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[Return to digest index] --------------------------------------------- This is a special digest of Co-Cure Research & Medical posts only Problems? Write to mailto:email@example.com --------------------------------------------- ---------------------------------------------------------------------- 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 firstname.lastname@example.org or call  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. email@example.com 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 (firstname.lastname@example.org) 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 email@example.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 fatigue and other symptoms (Bell, 1995b). On the other hand, inquiring about hobbies, social and leisure activities can provide an indication of the time wherein complaints started to significantly influence daily activities. Clinical practice shows that ME/CFS patients abandon their hobbies, social and leisure activities in order to keep up at school. This process starts when the first school demonstrates a decline in performance. Subsequently, parents will encourage their children to perform better and consequently to spend more time in order to achieve higher levels of functioning at school. Therefore, although no exact onset can be identified by the child or parents, through the assessment process, it is often possible to pinpoint the time point when the fatigue started to interfere with the children's daily functioning. Similarly, the provision that the symptoms such as sore throat or memory impairment not predate the fatigue has also been modified. It has been found that, in children with an insidious onset, such symptoms may in fact predate fatigue. Alternatively, children may have a history of sore throats, ear infections, or upper respiratory infections as part of the usual childhood series of illnesses. However, these illnesses may make it difficult to tease out the onset of ME/CFS symptoms. In addition, parents and children may not be aware of the fatigue but may notice other symptoms. Furthermore, children may also present as irritable rather than fatigued, and it may be difficult to date the onset of this symptom. The symptoms present at the time of diagnosis should, however, be associated in a complex of symptoms that occurs repetitively or chronically. Second, debate has also occurred regarding the six-month requirement for the fatigue and other symptoms (Kulig, 1991; Vereker, 1992). The Canadian criteria suggest that children with symptoms lasting more than three months duration can be diagnosed with the illness (Carruthers et al., 2004). We agree with this notion, as Fowler et al. (2005) did not find differences between 8-17 years olds with 3 versus 6 months of chronic fatigue. Overall, the criterion regarding the duration of the symptoms varies from two weeks to six months (Van Hoof & Maertens, 2002). Arbitrarily, we propose to diagnose a CFS-like condition after 1 to 2 months of duration. After three months, ME/CFS can be diagnosed. In clinical practice, however, it often takes more than one year before a ME/CFS diagnosis is given to children and adolescents (Van Hoof et al., in press). Third, the threshold number of four symptoms has been changed, as we now adopt a similar system to that used with the Canadian ME/CFS criteria of symptom clusters. Appendix A provides a copy of the Pediatric ME/CFS Questionnaire, which provides a way of gathering this information to help diagnose pediatric ME/CFS. It is generally recommended that adolescents age 12 and older fill it out themselves, and parents can assist or fill it out for the children 11 and under, although adherence to this guideline would vary depending on the comprehension level of the individual child. It is possible that more than one person (e.g., child only, parent only, both parents, other primary caregiver) could fill out the Questionnaire. Some clinicians feel that it is almost never acceptable to only involve one parent in doing a child/adolescent evaluation, because a limited and sometimes inaccurate view of the child and family often results from questioning only one parent. Research by Jones et al. (2004) revealed that significant differences exists between parental and children's descriptions of the illness. Thus, whenever possible, information from both parents should be collected. Further, it may be appropriate to gather information from grandparents, extended family members, or other caregivers if they are in close contact with the young person. For a diagnosis of pediatric ME/CFS, the following five classic ME/CFS symptom categories must occur (see Table 1). Post-exertional malaise, the first criteria symptom, must occur with loss of physical or mental stamina, rapid muscle or cognitive fatigability (or easy distraction