8 subscales of the SF-36 they used?
In the "empirical definition", they appear to me to use four: Role-Physical, Role-Emotional, Physical Functioning and Social Functioning:
[Reference: "We defined substantial reduction in occupational, educational, social, or recreational activities as scores lower than the 25th percentile of published US population [11] on the physical function (≤ 70), or role physical (≤ 50), or social function (≤ 75), or role emotional (≤ 66.7) subscales of the SF-36."]
However, in the pre-publication history they say:
".. We used only 3 of the 8 SF-36 and 2 of the 5 MFI scales in the empirical definition."
- see http://0-www-biomedcentral-com.brum.beds.ac.uk/imedia/7804319382956733_comment.pdf
I was just hoping that 3 is actually the number of subscales they used and that they didn't use the Role-Emotional subscale, as I question the value of using that subscale to satisfy functional impairment criteria.
Tom Kindlon
Competing interests
No Competing Interests
Data from another population study found scores on the RE subscale are similar in CFS patients to those found in healthy controls
Tom Kindlon, Irish ME/CFS Support Group
9 July 2007
In a previous comment I said that I questioned the value of using the Role Emotional (RE) subscale to satisfy functional impairment criteria.
Researchers deciding whether to follow the method of operationalizing the Fukuda [1] used in this study, might be interested at looking at Table 2 in Jason et al [2]. The subjects were also obtained from a random-digit population study.
Here is what the authors said in the text on this part of the results:
"A MANCOVA for the Medical Outcomes Study SF-36 Health Survey (controlling for the effects of work status) revealed significant differences in gradations of disability across the diagnostic categories of CFS only, MCS only, FM only, more than one diagnosis, and no diagnosis on seven of the eight subscales (F(4,208) = 1.82, p < .05). The role-emotional scale was the only scale that did not reveal significant differences between the groups (see Table 2). Significant post hoc tests revealed that individuals with CFS demonstrated greater disability than those with no diagnosis on the role-physical; bodily pain; vitality; and social functioning scales. Individuals with MCS demonstrated greater disability than the no diagnosis group on the physical functioning; role-physical; bodily pain; general health; vitality; social functioning; and mental health scales. Individuals with FM demonstrated greater disability than the no diagnosis group on the physical functioning; role-physical; bodily pain; and social functioning scales. In addition, individuals with more than one diagnosis demonstrated greater disability than those in the no diagnosis group on the physical functioning; role-physical; bodily pain; vitality; and social functioning scales. Means for each of the Medical Outcomes Study subscales are reported in Table 2."
This issue of how the Fukuda criteria [1] are operationalized is not a trivial matter. Using the previous method of operationalizing the criteria, a CDC team found a prevalence for CFS of 235 per 100,000 [3]. Using the method of operationalizing the criteria outlined in this study, the prevalence rate for CFS was found to be 2.54% or 2540 per 100,000 [4] or 10.81 times the previous prevalence rate!
Tom Kindlon
[1] Fukuda, K., Straus, S.E., Hickie, I., Sharpe, M.C., Dobbins, J.G., & Komaroff, A. (1994). The chronic fatigue syndrome: A comprehensive approach to its definition and study. Annals of Internal Medicine, 121 (12):953-959. http://www.annals.org/cgi/content/full/121/12/953
[2] Jason, L.E., Taylor, R.R., & Kennedy, C.L. "Chronic Fatigue Syndrome, Fibromyalgia, and Multiple Chemical Sensitivities in a Community-Based Sample of Persons With Chronic Fatigue Syndrome-Like Symptoms." Psychosomatic Medicine 62:655-663 (2000).
[3] Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N. Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Intern Med. 2003;163:1530–1536. doi: 10.1001/archinte.163.13.1530.
[4] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Population Health Metrics 2007, 5:5 doi:10.1186/1478-7954-5-5
Competing interests
No Competing Interests
This may not be a representative group of those who would be diagnosed in a random sample using the "standardized clinically empirical criteria"
Tom Kindlon, Irish ME/CFS Association - for Information, Support & Research
2 January 2008
This "empirical" method of operationalizing the CDC 1994 CFS criteria[1] has subsequently been used in a population study[2]. It found a prevalence rate for CFS of 2540 per 100,000 persons 18 to 59 years of age[2].
This is considerably higher than the prevalence rates found in earlier studies. For example, a previous study using this cohort using a "previous" method of operationalizing the CDC 1994 CFS criteria[1] found a prevalence rate of 235 per 100,000[3].
Given the way the cohort in this current study was drawn up, using 58 people who had previously been diagnosed using a "previous" method of operationalizing the CDC 1994 CFS criteria, the group satisfying the new method of operationalizing the CDC 1994 CFS criteria, the "empirical" criteria, in this study may well not be the same sort of people that would show up if the method was used on a random sample of the population. So for example the results in Table 6 may not be similar to the results one can get in a random sample.
Unfortunately the paper giving the prevalence rate for Georgia[2] does not give the same pieces of information as is in Table 6 in this study. However we do have a paper which uses a group from the Georgia cohort[4]. Table 1 of this study[4] includes similar data. Some of the numbers are somewhat similar. However one that particularly stands out is the Role Emotional score. It was 35.6 (95% CI: 26.3-44.8). That compares to the value in this paper of 55.8+/-42.2.
Perhaps other data will be published in time. The main point of this comment is to point out or remind people that the data presented in this paper may not be representative of those that would be diagnosed using the empirical criteria.
Tom Kindlon
[1] Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, & Komaroff A. (1994). The chronic fatigue syndrome: A comprehensive approach to its definition and study. Annals of Internal Medicine, 121 (12):953-959. http://www.annals.org/cgi/content/full/121/12/953
[2] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Population Health Metrics 2007, 5:5 doi:10.1186/1478-7954-5-5
http://www.pophealthmetrics.com/content/5/1/5
[3] Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC: Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Int Med 2003, 163:1530-1536.
[4] Nater UM, Maloney E, Boneva RS, Gurbaxani BM, Lin JM, Jones JF, Reeves WC, Heim C. Attenuated Morning Salivary Cortisol Concentrations in a Population-based Study of Persons with Chronic Fatigue Syndrome and Well Controls. J Clin Endocrinol Metab. 2007 Dec 26
Competing interests
No competing interests
Why is this definition being referred to as an "empirical definition"?
Tom Kindlon, Irish ME/CFS Association - for Information, Support & Research
18 June 2008
I believe most people's understanding of "empirical criteria" or an "empirical definition" would be that the data would speak for itself; it "would decide" the cut-off points through methods such as cluster analysis (for example).
Indeed this would seem to have been William Reeves' understanding of an empirical definition. For example, in a presentation on the CDC's CFS research program (to a Task Force Meeting on the Epidemiology of Interstitial Cystitis)[1], he said:
"The problem with the CFS criteria was that they were not specific enough and not empiric-based. For example, one of the criteria stated that the research subject must have at least four of eight symptoms, among them, impaired concentration or memory and postexertional worsening of physical or mental fatigue. "The accompanying symptoms need to be defined in and of themselves," Dr. Reeves said. The 1994 International Study Group also hypothesized that fatigue led to patients' symptoms rather than the reverse. The CDC is currently conducting population studies to develop an empiric definition of CFS that is based on statistical modeling."
