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Co-Cure Weekly Digest of research and medical posts only - 5 Mar 2007 to 12 Mar 2007

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Date:    Tue, 6 Mar 2007 01:31:45 -0500
From:    "Pat Fero <bp.fero verizon.net> via Co-Cure Moderator"
Subject: NOT,RES: Whittemore Peterson Institute for Neuro-immune Disease

March 5, 2007
Tom Henkenius
Channel 2 News RENO, NV

Monday was a big day for the future of the University of Nevada School of
Medicine. They broke ground on the first medical research  facility built
on the campus in 20 years.

At 100,000 square feet the new $78-million Center for Molecular  Medicine
will double the medical school's research and lab space. The  additional
growth is also expected to help the medical school grow.  "It's going to be
a fabulous addition to our basic research base," says School of Medicine
Dean Dr. John McDonald. "I think it will be transforming for the campus."

The state currently ranks 47th in the nation for the number of patients per
doctor. The hope is, improving the medical school will attract more
students interested in a career in medicine.

"We believe that you cannot have a top flight medical school without a
research base. We have been hindered in that research base by the lack of
modern state of the art facilities," says University  President Dr. Milton

The new research facility will house some of the basic science  research
the university already conducts; it will also be home to the National
Cancer Institute and the Whittemore Peterson Institute for Neuro-immune

The first American institute of it's kind is looking for the cause and cure
of Chronic Fatigue Syndrome.

Annette Whittemore is a founding member of the Institute, "We had a  dream
for this Institute to be able to connect it to a fabulous research facility
like the University of Nevada. It's way beyond our wildest dreams."

The new building is scheduled for completion in 2009.

[Return to top]


Date:    Tue, 6 Mar 2007 14:38:29 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: NOT,RES: Whittemore Peterson Institute for Neuro-immune Disease (2)

Source: Center for Molecular Medicine
Date:   March 5, 2007
URL:    http://www.unr.edu/med/cmm/
Ref:    See also, http://www.unr.edu/nevadanews/detail.aspx?id=2049

Center for Molecular Medicine ushers in new era of research for the University
of Nevada School of Medicine

On Monday, March 5, 2007 the University of Nevada School of Medicine celebrated
the groundbreaking of the first new medical research facility to be built at the
University in more than 20 years. The Center for Molecular Medicine will house
portions of the medical school's basic science research departments and serve
as the headquarters for the Whittemore Peterson Institute for Neuro-Immune
Disease and the northern center for Nevada Cancer Institute.

Portions of the microbiology, pharmacology, and physiology departments will move
into the 100,000 square foot state-of-the-art facility, which will double the
medical school's research and laboratory space. In addition to creating more
space, the Center for Molecular Medicine is expected to increase the research
productivity and funding of the school's basic scientists.

'This new facility will significantly expand the School of Medicine's ability to
advance the work of our basic scientists,' said John A. McDonald, M.D., Ph.D.,
vice president of health sciences and dean of the medical school. 'Not only
will we have the ability to expand our current basic science operation, but the
building will allow us to develop new programs in addition to providing space
for our clinical faculty to conduct research.'

The Center for Molecular Medicine will also enable the medical school to
increase its graduate student programs. According to University of Nevada, Reno
President Milton Glick, Ph.D., breaking ground on the new facility is just one
of the first steps toward expanding the School of Medicine.

'We believe that research is at the heart of every top-notch medical school,'
Glick said. 'We have a very high quality medical school, but it is too small to
meet the ever increasing healthcare needs of Nevada. Our state ranks 47th in the
nation for physicians per 100,000 people. By expanding our medical school we
have an opportunity to produce more physicians who remain to practice patient
centered, highest quality medical care in our state. Building the new Center for
Molecular Medicine is the first step toward fulfilling that mission.'

Recognizing the need for improved health outcomes across the state, the
University of Nevada School of Medicine, Whittemore Peterson Institute and
Nevada Cancer Institute joined forces to secure state funding for the Center for
Molecular Medicine project during the 2005 legislative session. With the strong
support of State Senator William Raggio (R-Washoe), Senate Bill 105 passed
securing $10 million in support of the project's public-private partnerships.
Additional funding for the $78 million building stems from federal funds flowing
from the research activities of all of the University's research scientists.

'Public-private partnerships have become increasingly important to the
University,' said Glick. 'By sharing space in this new facility, all three
parties will be able to achieve more than if they were to work individually. By
coming together - the whole will be greater than the sum of its parts, - and we
will be able to make greater advances in research.'

At the heart of the Center for Molecular Medicine is the goal to improve the
health outcomes of Nevadans through research and clinical care. Sharing the
research facility with the Whittemore Peterson Institute and Nevada Cancer
Institute will create a synergistic environment for scientists to work together
to conduct cutting-edge research that leads to better treatments for patients.

More than 15,000 square feet on the second and third floors will house the
Whittemore Peterson Institute for Neuro-Immune Disease, the first institute of
its kind in the United States. Dedicated to finding a cause and cure for Chronic
Fatigue Syndrome and other neuro-immune diseases such as fibromyalgia, Gulf War
Illness and autism, the Whittemore Peterson Institute will not only conduct
research in the new facility but will also treat patients and develop
educational programs for complex disorders of the immune system and brain.

'We're so excited to finally break ground on this facility,' said Annette
Whittemore, founding member of the Whittemore Peterson Institute. 'The design of
the building creates a dynamic setting that encourages researchers, clinicians
and patients to interact. We have high hopes that in such a setting clinicians
will be able to go from bedside to bench and back to bedside to bring better
treatments to patients.'

Nevada Cancer Institute, which will conduct research and patient-centered
clinical trials in the new Center, will occupy 8,800 square feet on the first
floor of the building. The Center for Molecular Medicine will act as the
flagship for Nevada Cancer Institute's northern clinical and research

'The new center will allow us to extend our mission of bringing new in-class and
patient-tailored clinical trials to more of the state in support of the state's
Comprehensive Cancer Plan,' said Heather Murren, chief executive officer of
Nevada Cancer Institute. 'We have had great response already to the availability
of Phase I and II clinical trials with more than 200 patients consented to
participate in helping us to advance the search for the cure. We look forward to
making these potentially life-saving measures more accessible for all Nevadans.
In addition, we will be able to enhance and expand our Education and Outreach
mission as well as provide additional quality of life services that will expand
the services available to the community.'

The Center for Molecular Medicine, designed by Dekker/Perich/Sabatini Design,
will create a dynamic research environment inside the facility and dramatically
change the landscape of the medical school's Reno campus. Visible from McCarran
Boulevard, the Center will include two wings. The northwest wing will house the
vivarium and research space on the first floor with additional laboratory and
office space on the second and third floors. The southeast wing will provide
space to the Nevada Cancer Institute and Whittemore Peterson Institute in
addition to the 96-person capacity auditorium, two large meeting rooms and
shared food service area.

The facility will serve as the new focal point of the medical school complex and
will be accessed from a realigned and elevated Enterprise Road. Employees will
access their secured laboratories through entrances located along the northwest
research wing of the facility while patients will enter into the Center from a
covered canopy located on the southeast wing. The southeast wing, which acts as
the main entrance to the building, will open into a 30-foot tall glass enclosed
lobby offering sweeping views of the hillside to the east.

The two institutes and medical school's basic science research team are not the
only beneficiaries of the new facility. The Center for Molecular Medicine will
contribute substantially to the local economy. The additional research space is
anticipated to increase the School of Medicine's federally funded research
revenues that are returned to the local economy by salaries, supplies and
support services needed to carry out research. The clinical operations supported
by the Whittemore Peterson Institute and Nevada Cancer Institute are expected to
attract new patients to the area.

The Center for Molecular Medicine is anticipated to open its doors in 2009. For
additional information, please contact the School of Medicine's communications
department at 702-671-6455 or 775-784-6006.

(c) 2007 University of Nevada

[Return to top]


Date:    Thu, 8 Mar 2007 12:15:47 -0500
From:    "Sabrina Johnson <seminars fibrocop.org> via Co-Cure Moderator"
Subject: NOT,MED: The 2007 Midwestern Fibromyalgia, Chronic Fatigue Syndrome Conference - "Crossing the Chronic Pain and Fatigue Bridge" [US]

Join the Fibromyalgia Association Created for Education and Self-help
[commonly known as FACES, Inc.] for:

The 2007 Midwestern Fibromyalgia, Chronic Fatigue Syndrome Conference -
"Crossing the Chronic Pain and Fatigue Bridge"

Friday May 18 to Sunday May 20, 2007
Holiday Inn Matteson Hotel and Conference Center
Matteson, Illinois

Registration: $150 per person for 3 full days packed with education and
awareness information.

Pre-registration is required.
Space is Limited - register now at http://www.fibrocop.org/register.htm

visit www.fibrocop.org for complete conference and registration information.

Esteem Speakers scheduled to appear at the Chicago Fibromyalgia Conference:

Conference Honorary Chairs
Actress/Model: Francis Jenkins, and
Talk Show Host: George Blaise

Conference Medical Chair
Muhammad Yunus, MD

Jacob Teitelbaum, MD
Leonard Jason, PhD
Michael McNett, MD
Aristo Viojandi, PhD MT
Joan Shaver, PhD
Daniel Heffez, MD
Michael Rosner, MD
Hal Blatman, MD

Steve Krafchick, Esq.
Scott Davis, PC
Michael Rothmann, Esq.
Jeffrey Rabin, Esq.

Flora Stay, DDS
Roger Salter, CFP
Rev. Kurt Foundreist, PhD

Namita Ghandhi, M.S. M.B.A., M.A.
Dianne Adams, MPH
Derick Russell, MPT

Lynne Matallana
Victoria Gore
Dex Pierce

Cassandra Friedman, PhD, LCPC, CADC
Derek Miller, DO

Join us for the uniquely Chicago fundraiser, as we dine and dance for
Fibromyalgia awareness.  Hear the inspirational song written just for
Fibromyalgia, view the Fibromyalgia Photo Awareness Project and learn the
Sophisticated Chicago Form of dancing called Steppin.

Steppin Out on Fibromyalgia
Friday May 18, 2007
6 pm to 10 pm

Holiday Inn Matteson Hotel and Conference Center

Registration: $100 per person
Pre-registration is required.

Space is limited, register online now at http://www.fibrocop.org/register.htm

To register by mail for the conference, the opening gala or both - download
a registration booklet at http://www.fibrocop.org/RegistrationBrochure.pdf

For more information:
visit www.fibrocop.org
email seminars@fibrocop.org
or call [773] 936-4183

[Return to top]


Date:    Tue, 6 Mar 2007 10:57:21 -0500
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Helplessness and loss as mediators between pain and  depressive symptoms in fibromyalgia

Helplessness and loss as mediators between pain and depressive symptoms in

Pain. 2007 Feb 28; [Epub ahead of print]

Palomino RA, Nicassio PM, Greenberg MA, Medina EP Jr.

Helix Clinical Research, Inc., La Mesa, 9311 Mesa Vista Ave., La Mesa, CA
91941, USA.

PMID: 17335975

This study evaluated the contribution of condition-specific helplessness
and loss to depression in fibromyalgia (FM). Two models were tested. The
first model examined whether loss, measured by the West Haven-Yale
Multidimensional Pain Inventory (WHYMPI) Interference Scale, would mediate
the relationship between disability and depression. The second model
determined whether condition-specific helplessness and loss would mediate
the relationship between pain and depression with disability controlled.

Eighty patients with confirmed diagnoses of FM were recruited throughout
Southern California from general medical clinics, newspaper advertisements,
and rheumatology practices. The study design was cross-sectional, using
self-report, observational, and interview measures. A composite measure of
depression was adopted, consisting of the Center for Epidemiological
Studies-Depression Scale and the Hamilton Rating Scale for Depression.
Hierarchical multiple regression analyses were conducted using a path
analytic framework to examine each model.

In Model 1, loss fully mediated the relationship between disability and
depression. In Model 2, condition-specific helplessness mediated the
relationship between pain and depression, but the contribution of loss was
not significant.

The findings confirm the importance of helplessness and demonstrate that
the cognitive meaning of having FM plays a more central role in predicting
depressive symptomatology than illness-related stressors, such as pain or

[Return to top]


Date:    Thu, 8 Mar 2007 12:24:09 -0500
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: The problem of fatigue in neurological disorders

[The problem of fatigue in neurological disorders]
[Article in Polish]

Journal: Wiad Lek. 2006;59(9-10):685-91.

Authors: Kumor K, Pierzchala K.

Affiliation: Z Katedry i Kliniki Neurologii w Zabrzu Slaskiej Akademii
Medycznej w Katowicach. kum2@poczta.onet.pl

NLM Citation: PMID: 17338130

Fatigue or piercing feeling of weakness, lack of strength and energy or
total exhaustion is a common complaint of patients with neurological
disorders. From 40 to over 90 per cent of individuals with multiple
sclerosis, Parkinson disease, amyotrophic lateral sclerosis,
neuroboreliosis, post polio syndrome or stroke confirm its experience. It
is not infrequently numbered among most disabling complaints. A separate
entity, with fatigue as a cardinal sign, is a chronic fatigue syndrome, a
disorder, though controversial, more and more frequently diagnosed.

Fatigue ought to be discriminated from fatigability, paresis, somnolence
and, first of all depression which commonly coexists in chronic disorders.
The assessment is almost entirely based on self-estimate scales filled in
by a patient. Attainable results of neuroimaging, electrophysiological,
polisomnographic, vegetative, psychological and biochemical surveys have
not allowed yet to define the pathogenesis of fatigue. The treatment basis
consists of behavioral therapy, psychotherapy and a proper treatment of the
basic disease.

[Return to top]


Date:    Thu, 8 Mar 2007 19:05:20 +0100
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: not,res: Toured the Whittemore Peterson Nevada CFS Center site today


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From: Erik Johnson <erikmoldwarrior earthlink.net>

Toured the Whittemore Peterson Nevada CFS Center site today

To put the location in context, let me take you on a little tour of Reno.

We can start down by the South Meadows Parkway where you see
a few brand new multi-story medical clinics.

Very impressive. This is obviously a city that takes its health centers
very seriously. Now as we drive up Virginia St., the old main 395
highway before the new superhighway was built, we go further
towards the heart of Reno, and you see a few more medical
buildings here and there, all with that shiny new look and modern
architecture. By Kietzke Lane, there is simply no doubt that Reno is
a great place to be sick.

But keep going North, past Vassar, where the medical facilities take
up an entire block, and another, and another, and it looks like doctors
have taken over the midsection of town.

Then you come to Mill Street, with its massive Washoe Medical
Center, St. Mary's Regional Health facility, The Renown
neurosurgery group, with incredibly tall high rise structures and with
their helicoptor landing pads on the roofs, parking garages bigger
than most hospitals, and a constant stream of medical vehicles
pouring in and out of all the streets: A Mega Medical-plex!

The old casinos, Circus-Circus, Harrahs, Silver Legacy and the new
Reno Arch are completely dwarfed by the REAL business of Reno.
This is BIG HEALTH on an amazing scale. The medical complexes
push right up to the interstate 80 corridor - and even then there is a
pharmacy built right on a bridge which spans the Interstate, as if
room were so precious that going right over the main highway
connecting California to the rest of the United States is no obstacle.
Crossing Hwy 80, we keep going up toward the old University of
Nevada Reno campus, past the old buildings. This used to be the
northern fringe of Reno, and now it's entirely built up and citified.

The old Fleischman Planetarium, Mackay Stadium - home of the
Nevada Wolfpack, Lawlor Events Center and a bunch of others.

There's a lot going on up here. And right in the middle of it all is the
UNR medical complex. The Medical Education building, Childrens
services, Administration, NIH research facilities and more. No mere
smattering of buildings, this is a well-designed and coordinated
medical monolith.

This is the center of medical science for Northern Nevada. Standing
in the heart of all this, one can't help but be impressed.

Then you look straight through the main hall entrance to the Medical
Education building on the UNR plaza which gives a view clear
through to the field behind the structure, and there stands a giant
yellow "loader" tractor. Go through those gates, and you see there is
one precious patch of UNR territory that hasn't been taken over by
medical buildings yet. With a great view of Northern Reno and a
slight separation from the rest of the medical group, this is a setting
that screams of "prestige" and couldn't possibly be used for anything
that wasn't in keeping with its medical, educational, scientific

This is where the tractor just laid in the gravel road for the new
Whittemore Peterson Nevada CFS center for Neuro-Immune

The excitement on the UNR campus is palpable, with staff and
faculty eager to see the building done and the Neuro-Immune work

If someone wanted to make a statement that a building has a
purpose of uttermost importance, knocking down the State Capitol to
make room would barely be able to make the impact that this
particular spot does.

Although the foundations haven't been laid yet, just knowing that this
location has been set aside to be a cornerstone of CFS research
lends a tangible concrete credibility to the illness which denialists will
find incredibly difficult to discount.


[Return to top]


Date:    Thu, 8 Mar 2007 17:33:53 -0500
From:    Fred Springfield <fredspringfield VERIZON.NET>
Subject: RES: Protocol for the PACE trial: ...

Protocol for the PACE trial: A randomised controlled trial of adaptive pacing,
cognitive behaviour therapy, and graded exercise, as supplements to
standardised specialist medical care versus standardised specialist medical
care alone for patients with the chronic fatigue syndrome / myalgic
encephalomyelitis or encephalopathy

Journal:  BMC Neurology 2007, 7:6

Authors: Peter D White, Michael C Sharpe, Trudie Chalder, et al., on behalf
of the PACE trial group (pace@qmul.ac.uk)

This protocol is available in PDF at

[Return to top]


Date:    Fri, 9 Mar 2007 04:02:49 +0100
From:    Jan van Roijen <j.van.roijen CHELLO.NL>
Subject: act,res: ME/CFS -A debilitating condition, an uphill battle


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The Star Ledger

A debilitating condition, an uphill battle
Chronic fatigue is slowly gaining recognition

Thursday, March 08, 2007

Star-Ledger Staff

At age 11, Brian Bernard earned straight A's, played travel
soccer and seemed able to name every bird in the Western

Then in April 2005, he got the flu and never really recovered. He
spent months in bed. At his worst, he could barely lift his head
from the pillow, forcing his mother to spoon-feed him. He often
slept 15 hours a day.

At one point, Brian could no longer read and forgot simple
words. His mother, a physician, has a vivid memory of one day
when he saw a pigeon.

"He said to me: 'I know what that bird is -- it begins with a "P.'"
This was a kid who could have gone on 'Jeopardy!' and won the
bird category," said Donnica Moore, talking in the family's home
in Chester, where Brian's ornithology books line the library
Brian's diagnosis was one even his mother was not expecting:
chronic fatigue syndrome.

The illness still raises eyebrows and skepticism. Some
physicians doubt it exists. Yet the U.S. Centers for Disease
Control and Prevention now calls chronic fatigue syndrome a
very real and debilitating condition -- and a significant public
health threat.

The center is funding a $4.5 million campaign to educate the
public and physicians about CFS. The campaign comes to New
Jersey Saturday, when some of the nation's top experts will talk
about CFS at Robert Wood Johnson University Hospital in New

The disorder was first recognized in the early 1980s, when it
was often dismissed as "yuppie flu," since many of those
stricken seemed to be hard-charging professionals. Two
decades later, it is known CFS strikes previously healthy people,
most of them adult women, but much else about it remains a
puzzle. There is no diagnostic test and no known cure.

Besides crippling fatigue, patients may experience "brain fog,"
sleep disorders, muscle and joint aches, and tender lymph

Research emerging in the past two years has started to unravel
some of the puzzle. Scientists have identified different genetic
profiles for people with CFS. The different genes deal with
energy usage and the body's ability to cope with stress, such as
trauma and infection. Other research has found abnormalities in
blood pressure, blood volume to the brain and immune-cell
activity in CFS sufferers.

The CDC estimates 1 million Americans have the syndrome and
up to 80 percent of them have not been properly diagnosed.

Many sufferers are told their problems are imaginary. Some are
accused of faking illness.

CDC Director Julie Gerberding said she wanted the campaign
to "validate and understand the incredible suffering that many
people and their families experience."


CFS can come on gradually, though often the syndrome is
kicked off by some "first domino" such as a viral infection,
allergic reaction or stress, said Alan Pocinki, a Washington,
D.C., physician who has studied CFS at the National Institutes of

"A lot of research is chicken-and-egg. We don't know if the
abnormalities we see are the result of CFS or the cause," he
said. He helps patients by treating symptoms, such as giving
them medications for pain or insomnia. One study announced in
January found a subset of patients responded well to anti-viral

In Newark, Benjamin Natelson, director of the pain and fatigue
center at UMDNJ-New Jersey Medical School, fears the
disorder is particularly going undiagnosed in minorities.

Natelson is studying sleep disorders in CFS patients. "One
hypothesis is that some people with CFS have a sleep disorder
that just doesn't let them rest," he said.

To Pocinki and many other CFS researchers, the debate about
whether they are dealing with a true illness is over.

