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Co-Cure Weekly Digest of research and medical posts only - 4 Jun 2007 to 11 Jun 2007

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Date:    Tue, 5 Jun 2007 08:21:53 -0700
From:    Melissa O'Toole <m_otoole2 YAHOO.COM>
Subject: NOT,RES: William C. Reeves answers a few questions about "Identification of ambiguities in the 1994 CFS research case definition..."

ESI Special Topics, November 2006
Citing URL: http://www.esi-topics.com/fmf/2006/november06-WilliamCReeves.html

>From •>>November 2006

William C. Reeves answers a few questions about this month's fast moving front
in the field of Pharmacology & Toxicology.

Field: Pharmacology & Toxicology

Article: Identification of ambiguities in the 1994 chronic fatigue syndrome
research case definition and recommendations for resolution

Authors: Reeves, WC;Lloyd, A;Vernon, SD;Klimas, N;Jason, LA;Bleijenberg,
G;Evengard, B;White, PD;Nisenbaum, R;Unger, ER;Int Chronic Fatigue Syndrome

Journal: BMC HEALTH SERV RES 30 3: art. no.-25, DEC 31 2003

Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
Univ New S Wales, Sch Pathol, Inflammat Res Unit, Sydney, NSW, Australia.
Univ Miami, Miami, FL 33152 USA.
Dept Vet Affairs Med Ctr, Miami, FL USA.
Depaul Univ, Chicago, IL 60604 USA.
Univ Med Ctr Nijmegen, Nijmegen, Netherlands.
Huddinge Univ Hosp, Karolinska Inst, Stockholm, Sweden.
Barts & London Sch Med, London, England.

   Why do you think your paper is highly cited?

    This represents the key methodology paper in the field. The high citation
rate reflects international acceptance of the paper’s concept and increasing
scientific interest in chronic fatigue syndrome (CFS). The 1994 CFS case
definition (Fukuda et al., "The chronic fatigue syndrome: a comprehensive
approach to its definition and study," Ann. Int. Med. 121:953-959, 1994—1,110
citations recorded by ISI Web of Knowledge) represented the first international
consensus definition for the illness.

    However, in spite of wide acceptance, there has been a lack of consensus in
the findings of many well-conducted studies both within and between centers.
This reflects the lack of a common methodology to apply criteria of the case
definition. The 2003 paper specifies standardized and validated criteria for
measuring the clinical dimensions of CFS (impairment, fatigue, and accompanying
symptoms) and puts the weight of the International Chronic Fatigue Syndrome
Study Group behind the recommendations. Any investigator in the field needs to
consider and cite this paper to be considered for peer review. The paper is
particularly important for the pharmaceutical industry because it provides
standard methods to monitor the clinical course of CFS and response to therapy.

   Does it describe a new discovery, methodology, or synthesis of knowledge?

    An international collaborative group of experienced investigators met (in
2000, 2001, and 2002) for a series of 3-day workshops to identify and discuss
problems in application of the 1994 CFS case definition. This paper that
resulted from the deliberations represents a synthesis of evolving knowledge in
the field.

   Could you summarize the significance of your paper in layman’s terms?

    CFS is defined by symptoms and disability, has no diagnostic physical signs
or laboratory abnormalities, and its causes and pathology remain unknown. So,
diagnosis is based on self-reported symptoms and ruling out treatable medical
and psychiatric causes, and treatment is aimed at relieving symptoms rather
than a cure.

    Research has been constrained by ambiguities in the case definition. When
this happens it is difficult to compare different findings because different
subgroups of patients have been studied. In essence, one investigator is
studying apples, the next oranges.

    In this paper, an international group came together to reach an agreement
on exactly what the case definition means, agree on exclusion criteria, and
agree to use comparable measures to define CFS.

    Since this paper came out, nearly every study of CFS has relied on the
criteria it describes. Investigators can now compare apples to apples.
Moreover, many of the recommendations are useful for health care providers (and
their patients) because they specify standardized measures of the symptoms and
disability associated with CFS.

   How did you become involved in this research, and were there obstacles along
the way?

    CFS is a U.S. Department of Health and Human Services priority and the
Centers for Disease Control and Prevention (CDC) is responsible for public
health research to control the illness. The CDC has been involved in CFS
research since the illness was first recognized as a public health problem and
has been the international leader in developing diagnostic criteria. The
primary obstacle has been lack of medical and public acceptance of CFS as a
valid illness.

   Are there any social or political implications for your research?

    Every illness has societal and political implications. Between one and four
million Americans suffer CFS, half have been ill for at least seven years, a
quarter of those with the illness are unemployed or receiving disability, and
the average affected family forgoes approximately $20,000 in annual earnings
and wages. Yet, fewer than 20% of those afflicted have received medical care
for CFS.

    Despite more than 3,000 articles in the peer-reviewed medical literature,
the pathophysiology of CFS is not well understood. There are no diagnostic
laboratory abnormalities or clinical tests. There is no public health control
or prevention strategy for CFS. This paper helps to resolve some of the
research obstacles related to classification, provides investigators and
clinicians tools with which to evaluate the clinical course and response to
treatment, gives peer reviewers clearer guidelines, and removes some of the
obstacles for funding.End

William C. Reeves, MD, MSc
Chief of the Chronic Viral Diseases Branch
Coordinating Center for Infectious Diseases
U.S. Centers for Disease Control and Prevention
Atlanta, GA, USA

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Date:    Tue, 5 Jun 2007 11:42:24 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: The Experience of Cancer-Related Fatigue and Chronic  Fatigue Syndrome: A Qualitative and Comparative Study

The Experience of Cancer-Related Fatigue and Chronic Fatigue Syndrome: A
Qualitative and Comparative Study

Journal: J Pain Symptom Manage. 2007 May 31; [Epub ahead of print]

Authors: Bennett B, Goldstein D, Friedlander M, Hickie I, Lloyd A.
Affiliations: Department of Medical Oncology (B.B., D.G., M.F.), Prince of
Wales Hospital, Sydney, Australia, The Brain and Mind Research Institute
(I.H.), University of Sydney, Australia, and the School of Medical Sciences
(A.L.), University of New South Wales, Sydney Australia.

NLM Citation: PMID: 17544246

Cancer-related fatigue (CRF) is a common and disabling symptom complex
reported by survivors. This study aimed to better understand the
manifestations of CRF in women treated for breast cancer, and to compare
them with those of women diagnosed with chronic fatigue syndrome (CFS).

Women with CRF persisting 6 months after treatment for early stage breast
cancer, and women with CFS participated in separate, audiotaped focus
groups. Transcripts of the sessions were analyzed using the NUD*IST
software, and interpreted using grounded theory. Twenty-eight women
participated, 16 with CRF and 12 with CFS.

Analysis of transcripts from both groups revealed a similar core set of
symptoms, featuring fatigue, neurocognitive difficulties, and mood
disturbances. Women with CFS reported additional symptoms including
musculoskeletal pain and influenza-like manifestations. Both groups
suffered disabling behavioral consequences of the symptom complex.

Qualitatively, CRF appears closely related to CFS. These findings raise the
emergent hypothesis of a conserved neurobehavioral symptom complex, which
results from diverse triggering insults.

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Date:    Tue, 5 Jun 2007 14:01:29 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Longitudinal analysis of pro- and anti-inflammatory  cytokine production in severely fatigued adolescents

Longitudinal analysis of pro- and anti-inflammatory cytokine production in
severely fatigued adolescents.

Journal: Brain Behav Immun. 2007 May 31; [Epub ahead of print]

Authors: Ter Wolbeek M, van Doornen LJ, Kavelaars A, van de Putte EM,
Schedlowski M, Heijnen CJ.

Affiliations: Laboratory of Psychoneuroimmunology, University Medical
Center Utrecht, Room: KC03.068.0, P.O. Box 85090, 3508 AB Utrecht, The
Netherlands; Department of Health Psychology, Utrecht University, P.O. Box
80140, 3508 TC Utrecht, The Netherlands.

NLM Citation: PMID: 17544255

In the adolescent population, fatigue is associated with somatic
complaints, unrefreshing sleep, cognitive disturbances and symptoms of
depression and anxiety. This pattern of symptoms resembles the one
described in chronic fatigue syndrome (CFS). Since immunological
alterations have been reported in CFS patients, we wondered whether also
severely fatigued girls from a healthy population would show comparable
alterations in psychological and immunological parameters.

We tested this hypothesis in a longitudinal design, allowing a reliable
assessment of the participants' characteristic immune status. Groups of
severely fatigued (N=67) and non-fatigued (N=61) participants were selected.

Severely fatigued girls reported more depressive symptoms, anxiety, reduced
sleep quality, and somatic and CFS-related symptoms than non-fatigued
participants across three measurements during one year (T1: spring, T2:
autumn, T3: spring). In contrast, no group differences in mitogen-induced
cytokine production or T-cell proliferation in vitro or in leukocyte subset
counts were observed. Although absolute cytokine production and cell counts
were affected by seasonal variation, the within-subject values, relatively
to the rest of the participants, were fairly stable. Data from a small
group of CFS patients (N=11) showed similarities in self-reported
complaints between CFS patients and fatigued participants. Interestingly,
CFS patients showed a distinct immune profile when compared to the severely
fatigued or non-fatigued participants, i.e. increased levels of
anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and
reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all
three time points analyzed.