At the inaugural meeting of the US Department of Health and Human Services' Chronic Fatigue Syndrome Advisory Committee (CFSAC), Dr Reeves said the CDC team of research would "derive an empirical case definition based on data".[2]
The definition presented here does not seem to have been based either on "statistical modeling" or "data". It seems to involve relatively arbitrary cut-off points; for example, of the 8 subscales of the SF-36, four are chosen and, for each of these, the 25th percentile of the published US population is chosen as a cut-off point. A patient is required to be in the bottom quartile for just one of these subscales to satisfy the criteria. Where did this cut-off point come from? There is no mention of it in the paper that suggested the use of the SF-36[3]; nor is there any mention that these particular subscales should be chosen or that one would sufficient. One of the authors of the paper[3] has confirmed that cut-off points were never chosen nor was it decided which sub-scales would be used. Given that the CDC's definition of CFS tends to go on to be used in numerous studies, would it not be better to investigate which thresholds give a "better" definition e.g. with a higher specificity and sensitivity - for example, for some of the SF-36 subscales, perhaps (say) the 13th, 15th, 20th or even 30th percentiles may be more appropriate.
The cut-off points suggested in this paper may or may not be useful. But is it really accurate to suggest that they are "empirically" derived?
[1] Epidemiology of Interstitial Cystitis - Executive Committee Summary and Task Force Meeting Report October 29th, 2003. http://www.niddk.nih.gov/fund/reports/ic/task_force_summary.pdf
[2] US Department of Health and Human Services - Chronic Fatigue Syndrome Advisory Committee (CFSAC). Inaugural Meeting. September 29th, 2003
[3] Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER, International Chronic Fatigue Syndrome Study Group: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Services Research 2003, 3:25
Competing interests
No competing interests
Using two MFI scales ("General Fatigue" or "Reduced Activity") to ensure patients satisfying the definition have "severe fatigue"
Tom Kindlon, Irish ME/CFS Association - for Information, Support & Research
30 June 2008
Initially when I read this paper, where it says "we defined severe fatigue as >= medians of the MFI general fatigue (>=13) or reduced activity (>=10) scales", I thought this referred to medians of the general population.
Hearing other people commenting on it, that's how some other people have been interpreting it also. It is probably somewhat natural to do this as the sentence before reads: "We defined substantial reduction in occupational, educational, social, or recreational activities as scores lower than the 25th percentile of published US population [11] on the physical function (<=70), or role physical (<=50), or social function (<=75), or role emotional (<=66.7) subscales of the SF-36."
However from looking at the scores for controls in other papers, these MFI scores do not look like medians for the whole US population but in fact are medians for this particular group of patients. This seems a strange way to set cut-off points for a CFS definition that is used for numerous studies into the illness, given the cohort that is being used as a basis:
"This population-based case control study enrolled 227 adults identified from the population of Wichita with: (1) CFS (n = 58); (2) non-fatigued controls matched to CFS on sex, race, age and body mass index (n = 55); (3) persons with medically unexplained fatigue not CFS, which we term ISF (n = 59); (4) CFS accompanied by melancholic depression (n = 27); and (5) ISF plus melancholic depression (n= 28)." i.e. this is not a random sample of the US population but a group of people selected for a specific purpose (or purposes) (not necessarily to design a definition, but as a follow-up study of people previously diagnosed with CFS or given some other label). Some of the groups are of different sizes - if the relative size of these groups had been changed, with relatively more people taken from some classification groups and less people taken from other groups, the median scores would likely have been different.
It should also be remembered that in this context the categories listed in the last paragraph refer to their classification when they evaluated years before (from 1997 to 2000), and not necessarily at the time when they were evaluated in this study (December 2002 to July 2003) (as is clear from the tables in this paper).
I thought it would be interesting to look at MFI scores in some other papers on CFS that did not use the "empirical definition".
I don't claim this is a definitive list but, at the same time, mean MFI scores with standard deviations only seem to be listed in a small percentage of papers.
The papers use cohorts from a variety of locations: England [3], The Netherlands [4], Germany [5] and the USA (New Jersey) [6].
I did not see any ranges given which would be useful given the task at hand (selecting cut-off points for a definition).
Unfortunately not all of the papers I found used the Fukuda [1] definition for CFS; some also used the Sharpe [2] definition for CFS. I indicate which definition is used in each case.
MFI: General Fatigue
Sample Sample Size Mean SD (Mean - 13)/SD Definition
Combining these give a sample of 229 patients with a mean "General Fatigue" score of 18.45655022.
This data suggests that a threshold of >=13 will have a very very high sensitivity. This would suggest that another measure would not be necessary (unless it was being used as an extra criterion to increase the specificity, which isn't done with this definition).
However for completeness, I'm including the "Reduced Activity" data from the same papers:
Reduced activity (MFI)
Sample Sample Size Mean Score SE (Mean-10)/SD Definition
Combining these give a sample of 139 patients with a mean Reduced Activity score of 15.85431655.
Note: the Vermeulen paper[4] did not collect the MFI scores for Reduced Activity, just "the fatigue axes of the Multidimensional Fatigue Inventory" (which they defined as the MFI scores for General fatigue, Physical fatigue, Mental fatigue). It seems strange in the definition of Chronic Fatigue Syndrome defined in this paper (i.e. Reeves et al) that the "severe fatigue" criterion can be satisfied by a patient having a low score on a subscale of the MFI testing activity levels (as opposed to one of the 3 subscales measuring fatigue), especially when the function of the SF-36 is to "measure functional impairment". Just because someone is inactive doesn't mean they have severe fatigue. Allowing patients to be included if they simply have a "Reduced Activity" score of 10 or more (without necessarily having a low score on one of the fatigue axes of the MFI) risks reducing the specificity of the definition.
[1] 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 Int Med 1994, 121:953-959.
[2] Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ, et al. A report--chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991 Feb;84(2):118-21.
[3] Weatherley-Jones, E., Nicholl, JP., Thomas, KJ., Parry, GJ., McKendrick, MW., Green, ST., Stanley, PJ and Lynch, SPJ. A randomised, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome. Journal of Psychosomatic Research, 2004, 56, 2, 189-197.
[4] Vermeulen, RCW and Scholte, HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosomatic Medicine, 2004, 66, 276-282.
[5] Gaab J, Hüster D, Peisen R, Engert V, Heitz V, Schad T, Schürmeyer TH, Ehlert U. Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation.
Psychosom Med. 2002 Nov-Dec;64(6):951-62.
[6] Brimacombe, Michael; Lange, Gudrun; Bisuchio, Kim; Ciccone, Donald S.; Natelson, Benjamin. Cognitive Function Index for Patients with Chronic Fatigue Syndrome Journal of Chronic Fatigue Syndrome, 2004, vol 12; number 4, pages 3-24
Competing interests
No competing interests
Analyses of 2 separate CFS cohorts found 6 of the 8 SF-36 subscales group together - two that don't are MH and RE (the latter is being used in this definition)
Tom Kindlon, Irish ME/CFS Association - for Information, Support & Research
30 September 2008
This paper is supposed to operationalize the recommendations in the consensus paper by Reeves et al[1]. That paper suggested that the SF-36 could be useful as a measure of functional impairment but did not specify which subscales should be used.
The authors of the current paper chose to define "substantial reduction in occupational, educational, social, or recreational activities" as "scores lower than the 25th percentile of published US population [11] on the physical function (less than or equal to 70), or role physical (less than or equal to 50), or social function (less than or equal to 75), or role emotional (less than or equal to 66.7) subscales of the SF-36."