"I think certainly there are physicians who don't believe this
exists," Pocinki said. "These doctors are now out of the

Not everyone agrees.

Peter Manu, a professor of clinical medicine and psychiatry at
Albert Einstein College of Medicine in New York, says the
patients' suffering is real, but he called CFS a collection of

"There is no evidence at this time that CFS is a physical or
psychiatric disease," he said by e-mail. "I've done research and
seen the literature. I call it as I see it."


To Jackie Niederle of Annandale, CFS is indeed real, an illness
that stole her dreams. Growing up in a working-class family, she
longed to be a lawyer. She said she worked hard, saved her
money and eventually enrolled in Seton Hall Law School. During
her second year she suddenly experience a sore throat,
headache and profound exhaustion.

"I know bone-crushing exhaustion after a 60-hour workweek,"
she said, "but this is different. This is like being cut off at the
She began falling asleep during class and forgetting facts. In
1992, after a hospitalization and rounds of tests, she was
diagnosed with CFS and left school.

Today she copes with her limitations and conserves her energy.
She and her husband decided they could not raise a family
because of her illness -- another dream gone.

"CFS is a thief," she said. "It steals your health, your life and your

Brian Bernard, now 13, has improved greatly in the past year,
returning to school and soccer. He is a stellar student, articulate
beyond his years. But sometimes he still loses words, his blood
pressure fluctuates when he stands, and he has had relapses,
even a bout with pneumonia.

"It's like the ancient Greeks," he said. "They did not understand
lightning, but that doesn't mean it didn't exist."

Carol Ann Campbell may be reached at
ccampbell@starledger.com or (973) 392-4148.

[Return to top]


Date:    Fri, 9 Mar 2007 19:09:34 -0500
From:    Co-Cure Moderator <ray CO-CURE.ORG>
Subject: NOT,MED: FDA MedWatch: Erythropoiesis Stimulating Agents: studies in patients with cancer found a higher chance of serious and life-threatening side effects or death with the use of ESAs

[Moderator's Note: This may be of interest given that
Procrit (epoetin alfa) was and may still be an
investigational drug for the treatment of chronic
fatigue syndrome. It seems to be that all
erythropoiesis-stimulating agents are inappropriate
for those without substantial anemia, and may well be
highly problematic for those with substantial anemia.]

MedWatch - The FDA Safety Information and Adverse Event Reporting Program

FDA notified healthcare professionals of new safety information for
erythropoiesis-stimulating agents (ESAs) Aranesp (darbepoetin alfa),
Epogen (epoetin alfa), and Procrit (epoetin alfa). Four new studies in
patients with cancer found a higher chance of serious and
life-threatening side effects or death with the use of ESAs. These
research studies were evaluating an unapproved dosing regimen, a patient
population for which ESAs are not approved, or a new unapproved ESA. FDA
believes these new concerns apply to all ESAs and is re-evaluating how
to safely use this product class. FDA and Amgen, the manufacturer of
Aranesp, Epogen and Procrit, have changed the full prescribing
information for these drugs to include a new boxed warning, updated
warnings, and a change to the dosage and administration sections for all

Read the complete MedWatch 2007 Safety summary, including links to the
Public Health Advisory, Q and A's, and updated healthcare professional
information sheet, at:


[Return to top]


Date:    Sat, 10 Mar 2007 10:27:16 -0500
From:    "Jan van Roijen <j.van.roijen chello.nl> (via Co-Cure Moderators)
Subject: MED: Anemia drugs increase death risk

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Because these drugs are used by some ME/CFS
patients (in connection with orthostatic intolerance
and low RBC volume), this article may be of interest.




Non-food Things

By Ben Wasserman - foodconsumer.org

Mar 9, 2007 - 12:11:15 PM

Anemia drugs increase death risk

The Food and Drug Administration Friday issued a public health
advisory to warn care providers and patients that use of
common anemia drugs can increase the risk of death and other
serious problems in patients with cancer or kidney disease.

The drugs of concern are Procrit, Epogen and Aranesp, which
are erythropoiesis-stimulating agents. These drugs are
genetically engineered versions of a natural protein,
erythropoietin, that increases the number of red blood cells.

But recent studies show that the drugs at a dose higher than
indicated increased risk of death, blood clots, stroke and heart
attack in patients with chronic kidney failure.   In patients with
head and neck cancer, high doses of the agents promoted
tumor growth.

The FDA warned that even at the dose recommended by the
agency, the agents increased death risk in patients with cancer
who were not on chemotherapy.   In addition, patients receiving
orthopedic surgery would have a higher risk for blood clots when
the drugs were given to them.

The FDA wants a new boxed warning to advise physicians to
monitor red blood cell levels and to adjust the ESA dose to
maintain the lowest hemoglobin level needed to avoid the need
for blood transfusions.   The agency says doctors and patients
need to weigh the risks of these agents against the risk of

The safety concerns resulted from earlier ESA studies
discussed during a 2004 meeting of the Oncologic Drugs
Advisory Committee. Product labeling was previously revised in
1997, 2004, and 2005 to reflect new safety information.

The drugs, Aranesp, Epogen, and Procrit, are approved to treat
anemia in patients with chronic kidney failure and in patients with
cancer whose anemia is caused by chemotherapy.

Epogen and Procrit are indicated for patients scheduled for
major surgery to reduce potential blood transfusions and for the
treatment of anemia due to zidovudine therapy in HIV patients.

ESAs are not for treatment of the symptoms of anemia –
including fatigue – in cancer patients, surgical patients, or those
with HIV.

All three drugs are manufactured by Amgen Inc. based out of
Thousand Oaks, California. Procrit is marketed and distributed
by Ortho Biotech LP, a subsidiary of Johnson & Johnson, the
FDA says.

All the following information is updated on March 9, 2007 by the

FDA Public Health Advisory

Erythropoiesis-Stimulating Agents (ESAs)

Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa
(marketed as Aranesp)

Recent reports of studies with erythropoiesis-stimulating agents
(ESAs) have shown a higher chance of serious and
life-threatening side effects and greater number of deaths in
patients treated with these agents.  ESAs stimulate the bone
marrow to make more red blood cells and are FDA approved for
use in reducing the need for blood transfusions in patients with
chronic kidney failure, patients with cancer on chemotherapy,
patients scheduled for major surgery (except heart surgery) and
patients with HIV that are using AZT.  Because all ESAs work
the same way, the findings from these studies apply to all ESAs;
the FDA is re-evaluating the safe use of this drug class.

Patients currently using or considering the use of an ESA should
know the following:

*  A higher chance of death and an increased rate of tumor
growth were reported in patients with advanced head and neck
cancer receiving radiation therapy and in patients with
metastatic breast cancer receiving chemotherapy, when ESAs
were given to maintain hemoglobin levels of more than 12 g/dL.
*  A higher chance of death was reported and no fewer blood
transfusions were received when ESAs were given to patients
with cancer and anemia not receiving chemotherapy.
*  A higher chance of death was reported and an increased
number of blood clots, strokes, heart failure, and heart attacks
was reported in patients with chronic kidney failure when ESAs
were given to maintain hemoglobin levels of more than 12 g/dL.
*  A higher chance of blood clots was reported in patients who
were scheduled for major surgery and given ESAs.
*  ESAs are not approved for treatment of the symptoms of
anemia, such as fatigue in patients with cancer, surgical patients
and patients with HIV.
*  If you have any questions you should talk with your health care

Important study results include the following:

*  Patients with chronic kidney failure had an increased number
of deaths and of non-fatal heart attacks, strokes, heart failure,
and blood clots when ESAs were adjusted to maintain higher
red blood cell levels (hemoglobin more than 12 g/dL).
*  Patients with head and neck cancer receiving radiation
therapy had faster tumor growth when ESAs were adjusted to
maintain hemoglobin levels higher than 12 g/dL.
*  Patients with cancer not receiving chemotherapy died sooner
and had no fewer blood transfusions when ESAs were given
according to the dosing recommendations for cancer patients
receiving chemotherapy.
*  Patients scheduled for orthopedic surgery who received ESAs
to reduce blood transfusions during and after surgery had more
blood clots than those not given an ESA.
Physicians who prescribe ESAs should consider the important
study results above and:

*  Adjust the dose of ESA to maintain the lowest hemoglobin
level necessary to avoid the need for transfusions.
*  Monitor patients' hemoglobin levels to ensure they do not
exceed 12 g/dL;
*  Understand that ESAs are given to decrease the chances of
receiving transfusions;
*  Understand that ESAs have not been shown to improve the
outcomes of chemotherapy treatment (e.g., better tumor
shrinkage, delay in tumor growth or longer time for survival);
*  Consider both the risks of transfusions and those of ESAs
when deciding to prescribe an ESA; and
*  Understand that ESAs should not be given to treat the
symptoms of anemia, including shortness of breath, dizziness,
fatigue, low energy, or poor quality of life.

FDA and Amgen, the manufacturer of these products, and Ortho
Biotech Products, L.P, a Johnson & Johnson Pharmaceuticals
Research and Development subsidiary, the distributor of Procrit,
have agreed to change the labeling for Aranesp, Epogen, and
Procrit to reflect the new safety information and to provide
additional instructions for their use.

FDA-approved uses of ESAs are: for the treatment of anemia in
chronic kidney failure patients, in patients with cancer whose
anemia is caused by chemotherapy, in patients with HIV whose
anemia is caused by AZT (zidovudine), and to reduce the
number of transfusions in patients scheduled for major surgery
(except heart surgery).

You can find more details about  the use of ESAs in FDA's
Information for Healthcare Professional:
The FDA asks health care professionals and patients to report
serious side effects after using ESAs to the FDA through the
MedWatch program by phone (1-800-FDA-1088) or by the
Internet at           http://www.fda.gov/medwatch

Questions and Answers on
Erythropoiesis-stimulating Agents (ESAs)

Epoetin alfa (marketed as Procrit, Epogen)
Darbepoetin alfa (marketed as Aranesp)

What is the FDA announcing today?

The FDA is announcing new safety information about
erythropoiesis-stimulating agents (ESAs).
Erythropoiesis-stimulating agents (ESAs) are man-made
versions of a natural protein. The natural protein is made by the
kidney and stimulates the bone marrow to produce more red
blood cells.  ESAs are given to reduce the number of red blood
cell transfusions administered to patients with certain serious
diseases/conditions who are or may become anemic.  The new
information from recently reported clinical studies includes the

*  Chronic kidney failure patients had increased numbers of
deaths and of non-fatal heart attacks, strokes, heart failure, and
blood clots when ESAs were adjusted to maintain higher red
blood cell levels (hemoglobin more than 12 g/dL).
*  Head and neck cancer patients receiving radiation therapy
had faster tumor growth when ESAs were adjusted to maintain
hemoglobin levels higher than 12 g/dL.
*  Cancer patients not receiving chemotherapy died sooner and
had no fewer blood transfusions when ESAs were given
according to the dosing recommendations for cancer patients
receiving chemotherapy.
*  Patients scheduled for orthopedic surgery who received ESAs
to reduce blood transfusions during and after surgery had more
blood clots than those not given an ESA

What are the FDA-approved uses for ESAs?

ESAs are approved for use in anemic patients with chronic
kidney failure, for anemic patients with cancer taking
chemotherapy, for anemic patients with HIV taking zidovudine
(AZT), and for patients with hemoglobin levels of 10-13 g/dL
prior to surgical procedures expected to require blood
transfusions and who are unwilling to donate blood.

ESAs are not approved to treat the symptoms of anemia,
including fatigue, tiredness, low energy, poor quality of life,
shortness of breath, and dizziness.

What products are covered by FDA's public health

The products are darbepoetin alfa and epoetin alfa.
Darbepoetin alfa was approved for marketing on September 17,
2001 and is licensed and marketed by Amgen, Inc. as Aranesp.
Epoetin alfa was approved for marketing on June 1, 1989 and is
also licensed by Amgen, Inc.  It is marketed under the
proprietary name Procrit by Ortho Biotech L.P., a subsidiary of
Johnson and Johnson Pharmaceutical Research &
Development LLC (J&J PRD), and marketed under the
proprietary name Epogen by Amgen, Inc.

Does this new information about safety risks apply to all of
these products?

Yes, the safety risks apply to all ESAs.

What is FDA doing?

To inform the general public, FDA issued a public health
advisory, a press release, and scheduled a press call.  FDA has
approved revised product labeling for physicians and patients
that describes new warnings and dosing information. FDA
posted an "Information for Health Care Professionals" sheet to
further inform prescribers and other health care professionals

The Agency will present this new information to the Oncologic
Drugs Advisory Committee on May 10, 2007. FDA will seek
advice on the need for additional labeling changes and/or
additional studies to further assess safety.

FDA informed hematologists, oncologists and nephrologists via
an additional e-mail communication that will be distributed
through medical professional organizations; this will be posted
on FDA's Office of Oncology Drug Products website
(http://www.fda.gov/cder/Offices/OODP/default.htm), under the
"What's New" link.

FDA will issue a letter to all IND holders investigating new uses
of ESAs.  This letter will describe the new data, advise
discussion of this information with patients, investigators, and
IRBs, and recommend re-consideration of the safety of studies
in light of these new data.

FDA asked Amgen, Ortho Biotech, LP, and other ESA
manufacturers to provide FDA with the results of clinical studies
describing increased risks of ESAs.

FDA requested that Amgen and Ortho Biotech, LP provide an
overview and update on the status of all studies investigating
safety of ESAs, particularly agreed-upon post-marketing studies
and studies identified at the May 2004 ODAC meeting.

What are Amgen, Inc. and Ortho Biotech doing?

They have revised product labeling to include the new warnings
and dosing recommendations and will issue the revised labeling
with a Dear Health Care Provider letter. They have voluntarily
agreed to suspend broadcast (radio and television)
direct-to-consumer advertising for Aranesp, Procrit, and Epogen
regarding uses in cancer, with the exception of safety
information, under after the May 2007 ODAC meeting.  Amgen
and Ortho Biotech agreed to inform all investigators conducting
company-sponsored or supported studies of these data, to
revise investigational drug brochures, and to participate in the
May 2007 ODAC meeting.

What should physicians and healthcare professionals do
with this information?

Physicians should discuss this information with patients in
clinical studies and should ask patients to confirm their consent
for continued participation.  Institutional Review Boards should
also be advised of these findings.  Investigators should
re-evaluate whether clinical investigations should continue in
light of these new safety data.

What previous actions has FDA taken regarding safety
concerns with ESAs?

The product labels for all US marketed ESAs have been
updated several times since the original approvals to
incorporate new safety information. The FDA has closely
monitored emerging safety information and requested
post-marketing studies to address actual and potential safety
concerns.  These included requests for post-marketing studies
to assess risks of blood clots and effects on cancer. FDA has
requested and performed analyses of clinical studies to assess
the relationship between safety, dose, and pharmacodynamic
effects (e.g., rate of increase of red blood cells). FDA also
sought advice of the ODAC in May 2004 regarding assessment
of current information and design of studies to assess effects on
tumor growth, increased death rate, and blood clots.

As new data became available, FDA approved labeling
changes when the information available was determined to be
sufficient to support the change.

Should patients consider alternative products?

Yes, the patient and his/her physician should carefully consider
the risks of ESAs and the risks of red blood cell transfusions (an
alternative treatment for anemia) before making a decision to
use ESAs.

Why isn't FDA removing ESAs from the market?

At this time, ESAs appear to be safe and effective when used
according to the recently revised product labeling, at the
recommended dose and approved indication. The revised
labeling reflects the current knowledge regarding risks and
benefits that patients and their physicians should consider.  The
FDA continues to assess data as it becomes available.

ESAs may be used in ways that are not FDA-approved.
Should those users be concerned in the wake of these

Yes, all users of ESAs should be aware of these risks. Those
taking ESAs may be at increased risk of death and of serious
cardiovascular complications, including stroke, heart attack,
pulmonary embolism, and deep vein thrombosis (blood clots to
the heart and the blood vessels).

What are the previously reported serious and
life-threatening side effects of ESAs when used according
to FDA-approved product labeling?

Serious and life-threatening side effects common to all ESAs

*  An increased risk of blood clots in the lungs, brain and major
blood vessels.
*  Pure red cell aplasia.  This is a severe anemia that results
when patients become allergic to erythropoietins.

Serious and life-threatening side effects in patients with chronic
kidney failure

*  Seizures
*  Hypertensive encephalopathy (swelling of the brain caused by
very high blood pressure)

Where can I find more information about ESAs?

Please see the ESA information web page at

Information for Healthcare Professionals

Erythropoiesis Stimulating Agents (ESA)
[Aranesp (darbepoetin), Epogen (epoetin alfa), and Procrit
(epoetin alfa)]


FDA ALERT [11/16/2006, Updated 2/16/2007 and 3/09/2007]:
FDA is issuing this alert to provide new safety information for
erythropoiesis-stimulating agents (ESAs) [Aranesp (darbepoetin
alfa), Epogen (epoetin alfa), and Procrit (epoetin alfa)].
Analyses of four new studies in patients with cancer found a
higher chance of serious and life-threatening side effects and/or
death with the use of ESAs.  These research studies were
evaluating an unapproved dosing regimen, a patient population
for which ESAs are not approved, or a new unapproved ESA.  In
another study, patients scheduled for orthopedic surgery had a
higher rate of deep venous thrombosis when treated with Procrit
at the approved dose.  This new information is consistent with
risks found in two clinical studies in patients with chronic renal
failure treated with an unapproved regimen of an ESA that were
reported in November 2006 and are summarized in the data
section below.

All ESAs have the same mechanism of action.  As a result, FDA
believes these new concerns apply to all ESAs and is
re-evaluating how to safely use this product class.  FDA and
Amgen, the manufacturer of Aranesp, Epogen and Procrit, have
changed the full prescribing information for these drugs.  The
new product labeling includes a new boxed warning, updated
warnings, and a change to the dosage and administration
sections for all ESAs.  These changes are summarized below.

This information reflects FDA's preliminary analysis of data
concerning this drug.  FDA is considering, but has not reached a
final conclusion about, this information.  FDA intends to update
this sheet when additional information or analyses become


To report any serious adverse events associated with the use of
these drugs, please contact the FDA MedWatch program using
the contact information at the bottom of this sheet

Changes to the prescribing information for the ESAs (Aranesp,
Epogen and Procrit) are summarized here:

A New Boxed Warning providing the following information:

*  Avoid serious cardiovascular and arterial and venous
thromboembolic events by using the lowest dose of [Aranesp
/EPOGEN/PROCRIT] that will gradually raise the hemoglobin
concentration to the lowest level sufficient to avoid the need for
blood transfusion
*  [Aranesp /EPOGEN/PROCRIT] and other ESAs increased the
risk for death and for serious cardiovascular events when dosed
to achieve a target a hemoglobin of greater than 12 g/dL
*  Use of ESAs to achieve a target hemoglobin of 12 g/dL or
greater in cancer patients:

      *  shortened the time to tumor progression in
      patients with advanced head and neck cancer
      receiving radiation therapy;
      *  shortened overall survival and increased deaths
      attributed to disease progression in patients with
      metastatic breast cancer receiving chemotherapy;
      *  increased the risk of death in patients with active
      malignant disease not under treatment with
      chemotherapy or radiation therapy.  ESAs are not
      indicated for this patient population.

*  Patients treated before surgery with epoetin alfa to reduce
allogenic red blood cell transfusions had a higher incidence of
deep venous thrombosis. Aranesp is not approved for this

Additional Warnings about increased mortality,
cardiovascular events, tumor progression and
uncontrolled hypertension

*  Increased Mortality and Cardiovascular Events – the warnings
now describes the results of new studies showing an increased
incidenceof thrombotic events in patients with chronic renal
failure, cancer patients on chemotherapy, and surgical
*  Potential for Tumor Growth Progression – A new subsection in
Warnings describes the new data and emphasizes the evidence
for increased rate of tumor progression.
*  Hypertension - this subsection advises against the use of
ESAs in patients with uncontrolled hypertension, and describes
the risks to and guidance for managing controlled hypertensive

Recommendations and Considerations

Physicians and other healthcare professionals should consider
the following when using ESAs:

For all patients:

*  Use the lowest dose possible to gradually increase the
hemoglobin concentration to avoid the need for transfusion.
*  Measure hemoglobin twice a week for 2 to 6 weeks after any
dosage adjustment to ensure that hemoglobin has stabilized in
response to the dose change.
*  Withhold the dose of the ESA if the hemoglobin increase
exceeds 12 g/dL or rises by 1g/dL in any 2 week period.

For cancer patients:

*  Use of an ESA in anemic cancer patients who are not on
chemotherapy offered no benefit and may shorten the time to
*  ESAs are not FDA approved to treat anemia in cancer
patients not receiving chemotherapy
*  There is a potential risk of shortening the time to tumor
progression or disease-free survival
*  ESAs are administered only to avoid red blood cell
transfusions in cancer patients.  ESAs do not improve the
outcome of cancer treatment and do not alleviate fatigue or
increase energy.