These results show that, although overlap in symptomatology between the
general population and patients with CFS was observed, only CFS patients
show a skewing of the cytokine balance towards an anti-inflammatory profile.

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Date:    Tue, 5 Jun 2007 14:54:05 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients

Double-blind, multicenter trial comparing acetyl l-carnitine with placebo
in the treatment of fibromyalgia patients.

Clin Exp Rheumatol. 2007 Mar-Apr;25(2):182-8.

Rossini M, Di Munno O, Valentini G, Bianchi G, Biasi G, Cacace E, Malesci
D, La Montagna G, Viapiana O, Adami S.

Rheumatology Unit, University of Verona, Italy.

PMID: 17543140

OBJECTIVE: Fibromyalgia (FMS) is a chronic syndrome characterized by
widespread pain, troubled sleep, disturbed mood, and fatigue. Several
analgesic strategies have been evaluated but the results are moderate and
inconsistent. Antidepressant agents are now considered the treatment of
choice in most patients. It has been recently suggested that FMS may be
associated with metabolic alterations including a deficit of carnitine. In
this multicenter randomized clinical trial we evaluated the efficacy of
acetyl L-carnitine (LAC) in patients with overt FMS.

METHODS: One hundred and two patients meeting the American College of
Rheumatology criteria for FMS were randomized into the study. The treatment
consisted of 2 capsules/day of 500 mg LAC or placebo plus one intramuscular
(i.m.) injection of either 500 mg LAC or placebo for 2 weeks. During the
following 8 weeks the patients took 3 capsules daily containing either 500
mg LAC or placebo. The patients were seen during treatment after 2 (visit
3), 6 (visit 4) and 10 weeks (visit 5). The patients were also visited 4
weeks after treatment discontinuation (follow-up visit). Outcome measures
included the number of positive tender points, the sum of pain threshold
(kg/cm<sup>2</sup> or "total myalgic score"), the Short Form 36 (SF36), a
100 mm visual analog scale (VAS) for self-perceived stiffness, fatigue,
tiredness on awakening, sleep, work status, depression, and
muscular-skeletal pain, and the Hamilton depression scale.

RESULTS: The "total myalgic score" and the number of positive tender points
declined significantly and equally in both groups until the 6th week of
treatment. At the 10th week both parameters remained unchanged in the
placebo group but they continued to improve in the LAC group with a
statistically significant between-group difference. Most VAS scores
significantly improved in both groups. A statistically significant
between-group difference was observed for depression and musculo-skeletal
pain. Significantly larger improvements in SF36 questionnaire were observed
in LAC than in placebo group for most parameters. Treatment was well-tolerated.

CONCLUSION: Although this experience deserves further studies, these
results indicate that LAC may be of benefit in patients with FMS, providing
improvement in pain as well as the general and mental health of these patients.

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Date:    Wed, 6 Jun 2007 15:00:03 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Cytokine patterns in fibromyalgia and their correlation  with clinical manifestations

Cytokine patterns in fibromyalgia and their correlation with clinical

Clin Exp Rheumatol. 2007 Mar-Apr;25(2):225-30.

Bazzichi L, Rossi A, Massimetti G, Giannaccini G, Giuliano T, De Feo F,
Ciapparelli A, Dell'osso L, Bombardieri S.

Department of Internal Medicine, Division of Rheumatology, University of
Pisa, Pisa, Italy.

PMID: 17543146

OBJECTIVE: To examine the possible role of the soluble factor in
fibromyalgia (FM) by studying the correlation of cytokine levels with the
patients' clinical and psychiatric profile.

METHODS: Eighty FM patients underwent clinical and psychiatric evaluations,
and plasma levels of cytokines (IL-1, IL-6, IL-8, IL-10, TNF-alpha),
aspecific markers of inflammation, rheumatoid factor (RF), anti-extractable
nuclear antigen (ENA) antibodies, and anti-nuclear factor (FAN) were measured.

RESULTS: Higher levels of IL-10, IL-8 and TNF-alpha were found in FM
patients than in controls. Significant correlations between the biochemical
parameters and clinical data were found.

CONCLUSION: The higher levels of cytokines found in FM patients suggest the
presence of an inflammatory response system (IRS) and highlight a parallel
between the clinical symptoms and biochemical data. They support the
hypothesis that cytokines may play a role in the clinical features of
fibromyalgia. In addition, the similar cytokine patterns found in FM
patients with different psychiatric profiles suggests that IRS impairment
may play a specific role in the disease.

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Date:    Wed, 6 Jun 2007 15:04:58 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Fibromyalgia: revisiting the literature

Fibromyalgia: revisiting the literature.

JCCA J Can Chiropr Assoc. 2004 Jun;48(2):119-31.

Forbes D, Chalmers A.

Private practice, Vancouver, British Columbia.

PMID: 17549223

Fibromyalgia has a distinct clinical presentation. With no distinct
characteristic beyond the presence of 11 or more tender points and chronic
pain in all four quadrants of the body, it represents one extreme of a
normal distribution of pain states.

Research exploration utilizing the ACR criteria has not found solid
empirical evidence to link the finding of multiple tender points to a
specific pathological process. These points may be present as a concomitant
finding with psychological disease states but they have not lead to further
etiological understanding.

Measurement of outcomes is difficult and the prognosis for patients in the
specialty care setting is poor, however in the general population the
prognosis is variable, and includes improvement without treatment.

The success of treatments has been limited mainly to helping patients
improve their ability to cope with, but not to eliminate the tender points.

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Date:    Thu, 7 Jun 2007 15:08:02 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Effectiveness of Massage Therapy for Chronic, Non-malignant Pain: A Review

Effectiveness of Massage Therapy for Chronic, Non-malignant Pain: A Review.

Evid Based Complement Alternat Med. 2007 Jun;4(2):165-79. Epub 2007 Feb 5.

Tsao JC.

Pediatric Pain Program, Department of Pediatrics, David Geffen School of
Medicine at UCLA, USA.

PMID: 17549233

Previous reviews of massage therapy for chronic, non-malignant pain have
focused on discrete pain conditions. This article aims to provide a broad
overview of the literature on the effectiveness of massage for a variety of
chronic, non-malignant pain complaints to identify gaps in the research and
to inform future clinical trials.

Computerized databases were searched for relevant studies including prior
reviews and primary trials of massage therapy for chronic, non-malignant
pain. Existing research provides fairly robust support for the analgesic
effects of massage for non-specific low back pain, but only moderate
support for such effects on shoulder pain and headache pain. There is only
modest, preliminary support for massage in the treatment of fibromyalgia,
mixed chronic pain conditions, neck pain and carpal tunnel syndrome.

Thus, research to date provides varying levels of evidence for the benefits
of massage therapy for different chronic pain conditions. Future studies
should employ rigorous study designs and include follow-up assessments for
additional quantification of the longer-term effects of massage on chronic pain.

[Return to top]


Date:    Thu, 7 Jun 2007 15:15:45 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: The Impact of Increased Body Mass Index on Systemic Lupus Erythematosus: Data From LUMINA, a Multiethnic Cohort

The Impact of Increased Body Mass Index on Systemic Lupus Erythematosus:
Data From LUMINA, a Multiethnic Cohort.

J Clin Rheumatol. 2007 Jun;13(3):128-133.

Chaiamnuay S, Bertoli AM, Fernández M, Apte M, Vilá LM, Reveille JD,
Alarcón GS; for the LUMINA Study Group.

 From the *Department of Medicine, Division of Clinical Immunology and
Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama;
†Department of Medicine, Division of Rheumatology, University of Puerto
Rico Medical Sciences Campus, San Juan, Puerto Rico; ‡Department of
Medicine, Division of Rheumatology, University of Texas Health Science
Center at Houston, Houston, Texas.

PMID: 17551377

OBJECTIVE: The aim of this study was to examine the impact of an increased
body mass index (BMI) on disease activity, damage accrual, fatigue,
self-reported health-related quality of life (HRQOL), and fibromyalgia in
patients with lupus using longitudinal data from LUMINA, a large
multiethnic cohort.

METHODS: SLE patients (>/=4 ACR revised criteria), </=5 years disease
duration at entry into the cohort (T0), of Hispanic (from Texas or from the
Island of Puerto Rico), African American, or white ethnicity were included.
BMI was ascertained at T0 or first recorded. The average scores from all
visits for disease activity (SLAM-R), self-reported HRQOL (physical and
mental component summary measures of the SF-36) and fatigue (Fatigue
Severity Scale), the score at last visit for damage accrual (SLICC Damage
Index), and fibromyalgia (ACR criteria), if present at any visit, were
examined for their association with an increased BMI by univariable and
multivariable analyses.