Priebe et al[2] have just published an analysis of a cohort of CFS patients from the UK. "Principal-component analysis of all scale scores revealed 2 distinct components, explaining 53% of the total variance."
"Component 1 comprised 14 variables and had an eigenvalue of 7.9 (32.9% of the variance). It had positive loadings of the SCL-90-R subscales depression, anxiety, obsessive-compulsive symptoms, psychoticism, hostility, phobic anxiety, interpersonal sensitivity, paranoid ideation, the Spielberger Trait Anxiety Questionnaire, Health Anxiety Questionnaire and Beck Hopelessness Scale, and negative loadings of the SF-36 subscales of mental health and emotional role fulfilling." (Remember that lower the scores on the SF-36, the lower the reported functioning in that domain).
The other component involved the other 6 SF-36 subscales, The Fatigue Visual Analogue Scale, SCL-90-R subscale somatization and the Somatic Discomfort Questionnaire (SDQ) (the authors say "the majority of physical symptoms that were assessed was measured on only 2 scales, the somatization subscale of the SF-36* and the SDQ")
(*This is presumably a typo and what they are referring to is the SCL-90-R subscale somatization).
Hardt et al [3] have previously performed factor analyses on a large cohort of patients (740 CFS patients from the US, 82 from the UK, and 65 from Germany). They said: "Overall, there was a remarkable similarity in HRQoL among all CFS patients, regardless of location. Patients scored two to three standard deviations below normal on six subscales and one standard deviation below normal on the other two subscales. Factor analysis suggested a two-factor model where the same six subscales (i.e. Bodily pain, General health perception, Limitations due to physical problems, Physical functioning, Social functioning and Vitality) constitute the first factor and the two others (i.e. limitations due to emotional problems (RE) and Mental health) the second factor."
These result bring into question the use of the role emotional subscale alongside the other three subscales (physical function, role physical and social functioning) being used in this so-called "empirical definition".
[1] Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER: International Chronic Fatigue Syndrome Study Group: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution.
[2] Priebe S, Fakhoury WK, Henningsen P: Functional Incapacity and Physical and Psychological Symptoms: How They Interconnect in Chronic Fatigue Syndrome. Psychopathology. 2008 Sep 3;41(6):339-345.
[3] Hardt J, Buchwald D, Wilks D, Sharpe M, Nix WA, Egle UT: Health-related quality of life in patients with chronic fatigue syndrome: an international study. J Psychosom Res 2001; 51: 431-434.
Competing interests
No competing interests
Another CFS study raises questions about the use of the RE subscale in a definition of CFS
Tom Kindlon, Irish ME/CFS Association - for Information, Support & Research
23 January 2009
Firstly, apologies for sounding like a broken record but the definition the CDC proposes for CFS is an important issue - it tends to be the one adopted by researchers around the world. The definition laid out in this paper continues to be used in papers involving cohorts the CDC has gathered for CFS population studies such as the papers using this cohort (which has been analysed in numerous papers) as well as a later study in Georgia[1].
Fulcher (2000)[2] is another study which raises questions about the use of the Role Emotional (RE) subscale of the SF-36 to select patients with CFS. The study involved 66 patients with CFS without a current psychiatric disorder, 30 healthy but sedentary controls, and 15 patients with a current major depressive disorder. It found, amongst other things, that "the two patient groups were significantly more incapacitated than the sedentary controls on all SF-36 measures (p<0.001), except that the patients with CFS were not significantly different in emotional or mental function." Also, "the depressed subjects were significantly more incapacitated in emotional and mental functioning than the patients with CFS p<0.001)." These results suggest that low scores on the emotional and mental functioning subscales of the SF-36 do not seem to be an intrinsic part of CFS (if they're found, they could be related to comorbid psychiatric issues). They also points out the risks of using the RE subscale alone [especially given CFS shares some characteristics with depression and so some people with depression (but not CFS) could potentially score the required 25 points on the Symptom Inventory] i.e. one could inadvertently include some people who have depression but not CFS, as CFS patients.
[1] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr. 2007 Jun 8;5:5.
[2] Fulcher KY, White PD. Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 2000 Sep;69(3):302-7.
Competing interests
No competing interests
Exclusionary conditions or essential pathology?
John Mitchell jr, Patient Support Advocate
23 January 2009
One important criticism of the CDC CFS case definition as it stands is based on the following sentences- "CFS is defined as persistent or relapsing fatigue of at least 6-months' duration, that is not alleviated by rest, and that causes substantial reduction in activities. The fatigue cannot be explained by medical or psychiatric conditions and must be accompanied by at least 4 of 8 case defining symptoms (unusual post exertional fatigue, impaired memory or concentration, unrefreshing sleep, headaches, muscle pain, joint pain, sore throat and tender cervical nodes)."
By including the misleading and out of context 'cannot be explained by medical or psychiatric conditions', the authors set up a damaging catch-22 in regards to pathophysiology in CFS, being that if any underlying pathophysiology is found then that patient is then excluded from further study. This makes sense if one understands that fatigue is a common symptom of many illnesses and should not immediately be ascribed to CFS, however in the context the author's use it, it ends up being as if pneumonia or Kaposis Sarcoma were exclusionary conditions when studying AIDS, instead of correctly being considered co-morbid conditions that are results of the underlying disease process.
So although pnuemonia and Kaposis Sarcoma do happen in the population without a person having AIDS, to exclude them from being co-morbid conditions would be absolutely disasterous to AIDS patients; as many CFS patients argue that excluding any thyroid involvement, elevated c-reactive protein, inflammatory disease, etc. is to them, especially when you consider that these are some of the very areas in which progress is being made by other groups studying CFS.[1,2]
1.Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood. Aspler AL, Bolshin C, Vernon SD, Broderick G. Behav Brain Funct. 2008
2.Neuroendocrine and immune network re-modeling in chronic fatigue syndrome: An exploratory analysis. Fuite J, Vernon SD, Broderick G. Genomics. 2008 Sep 30.
Competing interests
none
Research Study finds 38% of those with a Major Depressive Disorder satisfied these criteria for CFS (i.e. they lack specificity)
Tom Kindlon, rish ME/CFS Support Group
17 March 2009
An interesting study [1] has recently been published on this issue: It investigated 37 participants with a diagnosis of a Major Depressive Disorder and 27 participants with a diagnosis of CFS. It found that 38% of those with a diagnosis of a Major Depressive Disorder were misclassified as having CFS using this new CFS definition [2]. That is to say these criteria lack specificity.
The authors gave some background to the study pointing out that that there are several CFS symptoms that are not commonly found in depression and that there has been previous research which has distinguished between CFS and depressed patients.
The authors screened participants from the MDD group to ensure that they did not have CFS as defined by the Fukuda et al. (1994) criteria [3].
For the data, the authors subdivided the MDD group into two groups: those that satisfied the new definition [2], called "MDD/CFS" and those that did not, called "MDD".
There were large differences between the "pure" CFS patients and the other two groups across some of the measures that make up the Reeves (2005) definition [2]. There were also not surprisingly differences in the percentage scores satisfying the criteria from the Reeves (2005) definition.