as the behavioral component of cognitive fatigability). The second symptom category is unrefreshing sleep, or disturbance of sleep quantity or rhythm. The third symptom category requires that the young person exhibit either 1. myofascial pain, 2. joint pain, 3. abdominal and/or 4. head pain. The fourth symptom category is the occurrence of two or more neurocognitive manifestations. Finally, the fifth symptom category requires at least one symptom from two of the following three subcategories: 1. Autonomic manifestations, or 2. Neuroendocrine manifestations, or 3. Immune manifestations. For those patients who do not have the minimum duration of 3 or more months for the 5 classic ME/CFS symptom categories, the diagnosis should be ME/CFS-like. In contrast, there are a small number of patients with no pain or sleep dysfunction, and some pediatric cases might have only 2 to 4 ME/CFS classic symptom categories above. For these individuals, a diagnosis of atypical pediatric ME/CFS can be given. Those individuals with pediatric ME/ CFS as well as atypical pediatric ME/CFS and pediatric ME/CFS-like are important to study. Some support for the inclusion of these symptoms emerged from Rowe and Rowe's (2002) confirmatory factor analysis, which found muscle pain and fatigue, neurocognitive, abdominal head and chest pain, neurophysiological, and immunological factors. Abdominal symptoms have been added to the list, and this is supported by the work by Rowe and Rowe (2002). Autonomic symptoms have also been added, and this is supported by the Canadian case definition, (Carruthers et al., 2003), which pointed to autonomic manifestations (neurally mediated hypotension, light headedness). In addition, a study by Jason, Torres-Harding et al. (2002) found a symptom currently not part of the Fukuda criteria, shortness of breath, did differentiate the groups in adults with ME/CFS. Given that autonomic manifestations might play a role in pediatric neurally mediated hypotension, which has been connected to ME/CFS (Poole et al., 2000), this symptom was also included. Overall, De Becker et al. validated the importance of the general, cognitive and musculoskeletal symptoms. These symptom factor scores were associated with differentiation of both the Holmes and Fukuda defined CFS patients from non-CFS patients (De Becker et al., 2001). It is important that each of the symptoms should be either moderate or severe, but this "severity index" has not been well defined in previous criteria. We now specify that symptoms that are present be rated on the following scale: 1 = not present, 3 = moderate, 7 = severe. Symptoms need to be rated at moderate or severe (e.g., 5 or higher) to meet criteria. The rating scale, rather than a simple yes/no dichotomy, will facilitate accurate diagnosis in the research setting for several reasons. First, it will eliminate false positives on a dichotomous symptom checklist, as most of these symptoms are common to a variety of childhood illnesses, although not to a moderate or severe degree. Second, it will assist the rater, who when faced with a dichotomous choice, may choose "no" if the symptoms are present sometimes or are not severe. Finally, the rating scale will increase the amount of information gathered about each symptom. This will also allow better comparison over time, as symptom severity may wax and wane. In addition, providing information concerning the date of onset of the symptoms might allow investigators to better understand the progression of this illness. This type scoring design allows a dimensional diagnostic evaluation based upon the presence of the symptoms and a traditional ICD-10 categorical diagnosis. This scoring design is implemented because in diagnosing, it is important to take into account both the presence of the symptoms as well as the distress they create. Fourth, the Canadian ME/CFS clinical case definition (Carruthers et al., 2003) states that the concurrent occurrence of the symptoms must have persisted or recurred during six or more consecutive months of illness. We think it is better to indicate the past 3 months, as we are attempting to diagnose current ME/CFS in pediatric cases. In addition, it is clear that the symptoms need not be continuous for the three-month period and may predate the onset of the recognized fatigue. However, it is unclear what is meant by "persisted or recurred" during the past three months. This is a rather complex concept and can lead to unreliability unless the criterion is better specified. We now operationalize this phrase by assessing how often the patient has experienced the symptom over the past 3 months using the following 7 point scale, from 1 = hardly ever to 7 = every day). To be counted as "persisted or recurred," the individual would have to indicate a score of at least 4. In addition to including criteria to determine the meaning of