RESULTS: Three-hundred sixty-four patients were included; 28% were obese
(BMI >/=30 kg/m). An increased BMI was associated with older age, less
social support, higher degree of helplessness, depression, more abnormal
illness-related behaviors, poorer self-reported HRQOL, fatigue, and
fibromyalgia, but not with disease activity or damage accrual by
univariable analyses. In multivariable analyses, BMI was independently
associated with fibromyalgia but not with disease activity, fatigue, or
self-reported HRQOL.

CONCLUSIONS:: An increased BMI is independently associated with presence of
fibromyalgia but not with disease activity, damage accrual, fatigue or
self-reported quality of life in patients with SLE. Optimizing weight
merits investigation to see if it can significantly impact this pervasive
SLE-associated manifestation.

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Date:    Thu, 7 Jun 2007 15:23:16 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Self-assessed pain intensity and disability in subjects diagnosed with fibromyalgia claiming retirement pension

[Self-assessed pain intensity and disability in subjects diagnosed with
fibromyalgia claiming retirement pension.]
[Article in German]

Schmerz. 2007 Jun 6; [Epub ahead of print]

Häuser W.

Zentrum für Schmerztherapie/Medizinische Klinik I (Gastroenterologie,
Hepatologie, Stoffwechsel- und Infektionskrankheiten, Psychosomatik),
Klinikum Saarbrücken gGmbH, Winterberg 1, 66119, Saarbrücken, Deutschland,

PMID: 17551757

INTRODUCTION: The clinical experience that subjects claiming retirement
pension tend to aggravate their symptoms in psychometric tests has not yet,
to our knowledge, been empirically tested.

METHODS: Pain intensities and the summary score of the Pain Disability
Index (PDI) of 83 consecutive subjects diagnosed with fibromyalgia syndrome
(FMS) claiming retirement pension in medical assessment for the German
Social Court were compared with 43 consecutive patients diagnosed with FMS
of an outpatient pain department who did not claim retirement pension.
Moreover, the relative predictive value of claiming retirement pension
compared to other potential sociodemographic and clinical predictors of
pain intensity and self-assessed disability was determined.

RESULTS: Subjects claiming retirement pension within the context of medical
testimony stated higher pain intensities and disabilities than patients who
did not claim retirement pension (P<0.01 in all cases). Claiming disability
pension was an independent predictor of minimum pain intensity (r(2)=0.10,
P=0.02), of maximum pain intensity (r(2)=0.16, P=0.002) and of the summary
score of the PDI (r(2)=0.08, P=0.008).

CONCLUSIONS: The association between claiming retirement pension and high
self-assessed pain and disability should be kept in mind in the context of
pain therapy as well of medical expertise.

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Date:    Thu, 7 Jun 2007 18:19:34 -0700
From:    Melissa O'Toole <m_otoole2@YAHOO.COM>
Subject: MED: Is pain a cause or symptom of depression?

>From the June 7, 2007 edition of HEALTHbeat, an electronic
publication of the Harvard School of Medicine:

Is pain a cause or symptom of depression?

Pain is depressing, and depression causes and intensifies pain. People with
chronic pain have three times the average risk of developing psychiatric
symptoms — usually mood or anxiety disorders — and depressed patients have
three times the average risk of developing chronic pain. When low energy,
insomnia, and hopelessness resulting from depression or anxiety perpetuate and
aggravate physical pain, it can be impossible to tell which came first or where
one leaves off and the other begins.

Pain slows recovery from depression, and depression makes pain more difficult
to treat. For example, depression may cause patients to drop out of pain
rehabilitation programs. So it often makes sense to treat both pain and
depression; that way they are more likely to recede together.
Brain pathways

Normally, the brain diverts signals of physical discomfort so that we can
concentrate on the external world. When this shut-off mechanism is impaired,
physical sensations like pain are more likely to become the center of
attention. Brain pathways that handle pain signals use some of the same
chemical messengers (neurotransmitters) that are involved in the regulation of

When these pathways start to malfunction, pain is intensified, along with
sadness, hopelessness, and anxiety. And as chronic pain, like chronic
depression, takes root in the nervous system, the problem perpetuates itself.
The mysterious disorder known as fibromyalgia may be an example of this kind of
biological process linking pain and depression. Its symptoms include widespread
muscle pain and tenderness at certain pressure points, with no evidence of
tissue damage. Brain scans of people with fibromyalgia show highly active pain
centers, and the disorder is more closely associated with depression than most
other medical conditions. This leads some experts to speculate that the pain
sensitivity and emotional storminess of fibromyalgia result from faulty brain

Treating pain and depression in combination

In pain rehabilitation centers, specialists treat both problems together, often
with the same techniques, including progressive muscle relaxation, hypnosis,
and meditation. Physicians prescribe standard pain medications — acetaminophen,
aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs),
and in severe cases, opiates — along with a variety of psychiatric drugs.
Almost every drug used in psychiatry can serve as a pain medication. By
relieving anxiety, fatigue, or insomnia, these medications also ease related
pain. In addition, antidepressants — sometimes given in low doses — may relieve
pain in ways unrelated to their antidepressant effects.

Exercise and psychotherapy are commonly used at pain centers, too. Physical
therapists help patients perform exercises not only to break the vicious cycle
of pain and immobility, but also to help relieve depression. Cognitive and
behavioral therapies teach pain patients how to avoid fearful anticipation,
banish discouraging thoughts, and adjust everyday routines to ward off physical
and emotional suffering. Psychotherapy helps demoralized patients and their
families tell their stories and describe the experience of pain in its relation
to other problems in their lives.

[Return to top]


Date:    Fri, 8 Jun 2007 14:52:40 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: The impact of a 4-hour sleep delay on slow wave activity  in twins discordant for chronic fatigue syndrome

The impact of a 4-hour sleep delay on slow wave activity in twins
discordant for chronic fatigue syndrome

Journal: Sleep. 2007 May 1;30(5):657-62.

Authors: Roseanne Armitage, PhD [1]; Carol Landis, DNSc, RN [2]; Robert
Hoffmann, PhD [1]; Martha Lentz, PhD, RN [2]; Nathaniel F. Watson, MD [3];
Jack Goldberg, PhD [4]; Dedra Buchwald, MD [5]

[1] Department of Psychiatry, University of Michigan, Ann Arbor, MI
<rosearmi med.umich.edu>
[2] Departments of Biobehavioral Nursing and Health Systems,
[3] Neurology,
[4] Epidemiology, and
[5] Medicine, University of Washington, Seattle, WA,
Work conducted at the University of Washington, Seattle WA.

Affiliation: Department of Psychiatry, University of Michigan, Ann Arbor,
MI 48105, USA. <rosearmi med.umich.edu>

NLM Citation: PMID: 17552382

OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with altered
amounts of slow wave sleep, which could reflect reduced delta
electroencephalograph (EEG) activity and impaired sleep regulation. To
evaluate this hypothesis, we examined the response to a sleep regulatory
challenge in CFS.

DESIGN: The first of 3 consecutive nights of study served as laboratory
adaptation. Baseline sleep was assessed on the second night. On the third
night, bedtime was delayed by 4 hours, followed by recovery sleep. Total
available sleep time was held constant on all nights.

SETTING: A research sleep laboratory. PARTICIPANTS: 13 pairs of monozygotic
twins discordant for CFS.


MEASUREMENTS AND RESULTS: Power spectral analysis quantified slow wave
activity (SWA) in the 0.5-3.9 Hz band in successive NREM periods (stage 2,
3, or 4) on each night. To ensure comparability, analyses were restricted
to the first 4 NREM periods on each night. Data were coded for NREM period
and twin pair. Repeated-measures analysis of variance (ANOVA) contrasted
sleep delay effects across NREM periods between twin pairs. A second ANOVA
calculated the SWA in each NREM period in recovery sleep relative to
baseline SWA. The 2 groups of twins were similar on baseline SWA power.
After sleep delay, CFS twins exhibited significantly less SWA power in the
first NREM period of recovery sleep and accumulated a smaller percentage of
SWA in the first NREM period than their co-twins.

CONCLUSIONS: CFS is associated with a blunted SWA response to sleep
challenge, suggesting that the basic sleep drive and homeostatic response
are impaired.

[Return to top]


Date:    Fri, 8 Jun 2007 14:58:58 -0400
From:    "Bernice A. Melsky" <bernicemelsky@VERIZON.NET>
Subject: RES: A closer look at pain and hepatitis C: Preliminary data  from a veteran population

A closer look at pain and hepatitis C: Preliminary data from a veteran

J Rehabil Res Dev. 2007;44(2):231-44.

Silberbogen AK, Janke EA, Hebenstreit C.

VA Boston Healthcare System, Psychology Service (116B), 150 South
Huntington Avenue, Boston, MA 02130. amy.silberbogen@va.gov.

PMID: 17551875

An association between the hepatitis C virus (HCV) and various pain
diagnoses, including arthritis, fibromyalgia, and peripheral neuropathy,
has been reported. In this article, we review the literature on the
relationship between HCV and pain, highlighting current knowledge as well
as methodological issues that exist in many studies.