For example, on the Role Physical subscale of the SF-36, the means scores (SDs) across the CFS, MDD/CFS and MDD groups were: 5.56 (16.01); 51.79 (40.98); 58.7 (45.61). (The data showed that there were the following statistically significant differences at the p ≤ 001 level: CFS<MDD/CFS and CFS<MDD). The percentages satisfying the criteria (RP less than or equal to 50) were, respectively, 96%, 50% and 44% (The data showed that there were the following statistically significant differences for the percentages at the p ≤ .001 level: CFS>MDD/CFS and CFS>MDD).
For the SF-36 Physical Functioning subscale the respective scores across the CFS, MDD/CFS and MDD groups were 37.41 (23.43); 70.36 (32.90); 76.74 (21.25). (The data showed that there were the following statistically significant differences at the p ≤ .001 level.: CFS<MDD/CFS and CFS<MDD). The percentages satisfying the criteria (PF less than or equal to 70) were, respectively, 93%, 43% and 35% (The data showed that there were the following statistically significant differences for the percentages at the p ≤ .001 level: CFS>MDD/CFS and CFS>MDD).
For the CDC Symptom Inventory CDC scores (i.e. for the 8 case-defining symptoms) the respective scores across the CFS, MDD/CFS and MDD groups were 43.97 (14.28); 37.56 (10.54); 17.05 (8.62). (The data showed that there were the following statistically significant differences at the p ≤ .001 level: CFS>MDD and MDD/CFS>MDD). The percentages satisfying the criteria (CDC Symptom Inventory greater than or equal to 25) were, respectively, 100%, 100% and 9% - this part of the definition should naturally the first two groups would be 100% (The data showed that there were the following statistically significant differences for the percentages at the p ≤ .001 level: CFS>MDD and MDD/CFS>MDD).
However the differences were the opposite (or "backwards") for the Role Emotional subscale of the SF-36 i.e. rather than the CFS group having the worst score, they actually had the best score - the scores across the CFS, MDD/CFS and MDD groups were: 69.14 (40.22); 19.05 (31.25); 30.43 (40.09) (The data showed that there were the following statistically significant differences at the p ≤ .001 level: CFS>MDD/CFS and CFS>MDD). The percentages satisfying the criteria (RE less than or equal to 67) were, respectively, 44%, 93% and 78% (The data showed that there were the following statistically significant differences for the percentages at the p ≤ .001 level: CFS<MDD/CFS and CFS<MDD).
For some subscales, there were no differences across the groups, which also brings about questions about their use in a CFS definition e.g.
(i) for the Social Functioning subscale of the SF-36, the mean scores (SDs) across the CFS, MDD/CFS and MDD groups were: 30.09 (28.43); 41.96 (23.31); 40.22 (25.27). The percentages satisfying the criteria (SF less than or equal to 75) were, respectively, 96%, 100% and 91% (The data showed that there were also no statistically significant differences for the percentages).
(ii) for the Reduced Activity scale of the Multidimensional Fatigue Inventory the scores were: 14.44 (3.79); 13.64 (3.95); 13.17 (4.77). The percentages satisfying the criteria (Reduced Activity score greater than or equal to 10) were, respectively, 85%, 86% and 78% (The data showed that there were also no statistically significant differences for the percentages).
The authors also calculated the total from each group that would satisfy each of the three criteria in the Reeves Definition[2]. This showed how poor the SF-36 and MFI criteria are for differentiating between CFS and MDD.
Using the SF-36 criteria, every one of the 37 patients with a Major Depressive Disorder satisfied the criteria used in the Reeves (2005) definition.
With the Multidimensional Fatigue Inventory criteria, 34 of the 37 patients (92%) with a Major Depressive Disorder satisfied the Reeves criteria.
The only measure that had any power to distinguish between the two groups was the CDC Symptom Inventory where 16 of the 37 patients (43%) with a Major Depressive Disorder satisfied the criteria. Of course, this is still not a particularly good percentage.
The authors make many of the points that have been made already in these comments. They point out that to score 25 on the CDC Symptom Inventory, somebody doesn't have to be that severely affected by more classic CFS symptoms. They could endorse symptoms such as unrefreshing sleep, impaired memory, headaches and muscle pain and score 25 without too much difficulty (one can score 16 from any one symptom).
This study clearly demonstrates that there is plenty of potential for a CFS definition to be "better" than the Reeves (2005) definition[2].
[1] Jason, L.A., Najar, N., Porter, N., Reh, C. Evaluating the Centers for Disease Control's empirical chronic fatigue syndrome case definition. Journal of Disability Policy Studies 2008, doi:10.1177/1044207308325995.
[2] Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic fatigue syndrome--a clinically empirical approach to its definition and study. BMC Med. 2005 Dec 15;3:19.
[3] 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 Int Med 1994, 121:953-959.
Competing interests
No competing interests
Who Can Be Diagnosed with CFS?
Kathryn Stephens, Patient Advocate
24 June 2009
When I read articles that exclude people with MDD or any other illnesses, I cannot help but wonder: cannot a person with MDD, MS, MCS, FM, Diabetes, CHD, CHF, and on, ad nauseum, get the Swine Flu? Thusly, cannot these patients also get Post-Viral Fatigue Syndrome, or CFS?
To me, the new Reeve's 'empirical' definition then not only excludes people with possible comorbid conditions, but has to also include them. Only then can the research into the genetic subtyping be accurate; Without them, research will be fragmented specificity-wise,treatments will not be specificically tailored and patients will continue to be misdiagnosed one way or another.
Competing interests
None
Source of threshold for Symptom Inventory (SI) criteria
Tom Kindlon, Irish ME/CFS Association - for Information, Support & Research
20 November 2009
This new set of criteria uses three sets of questionnaires: the SF-36, the MFI and the Symptom Inventory (SI).
In the paper, we are given information on where the thresholds came from for the first two instruments, but not the third one:
"We defined substantial reduction in occupational, educational, social, or recreational activities as scores lower than the 25th percentile of published US population [11] on the physical function (<= 70), or role physical (<= 50), or social function (<= 75), or role emotional (<= 66.7) subscales of the SF-36. We defined severe fatigue as >= medians of the MFI general fatigue (>= 13) or reduced activity (>= 10) scales. Finally, subjects reporting >=4 symptoms and scoring >= 25 on the Symptom Inventory Case Definition Subscale were considered to have substantial accompanying symptoms."
At the Chronic Fatigue Syndrome Advisory Committee (CFSAC) meeting [1], Dr Bill Reeves gives the source of the threshold for the third criteria: "And then we used the symptom inventory-a CFS individual had to have at least four symptoms in addition to fatigue, and to have a score above the 10th percentile of the nonfatigued group."
MDDm should be resolved for more than 5 years before a CFS diagnosis can be given
26 June 2007
In this paper, it says:
"Following recommendations of the International CFS Study Group, only current MDDm was considered exclusionary for CFS."
However, part of the specific recommendations of the International CFS Study Group [1] was that MDDm had to have been resolved for more than 5 years:
"The 1994 case definition stated that any past or current diagnosis of major depressive disorder with psychotic or melancholic features, anorexia nervosa, or bulimia permanently excluded a subject from the classification of CFS ... we now recommend that if these conditions have been resolved for more than 5 years before the onset of the current chronically fatiguing illness, they should not be considered exclusionary."
It might not be important to point this out for definitions for some illnesses: however if one looks at table 2, 6 of the 16 who are said to have CFS using the "current classification" of CFS, had been diagnosed with MDDm at a previous assessment which suggests it is important in this context.
Tom Kindlon
[1] Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER, International Chronic Fatigue Syndrome Study Group: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution.