substantial reductions in activity, associated criteria are needed to assess issues of illness severity and remission states. Borrowing from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (American Psychiatric Association, 1994) terminology and the CFS clinical case definition developed by Lapp and Cheney (1995), patients' severity of symptoms might be classified as follows: (A) minimal (just enough symptoms to meet the diagnosis, particularly occurring with exertion, usually able to attend school); (B) mild (few symptoms in excess of those in the diagnosis, occurring even at rest, may be able to attend school part of the time); (C) moderate (many symptoms in excess of those in the diagnosis, moderate symptoms at rest that become severe with effort, unable to attend school); (D) severe (often housebound or bedbound); (E) in partial remission (full criteria for the syndrome were previously met, but currently only a few symptoms remain with effort, able to attend school regularly); and (F) in full remission (no longer any symptoms, even with effort, able to attend school). For individuals who require a more differentiated way of classifying patients' severity of illness, we suggest using the AYME Functional Ability Scale (2005). Fifth, exclusionary medical diagnoses include genetic and other disorders usually first evident in childhood that would explain the fatigue and symptoms, as well as those exclusionary medical diagnoses enumerated in the adult definition. Medical diagnoses that have been adequately treated (e.g., Lyme disease) or that are not likely to cause fatigue should not be considered exclusionary. One change, however, revolves around the depression diagnosis. In the Fukuda et al. (1994) adult definition, melancholic and psychotic depression are considered exclusionary conditions, primarily due to the findings that melancholic and psychotic processes represent distinct biological or endocrinological processes and may respond well to antidepressant or anti-psychotic medications (Robbins et al.,1989; Schulkin, 1994). Depression is less common in childhood, compared with adolescence, and symptoms may differ between these two age groups. Depressed pre-pubertal children are more likely to present with psychomotor agitation, symptoms of phobic and separation anxiety, and somatic complaints. Adolescents with depression, on the other hand, are more likely to present with symptoms such as anhedonia, hypersomnia, weight loss or gain, hopelessness, and lethal suicide attempts. The two groups of depressed youth do not differ on symptoms such as depressed mood, guilt, fatigue, or negative self-image (Compas et al., 1993). As symptoms of depression overlap with those of ME/CFS (Hawk et al., in press), a careful evaluation must be conducted by the physician, with close attention to the differing developmental presentations (Jason, 1997). Inquiring about hobbies and leisure activities is important in distinguishing depression and ME/CFS. Those with the latter diagnosis will have abandoned their hobbies and leisure activities. In particular, if adolescents are sick, not diagnosed, and not believed, the youngsters could become depressed and anxious. Further inquiring about depressive or anxious feelings will reveal an underlying frustration as a result of loosing control rather than a negative self-image. Furthermore, if children experience frequent absences, but no "diagnosis" and no extra help or support, they will have to struggle to catch up when they have to return to school, and this can also lead to depression and anxiety. Thus, depressive feelings should not be considered necessarily exclusionary, as it may co-exist with ME/CFS, particularly if it is a reactive depression to the losses incurred by the illness. There could be a strong feeling of disappointment in ME/CFS children towards their support and peer group as they can not explain the child's condition. This differentiation may also be assisted by evaluating the course of both the depressive symptoms and fatigue symptoms, to determine whether depression and fatigue co-vary or appear to be separate diagnostic entities. However, depression is one of the major entities to be considered during differential diagnosis, and, when it may better explain the fatigue and child's symptom patterns, may be the appropriate diagnosis rather than ME/CFS. Reeves et al. (2003) has recommended that major depressive disorder with melancholic features, anorexia nervosa, or bulimia, not be considered exclusionary if these conditions have been resolved for more than 5 years before the onset of the current illness. We believe that pediatric psychotic disorders of any variety continue to be exclusionary. In addition, eating disorders (i.e., anorexia nervosa and bulimia nervosa) and substance abuse have been qualified to be exclusionary only if the diagnosis is current; a diagnosis