We also present preliminary findings from a survey conducted at two
Department of Veterans Affairs facilities to assess the scope and impact of
pain on functioning in veterans with HCV.

Our results indicate that pain is very prevalent within this population and
that HCV-positive veterans who experience persistent pain have significant
depressive symptoms and engage in high-risk behaviors, such as cigarette
smoking and alcohol use.

Finally, we draw upon our review and preliminary results to propose areas
of future rehabilitative research and to address the implications for
clinicians working with patients with comorbid HCV and pain.

[Return to top]


Date:    Sat, 9 Jun 2007 04:31:20 +0200
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: med: ME is a physical condition


Send an Email for free membership
       >>>> Help ME Circle  <<<<
 >>>>       9 June 2007       <<<<
Editorship : j.van.roijen chello.nl
Outgoing mail scanned by Norton AV

From: Stephen Ralph <stephen.e.ralph btinternet.com>


Disability Now, June 2007

Health News (p 13)

'ME is a physical condition'

Campaigners have welcomed new research that appears to
show that ME (myalgic encephalomyelitis) is a physical and not
a psychiatric condition.

The new definition, compiled by ME expert Dr Byron Hyde at the
Nightingale Research Foundation in Canada, separates ME
from chronic fatigue syndrome (CFS) and defines ME as a brain

ME is estimated to affect 250,000 people in the UK, around 10
per cent of whom are children.

Symptoms include loss of balance and memory, difficulties
speaking and thinking and abnormal sensory perception.
Inappropriate treatment can lead to pateints experiencing
seizures and paralysis and some may need to be tube-fed.

Jane Colby, executive director of The Young ME Sufferers Trust
(YMEST), who helped compile the new definition, said: "We
desperately need a testable definition which can show up the
serious physical disabilities that these children have.

"Viral damage to the brain is behind this illness and
the Nightingale definition reveals the pattern of damage

She added: "You will never get proper diagnosis and treatment
[of ME] until it is removed from the umbrella term of CFS."

For more information, contact the Trust: tel 01245 401080 or
visit:     www.tymestrust.org

Shannen Dabson, 12, an advocate of The Young ME Sufferers
Trust, with her Tymes Trustcard, which helps explain her
condition to school staff.

Jane Colby
Executive Director
The Young ME Sufferers Trust
PO Box 4347
Stock  Ingatestone
Essex  CM4 9TE

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Date:    Sat, 9 Jun 2007 10:14:49 -0400
From:    "John Herd <johnherd JOHNHERD.COM> [via Co-Cure Moderators]
Subject: NOT,RES:Is the latest CDC prevalence figure including everything, including the kitchen sink?

Is the latest CDC prevalence figure including everything including
the kitchen sink?

by John Herd
johnherd johnherd.com

In the CDC's recent article on the prevalence of CFS (1) the CDC
estimates that 2.54% of people between the age of 18 and 59 years
have CFS.

As Dr. Peter White comments in his editorial (2) that translates to
7.5 million afflicted Americans. [And that does not include
adolescents afflicted].  Dr. White goes on to point out that the
CDC's latest prevalence estimate represents a six to ten fold
increase from the CDC's previous prevalence estimate.

What causes such a huge increase?

The answer most likely is the methods of selection, the CDC's use of
a modified case definition and the CDC touted new diagnostic tools
being used.

In a November 2006 question and answer interview on Essential Science
Indicators' web site (3) Dr. Reeves states, "Research has been
constrained by ambiguities in the case definition. When this happens
it is difficult to compare different findings because different
subgroups of patients have been studied. In essence, one investigator
is studying apples, the next oranges." Later in the interview he
claims that because of an improved CFS diagnostic criteria with
"comparable measures" "investigators can now compare apples to

It seems that with the CDC new 7.5 million Americans afflicted
figure, that they've stepped backwards to not looking at apples and
oranges, but the whole food group.

Dr. White appears to have similar concern about the CDC's protocols
and findings in their latest research. He notes "there were important
differences in the method of ascertainment used in the Georgia study
that may help to explain the greater prevalence" with "different
initial screening question". "Instead of asking whether a household
member was suffering from 'fatigue', as previously done, the
screening question asked about being 'unwell'"...

Next Dr. white speculates whether "comorbid psychiatric conditions
may have inflated the [CDC's latest] prevalence." In an English study
of ME/CFS, when subjects with comorbid psychiatric conditions were
excluded the prevalence figure dropped by 80%.

To be fair there is a vast gray zone in which researchers of ME/CFS
have had difficult with the subject of identifying between those whom
have secondary (reactive) psychological difficulties from the many
impacts of having ME/CFS, the actual apples, and those whom have
primary psychiatric conditions, some of the oranges.

So is the CDC in actuality taking an accuracy step backward in the
research of ME/CFS?

It seems so since their newest possible 7.5 million prevalence figure
may be combining not just apples and oranges but the whole food group.


1. William C. Reeves, James F. Jones, Elizabeth Maloney, Christine
Heim, David C. Hoaglin, Roumiana S. Boneva, Marjorie Morrissey,
Rebecca Devlin, Prevalence of Chronic Fatigue Syndrome in
Metropolitan, Urban, and Rural Georgia, Population Health Metrics,

2. Peter D White, How common is chronic fatigue syndrome; how long is
a piece of string?,  Population Health Metrics 2007, 5:6
doi:10.1186/1478-7954-5-6, www.pophealthmetrics.com

3. Dr. William Reeves, William C. Reeves answers a few questions
about this month's fast moving front in the field of Pharmacology &
Toxicology, Essential Science Indicators, URL:

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Date:    Sat, 9 Jun 2007 13:34:41 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia

Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural

Journal: Population Health Metrics 2007, 5:5     doi:10.1186/1478-7954-5-5

Authors: William C. Reeves [1,*], James F. Jones [1], Elizabeth Maloney
[1], Christine Heim [2], David C. Hoaglin [3], Roumiana S. Boneva [1],
Marjorie Morrissey [4], Rebecca Devlin [4]

[1] Chronic Viral Diseases Branch, Coordinating Center for Infectious
Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
[2] Department of Psychiatry & Behavioral Sciences, Emory University School
of Medicine, Atlanta, GA, USA.
[3] Abt Associates Inc, Cambridge, MA, USA,
[4] Abt Associates Inc, Chicago, IL, USA.

Published 8 June 2007

Abstract (provisional)

Chronic fatigue syndrome (CFS) is a debilitating illness with no known
cause or effective therapy. Population-based epidemiologic data on CFS
prevalence are critical to put CFS in a realistic context for public health
officials and others responsible for allocating resources.

Based on a random-digit dialing survey we ascertained CFS cases and
controls to estimate the prevalence of CFS in metropolitan, urban, and
rural populations of Georgia. This report focuses on the 5,623 of 19,381
respondents ages 18 to 59 years old. Fatigued (2,438), randomly selected
unwell not fatigued (1,429) and randomly selected well (1,756) respondents
completed telephone questionnaires concerning fatigue, other symptoms, and
medical history. Subsets of those identified by interview as having
CFS-like illness (292), chronic unwellness which was not CFS-like
(268--randomly selected), and well subjects (223, matched to those with
CFS-like illness on sex, race, and age) completed a clinical evaluation.

We estimated that 2.54% of persons 18 to 59 years of age suffered from CFS.
There were no significant differences in prevalence of CFS between
metropolitan, urban or rural populations or between white and black
residents of the three regions. However, there were significant differences
in female-to-male ratios of prevalence across the strata (metropolitan
female : male 11.2 : 1, urban 1.7 : 1, rural 0.8 : 1).

We estimated that 2.54% of the Georgia population suffers from CFS, which
is 6 to 10 fold higher than previous population-based estimates in other
geographic areas. These differences may reflect broader screening criteria
and differences in the application of the case definition, however we
cannot exclude the possibility that CFS prevalence may be higher in Georgia
than other areas where it has been measured. Although the study did not
identify differences in overall prevalence between metropolitan, urban, and
rural Georgia populations, it did suggest the need for additional
stratified analyses by geographic strata.

[The complete article is available as a provisional PDF at
http://www.pophealthmetrics.com/content/pdf/1478-7954-5-5.pdf .
The fully formatted PDF and HTML versions are in production.]

[Return to top]


Date:    Sat, 9 Jun 2007 13:48:30 -0400
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: How common is chronic fatigue syndrome; how long is a piece of string?

How common is chronic fatigue syndrome; how long is a piece of string?