BMC Health Services Research 2003, 3:25.
http://0-dx-doi-org.brum.beds.ac.uk/10.1186/1472-6963-3-25
Competing interests
No Competing Interests
How many SF-36 subscales were used for the "standardized clinically empirical criteria"?
26 June 2007
I wonder whether the authors would confirm in a quick comment how many of the 8 subscales of the SF-36 they used?
In the "empirical definition", they appear to me to use four: Role-Physical, Role-Emotional, Physical Functioning and Social Functioning:
[Reference: "We defined substantial reduction in occupational, educational, social, or recreational activities as scores lower than the 25th percentile of published US population [11] on the physical function (≤ 70), or role physical (≤ 50), or social function (≤ 75), or role emotional (≤ 66.7) subscales of the SF-36."]
However, in the pre-publication history they say:
".. We used only 3 of the 8 SF-36 and 2 of the 5 MFI scales in the empirical definition."
- see http://0-www-biomedcentral-com.brum.beds.ac.uk/imedia/7804319382956733_comment.pdf
I was just hoping that 3 is actually the number of subscales they used and that they didn't use the Role-Emotional subscale, as I question the value of using that subscale to satisfy functional impairment criteria.
Tom Kindlon
Competing interests
No Competing Interests
Data from another population study found scores on the RE subscale are similar in CFS patients to those found in healthy controls
9 July 2007
In a previous comment I said that I questioned the value of using the Role Emotional (RE) subscale to satisfy functional impairment criteria.
Researchers deciding whether to follow the method of operationalizing the Fukuda [1] used in this study, might be interested at looking at Table 2 in Jason et al [2]. The subjects were also obtained from a random-digit population study.
Here is what the authors said in the text on this part of the results:
"A MANCOVA for the Medical Outcomes Study SF-36 Health Survey (controlling for the effects of work status) revealed significant differences in gradations of disability across the diagnostic categories of CFS only, MCS only, FM only, more than one diagnosis, and no diagnosis on seven of the eight subscales (F(4,208) = 1.82, p < .05). The role-emotional scale was the only scale that did not reveal significant differences between the groups (see Table 2). Significant post hoc tests revealed that individuals with CFS demonstrated greater disability than those with no diagnosis on the role-physical; bodily pain; vitality; and social functioning scales. Individuals with MCS demonstrated greater disability than the no diagnosis group on the physical functioning; role-physical; bodily pain; general health; vitality; social functioning; and mental health scales. Individuals with FM demonstrated greater disability than the no diagnosis group on the physical functioning; role-physical; bodily pain; and social functioning scales. In addition, individuals with more than one diagnosis demonstrated greater disability than those in the no diagnosis group on the physical functioning; role-physical; bodily pain; vitality; and social functioning scales. Means for each of the Medical Outcomes Study subscales are reported in Table 2."
This issue of how the Fukuda criteria [1] are operationalized is not a trivial matter. Using the previous method of operationalizing the criteria, a CDC team found a prevalence for CFS of 235 per 100,000 [3]. Using the method of operationalizing the criteria outlined in this study, the prevalence rate for CFS was found to be 2.54% or 2540 per 100,000 [4] or 10.81 times the previous prevalence rate!
Tom Kindlon
[1] Fukuda, K., Straus, S.E., Hickie, I., Sharpe, M.C., Dobbins, J.G., & Komaroff, A. (1994). The chronic fatigue syndrome: A comprehensive approach to its definition and study. Annals of Internal Medicine, 121 (12):953-959. http://www.annals.org/cgi/content/full/121/12/953
[2] Jason, L.E., Taylor, R.R., & Kennedy, C.L. "Chronic Fatigue Syndrome, Fibromyalgia, and Multiple Chemical Sensitivities in a Community-Based Sample of Persons With Chronic Fatigue Syndrome-Like Symptoms." Psychosomatic Medicine 62:655-663 (2000).
http://www.psychosomaticmedicine.org/cgi/reprint/62/5/655
[3] Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N. Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Intern Med. 2003;163:1530–1536. doi: 10.1001/archinte.163.13.1530.
[4] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Population Health Metrics 2007, 5:5 doi:10.1186/1478-7954-5-5
Competing interests
No Competing Interests
This may not be a representative group of those who would be diagnosed in a random sample using the "standardized clinically empirical criteria"
2 January 2008
This "empirical" method of operationalizing the CDC 1994 CFS criteria[1] has subsequently been used in a population study[2]. It found a prevalence rate for CFS of 2540 per 100,000 persons 18 to 59 years of age[2].
This is considerably higher than the prevalence rates found in earlier studies. For example, a previous study using this cohort using a "previous" method of operationalizing the CDC 1994 CFS criteria[1] found a prevalence rate of 235 per 100,000[3].
Given the way the cohort in this current study was drawn up, using 58 people who had previously been diagnosed using a "previous" method of operationalizing the CDC 1994 CFS criteria, the group satisfying the new method of operationalizing the CDC 1994 CFS criteria, the "empirical" criteria, in this study may well not be the same sort of people that would show up if the method was used on a random sample of the population. So for example the results in Table 6 may not be similar to the results one can get in a random sample.
Unfortunately the paper giving the prevalence rate for Georgia[2] does not give the same pieces of information as is in Table 6 in this study. However we do have a paper which uses a group from the Georgia cohort[4]. Table 1 of this study[4] includes similar data. Some of the numbers are somewhat similar. However one that particularly stands out is the Role Emotional score. It was 35.6 (95% CI: 26.3-44.8). That compares to the value in this paper of 55.8+/-42.2.
Perhaps other data will be published in time. The main point of this comment is to point out or remind people that the data presented in this paper may not be representative of those that would be diagnosed using the empirical criteria.
Tom Kindlon
[1] Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, & Komaroff A. (1994). The chronic fatigue syndrome: A comprehensive approach to its definition and study. Annals of Internal Medicine, 121 (12):953-959. http://www.annals.org/cgi/content/full/121/12/953
[2] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Population Health Metrics 2007, 5:5 doi:10.1186/1478-7954-5-5
http://www.pophealthmetrics.com/content/5/1/5
[3] Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC: Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Int Med 2003, 163:1530-1536.
[4] Nater UM, Maloney E, Boneva RS, Gurbaxani BM, Lin JM, Jones JF, Reeves WC, Heim C. Attenuated Morning Salivary Cortisol Concentrations in a Population-based Study of Persons with Chronic Fatigue Syndrome and Well Controls. J Clin Endocrinol Metab. 2007 Dec 26
Competing interests
No competing interests
Why is this definition being referred to as an "empirical definition"?
18 June 2008
I believe most people's understanding of "empirical criteria" or an "empirical definition" would be that the data would speak for itself; it "would decide" the cut-off points through methods such as cluster analysis (for example).
Indeed this would seem to have been William Reeves' understanding of an empirical definition. For example, in a presentation on the CDC's CFS research program (to a Task Force Meeting on the Epidemiology of Interstitial Cystitis)[1], he said:
"The problem with the CFS criteria was that they were not specific enough and not empiric-based. For example, one of the criteria stated that the research subject must have at least four of eight symptoms, among them, impaired concentration or memory and postexertional worsening of physical or mental fatigue. "The accompanying symptoms need to be defined in and of themselves," Dr. Reeves said. The 1994 International Study Group also hypothesized that fatigue led to patients' symptoms rather than the reverse. The CDC is currently conducting population studies to develop an empiric definition of CFS that is based on statistical modeling."