Dosing and Monitoring Recommendations

For chronic renal failure (CRF) patients

*  Measure hemoglobin twice a week after initiating treatment
until hemoglobin has stabilized.

For cancer patients and zidovudine-treated HIV patients

*  Measure hemoglobin once a week after initiating treatment
until hemoglobin has stabilized.

For patients with a history of cardiovascular disease or

*  Closely monitor and control blood pressure.

Patient Counseling Information

Physicians and other healthcare professionals should
discuss the following with their patients:

*  The goal of treatment with erythropoiesis stimulating agents
(ESA) is to increase the number of red blood cells to avoid
blood transfusions.
*  ESAs require at least 2-6 weeks of treatment before there is
an increase in the number of red blood cells.
*  The effects of treatment with an ESA can be harmful in certain
*  They should keep appointments for blood tests so they can be
adequately monitored.
*  They need to monitor blood pressure every day (if
appropriate) and to call you if there are any changes outside of
the range established for the patient.

      *  Call you if they experience any of the following
      *  Pain and/or swelling in the legs
      *  Worsening in shortness of breath
      *  Increases in blood pressure
      *  Dizziness or loss of consciousness
      *  Extreme tiredness
      *  Blood clots in hemodialysis vascular access ports

Data Summary

Studies in cancer patients receiving radiotherapy

In December, 2006 Amgen informed FDA of the interim results
of the Danish Head and Neck Cancer Study Group trial
(DAHANCA 10).  This open-label, randomized trial compared
radiation therapy alone to radiation therapy plus Aranesp in the
treatment of advanced head and neck cancer.  The trial
assessed whether treating anemia to maintain a hemoglobin
concentration of 14.0-15.5 g/dL during radiotherapy would
improve loco-regional disease control. The DAHANCA 10 data
monitoring committee found that 3-year loco-regional control in
subjects treated with Aranesp was significantly worse than for
those not receiving Aranesp (p=0.01).  Overall survival also
favored those not treated with Aranesp, though this finding was
not statistically significant (p=0.08). The data monitoring
committee recommended the trial's termination on December 1,
2006. See http://conman.au.dk/dahanca for additional
information on the DAHANCA 10 study.  FDA will review and
analyze the complete study results after they are submitted by

This study is similar in design and in outcomes to that reported
by Henke, et al. The data from the Henke study were presented
at the May 4, 2004 meeting of the Oncologic Drugs Advisory
Committee. The briefing information and transcript for the
Advisory Committee is available at
The increased rate of tumor progression and increased mortality
reported in the Henke study were incorporated into product
labeling (see: Precautions, Tumor Growth Factor Potential) in

Study in cancer patients not receiving chemotherapy

FDA was notified in January 2007 of the results of a 989 patient,
multi-center, double-blind, randomized, placebo-controlled study
of Aranesp (darbepoetin alfa) in anemic cancer patients who are
not receiving chemotherapy. The target hemoglobin in the
Aranesp treatment group was 12 g/dl. The study results provided
to FDA show Aranesp did not reduce the need for red blood cell
transfusions and showed an increase in mortality in patients
receiving Aranesp compared to those receiving placebo (hazard
ratio 1.25; 95% confidence interval: 1.04, 1.51).  FDA will review
and analyze the complete study results after they are submitted
by Amgen.   Additional information on the study is provided in a
January 26th, 2007 Dear Health Care Professional letter sent by
Amgen (see

FDA was notified in February 2007 of the final results of a
double-blind, placebo controlled study to evaluate whether use of
epoetin alpha in anemic non-small cell lung cancer patients not
on chemotherapy improved their quality of life.  The epoetin alfa
dose was titrated to maintain a hemoglobin level of 12 to 14
g/dL; epoetin alfa was dosed at 40,000 IU every week.  Though
planned to enroll 300 patients, the study was closed to accrual in
December 2003 after enrolling only 70 patients because its data
monitoring committee found higher mortality in those treated with
epoetin alfa.  Median time to death in those treated with epoetin
alfa was 68 days and significantly shorter than the median time
to death of 131 days in those treated with placebo (p = 0.04),
with the majority of deaths reported as disease progression.
Also, treatment with epoetin alfa did not significantly reduce the
need for red blood cell transfusion or improve quality of life.
Prognostic factors and previous treatments were reported to be
well balanced between the treatment groups.  FDA will review
and analyze the complete study results after they are submitted
by Johnson & Johnson Pharmaceutical Research and

Study in cancer patients with an investigational ESA

In February 2007 FDA was notified by Hoffmann-La Roche that
it was suspending a study of a new ESA product because of
safety concerns.  The study was a multi-center, randomized,
dose-finding assessment of a pegylated epoetin beta product in
anemic patients with Stage IIIB or IV non-small cell lung cancer
who were receiving first line chemotherapy. Three dosing
regimens of the investigational drug were being compared to
Aranesp (given according to an FDA-approved dosing
regimen). The dose of pegylated epoetin beta was titrated to
maintain the hemoglobin level between 11 and 13 g/dL. An
interim analysis, after randomization of 153 patients,
demonstrated a numerical imbalance in the number of deaths
across the four arms of the study.  FDA has not yet received the
complete study results, and will review and analyze the data after
they are submitted by Hoffmann-La Roche.

Study in patients undergoing surgery

FDA was notified in February 2007 of the preliminary results of a
681 patient, multi-center, randomized, open-label, non-inferiority
study of Procrit (Epoetin Alfa) compared to the standard of care
in adult patients undergoing elective spinal surgery.  Procrit was
administered according to the dosage and administration
section of the label for pretreatment hemoglobin values >10 and
< 13 g/dL.  The frequency of deep venous thrombosis in patients
treated with Procrit was 4.7 percent (16 patients), more than
twice that of patients who received usual blood conservation
care (frequency of 2.1 percent, seven patients). FDA will review
and analyze the complete study results after they are submitted
by Ortho Biotech, L.P.

Studies in patients with chronic renal failure

Two clinical studies and an editorial published in the New
England Journal of Medicine in November, 2006 addressed
safety concerns about the use of erythropoiesis stimulating
agents in the treatment of anemia of chronic renal failure (CRF).
The 1,400 subject CHOIR study demonstrated increases in
serious and potentially life threatening cardiovascular events
when epoetin alfa (Procrit) is administered to reach higher target
hemoglobin levels than lower target hemoglobin levels. The 600
subject CREATE study trended toward more cardiovascular
events in a pattern similar to the CHOIR study, thus
strengthening the findings of the CHOIR study.  The CREATE
study examined the use of epoetin beta, a product not approved
in the USA.

The CHOIR study was a randomized, open label design in which
anemic chronic kidney disease (CKD) subjects were
randomized to be dosed to either a higher target hemoglobin
(13.5 g/dL) or a lower target hemoglobin (11.3 g/dL).  All
subjects received Procrit.  The primary endpoint was a time to
event analysis for a composite cardiovascular endpoint (all
cause mortality, congestive heart failure (CHF) hospitalization,
non-fatal MI, or non-fatal stroke).

Procrit was administered as 10,000 U SC weekly and titration
allowed to a maximum dose of 20,000 U weekly.  Overall, 715
subjects were randomized to the high hemoglobin target (13.5
g/dL) and 717 randomized to the low target (11.3 g/dL).  At the
end of the study, the average hemoglobin was 12.6 g/dL for the
high group and 11.3 g/dL for the low group.  The primary
endpoint, composite of death, and cardiovascular events was
statistically significant worse outcome in the higher target
hemoglobin group (p = 0.03 by log rank test) with a hazard ratio
of 1.3 [95% CI 1.03, 1.74].  The rates for the individual
components of the composite primary endpoint were (high
target hemoglobin vs. low target hemoglobin):

Death:                   7.3% vs 5.0% (p = 0.07)
CHF hosp:             9.0% vs 6.6% (p = 0.07)
Non-fatal MI:         2.5% vs 2.8%
Non-fatal stroke:   1.7% vs 1.7%

*  The published analyses for this study found no correlation
between adverse cardiovascular events and rate of rise of

The published CHOIR and supportive CREATE study findings
underscore the importance of the warnings in the labeling for
Procrit, Epogen, and Aranesp regarding cardiovascular risks
that include thrombotic events and increased mortality observed
in hemodialysis patients with cardiac disease targeted to higher
hemoglobin levels (~14 g/dL), and warning regarding the
increased risk of death if ESAs are dosed to raise hemoglobin
levels to >12 g/dL.


Report serious adverse events to
FDA's MedWatch reporting system by completing a form on line at
http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178),
by mail using the postage-paid address form provided online
( 5600 Fishers Lane, Rockville, MD 20852-9787),
or by telephone (1-800-FDA-1088).

© Copyright 2004 - 2007 foodconsumer.org All right reserved

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Date:    Sat, 10 Mar 2007 21:03:49 -0500
From:    "Susanna <susannaa dodo.com.au> [via Co-Cure Moderators]
Subject: NOT,MED:Chronic Fatigue Syndrome in Parallel Universe

Chronic Fatigue Syndrome Placed in Parallel Universe

Susanna Agardy

Recently I discovered an alarming article on Kings College London
website which places CFS into a parallel universe. Nothing new in that.

version as at 11 March 2007) But, not only does it generally attribute
the continuation of CFS to inactivity and anxiety in the general way we
are accustomed to, it systematically goes through selected, serious
physiological findings and symptoms of CFS and equates them solely with
the physical consequences of inactivity and anxiety. It makes the claim
that these problems can be reversed with exercise. Notably, delayed and
long-lasting post-exertional malaise is omitted from the explanations.

There is one major flaw in this attribution: the wrong sequence of
events. Symptoms of CFS precede inactivity and not follow them, even if
subsequent prolonged inactivity has its own problems. Through failure of
logic, observation, or referring to the wrong type of patient, Dr
Burgess, the author, reverses the sequence of events in CFS. The
confused definition of ‘Chronic Fatigue Syndrome’ with its diverse
interpretations does not help.

In my own case of slow onset CFS there was no period of inactivity
preceding symptoms. An allergic event, triggered by a move to a new
office, which appeared to subside, gradually brought on the symptoms of
CFS. It was properly diagnosed only some 5 years later. Although I felt
awful most of the time I kept up my activities, going to work,
maintaining my climb up escalators on the way, trying to keep fit. As
time passed, I had to rest more and take more short sick breaks, but
carried on normally in between. I was forced to give up swimming when
one day, without warning I could barely lift my arms. This is not a good
way to be in a pool. Doctors could not find anything wrong with me, I
had barely heard of 'chronic fatigue’ and did not know what it was. In
spite of feeling worse and losing tolerance of exercise, I battled on
until a bout of pneumonia, after which I could not resume my normal
activities. However, I kept up a reduced level of exercise which has now
decreased to minor household chores and personal care. This is due to
the worsened reactions and lengthier periods of recovery required. I am
now mostly housebound. Exercise and activity over the years has
certainly not stopped me from getting worse.

In the case of sudden onset CFS it is also obvious that the symptoms
precede any reduction in activity.

Dr Burgess states that because of feeling awful, some ‘sufferers rest
for long periods and give up many of their previous activities. I
certainly did not ‘give up’ anything and in my worsened phase fought
tooth and nail to retain my job in the expectation of returning ‘in the
next two weeks’. It could not be done.

Embedded in her statements is the assumption that somewhere along the
line CFS people get better but unreasonably persist in inactivity. Yet,
if we listen to sufferers, it is clear that they are motivated to be as
active and normal as possible and often try to hide their poor health or
may be forced by circumstances to overextend themselves at times.
Engaging in too much activity demonstrates that as soon as sufferers
have some energy they become more active, disproving the false argument
that they are indulging themselves in inactivity.

In CFS reduced activity is not a strategic choice, but a necessity. Rest
improves my symptoms and activity makes them worse and there is no
amount of increase in exertion small enough which will not make them
worse, because the basic exertion needed for necessities is already

Dr Burgess fails to mention the scenario where sufferers do moderate
exercise and still do not get well or in fact get seriously worse as a
result. Thus, sufferers are deprived of the opportunity to make an
informed decision about the risks of their exercise treatment.

The assumption that CFS sufferers are responsible for their symptoms
because of their inactivity reminds me of Sigmund Freud’s judgment of
his patient, Emma, whom he diagnosed with sexual problems. This diagnosis
was confirmed by his ear, nose and throat specialist friend, Wilhelm Fliess.
When Fliess looked at Emma’s nose, he too, diagnosed a sexual problem. Surgery on
Emma’s nose was carried out. Unfortunately it was botched and Emma
almost bled to death. Rather than attributing her bleeding to the
botched operation, Freud and Fliess declared Emma a ‘hysterical
bleeder’. This rationalization technique is usefully adopted by the
Wessleyites: first define physical illness as behaviour, then you can
make the patient responsible and blame them. What is more, no further
evidence is required for your allegation. The Wessleyite method of
diagnosis and basis of treatment could also be compared in interesting
ways with that of Freud and Fliess.

Dr Burgess reduces CFS to ‘unpleasant sensations and symptoms’ which she
claims should not be interpreted as signs of a serious disease. The
inference is that if you have some of these symptoms, eg, cardiac
symptoms, it is because you are anxious. She encourages sufferers to
ignore these, as paying attention to them will only increase underlying
anxiety. She does not say if non-CFS people should also ignore similar
physical symptoms or at what point we should stop ignoring them. She
does not say all this outright, but much of the message is by innuendo
and indirect suggestion.

Dr Burgess seems confident that CFS has no underlying condition that
some exercise and anxiety control can’t reverse. From what she and her
colleagues write, we would be forgiven for concluding that they had
extensively tested all their CFS patients for the variety of pathogens
and other physiological processes which could affect them and for which
there is already evidence. This is not so. If they have doubts about the
evidence as to why CFS sufferers continue to be ill they could err on
the side of caution. Instead, they err on the side of lack of caution.

They seem to suggest that medical science has nothing more to learn
about pathogens and various physiological processes in CFS, while
ignoring, dismissing or misinterpreting existing evidence. Not long ago
it was thought impossible that bacteria could live in the acidic
environment of the stomach and that stomach ulcer was caused by stress
or spicy food. This dogma was demolished by Drs Barry Marshall and Robin
Warren when they found that the ulcers were caused by bacteria, earning
them the Nobel Prize for their discovery in 2005. Dr Marshall said on a
television program: ‘The diagnosis of an illness as stress is an
admission of defeat by the doctor.' Members of the Wessleyite school
have learnt nothing. But they do know how to suppress evidence which
fails to support their beliefs.

In this article misleading statements, distortions and lack of logic vie
with each other to convince the hapless CFS sufferer to adopt the
parallel universe version of CFS and go take up exercise. The gamble has
already been lost by many patients.

In conclusion, Dr Burgess states: ‘As we said there is */no/* good
evidence to show that all of the above effects are reversible by a
programme of gradual physical rehabilitation.’ (my bold italic for
‘no’). In view of the rest of the article, this would appear to be an
error which inadvertently reflects reality.

[Return to top]


Date:    Sat, 10 Mar 2007 17:09:55 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES,NOT: Pediatric CFS - Munchausen-By-Proxy

Source: Journal of Chronic Fatigue Syndrome
        Vol. 13, No. 2/3, 2006, pp. 45-53
Date:   2006
URL:                               http://jcfs.haworthpress.com

Pediatric Chronic Fatigue Syndrome and Munchausen-By-Proxy: A Case Study
E. Van Hoof, Clin Psych, PhD
P. De Becker, PhD
K. De Meirleir, MD, PhD
E. Van Hoof is affiliated with the Department of Human Physiology (MFYS),
   Faculty of Human Exercise and Human Education, and Cognitive and Biological
   Psychology, Faculty of Psychological and Educational Sciences, Vrije
   Universiteit Brussel (VUB), Belgium. E. Van Hoof is also affiliated
   with the University of Hasselt, Belgium.
P. De Becker and K. De Meirleir are affiliated with the Department of Human
   Physiology (MFYS), Faculty of Human Exercise and Human Education, Vrije
   Universiteit Brussel (VUB), Belgium.
Address correspondence to: Elke Van Hoof, Clin Psych, PhD, Universiteit
   Hasselt, Faculty of Medicine, Department of Behavioral Sciences, Agoralaan-
   Gebound, 3590 Diepenbeek, Belgium.


Pediatric chronic fatigue syndrome (CFS) posits even more challenges for
professional caregivers in comparison with adult CFS samples. Most children
with CFS display a decrease in school attendance and a decrease in social
activities. As several conditions such as school phobia, primary psychiatric
disorders or family disturbance present the same characteristics, the
diagnostic process appears more complex. Family disturbance, moreover, is
often specified as child abuse, neglect or even Munchausen-by-proxy. As
skepticism is frequently associated with a diagnosis of CFS, patients and
parents must fend for themselves, fighting allegations of child abuse and
neglect. This case study illustrates what happens when such allegations are
put forward.

KEYWORDS. Munchausen-by-proxy, pediatric chronic fatigue syndrome, child
protective services


Chronic fatigue syndrome (CFS) is still a controversial diagnosis in
adolescents. In studies of prolonged and chronic fatigue, the symptom
pattern observed in child and adolescents samples has been found to be
similar to that observed in adult presentation with a few exceptions (Smith
& Carter, 2003). Most children with CFS also display an impaired school
performance and a decrease in social activities (Van Hoof & Maertens, 2002).
The impact of this illness is profound as one survey suggested that CFS is
responsible for 50% of long term absences from school (Colby, 1994).

Widespread skepticism among the medical professionals increases when
confronted with child CFS. As a result, after routine examination, the child
is frequently dismissed, as also mentioned by Bell in this volume.

The core problem of this skepticism is that it spreads to educators and
possibly members of the family. Consequently, patients and parents must fend
for themselves, arranging school accommodations and fighting allegations of
child abuse and neglect for truancy from school. The lifelong potential for
harm in this scenario is enormous as it occurs during an important period of
identity formation.

This case study reports the experiences of an adolescent with CFS. The
subject is a 17 year old boy who reported significant complaints since
January 2004. In this period, he frequently fell ill and reported not to
recuperate from these seemingly benign infections. After examinations, his
general practitioner (GP) found several infections in his blood for which he
received treatment. In July 2004, he suffered from appendicitis and had an
emergency surgery. After this procedure, the subject reported an improvement
of his symptoms.

In September 2004, however, his condition began to deteriorate. He was
referred to a specialist in order to receive nutritional supplements and to
another specialist who performed intestinal lavages. Although he gradually
reported improvement and began to function at a higher level, he suffered a
relapse in March 2005. From this moment, his compliance to the medical
protocol decreased significantly.


>From the anamnestic information, the subject seemed to suffer from recurrent
infections during childhood. Nevertheless, he achieved 80-85% in primary
school. During primary school, he was viewed as an intelligent and
cooperative boy with lots of interests and good social interactions with his
peers. In seventh grade, more independence and effort was required from
students. The subjects' family reported that as he never had to study hard
in first grade up to sixth grade, he only achieved 60% which was still an
average result. In 8th grade, the infections became more frequent and
started to interfere with his school attendance. For every absenteeism, the
subject had a legal sickness certificate. Due to his frequent absenteeism,
he had to follow his 8th grade twice. Ninth grade was even more problematic
as he did not have the energy to keep up with his `healthy' peers. He became
an irregular pupil. In total, the subject attended 90 school days (accepted
<21 days). This academic year, his peers gave him class notes so he could
study for his exams. No other special arrangements were made.

At the moment, he is in 10th grade and still frequently absent. No special
arrangements or class notes are provided. Furthermore, he experiences no
support from his teachers. In general, the subject sense increasing
hostility from the school environment.


During his early childhood (<5 years of age), he experienced physical abuse
from his father. His parents eventually got divorced. After the divorce, he
did not want to keep in touch with his father. His father, however, had
legal visitation and forced his son to visit every Saturday during the next
two years. Consequently, the subject suffered from psychosomatic complaints.
Four years later, his father died. He followed psychological counseling in
7th and 8th grade to deal with his past. The therapy was successfully
terminated in 8th grade. After his father died, his siblings and mother all
became legal guardians over him.


The subject was referred to our department because he suffered from a severe
relapse in March 2005. The subject attributed this relapse to emotional
stress he experienced due to increasing hostility at school. His GP wanted
to introduce some special arrangement so he could recuperate. At the time
the intake took place, no leisure activities were present. He gradually gave
them up in order to keep up at school.

During the intake, the mother handed over a note from the child protective
services (CPS) that stated that they had to attend an inquiry in their

The physician from this center revealed to our department that the school
made a formal complaint against the mother and the school moreover suggested
the mother suffered from Munchausen-by-proxy.

Munchausen-by-proxy (MSBP) is described as the intentional production or
feigning of physical or psychological signs and/or symptoms in another
person who is under the individual's care for the purpose of assuming the
sick role by proxy. The child is presented for medical assessment and care,
usually persistently, often resulting in multiple medical procedures. The
perpetuator has to deny knowledge of the etiology of the child's illness.
Furthermore, in MSBP, acute symptoms and signs of the illness(es) decrease
when the child is separated from the perpetuator. There are about 2-4 cases
per million in the general population (Alexander et al., 1990). In general,
as the diagnosis is complex, a high index of suspicion is needed to make the
diagnosis of MSBP. The symptoms and signs also have to disappear when the
child is away from the perpetuator.