Journal: Population Health Metrics 2007, 5:6 doi:10.1186/1478-7954-5-6

Author: Peter D White

Affiliation: Centre for Psychiatry, Wolfson Institute of Preventive Medicine, Barts and the London,
Queen Mary School of Medicine and Dentistry, London, UK, EC1A 7BE
Email: <p.d.white qmul.ac.uk>

Submission date 8 May 2007
Acceptance date 8 June 2007
Publication date 8 June 2007
Article URL http://www.pophealthmetrics.com/content/5/1/6

Commentary on
Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia
William C Reeves, James F Jones, Elizabeth Maloney, Christine Heim, David C Hoaglin,
Roumiana S Boneva, Marjorie Morrissey and Rebecca Devlin

One of the most difficult tasks in medicine is to accurately measure how common
illnesses are. Why do we do it? Justifications include being able to plan health care and
public health priorities, as well as highlighting specific diseases for extra funding for both
health care and research. Yet the jobbing physician at the sharp edge of clinical practice
cares little about the exact prevalence of a disease or illness, since this is all too obvious
from the frequency of the problems presented by patients who come through the door.
How do you measure a syndrome?

If the disease in question has no biological marker and is difficult to define clinically, the
problem of working out the accurate prevalence becomes esoteric. Chronic fatigue
syndrome (CFS) is just such an illness. It has as many synonyms as putative causes,
being also called myalgic encephalomyelitis, chronic immune dysfunction syndrome, and
post-viral fatigue syndrome, amongst others. Since fatigue is one of the most common
symptoms reported by patients in general, delineating a specific syndrome with fatigue as
a central feature risks arbitrary decisions about ascertainment. Do we categorise the
syndrome on the basis of the severity of fatigue, the number of associated symptoms, or
the severity of the resultant disability? Even measuring the consequent disability gives us
problems since there are only weak correlations between subjective and objective
observations [1]. It is therefore no great surprise that half of all doctors do not even
believe it exists [2].

And yet, patients and their organisations constantly criticize doctors both for not
believing in the existence of CFS and for not taking patients seriously. Even politicians
seem to take the problem more seriously than some doctors do. This may be as much to
do with successful lobbying as the economic costs of CFS, which have been estimated as
$9 billion per annum just for lost productivity in the USA [3]. Doctors don’t understand
things they can’t see or measure, and patients mistrust doctors who don’t understand
them. We are in a conundrum.

One way forward
The Centers for Disease Control and Prevention (CDC) in the United States of America
are one of the few health care agencies who do take CFS seriously, to the extent of
supporting a $4 million public education campaign, which started last year [4]. They have
also led the way in providing operationalised criteria in order to standardize the diagnosis
of CFS [5]. Their latest research programme has been based on a large survey of the adult
(18-59 years old) population of the state of Georgia, USA, in order to better understand
the epidemiology and etiology of CFS [6]. Their previous study of prevalence, in
Wichita, Kansas, suggested a prevalence of 0.24% [7]. Another independent population
survey in Chicago suggested a prevalence of 0.42% [8]. The CDC has now repeated and
extended the Wichita study in Georgia, and found a prevalence of between six and ten
times greater, with 2.5% of the population suffering from CFS [6]. If this prevalence was
both accurate and representative of the USA as a whole, this would suggest that some 7.5
million Americans were sufferers, compared to the previous estimates of 0.7 to 1.2

A cautious interpretation
Could this really be true? The authors are sensibly cautious in their interpretations, and
point out the uncertainties inherent within the study. There are three main reasons why
we should be cautious about interpretation and generalizing from this finding. Compared
to previous studies, there were important differences in the method of ascertainment used
in the Georgia study that may help to explain the greater prevalence. Most importantly,
the Georgia study used a different initial screening question. Instead of asking whether a
household member was suffering from “fatigue”, as previously done, the screening
question asked about being “unwell”, by which was meant having one or more of the
following symptoms for a month or more: “fatigue, cognitive impairment, unrefreshing
sleep, muscle pain, joint pain, sore throat, tender lymph nodes, or headache” (all being
likely symptoms of CFS). The authors suggested that this stratagem picked up an extra
11.5% of CFS cases. A strength of the Georgia survey was the use of standardised
measures of symptoms and disability. However in order to count someone as fatigued -
the central criterion for a diagnosis of CFS - individuals only needed to score the median
or more of the well population, either for fatigue or inactivity. In a previous study, the
same authors found that using such standardised measures picked up three times as many
cases of CFS than verbatim enquiries [9]. These methodological differences mean it is
not possible to directly compare the prevalence of CFS in Georgia with previous studies.

Comorbid psychiatric conditions may have inflated the prevalence. A previous study
found an equally high point prevalence of CFS (2.6%), by surveying United Kingdom
primary care patients [10]. However, when those patients who also had a comorbid
psychiatric disorder were excluded, the prevalence fell to 0.5%. Although it will be
important to publish the prevalence of comorbid psychiatric disorders in the Georgian
survey, the argument can still be put that these comorbid psychiatric disorders were
secondary to having chronic ill-health, rather than the primary and explanatory condition.
The current design cannot determine the direction of causality, although previous
longitudinal studies suggest that psychiatric ill health can both follow and precede CFS
[11, 12].

Georgia may not be representative of the USA as a whole. For instance, we do not know
the body mass index (BMI) of the Georgian sample. The Wichita sample of CFS cases
contained 43% of subjects with a BMI of 30 or over, representing significant obesity [9].
This compares with 20% in the USA as a whole [13]. Since obesity is associated with
fatigue [14], a similar proportion in Georgia might inflate the prevalence of CFS.

To conclude
What can we conclude from this very large survey? Although methodological issues may
help to explain the high prevalence of CFS found in this study, the argument can still be
made that the prevalence of CFS is greater than previously thought [10, 15]. CFS is at
least as common in ethnic minorities in the USA as in the ethnic Caucasian majority; a
welcome replication of previous studies [8]. CFS is not an exclusively white syndrome.
Social issues may help to explain why women suffer CFS more than men. But perhaps
the most important conclusion is that there were about twice as many people in Georgia
who were unwell with fatigue, who did not meet the criteria for CFS. Our current criteria
for diagnosing CFS are arbitrary [16], and we need to widen the net to capture all those
people who become so chronically tired and unwell that they can’t live their lives to their
full potential. The jobbing physician does not close the door on those who don’t meet

Conflict of interest
Professor White has collaborated with some of the authors in research into CFS.

1. Afari N, Buchwald D: Chronic fatigue syndrome: a review. Am J Psychiatry 2003,
2. Thomas MA, Smith AP: Primary healthcare provision and chronic fatigue
syndrome: a survey of patients’ and General Practitioners’ beliefs. BMC Fam
Pract 2005, 6:49.
3. Reynolds KJ, Vernon SD, Bouchery E, Reeves WC: The economic impact of
chronic fatigue syndrome. Cost Effectiveness Resource Allocation 2004, 2:4.
4. Centers for Disease Control and Prevention: Chronic Fatigue Syndrome Awareness
campaign. 2006 [http://www.cdc.gov/cfs/awareness.htm]
5. Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B,
White PD, Nisenbaum R, Unger ER: Identification of ambiguities in the 1994
chronic fatigue syndrome research case definition and recommendations for
resolution. BMC Health Services Research 2003, 3:25.
6. Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva1 RS, Morrissey M,
Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and
rural Georgia. Population Metrics (this issue).
7. 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.
8. Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR,
McCready W, Huang CF, Plioplys S: A community-based study of chronic fatigue
syndrome. Arch Int Med 1999, 159:2129-2137.
9. 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 Medicine 2005,
10. Wessely S, Chalder T, Hirsch S, Wallace P, Wright D: The prevalence and
morbidity of chronic fatigue and chronic fatigue syndrome: a prospective
primary care study. Am J Public Health 1997, 87:14491455.
11. Hickie I, Koschera A, Hadzi-Pavlovic D, Bennett B, Lloyd A: The temporal
stability and co-morbidity of prolonged fatigue: A longitudinal study in primary
care. Psychol Med 1999, 29:855861.
12. van der Linden G, Chalder T, Hickie I, Koschera A, Sham P, Wessely S: Fatigue and
psychiatric disorder: different or the same? Psychol Med 1999, 29:863868.
13. Mokdad AH, Bowman BA, Ford ES, Vinicor F, Marks JS, Koplan SJ: The
continuing epidemics of obesity and diabetes in the United States. JAMA 2001,
14. Lim W, Hong S, Nelesen R, Dimsdale JE: The association of obesity, cytokine
levels, and depressive symptoms with diverse measures of fatigue in healthy
subjects. Arch Intern Med 2005, 165:910-915.
15. Evengård B, Jacks A, Pedersen NL, Sullivan PF: The epidemiology of chronic
fatigue in the Swedish twin registry. Psychol Med 2005, 35:1327-1336.
16. Sullivan PF, Pedersen NL, Jacks A, Evengård B: Chronic fatigue in a population
sample: definitions and heterogeneity. Psychol Med 2005, 35:1337-1348.

[Return to top]


Date:    Sun, 10 Jun 2007 12:43:47 -0700
From:    "Jill McLaughlin <jillmclaughlin comcast.net>.........via Co-Cure Moderators"
Subject: NOT, RES: Problems with the New CDC CFS Prevalence Estimate - Leonard Jason, Ph.D., DePaul University

The following has been posted to the IACFS/ME website.