At the inaugural meeting of the US Department of Health and Human Services' Chronic Fatigue Syndrome Advisory Committee (CFSAC), Dr Reeves said the CDC team of research would "derive an empirical case definition based on data".[2]
The definition presented here does not seem to have been based either on "statistical modeling" or "data". It seems to involve relatively arbitrary cut-off points; for example, of the 8 subscales of the SF-36, four are chosen and, for each of these, the 25th percentile of the published US population is chosen as a cut-off point. A patient is required to be in the bottom quartile for just one of these subscales to satisfy the criteria. Where did this cut-off point come from? There is no mention of it in the paper that suggested the use of the SF-36[3]; nor is there any mention that these particular subscales should be chosen or that one would sufficient. One of the authors of the paper[3] has confirmed that cut-off points were never chosen nor was it decided which sub-scales would be used. Given that the CDC's definition of CFS tends to go on to be used in numerous studies, would it not be better to investigate which thresholds give a "better" definition e.g. with a higher specificity and sensitivity - for example, for some of the SF-36 subscales, perhaps (say) the 13th, 15th, 20th or even 30th percentiles may be more appropriate.
The cut-off points suggested in this paper may or may not be useful. But is it really accurate to suggest that they are "empirically" derived?
[1] Epidemiology of Interstitial Cystitis - Executive Committee Summary and Task Force Meeting Report October 29th, 2003. http://www.niddk.nih.gov/fund/reports/ic/task_force_summary.pdf
[2] US Department of Health and Human Services - Chronic Fatigue Syndrome Advisory Committee (CFSAC). Inaugural Meeting. September 29th, 2003
Meeting Summary. http://www.hhs.gov/advcomcfs/CSFAC_mins_2003.09.29R.pdf
[3] Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER, International Chronic Fatigue Syndrome Study Group: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Services Research 2003, 3:25
Competing interests
No competing interests
Using two MFI scales ("General Fatigue" or "Reduced Activity") to ensure patients satisfying the definition have "severe fatigue"
30 June 2008
Initially when I read this paper, where it says "we defined severe fatigue as >= medians of the MFI general fatigue (>=13) or reduced activity (>=10) scales", I thought this referred to medians of the general population.
Hearing other people commenting on it, that's how some other people have been interpreting it also. It is probably somewhat natural to do this as the sentence before reads: "We defined substantial reduction in occupational, educational, social, or recreational activities as scores lower than the 25th percentile of published US population [11] on the physical function (<=70), or role physical (<=50), or social function (<=75), or role emotional (<=66.7) subscales of the SF-36."
However from looking at the scores for controls in other papers, these MFI scores do not look like medians for the whole US population but in fact are medians for this particular group of patients. This seems a strange way to set cut-off points for a CFS definition that is used for numerous studies into the illness, given the cohort that is being used as a basis:
"This population-based case control study enrolled 227 adults identified from the population of Wichita with: (1) CFS (n = 58); (2) non-fatigued controls matched to CFS on sex, race, age and body mass index (n = 55); (3) persons with medically unexplained fatigue not CFS, which we term ISF (n = 59); (4) CFS accompanied by melancholic depression (n = 27); and (5) ISF plus melancholic depression (n= 28)." i.e. this is not a random sample of the US population but a group of people selected for a specific purpose (or purposes) (not necessarily to design a definition, but as a follow-up study of people previously diagnosed with CFS or given some other label). Some of the groups are of different sizes - if the relative size of these groups had been changed, with relatively more people taken from some classification groups and less people taken from other groups, the median scores would likely have been different.
It should also be remembered that in this context the categories listed in the last paragraph refer to their classification when they evaluated years before (from 1997 to 2000), and not necessarily at the time when they were evaluated in this study (December 2002 to July 2003) (as is clear from the tables in this paper).
I thought it would be interesting to look at MFI scores in some other papers on CFS that did not use the "empirical definition".
I don't claim this is a definitive list but, at the same time, mean MFI scores with standard deviations only seem to be listed in a small percentage of papers.
The papers use cohorts from a variety of locations: England [3], The Netherlands [4], Germany [5] and the USA (New Jersey) [6].
I did not see any ranges given which would be useful given the task at hand (selecting cut-off points for a definition).
Unfortunately not all of the papers I found used the Fukuda [1] definition for CFS; some also used the Sharpe [2] definition for CFS. I indicate which definition is used in each case.
MFI: General Fatigue
Sample Sample Size Mean SD (Mean - 13)/SD Definition
Weatherley-Jones [3] 53 18.4 1.7 3.176470588 Sharpe (1991)
Vermeulen (Group 1) [4] 30 18.6 1.9 2.947368421 Fukuda (1994)
Vermeulen (Group 2) [4] 30 18.4 1.8 3 Fukuda (1994)
Vermeulen (Group 3) [4] 30 19.1 1.4 4.357142857 Fukuda (1994)
Gaab [5] 21 17.7 0.5 9.4 Sharpe (1991) and Fukuda (1994)
Brimacombe [6] 65 18.41 2.02 2.678217822 Fukuda (1994)
Combining these give a sample of 229 patients with a mean "General Fatigue" score of 18.45655022.
This data suggests that a threshold of >=13 will have a very very high sensitivity. This would suggest that another measure would not be necessary (unless it was being used as an extra criterion to increase the specificity, which isn't done with this definition).
However for completeness, I'm including the "Reduced Activity" data from the same papers:
Reduced activity (MFI)
Sample Sample Size Mean Score SE (Mean-10)/SD Definition
Weatherley-Jones [3] 53 16.1 3.1 1.967741935 Sharpe(1991)
Gaab [5] 21 15 0.7 8.714285714 Sharpe (1991) and Fukuda(1994)
Brimacombe [6] 65 15.93 4.55 1.340659341 Fukuda 1994
Combining these give a sample of 139 patients with a mean Reduced Activity score of 15.85431655.
Note: the Vermeulen paper[4] did not collect the MFI scores for Reduced Activity, just "the fatigue axes of the Multidimensional Fatigue Inventory" (which they defined as the MFI scores for General fatigue, Physical fatigue, Mental fatigue). It seems strange in the definition of Chronic Fatigue Syndrome defined in this paper (i.e. Reeves et al) that the "severe fatigue" criterion can be satisfied by a patient having a low score on a subscale of the MFI testing activity levels (as opposed to one of the 3 subscales measuring fatigue), especially when the function of the SF-36 is to "measure functional impairment". Just because someone is inactive doesn't mean they have severe fatigue. Allowing patients to be included if they simply have a "Reduced Activity" score of 10 or more (without necessarily having a low score on one of the fatigue axes of the MFI) risks reducing the specificity of the definition.
[1] 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 Int Med 1994, 121:953-959.
[2] Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ, et al. A report--chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991 Feb;84(2):118-21.
[3] Weatherley-Jones, E., Nicholl, JP., Thomas, KJ., Parry, GJ., McKendrick, MW., Green, ST., Stanley, PJ and Lynch, SPJ. A randomised, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome. Journal of Psychosomatic Research, 2004, 56, 2, 189-197.
[4] Vermeulen, RCW and Scholte, HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosomatic Medicine, 2004, 66, 276-282.
[5] Gaab J, Hüster D, Peisen R, Engert V, Heitz V, Schad T, Schürmeyer TH, Ehlert U. Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation.