A meeting was organized involving the CPS, our department, all legal
guardians of the subject, the school and the medical staff of the school.
The medical staff of the school who filed the complaint did not attend. In
this meeting, it became clear that the confidence in the school and its
personnel was affected. There had been no contact with the family (mother or
legal guardians) regarding possible concerns the teaching staff and the
medical staff might have. Rightfully, the physician of the CPS requested a
medical as well as a psychological report.


The subject reports fatigue that increases due to physical activity, re-
current flu-like illness, early awakenings during sleep, headaches,
dizziness, non-restorative sleep, muscle and joint pains, fever, recurrent
herpes infections, attention problems, sore throat, recurrent sinusitis,
dyspnoa when exercising, and concentration disorders.

He reported a significant level of psychological and physical dysfunctioning
indicating anxiety, physical symptoms, interpersonal sensitivity, hostility
and sleep problems. Avoidant behavior was present including minimizing the
threat of the stressor using emotion-focused as well as avoiding the actual
situation (for example distracting himself by thinking of pleasant
thoughts). His physical functioning appeared significantly lower in
comparison with healthy age-matched controls. Especially, physical and
social functioning are problematic as well as bodily pain. He reported
significant fatigue and motivational problems that significantly influenced
his daily activities. No depressive or anxiety disorder was apparent.
Reduced motivation could be related to the situation that presented itself
at school. The subject attributed a part of his complaints directly to the
complaint and subsequent anxiety and worries.

A neurocognitive screening revealed memory problems, especially with
short-term memory. No attention problems could be objectified. The subject
seemed an intelligent person with otherwise average neuro-cognitive
capacities in comparison with his peers.

The medical investigation indicated he complied to the CDC criteria for CFS
of 1994 (Fukuda et al., 1994). Physical findings included monocytosis, bowel
dysbiosis, low natural killer cells percentage as well as activity, and a
RNase L ratio of 0.8 (normal < 0.5). The maximal exercise capacity was 39.4
ml.min 1kg 1 which falls in the normal range. The medical treatment focused
on the bowel dysbiosis that is hypothesized to be a sustaining factor.


Due to the investigation into the possible presence of MSBP, the
communication between the school staff, the legal guardians and the subject
became problematic. No arrangements were put forward in order to ensure the
education of the subject. Meanwhile, the academic year was half way.

Unfortunately, during the inquiries, the assigned physician went on
maternity leave. As a consequence, the whole procedure needed to start from
the beginning because the new physician wanted to conduct her own

At this point, the legal guardians were fed up. The subject refused to
conduct any more interviews as he already lost several months at school. The
physician, on the other hand, became restless and confused as she was never
confronted with a patient with CFS nor a MSBP case before. Finally, the
physician turned to our specialized center for information. She received
recommendations on how to establish an individualized educational program in
CFS. Furthermore, contacts were offered of other schools that had already
implemented such a program. Finally, scientific information was handed over
to this physician.

A couple of weeks later, the physician was ready to take a final decision
and again invited all parties involved. However, some of the parties were
reluctant to participate. Fortunately, some arrangements could be made at
the end.

The subject was able to do his exams at the same school. The school was
going to prepare the notes on which he had to study. Furthermore, an exam
roster was prepared. Two days before his first exam, the subject and its
family received all study information. The family was responsible to tutor
and prepare the subject. This procedure again led to mistrust and a lot of

During this exam period, the family got an invitation of the committee for
special youth care for again, another interview. This invitation had a very
stressful connotation as this committee can hand over children to foster
care and deny parental rights.

Although some guidelines were put forward, the CPS thus forwarded the
complaint to a higher level without consulting the family. Once again, all
medical records were forwarded to a new physician. After reviewing all
records, the complaint was dismissed and sent back to the CPS. Surprisingly,
this department now closed the file and dismissed the complaint after a
short phone call with the subject. Finally, in August 2005, no MSBP seems
present according to the CPS.

As a result, the school that the student was attending requested a
replacement to another school.

The subject began to look for another school where he could integrate and
start education. The new school was immediately informed and all possible
information was handed over. At first, they appeared reluctant to accept the
patient as no legal document could validate the closure of the file and the
dismissal of the complaint at that time.

Finally, the official documents arrived and by the end of September 2005, an
individualized educational program was implemented. The subject is going to
divide his next year into halves and will be tutored by a home-tutoring


This case study clearly indicates the mistrust and dismissal some CFS
patients experience. Pediatric CFS is still an unknown condition. This case
study shows that CPS should be informed about chronic conditions as here
it was mistaken for MSBP.

MSBP is a serious and potentially lethal form of child abuse in which a
person who assumes the role of a caretaker induces or reports factitious
symptoms in a child. The child-victim suffers from the caregiver's actions
and health care providers unknowingly become `accomplices' when they provide
unnecessary testing and therapies. The perpetuators are nearly always the
mother and psychiatric disorders are common in particular personality
disorders and depression. Family history often reveals evidence of similar
abuse affecting other siblings. An illness or condition that happens `all
the time,' or only when observed at home, but never in the hospital, is
suspect. Furthermore, inconsistencies or contradictions among findings and
presentation of child are suspect. In this case, no inconsistencies or
contradictory medical findings were reported by the treating team. Both the
medical and psychological evaluations did not indicate anything suspicious.
The family history did not reveal similar problems in other siblings, except
for physical abuse by an alcoholic father. After his death, all other
siblings became legal guardians over the subjects. The siblings are all
included in the decision-making process regarding the subject. The
psychologist who the subject visited in 7th and 8th grade could not present
anything other than the presence of psychosomatic complaints during the
legal visitation right of the father. She successfully closed the counseling
sessions and described the subject as an intelligent person with a lot of
capacities. He had and has a good social network and a lot of support. The
psychologist indicated that he had a good self-esteem and reported insight
in the problems. However, due to the allegation, the subject lost half of a
school year. He lost confidence in the institutions that were created to
protect and listen to children. Due to the unpredictability of the process
in CPS and the committee for special youth care, he became worrisome and

His relapse in March 2005 was thus directly related to the increasing
hostility he experienced from school. He sensed something was wrong but no
one discussed these issues with him. As a result, the family was severely
affected by the complaint and the subsequent process. The mother felt
humiliated and reported feelings of failure. The whole family is currently
trying to put things in perspective and works closely together to deal with
this experience. The subject found support in his new school but is still
physically recuperating from his last school year. Due to increased anxiety
and stress, his condition deteriorated. At the moment, he is back at the
functional level he had before his relapse.

It is thus important to keep in mind that an allegation of MSBP is serious
and potentially life altering for the suspected perpetrator, regardless of
the outcome of the case. Therefore, it is necessary for the primary
caregiver, in this case the medical staff at school, to conduct competent,
thorough, professional and well-documented investigative work before they
levy any such allegation. Commonly, the diagnosis is made following the
sharing of information, thus underlying the importance of good communication
between those involved in the case.

Again, if the medical staff and the school personnel were informed on
chronic conditions such as CFS, this situation could have been prevented. In
adolescents with CFS, school attendance and leisure activities are most
affected by the functional impairment. Functional impairment is a key aspect
of the condition and it affects most areas in children's lives. Most
striking, according to Rangel, Garralda, Lavin and Roberts (2000),
two-thirds of the children with CFS had been totally unable to attend
school, with a mean time out of school of at least one year. In a recent
study, only 22% went to school full-time and 30% went through a standard
exam schedule (Van Hoof et al., in press). Prolonged school absenteeism
consequently is included in the definition as a proxy measure for functional
impairment and severity (De Jong et al., 1997; Vereker, 1992; Garralda &
Rangel, 2004). A lot of adolescents, furthermore, do not believe their
grades match their capacities (Van Hoof et al., in press). In real life, the
outcome of education is generally seen as the degree of success at national
examinations and entry to further education. These are rarely reported in
clinical literature. Furthermore, they experience a lot of conflicts at
school and less help and support from the school environment. Summarizing,
adolescents with CFS can not attend school full-time, do not get grades
according to their intellectual capacities, and can not participate in a
social culture due to their complaints. If not supported in a correct
fashion, their identity, their sense of self esteem, their value systems
could be affected, and this creates insecurity.

To protect a healthy development of identity and sense of self, more support
should be offered at school. Information about this condition should be
presented to the school personnel. Moreover, information on development
should be given. Subsequently, school personnel and family would be able to
integrate education and social development. One could argue that an
arbitrary division of 60% of the energy for school and education, and 40% of
energy to social activities could improve and protect their identity
development. Correlations revealed that a positive attitude of the teachers
could create a positive attitude in fellow students and receiving
appropriate guidance (Van Hoof et al., in press). This could diminish the
chance of conflicts and would create an adapted school environment for the
child with CFS.


Alexander R., Smith W., Stevenson R. (1990) Serial Munchausen Syndrome by
   Proxy. Pediatrics S6(4): S81-S86.
Colby, J. (1994) Study finds 12000 pupils may be suffering from ME. Sunday
   Times, 5 June 1994.
De Jong, L.W., Prins, J.B., Fiselier, T.J., Weemaes, C.M., Meijer-van den
   Bergh, E.M., Blijenberg, G. (1997) [Chronic fatigue syndrome in young
   persons]. Nederlands Tijdschrift voor Geneeskunde 141:1513-16.
Fukuda, K., Strauss, 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.
Garralda, M.E., Rangel, L. (2004) Impairment and coping in children and
   adolescents with chronic fatigue syndrome: A comparative study with other
   pediatric disorders. Journal of Child Psychology and Psychiatry 45(3):
Smith, M.S., Carter, B.D. (2003) Chronic fatigue syndrome in adolescence.
   In: Jason, L.A., Fennell, P., Taylor, R.R. (Eds.) Handbook of chronic
   fatigue syndrome and fatiguing illnesses. New York, NY: Wiley, 693-712.
Van Hoof E., De Becker P., Lapp, C., De Meirleir K. (in press) How do
   adolescents with chronic fatigue syndrome perceive their school
   environment? A qualitative study. Journal of Child Health Care.
Van Hoof, E., Maertens, M. (2002). Neen, ik ben niet lui! Een gids voor
   jongeren met CVS/ME en hun opvoeders (No, I am not lazy! A guide for
   adolescents with CFS/ME and their caretakers). Brussel: VUB Press.
Vereker, M. (1992) Chronic fatigue syndrome: A joint pediatric-psychiatric
   approach. Archives of Disease in Childhood 67:550-555.

(c) 2006 The Haworth Press, Inc.

[Return to top]


Date:    Sun, 11 Mar 2007 09:52:12 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES,NOT: Pediatric CFS - Introduction

Source: Journal of Chronic Fatigue Syndrome
        Vol. 13, No. 2/3, 2006, pp. 1-44
Date:   2006
URL:                               http://jcfs.haworthpress.com
Ref:    See also,

A Pediatric Case Definition for Myalgic Encephalomyelitis and Chronic Fatigue
Leonard A. Jason, PhD
David S. Bell, MD, FAAP
Kathy Rowe, MD
Elke L. S. Van Hoof, Clin Psych, PhD
Karen Jordan, PhD
Charles Lapp, MD
Alan Gurwitt, MD
Teruhisa Miike, MD
Susan Torres-Harding, PhD
Kenny De Meirleir, MD, PhD
Leonard A. Jason (Chairperson), David S. Bell, Kathy Rowe, Elke L. S. Van Hoof,
Karen Jordan, Charles Lapp, Alan Gurwitt, Teruhisa Miike, Susan Torres-Harding,
and Kenny De Meirleir are members of IACFS (International Association for Chronic
Fatigue Syndrome).
Leonard A. Jason is affiliated with the Center for Community Research, DePaul
   University, Chicago, IL, USA.
David S. Bell is Clinical Associate Professor of Pediatrics, State University of
   New York at Buffalo, Buffalo, NY, USA.
Kathy Rowe is affiliated with the Department of General Paediatrics, Royal
   Children's Hospital, Parkville, Victoria, Australia.
Elke L.S. Van Hoof is affiliated with Cognitive and Biological Psychology,
   Faculty of Psychological and Educational Sciences, Vrije Universiteit Brussel,
Karen Jordan is in Private Practice, Seattle, WA, USA.
Charles Lapp is affiliated with Hunter-Hopkins Center, PA, Charlotte, NC, USA.
Alan Gurwitt is affiliated with Boston Psychoanalytic Institute and Society, MA,
Teruhisa Miike is affiliated with the Department of Child Development, Faculty of
   Medical and Pharmaceutical Sciences, Kumamoto University Graduate School,
Susan Torres-Harding is affiliated with the Center for Community Research, DePaul
   University, Chicago, IL, USA.
Kenny De Meirleir is affiliated with the Department of Human Physiology, Faculty
   of Physical Education and Physical Therapy, Vrije Universiteit Brussel,
Address correspondence to: Leonard A. Jason, PhD, DePaul University, Center for
Community Research, 990 West Fullerton Avenue, Suite 3100, Chicago, IL 60614
(E-mail: Ljason depaul.edu).


For a diagnosis of chronic fatigue syndrome (CFS), most researchers use
criteria that were developed by Fukuda et al. (1994), with modifications
suggested by Reeves et al. (2003). However, this case definition was
established for adults rather than children. A Canadian Case Definition
(ME/CFS; Myalgic Encephalomyelitis/CFS) has recently been developed, with
more specific inclusion criteria (Carruthers et al., 2003). Again, the
primary aim of this case definition is to diagnose adult CFS. A significant
problem in the literature is the lack of both a pediatric definition of
ME/CFS and a reliable instrument to assess it. These deficiencies can lead to
criterion variance problems resulting in studies labeling children with a
wide variety of symptoms as having ME/CFS. Subsequently, comparisons between
articles become more difficult, decreasing the possibility of conducting a
meta-analysis. This article presents recommendations developed by the
International Association of Chronic Fatigue Syndrome Pediatric Case
Definition Working group for a ME/CFS pediatric case definition. It is hoped
that this pediatric case definition will lead to more appropriate
identification of children and adolescents with ME/CFS.

KEYWORDS. Pediatric CFS, definition, pediatric questionnaire


ME/CFS1 is a persistent disabling disorder that is characterized by severe,
overwhelming fatigue along with a number of other symptoms (Fukuda et al.,
1994; Joyce et al., 1997). The origins and boundaries of the syndrome are
still unclear (Jason et al., 2003; Komaroff & Buchwald, 1998). Illnesses that
are consistent with ME/CFS definitely occur in adolescents and children
(Breau et al., 1999; Jordan et al., 1997; Marshal, 1999; Wright & Beverly,
1998). However, the case definition was developed for adults (Fukuda et al.,
1994) and may not be appropriate for use with children and adolescents.
Currently, no ME/CFS case definition exists for children and adolescents. The
lack of application of a consistent pediatric definition of ME/CFS and the
lack of a reliable instrument to assess it (Jordan, Kolak, & Jason, 1997)
might lead to studies which inaccurately label children with a wide variety
of symptoms as having ME/CFS as well as possibly missing children who do have

In The Netherlands, a case definition was proposed in order to increase
coherence in child ME/CFS (De Jong et al., 1997). According to this case
definition, as with adult ME/CFS, no somatic or psychiatric condition should
be able to explain the symptom pattern presented by the child/adolescent. In
addition, there should be a distinct onset of the symptom pattern. In
contrast to adult ME/CFS, where patients need to present a significant
decrease in their physical functioning, children or adolescents are not able
to compare premorbid or morbid physical functioning due to their lack of
reference and due to their flexibility. Both are characteristics of the
process of identify formation. Therefore, the assessment of leisure, social
and educational activities are indispensable to being able to detect a
decrease in their functionality.

here has been controversy over whether the assignment of a diagnosis of
ME/CFS in children may lead to omissions or errors in the appropriate
diagnostic evaluations of fatigued children (Harris & Taitz, 1989; Jones,
1997; Lask, & Dillon, 1990). Some believe that the diagnosis of ME/CFS in
this age group should be considered only an interim diagnosis but not a
definitive disease (Jones, 1997). Another concern about applying a ME/CFS
diagnosis to a young child is the potential damage inflicted on a child by
conferring a diagnosis that is open-ended. However, this possibility must be
weighed against the advantages of naming the illness that may alleviate
anxiety and uncertainty in both the child and family as well as having a
clarifying impact on the school environment. These arguments do not address
the reality that many clinicians are, indeed, faced with children with
unexplained fatigue and other symptoms for which exhaustive medical and
psychosocial evaluations have not revealed an acceptable explanation. In
these children, no diagnosis may be made, often leading to the inappropriate
assumption of malingering or diagnosis of psychiatric disease. These
incorrect diagnoses may be more damaging than the diagnostic label of ME/CFS.
It seems clear that for any child with a chronic illness, an ongoing
diagnostic evaluation that involves looking for either primary causes of fa-
tigue and other symptoms or complications of underlying process, is essential
(Carter & Marshall, 1995). There is now enough clinical experience and
research findings to put forward a case definition for children and

One of the main goals of classifying any disease or illness is to group
together patients who have an illness that may have many manifestations, but
a common underlying pathophysiological pathway (Hartz et al., 1998). The
benefit of classifying patients into diagnostic categories is that it
facilitates communication among clinicians/researchers, selection of
appropriate treatment methods, and prediction of response to treatment. Past
experience has shown that even in cases where the underlying
pathophysiological pathway has not been identified, research on the etiology
and treatment of the illness has been facilitated by simply classifying these
illnesses as syndromes of signs and symptoms (e.g., systemic lupus
erythematosus or tuberculosis). One of the greatest sources of diagnostic
unreliability is criterion variance, differences in the formal inclusion and
exclusion criteria used by clinicians to classify patients into diagnostic
categories (Spitzer et al., 1975). The addition of specific criteria and
standardized measures with scoring guidelines would likely improve the
reliability of diagnostic decisions by providing clinicians with objective
standards to follow when assessing the various features of this syndrome
(King & Jason, 2005). Collecting very careful clinical, family, and
developmental histories is also important to ensure a differential diagnosis.

In order to address these important classification and diagnostic issues,
this paper proposes a case definition for diagnosing ME/CFS in children and
adolescents. It is hoped that this case definition for children and
adolescents with ME/CFS will serve as a developmentally appropriate
diagnostic tool for clinicians and researchers. Further, development of a
pediatric definition of ME/CFS will allow for the application of consistent
and objective criteria, and may serve to stimulate research which will then
not only further test the validity of this case definition but also elucidate
pathophysiology and improve treatment approaches.


It is critical that those conducting studies attempting to diagnose children
with ME/CFS carry out a thorough evaluation, including a comprehensive
medical and developmental history, physical examination, and laboratory tests
to confirm diagnosis. The history should involve both of the parents as well
as the child because children are still constructing their identity.
Subsequently, they do not have a reference to which they can compare before
and after situations.

Arav-Boger and Spirer (1995) describe the usual patient as being previously
athletic and ambitious, upper middle-class, and having close relatives with
ME/CFS. Similarly, while clinic and community samples have found more female
than male adults with ME/CFS (Gunn et al., 1993; Jason et al., 1999), several
studies involving children have shown an equal representation of females to
males (e.g., Jordan et al., 1998). A recent study by Van Hoof et al. (in
press) shows the same gender representations compared to adults (80% females
vs. 20% males) in adolescents. This finding might suggest that hormonal
changes in adolescence trigger this difference in gender prevalence. Another
recent study by Viner and Hotopf (2004) found that a higher risk of ME/CFS
was associated with having a limiting longstanding condition in childhood,
female sex, and high social class in childhood. Higher levels of exercise
in childhood were associated with lower risk of ME/CFS.

Among adolescents, easy fatigability and disturbed learning and memorization
are several of the primary characteristics of this syndrome (Miike et al.,
2003). As is often so with adults, the fatigue may be quite severe to the
point that "exhaustion" would be a more apt description. Another striking
feature of this illness is the individuality of symptom patterns and
unpredictability of symptom severity among youngsters with ME/CFS. The
unpredictable fluctuation of symptom severity is one of the more stressful
features for youth and family alike. Children may have a few good days and
then end up in bed. When others see them on "good days," they might become
confused or skeptical about the seriousness and debilitating effects of the
illness. This can become a serious matter as it can lead to rejection of the
diagnosis by school authorities and others and relentless pursuit of
psychological explanations even to the point of inappropriately diagnosing

Children may experience different symptoms than adults with ME/CFS (Jordan et
al., 1997). Symptoms such as rashes and abdominal pain may be frequently
present in pediatric ME/CFS, but may not be as common in adults. Bell (1995b)
reported that the three most common complaints, besides fatigue, in children
and adolescents with ME/CFS were headaches, sleep disturbance, and cognitive
difficulties. As children are still learning effective coping skills, they
frequently react upon their complaints by increased irritability (Van Hoof &
Maertens, 2002).