Jill McLaughlin


At the last IACFS/ME Board meeting in Salt Lake City, we were informed that an
article would soon be published concerning the CDC's new prevalence estimates
indicating six to ten times more individuals in the US had CFS. On scientific
grounds, I had several concerns with these estimates, and after I brought up
my concerns, the Board asked if I might post my reactions on the IACFS/ME
I agreed to do this, and my opinions are below and do not represent the views
of the IACFS/ME.

Leonard Jason, Ph.D., DePaul University


Problems with the New CDC CFS Prevalence Estimates

Leonard Jason, Ph.D., DePaul University

By the early to mid 1990s, the general consensus was that CFS was a relatively
rare disorder affecting primarily white, middle-class women. Prevalence
estimates of this illness from the CDC ranged from .002% to .0073% (Gunn et
al., 1993) suggesting that there were less than 20,000 individuals in the U.S. with
this illness. Toward the late 1990s, Jason, Richman and colleagues (1999) used
more rigorous community-based samples and found that approximately .42% of the
sample was determined to have CFS, or approximately 800,000 people from the US
(Jason, Richman et al., 1999). These overall prevalence estimates were later
corroborated by the CDC in another community-based sample (Reyes et al., 2003
estimated the CFS prevalence to be .24%).

In Great Britain, community estimates of CFS rates were estimated to be 2.6% (or
2.6 cases among every 100 people; Wessely et al., 1997).  One needs to examine a
broadened CFS case definition to understand these CFS rates in Great Britain,
and if these rates were applied to the US, there would be about 4 million people
in the US with CFS. Wessely et al. (1997) indicated that of the 2.6% with CFS,
psychological disorders were absent in only .5%. Individuals diagnosed with CFS
in this epidemiologic study were subsequently compared to a sample of people
with CFS who had been diagnosed from a hospital unit (Euba, Chalder, Deale &
Wessely, 1995). Of the community sample, 59% felt their illness might be due to
psychological or psychosocial causes compared to 7% for the hospital sample. In
Wessely et al.'s (1996) community based sample, only 64% had sleep disturbances
and 63% had postexertional malaise.  These percentages are rather low, as both
symptoms are critical features of CFS. These findings might provide a clue as to
why Wessely and colleagues found CFS prevalence rates that were appreciably higher
than those found by a second generation of CFS epidemiologic studies in the United
States (Jason et al., 1999; Reyes et al., 2003).

It is of interest that the Great Britain CFS rates are within the range of
several mood disorders. Mood disorders are the most prevalent psychiatric
disorders after anxiety disorders: for major depressive episode, the one-month
prevalence is 2.2%, and lifetime prevalence is 5.8% (Regier et al., 1988). Major
Depressive Disorder is an example of a primary psychiatric disorder, which has
some overlapping symptoms with CFS. Fatigue, sleep disturbances and poor
concentration occur in both depression and CFS.  Some patients with Major
Depressive Disorder also have chronic fatigue and other symptoms that can occur
with depression (e.g., unrefreshing sleep, joint pain, muscle pain, impairment
in concentration).  Fatigue and these four symptoms also are defining criteria
for CFS, based on the Fukuda et al. (1994) criteria. It is possible that some
patients with a primary affective disorder could be misdiagnosed as having CFS.
While fatigue is the principal feature of CFS, fatigue does not assume equal
prominence in depression (Friedberg & Jason, 1998; Komaroff et al.,
1996).  Several CFS symptoms, including prolonged fatigue after physical
exertion, night sweats, sore throats, and swollen lymph nodes, are not
commonly found in depression. Moreover, illness onset with CFS is often sudden,
occurring over a few hours or days, whereas primary depression generally shows a more
gradual onset. Some individuals with CFS might have had psychiatric problems
before and/or after CFS onset and yet, other individuals may only have primary
psychiatric disorders with prominent somatic features. Including the latter type
of patients in the current CFS case definition could confound the interpretation
of epidemiologic and treatment studies.

The CDC has recently released findings from a community-based epidemiologic
study that occurred in Georgia (Reeves, Jones, Maloney, Heim, Hoaglin, Boneva,
Morrissey, & Devlin, 2007). While the prior CFS prevalence rate was estimated
to be .24% in  Wichita, Kansas (Reyes et al., 2003), their new estimated prevalence
rates were reported to be considerably higher with 2.54% (remarkably similar to
the 2.6% rate in Great Britain, Wessely et al., 1997). The CDC now estimates
that six to ten times more people have this illness than their previous reports
in the US.  In this study, the authors screened for persons who reported
fatigue, problems with memory/concentration, unrefreshing sleep or pain rather
than simply focusing on the single symptom of fatigue, and the authors indicated
that these criteria increased the identified cases by 13%. In addition, the
authors used what they referred to as standardized criteria to identify cases,
and below we evaluate this new empirical CDC case def inition of CFS. To meet the
new CFS criteria, individuals need to meet criteria on symptoms, level of disability
and degree of fatigue, and each of these areas is described below.

As one part of the standardized CDC criteria, the Symptom Inventory is used to
operationalize the symptoms of CFS (Wagner et al., 2005). For each of 8 critical
Fukuda et al. definitional symptoms, patients are asked to rate the symptom on
perceived frequency (1 = a little of the time; 2 = some of the time; 3 = most of
the time; 4 = all of the time) and severity or intensity of symptoms (the
ratings were transformed to the following scale: 1 = mild, 2.5 = moderate, 4 =
severe). The frequency and severity scores were multiplied, and the sums for the
8 critical Fukuda et al. (1994) symptoms were summed. Even with summed scores
for the empirical case definition needing to be greater or equal to 25 (Reeves
et al., 2005), the overall level of symptoms seems relatively low for patients
with classic CFS symptoms (the criterion would be met if an individual rated
only 2 symptoms as occurring all the time, and one was of moderate and the other
of severe severity). In addition, the 8 case definition symptoms were based on a
time period comprising the last month compared to what is specified in the Fukuda
et al. (1994) criteria, which states that:
"There needs to be the concurrent occurrence of 4 or more of the following
symptoms, and all must be persistent or recurrent during 6 or more months of the
illness and not predate the fatigue."

This change in the case definition has the potential of including more individuals.

Also, part of this new CDC empirical CFS criteria is the use of the Medical
Outcomes Survey Short Form-36 (SF-36) to assess substantial reductions in
occupational, educational, social or recreational activities. Using the SF-36,
these criteria were defined as scores lower that the 25th percentile on the
physical function, role physical function, social function, or role emotional.
Because the individual only needs to meet one of these areas to meet the CFS
criteria, the individual might not have any reductions in key areas of physical
functioning, and only impairment in role emotional areas (e.g., problems with
work or other daily activities as a result of emotional problems), and then the
person could meet disability criteria for CFS. Ware, Snow, and Kosinsi (2000)
found that mean for  role emotional for a clinical depression group was 38.9,
indicating that almost all those with clinical depression would meet criteria
for being within the lower 25th percentile on this scale (which was a score of
less than or equal to 66.7).  In Peter White's Dec. 3. 2006
review (http://www.biomedcentral.com/imedia/1083914155124266_comment.pdf) of
Reeves et al.'s (2007) article, he states: The use of physical function, role
physical and social function sub-scales is consistent with the International
Study criteria for CFS, which states that the illness "results in substantial
reduction in previous levels of occupational, educational, social, or personal
activities." (Reeves et al, 2003). The use of role emotional is not, since it
specifically asks about change in function "as a result of any emotional
problems". And later White states that "In order to make these important
criteria consistent with other studies, I think the authors need to re-analyse
their data, omitting this sub-scale."

The last instrument used with the new CDC empirical CFS criteria is the
Multidimensional Fatigue Inventory (MFI) (Smets, Garssen,  Bonke, & DeHaes,
1995).  Severe fatigue was defined as greater than or equal to 13 on the MFI
general fatigue or greater than or equal to 10 on the reduced activity. In
Peter White's Dec. 3, 2006 review of the Reeves et al.'s (2007) article
(http://www.biomedcentral.com/imedia/1083914155124266_comment.pdf), he wrote:
"This means that it would be possible to meet the fatigue criterion without
significant fatigue; i.e. with reduced activity alone. This is inconsistent with
the international study criteria for CFS." In support of this criticism by
White, I believe that the general activity items refer to issues that a person
with depression might easily endorse. If a person indicated that the following
two items were entirely true: "I get little done", "I think I do very little in
a day"; they would meet the fatigue criterion for the new CDC empirical cas
e definition.  Our group is currently studying individuals with major depressive
disorder versus those with CFS, and we are finding individuals with a purely
affective disorder being classified as having CFS with this new empirical case
definition (Najar, Porter, & Jason, 2007).