Psychosom Med. 2002 Nov-Dec;64(6):951-62.
[6] Brimacombe, Michael; Lange, Gudrun; Bisuchio, Kim; Ciccone, Donald S.; Natelson, Benjamin. Cognitive Function Index for Patients with Chronic Fatigue Syndrome Journal of Chronic Fatigue Syndrome, 2004, vol 12; number 4, pages 3-24
Competing interests
No competing interests
Analyses of 2 separate CFS cohorts found 6 of the 8 SF-36 subscales group together - two that don't are MH and RE (the latter is being used in this definition)
30 September 2008
This paper is supposed to operationalize the recommendations in the consensus paper by Reeves et al[1]. That paper suggested that the SF-36 could be useful as a measure of functional impairment but did not specify which subscales should be used.
The authors of the current paper chose to define "substantial reduction in occupational, educational, social, or recreational activities" as "scores lower than the 25th percentile of published US population [11] on the physical function (less than or equal to 70), or role physical (less than or equal to 50), or social function (less than or equal to 75), or role emotional (less than or equal to 66.7) subscales of the SF-36."
Priebe et al[2] have just published an analysis of a cohort of CFS patients from the UK. "Principal-component analysis of all scale scores revealed 2 distinct components, explaining 53% of the total variance."
"Component 1 comprised 14 variables and had an eigenvalue of 7.9 (32.9% of the variance). It had positive loadings of the SCL-90-R subscales depression, anxiety, obsessive-compulsive symptoms, psychoticism, hostility, phobic anxiety, interpersonal sensitivity, paranoid ideation, the Spielberger Trait Anxiety Questionnaire, Health Anxiety Questionnaire and Beck Hopelessness Scale, and negative loadings of the SF-36 subscales of mental health and emotional role fulfilling." (Remember that lower the scores on the SF-36, the lower the reported functioning in that domain).
The other component involved the other 6 SF-36 subscales, The Fatigue Visual Analogue Scale, SCL-90-R subscale somatization and the Somatic Discomfort Questionnaire (SDQ) (the authors say "the majority of physical symptoms that were assessed was measured on only 2 scales, the somatization subscale of the SF-36* and the SDQ")
(*This is presumably a typo and what they are referring to is the SCL-90-R subscale somatization).
Hardt et al [3] have previously performed factor analyses on a large cohort of patients (740 CFS patients from the US, 82 from the UK, and 65 from Germany). They said: "Overall, there was a remarkable similarity in HRQoL among all CFS patients, regardless of location. Patients scored two to three standard deviations below normal on six subscales and one standard deviation below normal on the other two subscales. Factor analysis suggested a two-factor model where the same six subscales (i.e. Bodily pain, General health perception, Limitations due to physical problems, Physical functioning, Social functioning and Vitality) constitute the first factor and the two others (i.e. limitations due to emotional problems (RE) and Mental health) the second factor."
These result bring into question the use of the role emotional subscale alongside the other three subscales (physical function, role physical and social functioning) being used in this so-called "empirical definition".
[1] Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER: International Chronic Fatigue Syndrome Study Group: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution.
[2] Priebe S, Fakhoury WK, Henningsen P: Functional Incapacity and Physical and Psychological Symptoms: How They Interconnect in Chronic Fatigue Syndrome. Psychopathology. 2008 Sep 3;41(6):339-345.
[3] Hardt J, Buchwald D, Wilks D, Sharpe M, Nix WA, Egle UT: Health-related quality of life in patients with chronic fatigue syndrome: an international study. J Psychosom Res 2001; 51: 431-434.
Competing interests
No competing interests
Another CFS study raises questions about the use of the RE subscale in a definition of CFS
23 January 2009
Firstly, apologies for sounding like a broken record but the definition the CDC proposes for CFS is an important issue - it tends to be the one adopted by researchers around the world. The definition laid out in this paper continues to be used in papers involving cohorts the CDC has gathered for CFS population studies such as the papers using this cohort (which has been analysed in numerous papers) as well as a later study in Georgia[1].
Fulcher (2000)[2] is another study which raises questions about the use of the Role Emotional (RE) subscale of the SF-36 to select patients with CFS. The study involved 66 patients with CFS without a current psychiatric disorder, 30 healthy but sedentary controls, and 15 patients with a current major depressive disorder. It found, amongst other things, that "the two patient groups were significantly more incapacitated than the sedentary controls on all SF-36 measures (p<0.001), except that the patients with CFS were not significantly different in emotional or mental function." Also, "the depressed subjects were significantly more incapacitated in emotional and mental functioning than the patients with CFS p<0.001)." These results suggest that low scores on the emotional and mental functioning subscales of the SF-36 do not seem to be an intrinsic part of CFS (if they're found, they could be related to comorbid psychiatric issues). They also points out the risks of using the RE subscale alone [especially given CFS shares some characteristics with depression and so some people with depression (but not CFS) could potentially score the required 25 points on the Symptom Inventory] i.e. one could inadvertently include some people who have depression but not CFS, as CFS patients.
[1] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr. 2007 Jun 8;5:5.
[2] Fulcher KY, White PD. Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 2000 Sep;69(3):302-7.
Competing interests
No competing interests
Exclusionary conditions or essential pathology?
23 January 2009
One important criticism of the CDC CFS case definition as it stands is based on the following sentences- "CFS is defined as persistent or relapsing fatigue of at least 6-months' duration, that is not alleviated by rest, and that causes substantial reduction in activities. The fatigue cannot be explained by medical or psychiatric conditions and must be accompanied by at least 4 of 8 case defining symptoms (unusual post exertional fatigue, impaired memory or concentration, unrefreshing sleep, headaches, muscle pain, joint pain, sore throat and tender cervical nodes)."
By including the misleading and out of context 'cannot be explained by medical or psychiatric conditions', the authors set up a damaging catch-22 in regards to pathophysiology in CFS, being that if any underlying pathophysiology is found then that patient is then excluded from further study. This makes sense if one understands that fatigue is a common symptom of many illnesses and should not immediately be ascribed to CFS, however in the context the author's use it, it ends up being as if pneumonia or Kaposis Sarcoma were exclusionary conditions when studying AIDS, instead of correctly being considered co-morbid conditions that are results of the underlying disease process.
So although pnuemonia and Kaposis Sarcoma do happen in the population without a person having AIDS, to exclude them from being co-morbid conditions would be absolutely disasterous to AIDS patients; as many CFS patients argue that excluding any thyroid involvement, elevated c-reactive protein, inflammatory disease, etc. is to them, especially when you consider that these are some of the very areas in which progress is being made by other groups studying CFS.[1,2]
1.Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood. Aspler AL, Bolshin C, Vernon SD, Broderick G. Behav Brain Funct. 2008
2.Neuroendocrine and immune network re-modeling in chronic fatigue syndrome: An exploratory analysis. Fuite J, Vernon SD, Broderick G. Genomics. 2008 Sep 30.
Competing interests
none
Research Study finds 38% of those with a Major Depressive Disorder satisfied these criteria for CFS (i.e. they lack specificity)
17 March 2009
An interesting study [1] has recently been published on this issue: It investigated 37 participants with a diagnosis of a Major Depressive Disorder and 27 participants with a diagnosis of CFS. It found that 38% of those with a diagnosis of a Major Depressive Disorder were misclassified as having CFS using this new CFS definition [2]. That is to say these criteria lack specificity.