The prognosis for a child or adolescent diagnosed with ME/CFS has been
considered to be better than with adults with this diagnosis (AravBoger &
Spirer, 1995; Smith & Carter, 2003). While the condition has not been found
to be progressive nor life-threatening (Carter et al., 1995), it is
noteworthy that some children continue to experience significant fatigue and
disability. It is possible that children who do not show any improvements
over time have a more severe form of the illness or differ in other important
genetic or biological ways. Bell (1995a) notes that this persistently
disabled group tends to have fatigue and other symptoms that are worse from
onset and result in severe activity limitation. Recent guidelines for the
management of patients with this condition have been published (Baumer,


Formal psychological assessment may be useful in determining if a child's
symptoms are attributable to factors such as a primary psychiatric disorder,
school phobia, or family dysfunction (Jordan et al., 1998). One study
(Pelcovitz et al., 1995) that examined psychological factors found that
adolescent ME/CFS patients reported higher levels of internalizing symptoms
(i.e., fearful, depressed, and overcontrolled behavior) than a comparison
group of adolescent cancer patients. Another study (Smith et al., 1991) found
that one third of the children and adolescents with ME/CFS met criteria for
major depressive disorder as diagnosed by clinical interview. Similarly,
Walford et al. (1993) compared three groups: children and adolescents with
ME/CFS, cystic fibrosis and healthy controls. It was found that the ME/CFS
group had significantly higher depression scores than other groups.
Furthermore, significant social and academic impairment was present in the
ME/CFS group. Although recurrent, medically unexplained physical symptoms are
common in children and adolescents, somatization disorder that meets DSM-IV
criteria is rare in this age group. Many of these studies have flaws within
them, and they often do not clearly differentiate between pre-illness
symptoms and post-illness symptoms, and therefore it is conceivable that
higher rates of psychological problems are secondary to having ME/CFS.

In children and adolescents, school phobia or school refusal is another
diagnostic category to be considered in differential diagnosis. However,
school phobia can generally be distinguished from ME/CFS after a
comprehensive evaluation, as once the child with school phobia is allowed to
remain home, symptoms typically disappear, and there are usually no
complaints on weekends or holidays or during the summer. Inquiring about
hobbies/leisure activities is important in distinguishing school phobia (or
social phobia) and CFS. The latter will have abandoned their hobbies and
leisure activities. Some physicians have suggested that ME/CFS in children
and adolescents is a physical manifestation of family dysfunction claiming
that ME/CFS symptoms may be utilized by the child for primary or secondary
gain, to cope with developmental issues or change, or to deal with family
problems. However, Pelcovitz et al. (1995) found no differences between
families of adolescents with ME/CFS and families of adolescents with cancer
and control families on family functioning measures and marital problems

It should be noted that for children ill with this syndrome, after 6 months
or so, friends often stop calling or visiting the youngster. If there are no
peers, cousins or extended family or anyone close in age, the isolation can
be devastating. Other changes and losses include no longer being able to
participate in normal activities with peers, loss of self-confidence and self
esteem if teachers and physicians are overly skeptical. School attendance
then may not only be physically taxing but psychologically stressful as well.


Much of the epidemiological research to date has focused on adults, with
minimal focus on children and adolescents. A study that ME/CFS-like illness,
characterized by prolonged fatigue (= 1 month) accompanied by fever,
decreased endurance with exertion, and pain symptoms, occurs at a rate of
4.4% among adolescents seen in primary care settings indicates that this
syndrome is an important medical concern among youth (Mears et al., 2004).
Whether or not the syndrome occurs as a readily recognizable illness in
younger children is still an open question. The main reason to be cautious in
this regard is that the diagnosis was based on patient complaints and the
self-reported consequences of the illness.

Lloyd and associates (1990) included information regarding children of all
ages in their published prevalence estimates from an Australian community
population study. Prevalence estimates of 5.5 cases per 100,000 were
determined for children ages 0 to 9 and 47.9 cases per 100,000 cases for
children and adolescents aged 10 to 19. A major problem with the study that
limits the validity of prevalence estimates was the low number of medical
practitioners who participated and identified cases in their practices (11
out of 50 doctors participated). This problem may have been due to lack of
information about the syndrome or doubts about the validity of ME/CFS. Given
that the population in this study was obtained through physician referral,
members of the community that do not or cannot access medical care for their
symptoms were not included in the study.

The CDC has conducted several studies to estimate the prevalence of pediatric
ME/CFS in different geographical areas (Dobbins et al., 1997). A surveillance
study was performed in Atlanta, Reno, Grand Rapids, and Wichita (Gunn et al.,
1993). Local physicians identified and referred patients who fulfilled CDC
diagnostic criteria for the syndrome. Only 44% of eligible physicians agreed
to participate in the study. Based on the Holmes et al. (1988) definition,
the authors estimated that among adolescents aged 12-17, 8.7 cases per
100,000 showed chronic fatigue symptomatology and 2.7 per 100,000 had ME/CFS.
No inquiries regarding fatigue or ME/CFS symptoms were made regarding
children under the age of 12.

Among a second generation of CDC studies was a community-based investigation
conducted in San Francisco (Dobbins et al., 1997). This study employed random
digit dialing to households as a means of identifying children and
adolescents with chronic fatigue and ME/CFS-like illness. Estimates were made
for children aged 2-11, indicating that 71.9 per 100,000 suffered symptoms of
chronic fatigue, and 0 per 100,000 presented with ME/CFS-like symptoms. In
adolescents aged 12-17, 465.7 per 100,000 were found to suffer chronic
fatigue symptoms, and 116.4 per 100,000 were diagnosed with ME/CFS-like
conditions. Jones et al. (2004) performed a random digit dialing survey of
the residents of Wichita, Kansas. Adults identified fatigued adolescents in
the household and answered questions relating to the child's health. Selected
adolescents were invited to attend a clinic with a parent/guardian. After
clinical evaluation they were classified as CFS or another fatigue state as
defined in the 1994 CFS definition. The survey contacted 34,018 households
with 90,316 residents. Of 8,586 adolescents, 138 had fatigue for more than
one month, and most (107 or 78%) had chronic fatigue (more than 6 months) at
some point during the 3 year follow up. The baseline weighted prevalence of
CFS-like illness was 338 per 100,000. However, because these studies did not
include a medical evaluation, the actual number of cases in that population
could not be determined, and thus, only "ME/CFS-like" illness could be

The CDC conducted another study involving referrals from school nurses from
junior and senior high schools in Wichita, Kansas, and Reno, Nevada. A
prevalence of 24.0 per 100,000 ME/CFS was found for the 12 to 17 year old age
group (Dobbins et al., 1997). As in other medical referral studies, the
gatekeeper methodology, as well as reliance on previous diagnoses by
physicians (rather than current evaluations), limited the reliability and
generalizability of these findings. In a community-based study that occurred
in Wichita, Kansas, Jones et al. (2004) estimated CFS-like pediatric
prevalence rates to be 338 per 100,000, but no cases of CFS were found.

In a community epidemiology study in Chicago (Jason et al., 1999), a
pediatric screening questionnaire was administered to the adult respondents
at the completion of the adult ME/CFS screening questionnaire. Follow-up
interviews were conducted with children and adolescents identified through
the initial telephone screening process. Following the psychiatric
assessment, children and adolescents underwent a complete physical
examination with laboratory testing to diagnose the presence of ME/CFS and
rule out exclusionary medical conditions (Fukuda et al., 1994). Physician
reviews were completed on 34 screened positive cases and 23 screened negative
cases. Results of physician review revealed a prevalence of .06%, or 60 cases
per 100,000 (Jordan et al., 2006).

In addition, some of the published reports follow widely reported "epidemics"
or cluster outbreaks of the syndrome (e.g., Bell et al., 1991). As the
syndrome remains to be precisely defined, both in adults and children, such
epidemics may be considered unique events at this time, as there is no
conclusive evidence that the same illness process is at work in both the
cluster outbreaks and isolated cases.


The adult definition (Fukuda et al., 1994) has been used to diagnose
pediatric samples. It is critical for future studies examining this disorder
in pediatric populations that a consistent definition, which has been adapted
from the adult definition to take into account special circumstances of
children, be utilized. In addition to facilitating coherent research on this
population, a case definition adapted for children will facilitate diagnosis
and management by pediatricians and primary care physicians confronted with
unexplained, chronic fatigue in children.

The definition presented in Table 1 has elements of the Fukuda et al. (1994)
adult case definition, along with of recommendations of Reeves et al. (2003).
We have also incorporated the structure of a new clinical case definition for
ME/CFS that has been developed in Canada (Carruthers et al., 2003). We
believe that requiring certain symptoms does provide more specification of
critical symptoms for a case definition. However, we have tried to limit the
types of symptoms within each of the Canadian criteria categories to allow
investigators to more reliably categorize pediatric patients. We also believe
that this case definition does reduce the prominence of the symptom fatigue
and more explicitly highlights the importance of symptoms such as dizziness,
decreased endurance with symptoms, pain, and flu-like symptoms. Indirectly,
fatigue will accompany such infectious or neurological illnesses, but may not
be the main focus.

Several changes were made to adult case definition based on the conception
that the diagnosis of ME/CFS in children should be made based upon the
symptom complex present at the time of evaluation.

First, the adult definition requires that the fatigue not be lifelong and
that it be of a new and definite onset. In a revision of the Fukuda et al.
(1994) criteria, Reeves et al. (2003) state that only participants who
recount having always felt severely fatigued should be excluded as having
"lifelong" fatigue. We also decided to not use this criterion in formulating
the diagnostic criteria for children for two reasons. First, children and
their families may not be able to pinpoint a definite onset because, in up to
25% of pediatric cases, the onset is insidious rather than sudden (Bell,
1992). Second, children may not be able to compare their current functioning
with a healthy baseline as, due to developmental events and progress, they
may not have a comparable period with which to compare their current
functioning. Further, children themselves may be unable to judge onset
because variations in cognitive development might affect their ability to
remember their functioning at previous points in time. Finally, children may
be more adaptable than adults and, consequently able to make accommodations
for their fatigue and other symptoms (Bell, 1995b). On the other hand,
inquiring about hobbies, social and leisure activities can provide an
indication of the time wherein complaints started to significantly influence
daily activities. Clinical practice shows that ME/CFS patients abandon their
hobbies, social and leisure activities in order to keep up at school. This
process starts when the first school demonstrates a decline in performance.
Subsequently, parents will encourage their children to perform better and
consequently to spend more time in order to achieve higher levels of
functioning at school. Therefore, although no exact onset can be identified
by the child or parents, through the assessment process, it is often possible
to pinpoint the time point when the fatigue started to interfere with the
children's daily functioning.

Similarly, the provision that the symptoms such as sore throat or memory
impairment not predate the fatigue has also been modified. It has been found
that, in children with an insidious onset, such symptoms may in fact predate
fatigue. Alternatively, children may have a history of sore throats, ear
infections, or upper respiratory infections as part of the usual childhood
series of illnesses. However, these illnesses may make it difficult to tease
out the onset of ME/CFS symptoms. In addition, parents and children may not
be aware of the fatigue but may notice other symptoms. Furthermore, children
may also present as irritable rather than fatigued, and it may be difficult
to date the onset of this symptom. The symptoms present at the time of
diagnosis should, however, be associated in a complex of symptoms that occurs
repetitively or chronically.

Second, debate has also occurred regarding the six-month requirement for the
fatigue and other symptoms (Kulig, 1991; Vereker, 1992). The Canadian
criteria suggest that children with symptoms lasting more than three months
duration can be diagnosed with the illness (Carruthers et al., 2004). We
agree with this notion, as Fowler et al. (2005) did not find differences
between 8-17 years olds with 3 versus 6 months of chronic fatigue. Overall,
the criterion regarding the duration of the symptoms varies from two weeks to
six months (Van Hoof & Maertens, 2002). Arbitrarily, we propose to diagnose a
CFS-like condition after 1 to 2 months of duration. After three months,
ME/CFS can be diagnosed. In clinical practice, however, it often takes more
than one year before a ME/CFS diagnosis is given to children and adolescents
(Van Hoof et al., in press).

Third, the threshold number of four symptoms has been changed, as we now
adopt a similar system to that used with the Canadian ME/CFS criteria of
symptom clusters. Appendix A provides a copy of the Pediatric ME/CFS
Questionnaire, which provides a way of gathering this information to help
diagnose pediatric ME/CFS. It is generally recommended that adolescents age
12 and older fill it out themselves, and parents can assist or fill it out
for the children 11 and under, although adherence to this guideline would
vary depending on the comprehension level of the individual child. It is
possible that more than one person (e.g., child only, parent only, both
parents, other primary caregiver) could fill out the Questionnaire. Some
clinicians feel that it is almost never acceptable to only involve one parent
in doing a child/adolescent evaluation, because a limited and sometimes
inaccurate view of the child and family often results from questioning only
one parent. Research by Jones et al. (2004) revealed that significant
differences exists between parental and children's descriptions of the
illness. Thus, whenever possible, information from both parents should be
collected. Further, it may be appropriate to gather information from
grandparents, extended family members, or other caregivers if they are in
close contact with the young person.

For a diagnosis of pediatric ME/CFS, the following five classic ME/CFS
symptom categories must occur (see Table 1). Post-exertional malaise, the
first criteria symptom, must occur with loss of physical or mental stamina,
rapid muscle or cognitive fatigability (or easy distraction as the behavioral
component of cognitive fatigability). The second symptom category is
unrefreshing sleep, or disturbance of sleep quantity or rhythm. The third
symptom category requires that the young person exhibit either 1. myofascial
pain, 2. joint pain, 3. abdominal and/or 4. head pain. The fourth symptom
category is the occurrence of two or more neurocognitive manifestations.
Finally, the fifth symptom category requires at least one symptom from two of
the following three subcategories: 1. Autonomic manifestations, or 2.
Neuroendocrine manifestations, or 3. Immune manifestations. For those
patients who do not have the minimum duration of 3 or more months for the 5
classic ME/CFS symptom categories, the diagnosis should be ME/CFS-like. In
contrast, there are a small number of patients with no pain or sleep
dysfunction, and some pediatric cases might have only 2 to 4 ME/CFS classic
symptom categories above. For these individuals, a diagnosis of atypical
pediatric ME/CFS can be given. Those individuals with pediatric ME/ CFS as
well as atypical pediatric ME/CFS and pediatric ME/CFS-like are important to

Some support for the inclusion of these symptoms emerged from Rowe and Rowe's
(2002) confirmatory factor analysis, which found muscle pain and fatigue,
neurocognitive, abdominal head and chest pain, neurophysiological, and
immunological factors. Abdominal symptoms have been added to the list, and
this is supported by the work by Rowe and Rowe (2002). Autonomic symptoms
have also been added, and this is supported by the Canadian case definition,
(Carruthers et al., 2003), which pointed to autonomic manifestations
(neurally mediated hypotension, light headedness). In addition, a study by
Jason, Torres-Harding et al. (2002) found a symptom currently not part of the
Fukuda criteria, shortness of breath, did differentiate the groups in adults
with ME/CFS. Given that autonomic manifestations might play a role in
pediatric neurally mediated hypotension, which has been connected to ME/CFS
(Poole et al., 2000), this symptom was also included. Overall, De Becker et
al. validated the importance of the general, cognitive and musculoskeletal
symptoms. These symptom factor scores were associated with differentiation of
both the Holmes and Fukuda defined CFS patients from non-CFS patients (De
Becker et al., 2001).

It is important that each of the symptoms should be either moderate or
severe, but this "severity index" has not been well defined in previous
criteria. We now specify that symptoms that are present be rated on the
following scale: 1 = not present, 3 = moderate, 7 = severe. Symptoms need to
be rated at moderate or severe (e.g., 5 or higher) to meet criteria. The
rating scale, rather than a simple yes/no dichotomy, will facilitate accurate
diagnosis in the research setting for several reasons. First, it will
eliminate false positives on a dichotomous symptom checklist, as most of
these symptoms are common to a variety of childhood illnesses, although not
to a moderate or severe degree. Second, it will assist the rater, who when
faced with a dichotomous choice, may choose "no" if the symptoms are present
sometimes or are not severe. Finally, the rating scale will increase the
amount of information gathered about each symptom. This will also allow
better comparison over time, as symptom severity may wax and wane. In
addition, providing information concerning the date of onset of the symptoms
might allow investigators to better understand the progression of this
illness. This type scoring design allows a dimensional diagnostic evaluation
based upon the presence of the symptoms and a traditional ICD-10
categorical diagnosis. This scoring design is implemented because in
diagnosing, it is important to take into account both the presence of the
symptoms as well as the distress they create.

Fourth, the Canadian ME/CFS clinical case definition (Carruthers et al.,
2003) states that the concurrent occurrence of the symptoms must have
persisted or recurred during six or more consecutive months of illness. We
think it is better to indicate the past 3 months, as we are attempting to
diagnose current ME/CFS in pediatric cases. In addition, it is clear that the
symptoms need not be continuous for the three-month period and may predate
the onset of the recognized fatigue. However, it is unclear what is meant by
"persisted or recurred" during the past three months. This is a rather
complex concept and can lead to unreliability unless the criterion is better
specified. We now operationalize this phrase by assessing how often the
patient has experienced the symptom over the past 3 months using the
following 7 point scale, from 1 = hardly ever to 7 = every day). To be
counted as "persisted or recurred," the individual would have to indicate a
score of at least 4.

In addition to including criteria to determine the meaning of substantial
reductions in activity, associated criteria are needed to assess issues of
illness severity and remission states. Borrowing from Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (American
Psychiatric Association, 1994) terminology and the CFS clinical case
definition developed by Lapp and Cheney (1995), patients' severity of
symptoms might be classified as follows: (A) minimal (just enough symptoms to
meet the diagnosis, particularly occurring with exertion, usually able to
attend school); (B) mild (few symptoms in excess of those in the diagnosis,
occurring even at rest, may be able to attend school part of the time); (C)
moderate (many symptoms in excess of those in the diagnosis, moderate
symptoms at rest that become severe with effort, unable to attend school);
(D) severe (often housebound or bedbound); (E) in partial remission (full
criteria for the syndrome were previously met, but currently only a few
symptoms remain with effort, able to attend school regularly); and (F) in
full remission (no longer any symptoms, even with effort, able to attend
school). For individuals who require a more differentiated way of classifying
patients' severity of illness, we suggest using the AYME Functional Ability
Scale (2005).

Fifth, exclusionary medical diagnoses include genetic and other disorders
usually first evident in childhood that would explain the fatigue and
symptoms, as well as those exclusionary medical diagnoses enumerated in the
adult definition. Medical diagnoses that have been adequately treated
(e.g., Lyme disease) or that are not likely to cause fatigue should not be
considered exclusionary. One change, however, revolves around the depression
diagnosis. In the Fukuda et al. (1994) adult definition, melancholic and
psychotic depression are considered exclusionary conditions, primarily due to
the findings that melancholic and psychotic processes represent distinct
biological or endocrinological processes and may respond well to
antidepressant or anti-psychotic medications (Robbins et al.,1989; Schulkin,
1994). Depression is less common in childhood, compared with adolescence, and
symptoms may differ between these two age groups. Depressed pre-pubertal
children are more likely to present with psychomotor agitation, symptoms of
phobic and separation anxiety, and somatic complaints. Adolescents with
depression, on the other hand, are more likely to present with symptoms such
as anhedonia, hypersomnia, weight loss or gain, hopelessness, and lethal
suicide attempts. The two groups of depressed youth do not differ on symptoms
such as depressed mood, guilt, fatigue, or negative self-image (Compas et
al., 1993). As symptoms of depression overlap with those of ME/CFS (Hawk et
al., in press), a careful evaluation must be conducted by the physician, with
close attention to the differing developmental presentations (Jason, 1997).
Inquiring about hobbies and leisure activities is important in distinguishing
depression and ME/CFS. Those with the latter diagnosis will have abandoned
their hobbies and leisure activities. In particular, if adolescents are sick,
not diagnosed, and not believed, the youngsters could become depressed and
anxious. Further inquiring about depressive or anxious feelings will reveal
an underlying frustration as a result of loosing control rather than a
negative self-image. Furthermore, if children experience frequent absences,
but no "diagnosis" and no extra help or support, they will have to struggle
to catch up when they have to return to school, and this can also lead to
depression and anxiety. Thus, depressive feelings should not be considered
necessarily exclusionary, as it may co-exist with ME/CFS, particularly if it
is a reactive depression to the losses incurred by the illness. There could
be a strong feeling of disappointment in ME/CFS children towards their
support and peer group as they can not explain the child's condition. This
differentiation may also be assisted by evaluating the course of both the
depressive symptoms and fatigue symptoms, to determine whether depression and
fatigue co-vary or appear to be separate diagnostic entities. However,
depression is one of the major entities to be considered during differential
diagnosis, and, when it may better explain the fatigue and child's symptom
patterns, may be the appropriate diagnosis rather than ME/CFS.