It is important to better understand the two CDC community based studies (Reyes
et al., 2003; Reeves et al., 2007), and this is particularly important as their
CFS estimated prevalence rates have changed so dramatically. Of the individuals
who were identified as having CFS during the first study (Reyes et al., 2003)
that occurred over a three year period (1997 through 2000), 58 were brought back
for a two day inpatient study that occurred from December 2002 to July 2003, and
only 16 (28% of the original group diagnosed with CFS) had a current consistent
diagnosis of CFS, using traditional methods of making this diagnosis. When these
investigators employed an empirically derived system (that was used in deriving
the higher prevalence rates of 2.54% in the Georgia community based study), 43
rather than 16 individuals who had been traditionally diagnosed as having CFS
met this new system. Clearly, this newly developed empirical system brings in
many additional people to a CFS diagnosis. It is very possible that this new
empirical classification does identify a group of individuals with high levels
of fatigue, impairment, and symptoms, but it might also be identifying a group
with high chronic distress and illness, rather than CFS as a unique disorder.

It is at least possible that the 2.54% to 2.6% CFS rates both the United States
and Great Britain are due to a broadening of the case definition and possible
inclusion of cases with primary psychiatric conditions. Some CFS investigators
would not see this as a confounding problem because they believe that high rates
of psychiatric comorbidity indicate that CFS is mainly a psychiatric disorder
(Abbey, 1993). CFS and depression are two distinct disorders, however, even if
they share a number of common symptoms. Most importantly, the erroneous
inclusion of people with primary psychiatric conditions in CFS samples will have
detrimental consequences for the interpretation of both epidemiologic and
treatment efficacy findings.

Reeves et al. (2005) claims that the empirical definition identifies people with
CFS in a more precise manner than can occur in the more traditional way. It is
primarily the use of this new empirical case definition that has lead to the
increase in CFS prevalence rates in the United States.  In their use of the
empirical case definition, several changes occurred to what had been previously
recommended by an international expert committee (Reeves et al., 2003) of
recommendations for the case definition of Fukuda et al. (1994). First, rather
than excluding those with depressive disorder with melancholic features, only
those with a current condition were excluded as opposed to what had been
recommended.  Of interest, of those 16 within the Reyes et al. (2003) study who
had been classified with CFS using the more traditional methods, 6 had a past
history of major depressive disorder with melancholic features (Reeves et al.,
2005); and it is unclear how many of those 43 who were diagnosed using the
empiric case definition had past depressive disorder with melancholic features. 
These individuals should have been excluded, and by including them, the
broadening of the case definition has the potential to bring into the CFS
category those with a primary psychiatric condition. More importantly, there
was little agreement between the empirical method of classifying individuals
with the more traditional method of comparing whether an individual met the
case definition on their critical symptoms. Rather than assuming that this
might be a problem with the CFS empirical case definition, they concluded
that the more traditional way of diagnosing patients was flawed.

As an example of this problem, one individual who was classified as being in
remission for CFS using the traditional method was diagnosed with current CFS
using the CDC's empirical approach.

Papers are now appearing in the literature using this empirical case definition
of CFS, and many have received considerable media attention. For example, Heim
et al. (2006) recently used this new empiric case definition and the Wichita
study to explore the influence of early adverse experience on risk for
developing CFS. The authors concluded that childhood trauma is an important risk
factor for CFS. In fact, among those with CFS, 62.8% had some type of early
abuse. This is in contrast to findings reported by Taylor and Jason (2002) who
found prevalence rates of sexual and physical abuse history among individuals
with CFS were comparable with those found in individuals with other conditions
involving chronic fatigue, including medically based conditions. Relative to
those with CFS who report such history, most individuals with CFS did not
report histories of interpersonal abuse.

The Reeves et al. (2005) article clearly used instruments (such as the SF-36)
to make diagnostic decisions, rather than encompassing more specific criteria
involving aspects of the illness (for example, whether with rest, all symptoms
disappear). Given the high variability in symptom severity among persons with
fatigue, standardized procedures should be employed for determining whether or
not a particular symptom is severe enough to qualify as one of the symptoms
required for the diagnosis of fatigue. But one needs to be extremely careful
about deciding whether standardized instruments and scores need to include
contextual issues, and often they do not.  For example, if a patient endorses
a symptom such as post-exertional malaise, standardized questions should include
duration, frequency, and severity of the symptom including onset, pattern,
intensity, and associated factors (see Hawk et al. 2007). Clinical judgment,
which has been used in most past studies to diagnoses CFS, remain
s an important role even for diseases like lupus, which use a combination of
clinical judgment, patient report, and objective measures to come up with a
diagnosis. This currently is not occurring with the CFS empirical case
definition developed by the CDC.

Some researchers have posited that FMS, CFS, and IBS can be considered
functional somatic syndromes (Barsky & Borus, 1999). Functional somatic
syndromes are characterized by diffuse, poorly-defined symptoms that cause
significant subjective distress and disability, cannot be corroborated by
consistent documentation of organic pathology, and are highly prevalent even in
healthy, non-patient groups (Barsky & Borus, 1999). Accurate measurement and
classification of CFS, FMS and IBS is imperative when evaluating the diagnostic
validity of controversial disease entities alternatively labeled, 'functional
somatic syndromes'. For example, results of a study by Taylor, Jason and Schoeny
(2001) provided support for distinctions between the five conditions of FMS,
CFS, somatic depression, somatic anxiety, and IBS, but this will only occur when
using symptom criteria that matches actual diagnostic criteria for these
illnesses. Measurement that fails to capture the unique characteristics of th
ese illnesses might inaccurately conclude that only distress and unwellness
characterize these illnesses, thus inappropriately supporting a unitary
hypothetical construct called functional somatic syndromes. Ultimately, using
a broad or narrow definition of CFS will have important influences on CFS
epidemiologic findings, on rates of psychiatric comorbidity, and ultimately on
the likelihood of finding biological markers.


Abbey, S.E. (1993). Somatization, illness attribution and the sociocultural
psychiatry of chronic fatigue syndrome. In B.R. Bock & J. Whelan (Eds.),
Chronic Fatigue Syndrome. (pp. 238-261). New York: John Wiley & Sons.

Barsky AJ, & Borus JF (1999) Functional somatic syndromes. Annals of  Internal
Medicine,  130,  910-921.

Euba, R., Chalder, T., Deale, A., & Wessely, S. (1996). A comparison of the
characteristics of Chronic Fatigue Syndrome in primary and tertiary care.
British Journal of Psychiatry, 168, 121-126.

Friedberg, J.R., & Jason, L.A. (1998). Assessment and treatment of Chronic
Fatigue Syndrome. Washington, D.C.: American Psychological Association.

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, 953-959.

Gunn, W.J., Connell, D.B., & Randall, B. (1993). Epidemiology of chronic fatigue
syndrome: The Centers-for-Disease-Control study.  In B.R. Bock & J. Whelan
(Eds.), Chronic Fatigue Syndrome.  (pp. 83-101). New York: John Wiley & Sons.

Hawk, C., Jason, L.A., & Torres-Harding, S. (2007). Reliability of a chronic
fatigue syndrome questionnaire. Journal of Chronic Fatigue Syndrome, 13,

Heim, C., Wagner, D., Maloney, E., Papanicolauo, D.A., Solomon, L., Jones, J.F.,
Unger, E.R., & Reeves, W.C. (2006). Early adverse experience and risk for
chronic fatigue syndrome: Results from a population-based study. The Archives
of General Psychiatry, 63, 1258-1266.

Jason, L.A., Richman, J.A., Rademaker, A.W., Jordan, K.M., Plioplys, A.V.,
Taylor, R., et al. (1999). A community-based study of chronic fatigue syndrome.
Archives of Internal Medicine. 159, 2129-2137.

Komaroff, A.L., Fagioli, L.R., Geiger, A.M., Doolittle, T.H., Lee, J., Kornish,
R.J., Gleit, M.A., Guerriero, R.T. (1996). An examination of the working case
definition of Chronic Fatigue Syndrome. The American Journal of Medicine, 100,

Najar, N., Porter, N., & Jason, L.A. (2007, Jan.).  Evaluating the CDC new
case definition. Poster presented at the International Association of Chronic
Fatigue Syndrome, Ft. Lauderdale, Fl.

Reeves, W.C., Lloyd, A., Vernon,  S.D., Klimas, N., Jason, L., Bleijenberg, G.,
Evengard, B., White, P.D., Nisenbaum, R., Unger, E.R.(2003). Identification of
ambiguities in the 1994 chronic fatigue syndrome research case definition and
recommendations for resolution. BMC Health Services Research, 3, 25.

Reeves, W.C., Jones, J.J., Maloney, E., Heim, C., Hoaglin, D.C., Boneva, R.,
Morrissey, M., & Devlin, R. (2007). New study on the prevalence of CFS in
metro, urban and rural Georgia populations. Population Health Metrics 2007, 5:5

Reeves, W.C., Wagner, D.,  Nisenbaum, R.,  Jones, J.F., Gurbaxani, B., Solomon,
L., Papanicolaou, D., Unger, E.R., Vernon, S.D., &  Heim, C. (2005). Chronic
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http://www.biomedcentral.com/content/pdf/1741-7015-3-19.pdf )

Reyes, M., Nisenbaum, R., Hoaglin, D.C., Unger, E.R., Emmons, C., Randall, B.,
Stewart, G., Abbey, S., Jones, J. F., Gantz, N., Minden, S., & Reeves, W.C.
(2003) Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas.
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Regier, D.A., Boyd, J.H., Burke, J.D., Jr., Rae, D.S., Myers, J.K., Kramer, M.,
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Taylor, R.R., Jason, L.A., & Schoeny, M.E. (2001). Evaluating latent variable
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Mental Health, 10, 335-349.