of melancholic depression, substance abuse or eating disorder that has been appropriately treated and resolved should not be considered exclusionary. Table 1 also lists disorders that should not necessarily be considered exclusionary, although they may present comorbidly with ME/CFS. Such disorders include school phobia, separation anxiety disorder, and fibromyalgia. School phobia and separation anxiety disorder are two disorders that should be carefully considered in the differential diagnosis. When school phobia or separation anxiety disorder predate the fatigue and other symptoms, it is possible that a diagnosis of ME/CFS is inappropriate and that the symptoms are better explained by a psychological disorder. Children with school phobia may be differentiated from children with ME/CFS in that the former typically feel ill in the morning but recover once allowed to remain home from school (Pilkington & Piersel, 1991). In contrast, children and adolescents with ME/CFS would experience symptoms not only at school, but in other settings. Furthermore, with school phobia, symptoms are typically present only on school days, not weekends or holidays. Similarly, familial disturbance and dysfunction should be closely examined during the diagnostic process. In cases where a child's symptoms are clearly the result of such dysfunction (e.g., the child's illness holding an unstable marriage together), a diagnosis of ME/CFS would be inappropriate. However, it is just as likely that a child may be truly ill with ME/CFS and be part of an unhealthy family system. CLARIFICATION OF DIAGNOSTIC CRITERIA The criterion that the fatigue not be the result of ongoing exertion (Criterion 1A) has been criticized as too vague. For the purposes of clarification and consistency, in the case of a child who is active (e.g., participates in extracurricular activities, sports, outings with friends) but exhausted yet recovers quickly when activity is decreased, the fatigue would be considered to be the result of ongoing exertion or activity and, thus, would exclude a ME/CFS diagnosis. However, a child who participates in very little activity (possibly to minimize ME/CFS symptoms) when compared to his or her same-age peers, and becomes exhausted upon minimal exertion would not be excluded from a ME/CFS diagnosis due to the ongoing exertion clause. Inquiring about hobbies and leisure activities will reveal abandonment of their hobbies and leisure activities. In summary, normal fatigue is not activity limiting, whereas the fatigue present in ME/CFS limits the individual's activity to varying degrees. Similarly, the provision that the fatigue is not substantially alleviated by rest (Criterion 1B) requires clarification. Although a child with ME/CFS may feel better after rest, he or she may get sick again quickly upon minimal activity or exertion. Thus, in this case, the rest does not completely eliminate the syndrome, although it may provide some relief, and this symptom pattern should not exclude a ME/CFS diagnosis. The duration of the post-exertional fatigue is important. It can last for a considerable time and be accompanied by other symptoms such as cognitive downturn, muscle fatigability, as well as resurgence of other CFS symptoms. Another symptom that frequently occurs is social withdrawal to minimize ME/CFS symptoms. Previously extraverted, easy-going and happy children become introvert and quiet. Their parents talk about the perceived desire of their children to withdraw from social interactions and become less noticeable. The criterion that the illness results in a substantial reduction in level of academic, social, or personal functioning (Criterion 1C) requires some clinical judgment. It may be difficult to determine changes from previous level of functioning in very young children who may not be able to recall, nor may their parents be able to recall, their previous activity levels. School personnel school reports can provide an estimate of the premorbid intellectual capacities of the ME/CFS child. It is possible to assess premorbid functioning by reviewing teacher reports before and after the onset of the symptoms. Clinical practice indicates that ME/CFS patients had good premorbid functioning and were considered as easy-going and motivated students. With onset of the illness, this level of functioning decreases and it is reflected in the school reports. In these cases, it is appropriate to compare the child's daily functioning with what would be expected of a same-age peer. For example, inability to attend school, difficulty attending to activities of daily living (e.g., bathing, dressing, or feeding), or lack of participation in social activities due to illness or symptoms such as dizziness should be considered when making the diagnosis. Where possible, there should be validation of decreased activity level and other symptoms by outside