Reeves et al. (2003) has recommended that major depressive disorder with
melancholic features, anorexia nervosa, or bulimia, not be considered
exclusionary if these conditions have been resolved for more than 5 years
before the onset of the current illness. We believe that pediatric psychotic
disorders of any variety continue to be exclusionary. In addition, eating
disorders (i.e., anorexia nervosa and bulimia nervosa) and substance abuse
have been qualified to be exclusionary only if the diagnosis is current; a
diagnosis of melancholic depression, substance abuse or eating disorder that
has been appropriately treated and resolved should not be considered

Table 1 also lists disorders that should not necessarily be considered
exclusionary, although they may present comorbidly with ME/CFS. Such
disorders include school phobia, separation anxiety disorder, and
fibromyalgia. School phobia and separation anxiety disorder are two disorders
that should be carefully considered in the differential diagnosis. When
school phobia or separation anxiety disorder predate the fatigue and other
symptoms, it is possible that a diagnosis of ME/CFS is inappropriate and that
the symptoms are better explained by a psychological disorder. Children with
school phobia may be differentiated from children with ME/CFS in that the
former typically feel ill in the morning but recover once allowed to remain
home from school (Pilkington & Piersel, 1991). In contrast, children and
adolescents with ME/CFS would experience symptoms not only at school, but in
other settings. Furthermore, with school phobia, symptoms are typically
present only on school days, not weekends or holidays. Similarly, familial
disturbance and dysfunction should be closely examined during the diagnostic
process. In cases where a child's symptoms are clearly the result of such
dysfunction (e.g., the child's illness holding an unstable marriage
together), a diagnosis of ME/CFS would be inappropriate. However, it is just
as likely that a child may be truly ill with ME/CFS and be part of an
unhealthy family system.


The criterion that the fatigue not be the result of ongoing exertion
(Criterion 1A) has been criticized as too vague. For the purposes of
clarification and consistency, in the case of a child who is active (e.g.,
participates in extracurricular activities, sports, outings with friends) but
exhausted yet recovers quickly when activity is decreased, the fatigue would
be considered to be the result of ongoing exertion or activity and, thus,
would exclude a ME/CFS diagnosis. However, a child who participates in very
little activity (possibly to minimize ME/CFS symptoms) when compared to his
or her same-age peers, and becomes exhausted upon minimal exertion would not
be excluded from a ME/CFS diagnosis due to the ongoing exertion clause.
Inquiring about hobbies and leisure activities will reveal abandonment of
their hobbies and leisure activities. In summary, normal fatigue is not
activity limiting, whereas the fatigue present in ME/CFS limits the
individual's activity to varying degrees.

Similarly, the provision that the fatigue is not substantially alleviated by
rest (Criterion 1B) requires clarification. Although a child with ME/CFS may
feel better after rest, he or she may get sick again quickly upon minimal
activity or exertion. Thus, in this case, the rest does not completely
eliminate the syndrome, although it may provide some relief, and this symptom
pattern should not exclude a ME/CFS diagnosis. The duration of the
post-exertional fatigue is important. It can last for a considerable time and
be accompanied by other symptoms such as cognitive downturn, muscle
fatigability, as well as resurgence of other CFS symptoms. Another symptom
that frequently occurs is social withdrawal to minimize ME/CFS symptoms.
Previously extraverted, easy-going and happy children become introvert and
quiet. Their parents talk about the perceived desire of their children to
withdraw from social interactions and become less noticeable.

The criterion that the illness results in a substantial reduction in level of
academic, social, or personal functioning (Criterion 1C) requires some
clinical judgment. It may be difficult to determine changes from previous
level of functioning in very young children who may not be able to recall,
nor may their parents be able to recall, their previous activity levels.
School personnel school reports can provide an estimate of the premorbid
intellectual capacities of the ME/CFS child. It is possible to assess
premorbid functioning by reviewing teacher reports before and after the onset
of the symptoms. Clinical practice indicates that ME/CFS patients had good
premorbid functioning and were considered as easy-going and motivated
students. With onset of the illness, this level of functioning decreases and
it is reflected in the school reports.

In these cases, it is appropriate to compare the child's daily functioning
with what would be expected of a same-age peer. For example, inability to
attend school, difficulty attending to activities of daily living (e.g.,
bathing, dressing, or feeding), or lack of participation in social activities
due to illness or symptoms such as dizziness should be considered when making
the diagnosis. Where possible, there should be validation of decreased
activity level and other symptoms by outside sources, such as teachers or
school nurses who are familiar with ME/CFS. The AYME Functional Ability Scale
(2005) is a promising way of differentiating patients' functional abilities.


To assess comorbid neuropsychiatric conditions, instruments such as the
Diagnostic Interview for Children and Adolescents-Revised (DICA; Herjanic &
Reich, 1982) or the Structured Clinical Interview for the DSM-IV for Children
(KID-SCID; Hein) may be used to determine diagnoses. Instruments such as the
Children's Depression Inventory (CDI; Kovacs, 1992) or the Schedule for
Affective Disorders and Schizophrenia-Children's Version (K-SADS; Chambers et
al., 1985) may be used to assess level of depression. Minimal work has been
done in the area of assessment of children's fatigue. Walford, Nelson, and
McCluskey (1992) report the satisfactory adaptation of the fatigue
questionnaire by Wessely and Powell (1989), later revised by Chalder et al.
(1993), for use with children. However, no psychometric data are available
for this scale in relation to the pediatric population. As Stouten (2005)
recently pointed out, many frequently used fatigue scales do not accurately
represent the severe fatigue that is characteristics of CFS (although this
problem is avoided with the Profile of Fatigue-Related Symptoms, Ray et al.,

Sleep disturbances can be assessed by using the Pittsburgh Sleep Quality
Index (Buysse, 1989), which has been effectively used in elementary school
age samples (Tan, 2004). This Index measures sleep disruptions and sleep
quality. The McGill Pain Questionnaire is well validated, is available in a
short form (Melzack, 1975), and has been reliably used with pediatric samples
(O'Rourke, 2004). Finally, children's functional status may be assessed using
the Children's Health Questionnaire (Landgraf, Abetz, & Ware, 1996), an
instrument that will assess physical and psychosocial well-being. The 12
concepts measured by both forms of the CHQ include physical functioning,
bodily pain, general health perceptions, and self-esteem. As mentioned in the
manual, the Changed GHQ-score is most appropriate in chronic conditions as
children will incorporate their symptoms in their own `conceptual frame.' The
scale `no more than usual' is included in the changed GHQ scoring procedure.


In the case of children, day-to-day management of a chronic disease and its
psychological consequences becomes a family affair with parents in particular
having a key role to play. Thus, it is not surprising that the role of
interventions in facilitating adaptation to the challenges of chronic disease
has received growing recognition. Information presented to the child, parents
and other primary caregivers should make them equipped to play an active role
in the daily management of their illness. A number of interventions are drawn
on theoretical concepts such as self-efficacy and empowerment. At the
individual level, key elements of empowerment include access to information,
ability to make choices, effective change in one's life, assertiveness and
self-esteem (Rogers et al., 1997). Similarly, self-efficacy has been posited
as a central, mediating mechanism in human agency (Bandura, 1988), whereby
perceptions of capabilities to carry out the courses of action necessary to
meet situational demands influence choice of actions pursued, level of
motivation, thought pattern and emotional reactions experienced. There is
evidence of effectiveness for interventions incorporating
cognitive-behavioral techniques on variables such as self-efficacy,
self-management of disease, family functioning, psychosocial well-being,
reduced isolation and social competence. Overall, psycho-educational
interventions can take many forms including simple provision of information
via written materials, computer programs or the Internet.

Psycho-educational interventions for children and their families, however,
need to take account of developmental age as well as disease progression.
Glasgow and colleagues (1999) suggest that problems with self-care typically
emerge during the first few years after diagnosis or during early adolescence
(13-15 years). Thus, educational and skills training approaches may be
particularly important for both child and family at the time of diagnosis and
for adolescents who are assuming responsibility for self-care. In CFS/ME area
with pediatric samples, there have been only a few implemented
non-pharmacologic interventions, and few had appropriate controls or
long-term follow-up (Whiting et al., 2001; Barlow & Ellard, 2004).


The definition proposed here is provided as a starting point for facilitating
consistent research on pediatric ME/CFS. This definition should be subjected
to rigorous scientific study to determine its efficacy. In particular,
reliability studies should be conducted to determine if the definition
facilitates consistent diagnosis (Jason et al., 1997). Rowe and Rowe (2002)
used 24 key symptoms and found one underlying syndrome factor, suggesting
that the syndrome complex can be legitimately designated as a syndrome. In
addition, Komaroff and colleagues (1996) compared symptoms and fatigue
characteristics of a large sample of adult ME/CFS patients with three other
groups (healthy controls, depressed subjects, and patients with multiple
sclerosis) to determine the validity of each symptom and its contribution to
differential diagnosis. Similar techniques would be useful in validating the
pediatric definition.

Future research on pediatric ME/CFS should carefully word questions aimed at
identifying children's level of fatigue, and the developmental context of the
children and adolescents being assessed should be taken into account. As
children may present as irritable rather than complain of fatigue, questions
that focus on school problems (e.g., learning or memory problems) or other
consequences of fatigue may need to be asked in addition to questions
regarding fatigue. In addition, as there may be discrepancies between
caregiver's reports of the child's functioning and the child's own
assessment, a comparison of these two descriptions of symptomatology should
be made.

Fukuda et al. (1994) recommended subgrouping adult ME/CFS patients and
similar efforts would be appropriate in the study of pediatric ME/CFS. In
addition, it is clear that the current cohort of individuals diagnosed with
ME/CFS is a diverse group with varying disease course and disability
patterns, offering limited understanding of the etiology or pathology of the
illness and its components when considered together (Jason et al., 2005).
Patterns of illness course and duration are difficult to decipher when using
the current diagnostic criteria to identify individuals with this illness.
Similar to disorders such as cancer, it is highly likely that a number of
distinct types of ME/CFS exist and that the current method of grouping all
individuals who meet diagnostic criteria together complicates the
identification of biological markers in these subgroups.

The arguments against articulating a definition of ME/CFS specifically for
pediatric patients revolve primarily around the harm of an inaccurate
diagnosis. These arguments include the uncertainty in diagnosing children due
to difficulty in obtaining an accurate self-report from young children. In
addition, premature diagnosis may prevent recognition of a treatable
condition. Finally, some researchers and clinicians doubt that ME/CFS exists
as a clinical entity in children, particularly young ones. However, a
consistent case definition is needed to facilitate research on pediatric
ME/CFS and to assist in the identification of homogenous groups. While some
researchers have suggested that children and adolescents have a higher rate
of recovery from ME/CFS when compared to adults, there is still a subgroup of
pediatric cases whose illness persists for extended periods of time
(Arav-Boger & Spirer, 1995; Smith & Carter, 2003). A consistent case
definition would facilitate longitudinal investigations into the prognosis of
CFS and help identify risk factors which may predict poorer prognosis, so
that these higher risk children and adolescents receive earlier intervention.

The summary of symptoms in Table 1 could be referenced by pediatricians,
school nurses, and even school teachers and staff responsible for Individual
Education Plan development and implementation. In addition, the criteria list
could be useful to the young person, parents or others advocating for the
youth with ME/CFS in need of accommodations since it would give legitimacy to
the child's symptoms. The rapid, accurate identification of cases of ME/CFS
followed by comprehensive and appropriate support and treatment might
increases chances of recovery for all children and adolescents with this
debilitating illness.


The authors appreciate the support from the Board members of the International
Association for Chronic Fatigue Syndrome. In addition, they thank the following
people who have provided them constructive feedback: Pat Fero, Jill McLaughlin,
Eleanor Stein, Mary Schweitzer, Michael Yogman, Kathleen Gale, Connie Vander
Eb, and John Herd.


1. The acronym ME/CFS refers to Myalgic Encephalomyelitis and Chronic Fatigue
Syndrome, according to the Canadian Case Definition. The patient community
has felt that the term chronic fatigue syndrome trivializes the seriousness
of this illness, as the illness is typified by many severe symptoms in
addition to fatigue, and fatigue is generally regarded as a common symptom
experienced by many otherwise healthy individuals in the general population.
The term Myalgic Encephalomyelitis had been used prior to the use of the term
chronic fatigue syndrome (Acheson, 1959). Some individuals have preferred to
use the term Myalgic Encephalopathy rather than Myalgic Encephalomyelitis, as
the former term does not suggest brain inflammation.


TABLE 1. Definition of ME/CFS for Children
I.   Clinically evaluated, unexplained, persistent or relapsing chronic fatigue
     over the past 3 months that:
       A. Is not the result of ongoing exertion
       B. Is not substantially alleviated by rest
       C. Results in substantial reduction in previous levels of educational,
          social and personal activities
       D. Must persist or reoccur for at least three months
II.  The concurrent occurrence of the following classic ME/CFS symptoms, which
     must have persisted or recurred during the past three months of illness
     (symptoms may predate the reported onset of fatigue).
       A. Post-exertional malaise and/or post-exertional fatigue.
          With activity (it need not be strenuous and may include walking up a
          flight of stairs, using a computer, or reading a book), there must be
          a loss of physical or mental stamina, rapid/sudden muscle or cognitive
          fatigability, post-exertional malaise and/or fatigue and a tendency
          for other associated symptoms within the patient's cluster of symptoms
          to worsen. The recovery is slow, often taking 24 hours or longer.
       B. Unrefreshing sleep or disturbance of sleep quantity or rhythm
          May include prolonged sleep (including frequent naps), disturbed sleep
          (e.g., inability to fall asleep or early awakening), and/or day/night
       C. Pain (or discomfort) that is often widespread and migratory in nature.
          At least one symptom from any of the following:
          Myofascial and/or joint pain (Myofascial pain can include deep pain,
          muscle twitches, or achy and sore muscles. Pain, stiffness, or
          tenderness may occur in any joint but must be present in more than one
          joint and lacking edema or other signs of inflammation.)
          Abdominal and/or head pain (May experience eye pain/sensitivity to
          bright light, stomach pain, nausea, vomiting, or chest pain. Headaches
          often described as localized behind the eyes or in the back of the
          head. May include headaches localized elsewhere, including migraines.)
       D. Two or more neurocognitive manifestations:
          Impaired memory (self-reported or observable disturbance in ability to
            recall information or events on a short-term basis)
          Difficulty focusing (disturbed concentration may impair ability to
            remain on task, to screen out extraneous/excessive stimuli in a
            classroom, or to focus on reading, computer/work activity, or
            television programs)
          Difficulty finding the right word
          Frequently forget what wanted to say
          Absent mindedness
          Slowness of thought
          Difficulty recalling information
          Need to focus on one thing at a time
          Trouble expressing thought
          Difficulty comprehending information
          Frequently lose train of thought
          New trouble with math or other educational subjects
       E. At least one symptom from two of the following three categories:
           1. Autonomic manifestations: Neurally mediated hypotension, postural
              orthostatic tachycardia, delayed postural hypotension, palpitations
              with or without cardiac arrhythmias, dizziness, feeling unsteady on
              the feet-disturbed balance, shortness of breath.
           2. Neuroendocrine manifestations: Recurrent feelings of feverishness
              and cold extremities, subnormal body temperature and marked diurnal
              fluctuations, sweating episodes, intolerance of extremes of heat
              and cold, marked weight change-loss of appetite or abnormal
              appetite, worsening of symptoms with stress.
           3. Immune manifestations: Recurrent flu-like symptoms, non-exudative
              sore or scratchy throat, repeated fevers and sweats, lymph nodes
              tender to palpitation - generally minimal swelling noted, new
              sensitivities to food, odors, or chemicals.
III. Exclusionary conditions:
       A. Any active medical condition that may explain the presence of chronic
          fatigue, such as:
           1. Untreated hypothyroidism
           2. Sleep apnea
           3. Narcolepsy
           4. Malignancies
           5. Leukemia
           6. Unresolved hepatitis
           7. Multiple Sclerosis
           8. Juvenile rheumatoid arthritis
           9. Lupus erythematosus
          10. HIV/AIDS
          11. Severe obesity (BMI greater than 40)
          12. Celiac disease
          13. Lyme disease
       B. Some active psychiatric conditions that may explain the presence of
          chronic fatigue, such as:
           1. Childhood schizophrenia or psychotic disorders
           2. Bipolar disorder
           3. Active alcohol or substance abuse - except as below:
               a) Alcohol or substance abuse that has been successfully treated
                  and resolved should not be considered exclusionary.
           4. Active anorexia nervosa or bulimia nervosa - except as below:
               a) Eating disorders that have been treated and resolved should
                  not be considered exclusionary.
           5. Depressive disorders
IV.  May have presence of concomitant disorders that do not adequately explain
     fatigue, and are, therefore, not necessarily exclusionary.
           1. Psychiatric diagnoses such as:
               a) School phobia
               b) Separation anxiety
               c) Anxiety disorders
               d) Somatoform disorders
               e) Depressive disorders
           2. Other conditions defined primarily by symptoms that cannot be
              confirmed by diagnostic laboratory tests, such as:
               a) Multiple food and/or chemical sensitivity
               b) Fibromyalgia
           3. Any condition under specific treatment sufficient to alleviate all
              symptoms related to that condition and for which the adequacy
              of treatment has been documented.
           4. Any condition, that was treated with definitive therapy before
              development of chronic symptomatic sequelae.
           5. Any isolated and unexplained physical examination, laboratory or
              imaging test abnormality that is insufficient to strongly suggest
              the existence of an exclusionary condition.


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[APPENDIX A. Pediatric Health Questionnaire]

(c) 2006 The Haworth Press, Inc.

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Date:    Sun, 11 Mar 2007 20:22:35 -0000
From:    Tom Kindlon <tomkindlon@OCEANFREE.NET>
Subject: RES: An internet survey of 2,596 people with fibromyalgia

An internet survey of 2,596 people with fibromyalgia
Robert M Bennett , Jessie Jones , Dennis C Turk , I. Jon Russel  and Lynne
BMC Musculoskeletal Disorders 2007, 8:27     doi:10.1186/1471-2474-8-27


Published   9 March 2007

Abstract (provisional)

The complete article is available as a provisional PDF
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This study explored the feasibility of using an Internet survey of people
with fibromyalgia (FM), with a view to providing information on
demographics, sources of information, symptoms, functionality, perceived
aggravating factors, perceived triggering events, health care utilization,
management strategies, and medication use.


A survey questionnaire was developed by the National Fibromyalgia
Association (NFA) in conjunction with a task force of "experts in the
field". The questionnaire underwent several rounds of testing to improve its
face validity, content validity, clarity and readability before it was
mounted on the internet. The questionnaire consisted of 121 items and is
available online at the website of the National Fibromyalgia Foundation.


The questionnaire was completed by 2,569 people. Most were from the United
States, with at least one respondent from each of the 50 states. Respondents
were predominantly middle-aged Caucasian females, most of whom had FM
symptoms for 4 years or more. The most common problems were morning
stiffness, fatigue, nonrestorative sleep, pain, concentration, and memory.
Aggravating factors included: emotional distress, weather changes, insomnia,
and strenuous activity. Respondents rated the most effective management
modalities as rest, heat, pain medications, antidepressants, and hypnotics.
The most commonly used medications were: acetaminophen, ibuprofen, naproxen,
cyclobenzaprine, amitriptyline, and aspirin. The medications perceived to be
the most effective were: hydrocodone preparations, aprazolam, oxycodone
preparations, zolpidem, cyclobenzaprine, and clonazepam.


This survey provides a snap-shot of FM at the end of 2005, as reported by a
self-selected population of people. This descriptive data has a heuristic
function, in that it identifies several issues for further research, such as
the prescribing habits of FM health care providers, the role of emotional
precipitants, the impact of obesity, the significance of low back pain and
the nature of FM related stiffness.

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Date:    Sun, 11 Mar 2007 18:36:59 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: Variability of criteria used to diagnose myofascial trigger point pain syndrome-evidence from a review of the literature

Variability of criteria used to diagnose myofascial trigger point pain
syndrome-evidence from a review of the literature.

Clin J Pain. 2007 Mar-Apr;23(3):278-86.

Tough EA, White AR, Richards S, Campbell J.

Peninsula Medical School, Universities of Exeter and Plymouth, UK.

PMID: 17314589

OBJECTIVES: The aim of the literature review was to investigate the
criteria adopted by "experts" to diagnose myofascial trigger point (MTrP)
pain syndrome. Experts were defined as being either researchers
investigating MTrP pain syndrome or the "authority" the researchers cited
as a source of reference for MTrP pain syndrome diagnosis.