The authors gave some background to the study pointing out that that there are several CFS symptoms that are not commonly found in depression and that there has been previous research which has distinguished between CFS and depressed patients.
The authors screened participants from the MDD group to ensure that they did not have CFS as defined by the Fukuda et al. (1994) criteria [3].
For the data, the authors subdivided the MDD group into two groups: those that satisfied the new definition [2], called "MDD/CFS" and those that did not, called "MDD".
There were large differences between the "pure" CFS patients and the other two groups across some of the measures that make up the Reeves (2005) definition [2]. There were also not surprisingly differences in the percentage scores satisfying the criteria from the Reeves (2005) definition.
For example, on the Role Physical subscale of the SF-36, the means scores (SDs) across the CFS, MDD/CFS and MDD groups were: 5.56 (16.01); 51.79 (40.98); 58.7 (45.61). (The data showed that there were the following statistically significant differences at the p ≤ 001 level: CFS<MDD/CFS and CFS<MDD). The percentages satisfying the criteria (RP less than or equal to 50) were, respectively, 96%, 50% and 44% (The data showed that there were the following statistically significant differences for the percentages at the p ≤ .001 level: CFS>MDD/CFS and CFS>MDD).
For the SF-36 Physical Functioning subscale the respective scores across the CFS, MDD/CFS and MDD groups were 37.41 (23.43); 70.36 (32.90); 76.74 (21.25). (The data showed that there were the following statistically significant differences at the p ≤ .001 level.: CFS<MDD/CFS and CFS<MDD). The percentages satisfying the criteria (PF less than or equal to 70) were, respectively, 93%, 43% and 35% (The data showed that there were the following statistically significant differences for the percentages at the p ≤ .001 level: CFS>MDD/CFS and CFS>MDD).
For the CDC Symptom Inventory CDC scores (i.e. for the 8 case-defining symptoms) the respective scores across the CFS, MDD/CFS and MDD groups were 43.97 (14.28); 37.56 (10.54); 17.05 (8.62). (The data showed that there were the following statistically significant differences at the p ≤ .001 level: CFS>MDD and MDD/CFS>MDD). The percentages satisfying the criteria (CDC Symptom Inventory greater than or equal to 25) were, respectively, 100%, 100% and 9% - this part of the definition should naturally the first two groups would be 100% (The data showed that there were the following statistically significant differences for the percentages at the p ≤ .001 level: CFS>MDD and MDD/CFS>MDD).
However the differences were the opposite (or "backwards") for the Role Emotional subscale of the SF-36 i.e. rather than the CFS group having the worst score, they actually had the best score - the scores across the CFS, MDD/CFS and MDD groups were: 69.14 (40.22); 19.05 (31.25); 30.43 (40.09) (The data showed that there were the following statistically significant differences at the p ≤ .001 level: CFS>MDD/CFS and CFS>MDD). The percentages satisfying the criteria (RE less than or equal to 67) were, respectively, 44%, 93% and 78% (The data showed that there were the following statistically significant differences for the percentages at the p ≤ .001 level: CFS<MDD/CFS and CFS<MDD).
For some subscales, there were no differences across the groups, which also brings about questions about their use in a CFS definition
e.g.
(i) for the Social Functioning subscale of the SF-36, the mean scores (SDs) across the CFS, MDD/CFS and MDD groups were: 30.09 (28.43); 41.96 (23.31); 40.22 (25.27). The percentages satisfying the criteria (SF less than or equal to 75) were, respectively, 96%, 100% and 91% (The data showed that there were also no statistically significant differences for the percentages).
(ii) for the Reduced Activity scale of the Multidimensional Fatigue Inventory the scores were: 14.44 (3.79); 13.64 (3.95); 13.17 (4.77). The percentages satisfying the criteria (Reduced Activity score greater than or equal to 10) were, respectively, 85%, 86% and 78% (The data showed that there were also no statistically significant differences for the percentages).
The authors also calculated the total from each group that would satisfy each of the three criteria in the Reeves Definition[2]. This showed how poor the SF-36 and MFI criteria are for differentiating between CFS and MDD.
Using the SF-36 criteria, every one of the 37 patients with a Major Depressive Disorder satisfied the criteria used in the Reeves (2005) definition.
With the Multidimensional Fatigue Inventory criteria, 34 of the 37 patients (92%) with a Major Depressive Disorder satisfied the Reeves criteria.
The only measure that had any power to distinguish between the two groups was the CDC Symptom Inventory where 16 of the 37 patients (43%) with a Major Depressive Disorder satisfied the criteria. Of course, this is still not a particularly good percentage.
The authors make many of the points that have been made already in these comments. They point out that to score 25 on the CDC Symptom Inventory, somebody doesn't have to be that severely affected by more classic CFS symptoms. They could endorse symptoms such as unrefreshing sleep, impaired memory, headaches and muscle pain and score 25 without too much difficulty (one can score 16 from any one symptom).
This study clearly demonstrates that there is plenty of potential for a CFS definition to be "better" than the Reeves (2005) definition[2].
[1] Jason, L.A., Najar, N., Porter, N., Reh, C. Evaluating the Centers for Disease Control's empirical chronic fatigue syndrome case definition. Journal of Disability Policy Studies 2008, doi:10.1177/1044207308325995.
[2] Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic fatigue syndrome--a clinically empirical approach to its definition and study. BMC Med. 2005 Dec 15;3:19.
[3] 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 Int Med 1994, 121:953-959.
Competing interests
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Who Can Be Diagnosed with CFS?
24 June 2009
When I read articles that exclude people with MDD or any other illnesses, I cannot help but wonder: cannot a person with MDD, MS, MCS, FM, Diabetes, CHD, CHF, and on, ad nauseum, get the Swine Flu? Thusly, cannot these patients also get Post-Viral Fatigue Syndrome, or CFS?
To me, the new Reeve's 'empirical' definition then not only excludes people with possible comorbid conditions, but has to also include them. Only then can the research into the genetic subtyping be accurate; Without them, research will be fragmented specificity-wise,treatments will not be specificically tailored and patients will continue to be misdiagnosed one way or another.
Competing interests
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Source of threshold for Symptom Inventory (SI) criteria
20 November 2009
This new set of criteria uses three sets of questionnaires: the SF-36, the MFI and the Symptom Inventory (SI).
In the paper, we are given information on where the thresholds came from for the first two instruments, but not the third one:
"We defined substantial reduction in occupational, educational, social, or recreational activities as scores lower than the 25th percentile of published US population [11] on the physical function (<= 70), or role physical (<= 50), or social function (<= 75), or role emotional (<= 66.7) subscales of the SF-36. We defined severe fatigue as >= medians of the MFI general fatigue (>= 13) or reduced activity (>= 10) scales. Finally, subjects reporting >=4 symptoms and scoring >= 25 on the Symptom Inventory Case Definition Subscale were considered to have substantial accompanying symptoms."
At the Chronic Fatigue Syndrome Advisory Committee (CFSAC) meeting [1], Dr Bill Reeves gives the source of the threshold for the third criteria: "And then we used the symptom inventory-a CFS individual had to have at least four symptoms in addition to fatigue, and to have a score above the 10th percentile of the nonfatigued group."
References:
[1] Chronic Fatigue Syndrome Advisory Committee (CFSAC) Meeting Monday, April 24, 2006.
http://www.hhs.gov/advcomcfs/meetings/minutes/cfsac060424_min.html
Competing interests
No competing interests