Wagner, D., Nisenbaum, R., Heim, C., Jones, J.F., Unger, E.R., & Reeves, W.C.
(2005). Psychometric properties of the CDC Symptom Inventory for the Assessment
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The Lancet, 345, 1333-1338.

Copyright IACFS, 2007 All Rights Reserved

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Date:    Mon, 11 Jun 2007 12:22:35 -0400
From:    Co-Cure Moderator <ray@CO-CURE.ORG>
Subject: RES: Gabapentin (U.S. Brand Name: Neurontin) Shown Effective for Fibromyalgia Pain

U.S. Department of Health and Human Services
NIH News
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

FOR IMMEDIATE RELEASE: Monday, June 11, 2007

CONTACT: Ray Fleming, 301-496-8190, <e-mail: flemingr@mail.nih.gov>


New research supported by the National Institutes of Health's National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) shows
that the anticonvulsant medication gabapentin, which is used for certain
types of seizures, can be an effective treatment for the pain and other
symptoms associated with the common, often hard-to-treat chronic pain
disorder, fibromyalgia.

In the NIAMS-sponsored, randomized, double-blind clinical trial of 150
women (90 percent) and men with the condition, Lesley M. Arnold, M.D.,
director of the Women's Health Research Program at the University of
Cincinnati College of Medicine, and her colleagues found that those taking
gabapentin at dosages of 1,200 to 2,400 mg daily for 12 weeks displayed
significantly less pain than those taking placebo. Patients taking
gabapentin also reported significantly better sleep and less fatigue.  For
the majority of participants, the drug was well tolerated. The most common
side effects included dizziness and sedation, which were mild to moderate
in severity in most cases.

NIAMS Director Stephen I. Katz. M.D., Ph.D., remarked that "While
gabapentin does not have Food and Drug Administration approval for
fibromyalgia, I believe this study offers additional insight to physicians
considering the drug for their fibromyalgia patients. Fibromyalgia is a
debilitating condition for which current treatments are only modestly
effective, so a study such as this is potentially good news for people with
this common, painful condition."

Fibromyalgia is a chronic disorder characterized by chronic, widespread
muscle pain and tenderness, and is frequently accompanied by fatigue,
insomnia, depression, and anxiety. It affects three million to six million
Americans, mostly women, and can be disabling.

The precise cause of fibromyalgia in not known, but research suggests it is
related to a problem with the central nervous system's processing of pain.
As with some other chronic pain conditions, people with fibromyalgia often
develop a heightened response to stimuli, experiencing pain that would not
cause problems in other people. Yet, unlike many other pain syndromes,
there is no physical evidence of inflammation or central nervous system damage.

Although gabapentin has little, if any, effect on acute pain, it has shown
a robust effect on pain caused by a heightened response to stimuli related
to inflammation or nerve injury in animal models of chronic pain syndromes.
Researchers have suspected that it might have the same effect in people
with fibromyalgia. The new research, published in the April 2007 edition of
"Arthritis & Rheumatism", indicates the suspicions were correct.

Although the researchers cannot say with certainty how gabapentin helps
reduce pain, Dr. Arnold says one possible explanation involves the binding
of gabapentin to a specific subunit of voltage-gated calcium channels on
neurons.  "This binding reduces calcium flow into the nerve cell, which
reduces the release of some signaling molecules involved in pain
processing," she says.

How gabapentin improves sleep and other symptoms is less clear, and there
are probably different mechanisms involved in fibromyalgia
symptoms.  "Gabapentin improved sleep, which is an added benefit to
patients with fibromyalgia who often report unrefreshing or disrupted
sleep," Dr. Arnold says.

What is important is that people with fibromyalgia now have a potential new
treatment option for a condition with few effective treatments.  "Studies
like this give clinicians evidence-based information to guide their
treatment of patients," says Dr. Arnold.

The mission of the National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS), a part of the Department of Health and Human
Services' National Institutes of Health, is to support research into the
causes, treatment and prevention of arthritis and musculoskeletal and skin
diseases; the training of basic and clinical scientists to carry out this
research; and the dissemination of information on research progress in
these diseases. For more information about NIAMS, call the information
clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the
NIAMS website at <http://www.niams.nih.gov>.

The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the U.
S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical, and translational
medical research, and it investigates the causes, treatments, and cures for
both common and rare diseases. For more information about NIH and its
programs, visit <http://www.nih.gov>.

Arnold, LM et al. Gabapentin in the treatment of fibromyalgia; a
randomized, double-blind, placebo-controlled multicenter trial. "Arthritis
Rheum". 2007; 56: 1336-1344.


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Date:    Mon, 11 Jun 2007 12:49:09 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Fibromyalgia syndrome

Fibromyalgia syndrome.

J Rheumatol. 2007 Jun;34(6):1415-25.

Mease P, Arnold LM, Bennett R, Boonen A, Buskila D, Carville S, Chappell A,
Choy E, Clauw D, Dadabhoy D, Gendreau M, Goldenberg D, Littlejohn G, Martin
S, Perera P, Russell IJ, Simon L, Spaeth M, Williams D, Crofford L.

Division of Rheumatology Research, Swedish Medical Center, Clinical
Professor of Medicine, University of Washington, Seattle, WA, USA.

PMID: 17552068

The fibromyalgia syndrome (FM) workshop at OMERACT 8 [Note: OMERACT =
"Outcome Measures in Rheumatoid Arthritis Clinical Trials"] continued the
work initiated in the first FM workshop at OMERACT 7 in 2004.

The principal objectives were to work toward consensus on core domains for
assessment in FM studies, evaluate the performance quality of outcome
measures used in a review of recent trials in FM, and discuss the research
agenda of the FM working group. An initiative to include the patient
perspective on identification and prioritization of domains, consisting of
focus groups and a patient Delphi exercise, was completed prior to OMERACT 8.

Patient-identified domains were, for the most part, similar to those
identified by clinician-investigators in terms of symptoms and relative
importance. However, patients identified certain domains, such as
stiffness, that were not included by physicians, and emphasized the
importance of domains such as dyscognition and impaired motivation.

Many of the principal domains agreed upon by the clinician-investigators,
patients, and OMERACT participants, including pain, fatigue, sleep, mood,
and global measures, have been used in clinical trials and performed well
when viewed through the OMERACT filter.

The research agenda items reviewed and approved for continued study
included development of objective "biomarkers" in FM, development of a
responder index for FM, and coordination with the WHO's International
Classification of Functioning Disability and Health (ICF) Research Branch
and the US National Institutes of Health's Patient Reported Outcome
Measures Information System network (PROMIS) to develop improved measures
of function, quality of life, and participation.

The OMERACT process has provided a framework for identification of key
domains to be assessed and a path toward validation and standardization of
outcome measures for clinical trials in FM.

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Date:    Mon, 11 Jun 2007 11:09:24 -0700
From:    Kimberly Hare <kimberly_ohare YAHOO.COM>
Subject: RES: Multiple chemical sensitivity and workplace discrimination: The national EEOC ADA research project

[This may be of interest given the fact that a subset of people with ME/CFS
also have MCS.]

Multiple chemical sensitivity and workplace discrimination: The national EEOC
ADA research project.

Work. 2007;28(4):391-402.Click here to read Links

Vierstra CV, Rumrill PD, Koch LC, McMahon BT.

Kent State University, Department of Educational Foundations & Special
Services, Kent, OH, USA.

PMID: 17522460

Information from the Integrated Mission System of the United States Equal
Employment Opportunity Commission (EEOC) was used to investigate the employment
discrimination experiences of Americans with multiple chemical sensitivity
(MCS) in comparison to Americans in a general disability group with allergies,
asthma, HIV, gastrointestinal impairment, cumulative trauma disorder and

Specifically, the researchers examined demographic characteristics of the
charging parties; the industry designation, location, and size of employers
against whom allegations were filed; the nature of discrimination (i.e., type
of adverse action) alleged to occur; and the legal outcomes or resolutions of
these allegations.

Findings indicate that persons with MCS were, on average, older than the
comparison group and comparatively overrepresented by Caucasians and women.

People with MCS were proportionally more likely than the comparison group to
allege discrimination related to reasonable accommodations. People with MCS
were proportionally more likely than the comparison group to file allegations
against employers in the manufacturing and public administration industries,
employers with 201-500 workers, and employers in the Western Census region.
People with MCS were proportionally more likely than the comparison group to
receive non-merit resolutions as a result of the EEOC's Americans with
Disabilities Act Title I investigatory process.

Implications for policy and advocacy are addressed.

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End of Co-Cure Weekly Digest of research and medical posts only - 4 Jun 2007 to 11 Jun 2007

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