METHODS: We searched electronic databases to identify relevant empirical
research (excluding studies not in English and those relating to dental
pathology). Of 607 possibly relevant publications 93 met our inclusion
criteria. We recorded (1) the individual criterion and criteria
combinations used to diagnose MTrP pain syndrome; (2) the cited
"authoritative" publications and (3) the criteria recommended by the
authoritative publications as being essential for MTrP pain syndrome

RESULTS: The review identified 19 different diagnostic criteria. The 4 most
commonly applied criteria were: "tender spot in a taut band" of skeletal
muscle, "patient pain recognition," "predicted pain referral pattern," and
"local twitch response." There was no consistent pattern to the choice of
specific diagnostic criteria or their combinations. However, one pair of
criteria "tender point in a taut band" and "predicted or recognized pain
referral" were used by over half the studies. The great majority of studies
cited publications by Travell and more recently Simons as a principal
authoritative source for MTrP pain syndrome diagnosis, yet most of these
studies failed to apply the diagnostic criteria as described by these

DISCUSSION: We conclude that there is as yet limited consensus on case
definition in respect of MTrP pain syndrome. Further research is needed to
test the reliability and validity of diagnostic criteria. Until reliable
diagnostic criteria have been established, there is a need for greater
transparency in research papers on how a case of MTrP pain syndrome is
defined, and claims for effective interventions in treating the condition
should be viewed with caution.

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Date:    Sun, 11 Mar 2007 18:40:25 -0400
From:    "Bernice A. Melsky" <bernicemelsky VERIZON.NET>
Subject: RES: The myofascial trigger point region: correlation between the degree of irritability and the prevalence of endplate noise

The myofascial trigger point region: correlation between the degree of
irritability and the prevalence of endplate noise.

Am J Phys Med Rehabil. 2007 Mar;86(3):183-9.

Kuan TS, Hsieh YL, Chen SM, Chen JT, Yen WC, Hong CZ.

Department of Physical Medicine and Rehabilitation, College of Medicine,
National Cheng Kung University, Tainan, Taiwan.

PMID: 17314703

OBJECTIVE: This study was designed to investigate the correlation between
the irritability of the myofascial trigger point (MTrP) and the prevalence
of endplate noise (EPN) in the MTrP region of human skeletal muscle.

DESIGN: Twenty normal subjects with latent MTrPs and 12 patients with
active MTrPs in the upper trapezius muscles were recruited for this study.
The patients reported the subjective pain intensity of the active MTrP
(0-10). The MTrP and an adjacent non-MTrP site were confirmed and marked
for the measurement of pressure pain threshold (with a pressure algometer)
and the prevalence of EPN (with electromyographic recordings).

RESULTS: The prevalence of EPN in the MTrP regions was significantly higher
(P < 0.01) in the active MTrPs than in the latent ones. However, no EPN
could be found in the non-MTrP region near either the active or the latent
MTrPs. The pain intensity and the pressure pain threshold were highly
correlated with the prevalence of EPN in the MTrP region (r = 0.742 and
-0.716, respectively).

CONCLUSIONS: The irritability of an MTrP is highly correlated with the
prevalence of EPN in the MTrP region of the upper trapezius muscle. The
assessment of EPN prevalence in an MTrP region may be applied to evaluate
the irritability of that MTrP.

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Date:    Mon, 12 Mar 2007 09:39:33 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES,NOT: Pediatric CFS - Psychosocial and Physical Impact

Source: Journal of Chronic Fatigue Syndrome
        Vol. 13, No. 2/3, 2006, pp. 55-74
Date:   2006
URL:                               http://jcfs.haworthpress.com
Ref:    See also,






Psychosocial and Physical Impact of Chronic Fatigue in a Community-Based Sample
of Children and Adolescents
Susan R. Torres-Harding, PhD
Karen Jordan, PhD
Leonard A. Jason, PhD
Renee Arias, BA
Susan R. Torres-Harding, Leonard A. Jason, and Renee Arias are affiliated with
  the Center for Community Research, DePaul University, Chicago, IL.
Karen Jordan is Associate Professor, Louisville School of Medicine, Louisville,
Address correspondence to: Leonard A. Jason, PhD, Center for Community Re-
  search, DePaul University, 990 West Fullerton Avenue, Room 3100, Chicago,
  IL 60614 (E-mail: Ljason depaul.edu).


Few studies have examined the problem of chronic fatigue in children and
adolescents and its potential impact on functioning. Chronic fatigue may have
a negative impact on school functioning, family activities, psychological
well-being, physical functioning, and severity of medical symptomatology.

This study compared psychosocial, family, and physical functioning between a
randomly selected community based sample of 36 children and adolescents with
chronic fatigue and a group of 21 children and adolescents without fatigue.

Children and parents completed a comprehensive medical history questionnaire
and questionnaires assessing psychological functioning, family functioning,
and school attendance.

Results indicated that children with chronic fatigue tended to have more
difficulties in overall physical and psychological functioning, as measured
by the Child Health Questionnaire and the Child Behavior Checklist. In
addition, children in the chronic fatigue group experienced disruptions in a
range of activities and reported more severe physical symptomatology when
compared to children without fatigue.

Findings suggest that children and adolescents with chronic fatigue may have
a range of associated difficulties, including limitations in physical and
psychosocial functioning and a negative impact on the ability to engage in
normative activities.

KEYWORDS. Chronic fatigue, children, adolescents, psychosocial functioning,
physical functioning


Fatigue has been found to be a significant problem in adult populations, but
has less frequently been studied in children. Fatigue is a common symptom
among pediatric populations, particularly adolescents (1). Children and
adolescents are generally less at risk for fatigue than adult populations;
however, when fatigue has been found in pediatric populations, it has been
associated with negative consequences, including increased psychiatric
comorbidity, decreases in functioning, and school disruption (2).

Some researchers have investigated the occurrence of chronic fatigue syndrome
(CFS) in children, a chronic condition characterized by severe disabling
fatigue. When using criteria developed by Fukuda et al. (3), this condition
also encompasses a variety of additional symptoms, including sore throat,
headache, joint pain, muscle pain, lymph node pain or tenderness,
unrefreshing sleep, post-exertional malaise, memory and concentration
impairment. However, the application of the Fukuda case definition to
pediatrics is controversial because these criteria were developed for adults,
and some have questioned its applicability to children (4,5). For this
reason, some researchers have focused on children with chronic fatigue, or
severe fatigue lasting 6 months or more, to determine whether children and
adolescents with longer-lasting fatigue that does not resolve on its own
might be more indicative of difficulties in this population (1). It is
possible that children and adolescents with chronic fatigue, even if they do
not fully meet the Fukuda criteria for chronic fatigue syndrome, might still
be experiencing significant difficulties and disruption in functioning due to
the presence of chronic fatigue.

The prevalence of children and adolescents with either general fatigue
(lasting more than a few days) or prolonged fatigue (fatigue lasting one
month or more) range from .06% (6) to 16% (7). The prevalence of pediatric
chronic fatigue, or fatigue lasting 6 months or more, has been estimated at
between .01% and 4% (8, 9). Farmer et al. (10) conducted a postal study of a
twin registry in Great Britain consisting of 3,051 pairs of twins, and they
found that 4.4% were identified as having more than a few days of disabling
fatigue. In this sample, the mean duration of fatigue was 9 months for boys
and 14 months for girls. Steele et al. (6) conducted a random digit-dialing
telephone survey of chronic fatigue in the San Francisco urban area with
8,004 households and found unexplained prolonged fatigue (fatigue lasting for
1 month or more) in .06% of the children and adolescents under the age of 18.
Peterson et al. (7) found that, among a randomized cluster sample of 1,155
Swedish schoolchildren ages 6-13 years, the prevalence of fatigue at least
once a week was 31%, and 16% felt tired almost every day, with older school
children reporting more recurrent fatigue. In a randomly-selected
community-based epidemiological study conducted in Wichita, Kansas, with
34,018 households, the prevalence of adolescents having chronic fatigue
(fatigue lasting 6 months or more) was 1,298 per 100,000, or .01% (8).
Finally, in a second large-scale community-based epidemiological study
conducted in the US among a socioeconomically and ethnically diverse random
community sample of 18,675 households, 4% of children and adolescents
exhibited either fatigue or school learning/memory problems (9).

In studies of children with fatigue or chronic fatigue, it has been found
that school difficulties and school failure are a significant problem. Nagane
(2) found, in a study of 32 healthy Japanese children age 9-10, that children
with greater fatigue had lower scores on some items of academic achievement
and sports ability. This study suggested that fatigue may be a risk factor
for reduced mental and physical activity in school children. Carter et al.
(1), in their study of 31 adolescents (average age 14.3) of unexplained
chronic fatigue lasting 6 months or more referred to a pediatric infectious
disease clinic, found that 55% of these participants had missed 20 to 60 days
of school during the most recent school year because of their fatigue.
Further, 35% of these participants indicated declines in academic performance
due to their illness, and 52% experienced declines in extracurricular
activities. These individuals also reported impairment in their social
activities (55%), problems with social relationships (35%) and feeling as if
their family members treated them differently (39%). Smith, Martin-Herz,
Womack, and Marsigan (11) also found that adolescents referred for evaluation
of chronic fatigue to a specialty clinic reported a greater level of
absenteeism from school, with those individuals with unexplained chronic
fatigue reporting an average of 44 school days missed within the past 6
months. Farmer et al. (10) identified 96 children and adolescents from a
community-based twin registry with disabling fatigue, and they found that the
boys missed a mean of 10 days of school during the past school term, and the
girls missed a mean of 15 days per school term. Finally, Van Hoof, De Becker,
Lapp, and DeMeirlier (12) conducted a qualitative study in 27 adolescents
diagnosed with CFS, and these adolescents reported a range of school
difficulties, including prolonged absenteeism, difficulty with completing
courses and the need for accommodations in order to complete exams, conflicts
and lack of support at school, impaired social interaction and fewer friends
after becoming ill, and participation in fewer extracurricular activities
because of illness.

Further, some researchers have suggested that children and adolescents with
chronic fatigue may be at more risk for poor psychological and psychosocial
functioning. Carter et al. (1) found that, on the Child Behavior Checklist
(CBCL), fatigued adolescents had more internalizing symptoms when compared to
healthy controls and had fewer externalizing symptoms when compared to
depressed adolescents. Fatigued adolescents exhibited lower scores on the
majority of the Children's Depression Inventory scales and the overall score
when compared to depressed adolescents and exhibited higher overall
depression and anhedonia than healthy controls. Thus, the fatigued
adolescents appeared to have poorer overall psychological functioning when
compared to controls, but this did not always fall into the clinical ranges
of these subscales, and these difficulties appeared to be less when compared
to depressed adolescents. Carter et al. (1) indicated that their results
suggest pediatric patients with chronic fatigue are at risk for psychological
disturbances. It is possible that psychological difficulties may result when
a child has difficulty coping with their fatigue illness, or may result from
the stress of having chronic medical problems. Similarly, Farmer et al. (10)
found that the parents of 96 children with chronic fatigue experienced
impaired relationships with family and friends and limitations in leisure
activity participation. Further, they found that individuals with disabling
fatigue were more likely to develop symptoms of depression during their
fatigue episodes, with 38% of boys and 39% of girls in their sample
experiencing DSM-IV criteria for depression (10). Limitations in energy may
have a significant impact in psychological functioning due to its impact on
school, academic, or social functioning.

While there have been limited studies that have examined the problem of
fatigue and chronic fatigue in children and adolescents, findings from
research cited above indicate that chronic fatigue may potentially be
disruptive, particularly to school functioning. It is possible that children
with chronic fatigue are experiencing an overall higher level of physical
impairment and other physical symptoms which may occur as a result of the
fatigue. Examining the effects of chronic fatigue is particularly important
to determine the impact of this symptom on everyday physical functioning.
Further, information regarding the associations with chronic fatigue may be
helpful for family care specialists and pediatricians who often must evaluate
the causes and significance of unexplained chronic fatigue in their

This study examined the effect of chronic fatigue on school functioning,
family functioning, and overall physical and emotional impairment in a
randomly selected community based sample of children with fatigue or other
health difficulties and in a group of children without fatigue. It was
hypothesized that children and adolescents with chronic fatigue would exhibit
increased difficulties in various areas of life functioning when compared to
a control group of children without chronic fatigue.



The data from this study are derived from a larger epidemiological prevalence
study of chronic fatigue in a randomly selected, community-based sample of
adults and children (13,14). This larger study of CFS entailed a
cross-sectional screening telephone survey of a random sample of 28,673
households. Procedures described in Jason et al. (13) were used to select one
adult from each household. Birth dates for each adult were gathered, and the
person with the most recent birth date was interviewed. A random sample of
adults (18 years or older) was screened for inclusion into the larger study,
and as part of the screening process, information regarding the fatigue and
illness status of all children in the household were collected. This
pediatric study was carried out in three stages.

Stage 1.
First, a brief screening questionnaire was added to the adult screening
questionnaire protocol several months after adult data collection had
commenced. This screening questionnaire took approximately one to two minutes
to administer. This brief questionnaire was developed for this study and
assessed for either the presence of severe fatigue and/or disruption in
school activities. This second question regarding school activities was asked
because previous research has suggested that children may not report fatigue
as their principal symptom or may exhibit fatigue through irritability or in
other ways (15). The questionnaire also assessed symptoms that commonly occur
in CFS, as defined by Fukuda et al. (3), as well as additional symptoms
proposed by Bell (16).

Stage 2.
Children and adolescents were invited to participate in the second and third
phases of the study if they had no exclusionary medical conditions, at least
4 of the additional CFS symptoms (sore throat, headache, lymph node pain,
joint pain, muscle pain, post-exertional malaise, unrefreshing sleep, and
memory/concentration problems), and significant fatigue or problems with
memory or learning at school. Further, a control group was randomly selected
from among those children who screened negative for study inclusion in stage 1.

The second phase of the study included a psychological examination with the
children and adolescents. The structured clinical interview for the DSM-IV,
Childhood version (KID-SCID, 17) was administered by one of three master's
level clinicians. The KID-SCID utilizes multiple information (i.e., parent
and child) to determine the presence of a psychiatric diagnosis.

Stage 3.
Following completion of the psychological examination, children and
adolescents received a medical evaluation to rule out medical conditions
leading to fatigue and to determine whether an individual met criteria for a
diagnosis of CFS. The medical evaluation included an extensive medical
history questionnaire which assessed the child's medical history, current
symptoms, and fatigue symptomatology. Also, a full medical evaluation was
conducted by a pediatrician, and laboratory testing was performed. The
laboratory testing included a urinalysis, complete blood count with
differential, erythrocyte sedimentation rate, chemistry panel, thyroid
function tests, and an HIV test. A chest x-ray was performed if one had not
been conducted within 8 months of the physical examination date, and a
tuberculosis skin test (PPD) was conducted. The medical examination and
laboratory testing were administered to rule other potential diseases, as
recommended by Fukuda et al. (3).

Finally, the results obtained from the all testing performed (medical,
psychiatric, etc.) were reviewed by an independent physician review panel who
were blind to the experimental status (experimental vs. control) of each
study participant. The team of four physicians determined the final diagnosis
for each participant after completion of all phases of the study. Final
diagnoses included a diagnosis of CFS, meaning that the participant met the
criteria for CFS as defined by Fukuda et al. (3). Alternately, individuals
were also diagnosed with Idiopathic Chronic Fatigue (ICF), defined as those
children experiencing unexplained fatigue that did not fully meet criteria
for CFS as defined by Fukuda et al. (3) or as having Chronic Fatigue
Explained, meaning that the individual was experiencing significant fatigue,
but that their fatigue was fully explained by a medical or psychiatric
diagnosis. Finally, individuals could be classified as No Fatigue, meaning
that the child was not currently experiencing significant problems with

Participants: Fifty-seven children and adolescents participated in stages 2
and 3. Because only 2 children were identified with CFS, it was decided that
children would be grouped into two categories. Those who exhibited CFS, ICF,
or Chronic Fatigue Explained were classified into the "Chronic Fatigue"
group. Individuals who did not exhibit chronic fatigue were classified into
the "No Fatigue" group.

The current study examined those individuals who had chronic fatigue (CFS,
ICF, or Chronic Fatigue Explained) and those individuals without ongoing
fatigue difficulties (No Fatigue). In addition, this investigation examined
among all respondents the association between whether one had chronic fatigue
or not, and the other psychosocial and disability-related measures to
determine whether chronic fatigue might also be associated with these

The final sample of 57 participants was 54.4% female and 45.6% male.
Regarding ethnicity, 22.8% were African-American, 24.6% were Caucasian, 49.1%
were Latino, and 3.5% were of another ethnicity. The average age of the
sample was 11.4, with the age range of the sample from 5 to 18 years old.
Using chi-square analyses, no statistically significant differences were
found between the two groups (Chronic Fatigue vs. No Fatigue) for gender,
age, or ethnicity.


CFS Medical Questionnaire: Parent and Child Report. This questionnaire
assessed the study participants' demographic information and complete medical
history, including current and past symptomatology, history of service
utilization, results of past medical and psychiatric evaluations, history and
course of illness, and effects of illness on overall functioning. This
questionnaire was developed for use specifically within this research
investigation. It was administered to both the parent and the child.

The Structured Clinical Interview for the DSM-IV, Childhood Version
(KID-SCID) (17) is a semi-structured psychiatric interview that assesses
for the presence of psychiatric disorders in children and adolescents age
5 to 18. The KID-SCID obtains information from multiple informants
(i.e., parent and child), and this information is then used by the clinician
to arrive at the appropriate diagnosis. This interview has demonstrated
good interrater reliability in the Disruptive Behavior module, .842 for
ODD and CD, and 1.0 for ADHD (18). In addition, this instrument has
demonstrated good test-retest reliability, with Kappa scores consisting
of .84 for Attention Deficit/Hyperactivity Disorder, .84 for Conduct
Disorder, .63 for Oppositional Defiant Disorder, 1.0 for Social Phobia,
.66 for Separation Anxiety Disorder, and .44 for Posttraumatic Stress
Disorder (19).

The Fatigue Scale (21). This scale was used to assess fatigue severity. This
scale was originally used in a hospital-based case control study (20) and was
further refined by Chalder et al. (21). Despite its brevity, the scale was
found to be reliable and valid, and it had good face validity and reasonable
discriminant validity. The fatigue scale consists of 11 items, and includes
items such as "Do you have problems with tiredness?" "Do you feel weak?" and
"Do you have difficulty concentrating?" with responses rated on a four-option
continuum. Total fatigue severity scale scores range from 0 to 33, with
higher scores signifying more fatigue.

Child Health Questionnaire (22). This instrument measure the physical and
psychosocial well-being of children 5 years of age and older. Several
versions for parent and child are available. In the current study, Parent
Form 50 (PF50) was administered to all parents; and the Child Form 87 (CH87)
was administered to all children age 10 and older. The PF50 and the CF87 each
yield the following subscales: Physical functioning (measure and extent of
physical limitations due to health-related problems); Role/Social Physical
(limitations in daily functioning as a result of physical health); General
Health Perceptions (subjective assessment of overall health and illness);
Bodily Pain (intensity and frequency of pain and discomfort);
Role/Social-Emotional (limitations in activities as a result of emotional
problems); Role/Social-Behavior (limitations in activities as a result of
behavior problems); Self-Esteem (satisfaction with academic, athletic
abilities, appearance, social functioning, and overall life satisfaction);
Mental Health (measures the frequency of both positive and negative mental
states); General Behavior (frequency of behavior problems and ability to get
along with others); Family-Limitations in Activities (degree of disruption in
usual family activities); Family-Cohesion (degree to which family members
'get along'); and Changes in Health (change in health over previous year). In
addition, the PF-50 also includes the following two subscales: Parent
Impact-Time (limitations in personal parental time as a result of child's
medical, psychological, or psychosocial difficulties) and Parent
Impact-Emotional (amount of parental distress as a result of child's medical,
psychological, or psychosocial difficulties). Finally, the PF-50 combined the
Role/Social-Emotional and Role/Social-Behavior scales into one scale,

The CHQ demonstrates adequate reliability and validity and has been used with
children with a range of physical and psychiatric difficulties (22,23). For
US representative samples, the Parent Form 50 exhibits high inter-item
consistency, with 91% of the items exceeding the minimum criteria for item
internal consistency (>=.40). The average success rate for tests of item
discriminant validity was 95%. Similarly, in a representative sample of
children in the US, 94% of the items met the minimum criteria for item
internal consistency (>=.40), and the average success rate for test of item
discriminant validity was 92%. Test-retest reliabilities for the CHQ fall
between .54-.73 for the parent version, and .18-.77 for the child version

Child Behavior Checklist and Youth Self-Report (24,25). The Child Behavior
Check List (CBCL) and Youth Self-Report (YSR) measure internalizing and
externalizing problems in children. The CBCL is a questionnaire containing
120 items that is completed by parents of children age 4 to 18 years. The YSR
is a self-report measure containing 119 items that is completed by
adolescents age 11 to 18 years. The CBCL and the YSR each yield nine
subscales: Withdrawn, Somatic Complaints, Anxious/Depressed, Social Problems,
Thought Problems, Attention Problems, Delinquent Behavior, Aggressive
Behavior, Sex Problems. In addition, there are two composite scales
(Internalizing and Externalizing) and three competence scales (Activities,
Social, and School).

