[Return to digest index]

              ---------------------------------------------
                       This is a special digest of
                  Co-Cure Research & Medical posts only
               Problems? Write to mailto:mods@co-cure.org
              ---------------------------------------------

----------------------------------------------------------------------

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
www.ktvn.com

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
Glick.

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
Disease.

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
operations.

'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
fibromyalgia.

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
disability.

[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

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>>       8 March 2007       <<<<
Editorship : j.van.roijen chello.nl
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~

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
surroundings.

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

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

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.


-Erik

[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
http://www.biomedcentral.com/content/pdf/1471-2377-7-6.pdf

[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

~~~~~~~~~~~~~~~~~~~~~~~~~~~~


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

http://www.nj.com/news/ledger/index.ssf?/base/news-11/11733327503690.xml&coll=1


The Star Ledger



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


Thursday, March 08, 2007

BY CAROL ANN CAMPBELL
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
hemisphere.

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
shelves.
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
Brunswick.

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
nodes.

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."


DOMINO THEORY

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
Health.

"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
medications.

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
mainstream."

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
complaints.

"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."


'CUT OFF AT THE KNEES'

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
knees."
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
dreams."

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
ESAs.

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:

http://www.fda.gov/medwatch/safety/2007/safety07.htm#ESA

[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

Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>>       10 March 2007      <<<<
Editorship : j.van.roijen chello.nl
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~

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.


~jvr


````````````

http://foodconsumer.org/7777/8888/Non-f_ood_Things_27/030912112007_Anemia_drugs_increase_death_risk_printer.shtml


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
transfusions.


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

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
provider.


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:
http://www.fda.gov/cder/drug/InfoSheets/HCP/RHE2007HCP.htm
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
following:

*  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
advisory?
```````````````````````````````````````````````````````````````````

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
(http://www.fda.gov/cder/drug/infopage/RHE/default.htm).

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
studies?
``````````````````````````````````````````````````````````````````````````

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
include:

*  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
http://www.fda.gov/cder/drug/infopage/RHE/default.htm.






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
available.


``````````````````````````````````````````````````````````````````````````

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
indication.


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
candidates.
*  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
patients.


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
death.
*  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
hypertension
``````````````````````````````````````````````````````````````````````

*  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
circumstances.
*  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
          symptoms:
      *  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
Amgen.

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
http://www.fda.gov/ohrms/dockets/ac/cder04.html#Oncologic.
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
2004.


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
http://www.fda.gov/medwatch/safety/2007/safety07.htm#Aranesp).

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
Development.


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
hemoglobin.

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

[Return to top]

------------------------------

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.

(http://www.kcl.ac.uk/projects/cfs/patients/physiology.html?m=print
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
exhausting.

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.


Summary.

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


INTRODUCTION

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.


SCHOOL ATTENDANCE

>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.


RELEVANT ANAMNESTIC INFORMATION

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.


CHRONIC FATIGUE SYNDROME

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
center.

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.


MUNCHAUSEN-BY-PROXY

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.


MEDICAL AND PSYCHOLOGICAL SCREENING

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.


INVESTIGATION

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
interviews.

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
anxiety.

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
service.


DISCUSSION

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
anxious.

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.


REFERENCES

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):
   543-552.
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,
       
       
       
       
       
       
       
       
       
        http://listserv.nodak.edu/cgi-bin/wa.exe?S2=co-cure&I=1&a=2007&b=2007&f=fluks&s=Pediatric+CFS


A Pediatric Case Definition for Myalgic Encephalomyelitis and Chronic Fatigue
Syndrome
-----------------------------------------------------------------------------
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,
   Belgium.
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,
   USA.
Teruhisa Miike is affiliated with the Department of Child Development, Faculty of
   Medical and Pharmaceutical Sciences, Kumamoto University Graduate School,
   Kumamoto,Japan.
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,
   Belgium.
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).


SUMMARY

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


A PEDIATRIC CASE DEFINITION FOR ME/CFS

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
it.

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
adolescents.

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.


DIAGNOSIS AND PROGNOSIS

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
Munchausen-by-proxy.

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,
2005).


DIFFERENTIATE BETWEEN DIAGNOSES

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
indices.

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.


PREVALENCE OF PEDIATRIC ME/CFS

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
diagnosed.

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.


CHANGES FROM THE ADULT DEFINITION

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 fatig