The CBCL and YSR both demonstrate adequate reliability and validity. Internal
consistency reliabilities for the CBCL range from .56 to .92, and inter-rater
reliability coefficients range from .26 to .86 (26). For the YSR, internal
consistency reliabilities range from .59 to .90, and test-retest
reliabilities range from .47 to .81 when re-tested over a 1-week interval
(26). Finally, the CBCL and YSR demonstrate satisfactory concurrent and
discriminant validity (26).

Family Environment Scale: Parent and Child Version (27). The Family
Environment Scale (FES) is a self-report questionnaire that measures a broad
array of family environment dimensions. There are parent and child versions
available for this scale. This scale consists of 90 true-false items that
assess ten dimensions of family environment: Cohesion, Expressiveness,
Conflict, Independence, Achievement, Intellectual-Cultural Orientation,
Active-Recreational Orientation, Moral-Religious Emphasis, Organization, and
Control. This scale has exhibited appropriate internal consistencies, ranging
from .61-.78 for all of the FES subscales. Further, two-month and four-month
test-retest reliabilities were also in the acceptable range, with two-month
test-retest reliabilities ranging from .68-.85, and four-month test-retest
reliabilities ranging from .54-.91 (27). Finally, this instrument has demon-
strated appropriate convergent and discriminant validity with other scales
measuring family interaction and family environment variables (27,28).

Statistical Analyses

Because the majority of variables were not normally distributed, Mann-Whitney
tests, the non-parametric alternative to the t-test, were used to compare
results between the chronic fatigue and no fatigue on the majority of the
subsequent analyses. However, when data was normally distributed, the t-test
statistic was used as indicated below. Because of the large number of
separate analyses conducted, a p-value of .01 or below was set as the
threshold for statistical significance in order to minimize Type I error.


First, analyses were conducted that examined the differences between the
chronic fatigue and no fatigue groups on the subscales of the Child Health
Questionnaire. Using the Mann-Whitney non-parametric test statistic, separate
analyses compared the two groups on each of the parent and child subscales.
On the Parent Form-50, children in the chronic fatigue group had
significantly poorer scores on the following subscales: physical functioning
(p<.01); behavior (p<.01); mental health (p<.01); general health (p<.01);
parent impact-emotional (p<.01); parent impact-time (p<.001); and family
activities (p<.01). On the Child Form-87, there were no statistically
significant differences between the chronic fatigue group and the no fatigue
group, when using the Mann-Whitney test statistic. These results are summarized
in Table 1.

Next, comparisons between the two groups on the CBCL subscales and the YSR
subscales were conducted. On the CBCL, children in the chronic fatigue group
were rated as having significantly poorer functioning on the following
subscales: Somatic problems (p<.01); Anxious/Depressed (p<.01); Thought
Problems (p<.01); and Attention Problems (p<.01). On the competence
scales, children with chronic fatigue scored more poorly on the Activities
subscale (p<.01)). On the composite scores, children with chronic fatigue
scored more poorly on the Total Score (p<.001) and the Internalizing (p<.01)
composite scales. None of the group means fell into the clinical range
(i.e., 65 and above), with the exception of the Somatic Problems subscale for
the chronic fatigue group. When examining the results of the Youth
Self-Report subscales, adolescents did not differ on any of the YSR individ-
ual subscales, not did they differ on the composite scales. None of the YSR
subscale or composite scores fell into the clinical range (i.e., 65 and
above). The results are summarized in Table 1.

Next, t-test analyses were used to compare mean subscale scores on the Family
Environment Scale for the two groups. The only statistically significant
different found between the families of children with chronic fatigue and
families of children with no fatigue were found on the parent report (t(51)=
3.236, p<.01) of the Active-Recreational subscale and on the child report
of the Control subscale (t(51)=-3.798, p<.01). These results are summarized
in Table 1.

Regarding missed days of school, separate t-test analyses were conducted to
compare number of missed days of school reported by the parent and the child.
Parents in the chronic fatigue group reported an average of 1.02 days missed
during the past month, as compared to .17 days reported missed in the no
fatigue group. Also, parents of children with chronic fatigue reported an
average of 3.40 days missed in the past 6 months and 6.94 days missed in the
past year, and parents of children with no fatigue reported an average of .94
days missed during the past month and 3.22 days in the past year. Children in
the chronic fatigue group self-reported that they missed 1.67 days during the
past month, as compared to .40 days reported in the control group. Using the
Mann-Whitney non-parametric test, there were no statistically significant
differences found in the number of days of school reported over the past
month by both the parent and the child, nor was there a difference in number
of days missed in the past 6 months or past year as reported by the parents.

Next, parent and child rating of overall activity level were compared between
the chronic fatigue and no fatigue group using separate Mann-Whitney tests.
These analyses found that both the parent ratings (p <.01) and the child
rating (p<.01) of activity levels in the chronic fatigue group were
significantly lower when compared to the no fatigue group.

Finally, the severity of physical symptoms reported by parent and child were
compared between the chronic fatigue group and the no fatigue group using the
Mann-Whitney test-statistic. Separate analyses were conducted for each of the
following symptoms: fatigue, sore throat, lymph node pain, eye pain/light
sensitivity, stomach pain, muscle pain, joint pain, headache,
memory/attention problems, dizziness/ fainting after standing quickly,
dizziness/fainting after hot shower, dizziness/fainting when turning head
fast, dizziness/fainting when bending over, sleep problems,
sick/worse/exhausted after physical exertion, fever/chills/night sweats, and
depression. Children in the chronic fatigue group reported significantly
higher levels of memory and attention problems (p<.01) and sleep problems
(p<.001), when compared to those in the no fatigue group. Parents of
children in the chronic fatigue group reported that their children were
experiencing more severe levels of fatigue (p<.01), eye pain/light
sensitivity (p<.01), headache (p<.01), memory and attention problems
(p<.001), and depression (p<.01). No other analyses were statistically


As hypothesized, children with chronic fatigue tended to exhibit difficulties
in psychosocial and physical functioning when compared to a control group of
children with no fatigue. The presence of chronic fatigue (fatigue lasting 6
months or more) was associated with impairments in overall functioning on the
Child Health Questionnaire. On this questionnaire, parents of children in the
chronic fatigue group reported more severe difficulties with in a variety of
areas, including physical functioning, general health perceptions, mental
health, family activities, and impact on parental time and parental emotions.
In contrast, children in the chronic fatigue group did not report poorer
functioning on any of the CHQ subscales when compared to the no fatigue
group. It should be noted that, when examining the mean scores between the
two groups, the majority of the statistically different subscale mean scores
did not fall below one standard deviation of the subscale mean for the
general population (22). For the chronic fatigue group, only the subscales of
Parent Impact-Time, Parental Impact-Emotional, and the Mental Health on the
parent report fell more than one standard deviation away from the respective
subscale means for the general US population. The presence of chronic fatigue
may negatively impact a child's overall mental health for many reasons. Not
being able to engage in the same normative activities as their peers, such as
being able fully participate in school, participate in active recreation with
their friends, attend peer or class functions, and even feeling singled out
or different because of their illness, may have a particularly devastating
impact on a child's sense of identity and subsequently lead to feelings of
sadness or anxiety. Regarding the other CHQ subscales, although functioning
was poorer when compared to the no fatigue group, the chronic fatigue group
appeared to be only mildly impaired.

Similarly, there were many differences found on the CBCL between the chronic
fatigue and no fatigue group, and it appeared that children in the chronic
fatigue group had more difficulties with internalizing behavior. However, as
with the CHQ, very few of these subscales scores fell within the clinical
range (i.e., above 65). Only the somatic problems subscale was considered to
be in the clinical range (i.e., above 65). Some (26) have noted that children
with physical disorders commonly score higher on this particular subscale
than children without physical or medical disorders, so whether this mean
score is truly indicative of abnormal functioning in the chronic fatigue
group is unclear. This results are similar to findings reported by Carter et
al. (1), who found that, when comparing a group of healthy controls,
depressed adolescents, and adolescents with unexplained chronic fatigue, the
latter group had scores that fell somewhere between the healthy controls and
the depressed adolescents. Thus, while there appear to be somewhat more
difficulty on this psychological measure, the changes within the chronic
fatigue group may in fact be milder than the difficulties reported in
children with primarily psychiatric difficulties.

Significant differences were found between when examining overall activity
levels and reported physical symptoms of children with chronic fatigue, in
that children with chronic fatigue appeared to be more physically limited
when compared to those in the no fatigue group and also exhibited more severe
physical symptoms. However, as with the other psychosocial measures, these
differences tended to be mild when examining the overall means reported for
the overall activity level and the reported physical symptoms. For the rating
of overall activity levels, the chronic fatigue group mean was at 85 on a
scale from 0-100. On this scale, a score of 85 corresponded roughly to a
level of disability where the children either exhibited no or mild symptoms
at rest, symptoms present primarily after physical exertion, activity
restriction was minimal, and the child was still able to go to school
full-time. Likewise, when examining the severity of the physical symptoms
scored on Likert-type scale from 0-7, the means of those symptoms which were
significantly different in the chronic fatigue group tended to fall within
2.32 and 3.14, whereas the means of those in the control group tended to fall
below one. A severity score of approximately 2 -3 corresponded to a
descriptor of 'mild' on the severity Likert-type item scale. Thus, the
symptom severity reported by the chronic fatigue group appeared to be mild.

In terms of associations with the family environment, few differences were
found. Only the active recreation subscale was reported to be significantly
different by parents when compared between the two groups. Also, children
with chronic fatigue were more likely to report higher levels of the control
dimension. It might be expected that families of children with chronic
fatigue would indeed engage in less active recreation due to the limited
ability or negative potential effects of engaging in active family
past-times. Regarding the perception of increased family control reported by
children with chronic fatigue, it is possible that this perception of more
rules and regulations in the family could have occurred because the children
are having more difficulty meeting their family roles and responsibilities.
Likewise, these additional rules and responsibilities might be perceived as
more burdensome by children who are experiencing problems with chronic
fatigue. In general, these findings are consistent with those reported above
that the presence of chronic fatigue appeared to be associated with a
negative impact on the family.

When examining the number of days of school missed, children and parents in
the chronic fatigue group reported slightly more days of school missed when
compared to the no fatigue group, but this difference was not statistically
significant. The total number of missed school days reported by children and
parents was fewer than days missed than reported in other research studies.
In the chronic fatigue group, parents reported that their children missed an
average of 1 day within the last month, 3 days within the past 6 months, and
7 days within the past year. However, other researchers have reported much
higher mean number of days of school missed within the past year. For
example, Carter et al. (1) reported that the majority of participants with
unexplained chronic fatigue missed between 20 to 60 days of school during the
past year; and Smith, Martin-Herz, Womack, and Marsigan (11) reported a mean
of 44 school days missed within the past 6 months in their sample of
chronically fatigued adolescents. Van Hoof et al. (12) reported that only 22%
of the adolescents with CFS in their sample attended school full-time. In
contrast, Farmer et al. (10) found that the boys missed a mean of 10 days of
school during the past school term, and the girls missed a mean of 15 days
per school term, and these days of missed school are similar to the results
found in the current study. This discrepancy in results might be due to the
fact that the individuals in the Carter et al. (1), Smith et al. (11), and
Van Hoof et al. (12) studies were samples of adolescents referred to
specialty and tertiary care clinics, whereas, children and adolescents in the
current investigation and in the Farmer et al. (10) were samples drawn from
the community. It is likely that young people drawn from tertiary care
clinics were more severely ill when compared to a community-based sample of
children and adolescents who may not have sought help from a medical
professional on their own. In the current sample, it is possible that the
number of days missed was not statistically different than healthy children
because these children were less severely ill when compared to
clinic-referred samples.

In general, when comparing the parent versus child report on these various
measures, many more significant differences arose on parent report, and few
differences were found on the child report of functioning. Thus, the parents'
assessment of their child's functioning may be particularly valuable in
identifying changes in their child's behavior. Some of the difficulty in
identifying and classifying the presence of chronic fatigue in children may
be due to the fact that, as with adults, fatigue is a vague, poorly defined
physical and emotional state, and children in particular may have difficulty
in accurately reporting the presence of fatigue and the effects of fatigue on
life. They may be less able to accurately verbally describe their emotional
and physical well-being because of their cognitive developmental level (15).
Parents, by contrast, may be better at noticing subtle changes in their
children's behavior, and thus, active involvement with the parents of
children with fatigue seems warranted in order to more fully assess the
presence of chronic fatigue and understand the impact that fatigue may be
having in their child's life.

Taken together, the results suggest that children in the chronic fatigue
group experienced a range of impairment at both the individual and family
level. However, most of the reported physical and psychological impairments
were mild and were not at the same level of severity as would be expected in
a psychiatrically ill or a hospital-based population. It is possible that the
mild impairments found in this study are due to the fact that the children in
adolescents in this study were drawn from a community based study, while
samples in other studies were drawn from clinic-referred samples. Also, as
noted above, the children and adolescents in the CF group engaged in fewer
overall activities as measured by the Activities competence scale on the CBCL
and a general activity scale, and engaged in fewer family activities, as
measured by the FES. While these children are not so ill that they miss more
days of school when compared to a healthy sample, there appears to be a
reduction in activities that occurs such that they may need to spend all of
their energy on school attendance and may not have any energy available for
other normative, out of school activities. This is consistent with Van Hoof
et al. (12), who found that adolescents with CFS reported not only school
failure or prolonged absenteeism, but a range of school-related problems
including reductions in social and extra-curricular activities. Further, it
is unknown whether these children might request help from their physicians or
mental health professionals, as the children in general still appeared to be
functioning with the average or non-clinical range, so these effects of
chronic fatigue may be harder to detect on an individual basis. In contrast,
clinic-referred samples may represent those children from the community whose
chronic fatigue is the most severe and disruptive to school functioning,
which may have caused them to seek out medical help.

In addition, it is unknown whether the presence of even these mild
difficulties might place a child 'at risk' for future difficulties, as the
long-term consequences are unknown. Research from the CFS literature, which
investigates the course of CFS in children and adolescents suggest that young
people with CFS recover much more quickly than adults with the disorder. It
is possible that, in contrast to their adult counterparts, these mild
difficulties may reflect the resilience experienced by children and
adolescents that has been often reported in the CFS literature. It is unknown
whether individuals in the current sample, many of whom are much less
severely affected than those fully meeting the stringent Fukuda et al. (3)
case definition for CFS, would be expected to show a relatively good
prognosis in recovering from their fatigue difficulties. It is also unknown
whether these children and adolescents recover from fatigue and other
symptoms on their own. However, it is also possible that the individuals in
the current sample, even though they experience less severe fatigue
difficulties when compared to children diagnosed with CFS, might still be
more at risk for developing more serious fatigue problems or even CFS in the

Limitations of this study include the fact that, due to the small sample
size, the chronic fatigue group as a whole was examined in the statistical
analyses, and other variables that might help predict differences in physical
and psychological status, such as age or ethnicity, could not be entered as
covariates. Further, because the data was correlational in nature, it is
unclear whether having chronic fatigue causes impairments in a range of
physical, psychosocial, and psychological functioning, whether deficits in
everyday functioning contribute to the experience or persistence of chronic
fatigue, or whether impairment and the presence of chronic fatigue are due to
other factors that were not measured as part of this study. Research
utilizing larger samples sizes and longitudinal data would allow for the
inclusion of other factors that may be related to the presence of chronic
fatigue, and may help provide support for the results found in this
investigation. Finally, research with pediatric samples having CFS rather
than just CF might more strongly differentiate this ill group from healthy
controls, particularly if more appropriate ways are developed to better
diagnosis CFS in pediatric samples (see article in this volume on the new
pediatric case definition).

In summary, these results suggest that children and adolescents with chronic
fatigue, defined as severe fatigue lasting 6 months or longer, may exhibit a
range of associated difficulties, including limitations in physical and
emotional functioning and a negative impact on parental and family
functioning. However, the functional limitations found in the current
investigation appear to be mild in severity, and it is currently unknown
whether this group of children and adolescents with chronic fatigue might be
at risk for other, longer-term fatigue difficulties. Longitudinal studies of
the course of fatigue symptomatology in a community sample of children and
adolescents are needed to better understand the prognosis and long-term
consequences of chronic fatigue.


TABLE 1. Results of comparisons between chronic fatigue and no fatigue group on
         psychosocial and behavioral rating scales, using the Mann-Whitney test
Child Health Questionnaire         Parent Report            Child Report
                                   -----------------------  ------------------------
                                   Chronic  No              Chronic  No
                                   Fatigue  Fatigue   Sig.  Fatigue  Fatigue  Sig.
                                   n=36     n=21            n=30     n=13
Physical Functioning               84.84    94.44     **    83.46    88.60
Role/Social-Physical               82.83    95.03           81.85    92.31
General Health Perceptions         59.00    73.96     **    61.47    69.10
Bodily Pain                        72.42    83.00           65.33    79.23
Parental Impact-Time               64.31    92.78     ***   -        -
Parental Impact-Emotional          52.27    75.42     **    -        -
Role/Social-Emotional/Behavior     77.44    94.44           -        -
Role/Social-Emotional              -        -               73.70    87.18
Role/Social-Behavior               -        -               86.30    98.29
Self-Esteem                        68.54    79.00           74.49    82.19
Mental Health                      64.73    81.00     **    61.35    73.77
Behavior Scale                     63.21    78.25     **    75.65    76.13
Family Activities                  72.35    88.33     **    67.64    77.56
Family Cohesion                    58.94    70.50           63.17    71.15
Achenbach Behavior Rating          Child Behavior           Youth Self-Report
Scales-CBCL and YSR                Checklist (CBCL)         (YSR)
                                   -----------------------  ------------------------
                                   n=36     n=21            n=21     n=9
Total T score                      61.36    49.62     ***   56.71    46.89
Internalizing T score              62.97    51.24     **    55.43    46.44
Externalizing T score              53.82    46.62           54.67    46.89
Withdrawn T score                  60.73    53.86           57.71    52.56
Somatic Problems T score           66.64    57.95     **    58.62    52.22
Anxious/Depressed T score          61.36    53.71     **    58.76    51.22
Social Problems T score            59.82    54.76           55.19    52.67
Thought Problems T score           60.58    53.52     **    53.29    53.33
Attention Problems T score         63.12    54.14     **    55.33    51.89
Delinquent Behavior T score        56.81    53.76           58.57    55.44
Aggressive Behavior T score        56.55    52.19           58.95    51.33
Sex Problems T score (ages 4-11)   52.27    51.27           -        -
Self-Destructive T score (boys)    -        -               58.25    52.75
Activities T score                 38.55    45.62     **    40.64    39.61
Social T score                     39.27    44.29           41.14    43.63
School T score                     41.43    44.58           -        -
Total Competence T score           37.20    44.58     **    49.74    46.00
Family Environment Scale           Parent version           Child version
                                   -----------------------  ------------------------
                                   n=36     n=21            n=34     n=21
Expressiveness T score             50.78    45.29           50.82    50.62
Independence T score               46.00    49.57           48.71    48.33
Achievement T score                50.97    53.67           50.24    46.81
Control T score                    54.25    55.67           56.50    48.14    ***
Cohesion T score                   50.38    55.48           49.35    52.19
Conflict T score                   50.78    45.43           42.41    41.19
Intellectual/Cultural T score      49.84    53.38           51.65    54.19
Active Rec. T score                43.41    51.67     **    42.21    48.29
Moral Religious T score            56.31    59.38           49.29    50.38
Organization T score               53.34    54.48           49.68    50.95
** = significant at the p<.01 level   *** = significant at the p<.001 level


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(c) 2006 The Haworth Press, Inc.

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Date:    Mon, 12 Mar 2007 22:14:18 +0100
From:    "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM>
Subject: RES,NOT: Did Charles Darwin suffer from CFS ?

Source: Metro U.K.
Date:   March 12, 2007
URL:    http://www.metro.co.uk/news/article.html?in_article_id=40772&in_page_id=34
Ref:    The Emma Wedgwood diaries can be viewed at

Darwin wife's diaries go online

The diaries of the wife of naturalist Charles Darwin have been published

Emma Darwin's diaries cover six decades of the couple's life together and
provide an insight into the daily life of the Victorian scientist and his

The 60 pocket books were previously known only to a handful of academics
familiar with the Darwin archive at Cambridge University Library.
Appointments, family visits and illnesses are all noted in the books.

The first diary is dated 1824 when the then Emma Wedgwood was 16 years
old. She married Charles, her first cousin, in 1839 and kept a diary until
the last year of her life. The diaries reveal how the Darwins entertained
visiting scientists - with guests sometimes numbering 10 or 15.

The complete works of Charles Darwin, who showed how natural selection
could explain evolution, were published online last year.

Project director Dr John van Wyhe said: "The diaries are extremely
fascinating and provide so many details about the private life of this
famous man who changed the world.

"They also fill in the gaps where we didn't know where Darwin was or what
he was doing because we find Emma has written 'Charles to London' or
'Charles returned'. The diaries also bring to life the domestic side of
Darwin as a father and as a husband. Having these diaries online is the
next big step towards making the complete collection that exists available
to everyone and not just to academics in big libraries."

(c) 2007 Metro U.K.

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