sources, such as teachers or school nurses who are familiar with ME/CFS. The AYME Functional Ability Scale (2005) is a promising way of differentiating patients' functional abilities. PSYCHOLOGICAL INSTRUMENTS To assess comorbid neuropsychiatric conditions, instruments such as the Diagnostic Interview for Children and Adolescents-Revised (DICA; Herjanic & Reich, 1982) or the Structured Clinical Interview for the DSM-IV for Children (KID-SCID; Hein) may be used to determine diagnoses. Instruments such as the Children's Depression Inventory (CDI; Kovacs, 1992) or the Schedule for Affective Disorders and Schizophrenia-Children's Version (K-SADS; Chambers et al., 1985) may be used to assess level of depression. Minimal work has been done in the area of assessment of children's fatigue. Walford, Nelson, and McCluskey (1992) report the satisfactory adaptation of the fatigue questionnaire by Wessely and Powell (1989), later revised by Chalder et al. (1993), for use with children. However, no psychometric data are available for this scale in relation to the pediatric population. As Stouten (2005) recently pointed out, many frequently used fatigue scales do not accurately represent the severe fatigue that is characteristics of CFS (although this problem is avoided with the Profile of Fatigue-Related Symptoms, Ray et al., 1992). Sleep disturbances can be assessed by using the Pittsburgh Sleep Quality Index (Buysse, 1989), which has been effectively used in elementary school age samples (Tan, 2004). This Index measures sleep disruptions and sleep quality. The McGill Pain Questionnaire is well validated, is available in a short form (Melzack, 1975), and has been reliably used with pediatric samples (O'Rourke, 2004). Finally, children's functional status may be assessed using the Children's Health Questionnaire (Landgraf, Abetz, & Ware, 1996), an instrument that will assess physical and psychosocial well-being. The 12 concepts measured by both forms of the CHQ include physical functioning, bodily pain, general health perceptions, and self-esteem. As mentioned in the manual, the Changed GHQ-score is most appropriate in chronic conditions as children will incorporate their symptoms in their own `conceptual frame.' The scale `no more than usual' is included in the changed GHQ scoring procedure. INTERVENTIONS TO INCREASE QUALITY OF LIFE In the case of children, day-to-day management of a chronic disease and its psychological consequences becomes a family affair with parents in particular having a key role to play. Thus, it is not surprising that the role of interventions in facilitating adaptation to the challenges of chronic disease has received growing recognition. Information presented to the child, parents and other primary caregivers should make them equipped to play an active role in the daily management of their illness. A number of interventions are drawn on theoretical concepts such as self-efficacy and empowerment. At the individual level, key elements of empowerment include access to information, ability to make choices, effective change in one's life, assertiveness and self-esteem (Rogers et al., 1997). Similarly, self-efficacy has been posited as a central, mediating mechanism in human agency (Bandura, 1988), whereby perceptions of capabilities to carry out the courses of action necessary to meet situational demands influence choice of actions pursued, level of motivation, thought pattern and emotional reactions experienced. There is evidence of effectiveness for interventions incorporating cognitive-behavioral techniques on variables such as self-efficacy, self-management of disease, family functioning, psychosocial well-being, reduced isolation and social competence. Overall, psycho-educational interventions can take many forms including simple provision of information via written materials, computer programs or the Internet. Psycho-educational interventions for children and their families, however, need to take account of developmental age as well as disease progression. Glasgow and colleagues (1999) suggest that problems with self-care typically emerge during the first few years after diagnosis or during early adolescence (13-15 years). Thus, educational and skills training approaches may be particularly important for both child and family at the time of diagnosis and for adolescents who are assuming responsibility for self-care. In CFS/ME area with pediatric samples, there have been only a few implemented non-pharmacologic interventions, and few had appropriate controls or long-term follow-up (Whiting et al., 2001; Barlow & Ellard, 2004). SUGGESTIONS FOR FUTURE RESEARCH ON PEDIATRIC ME/CFS The definition proposed here is provided as a starting point for facilitating consistent research on pediatric ME/CFS. This definition should be subjected to rigorous scientific study to determine its efficacy. In particular, reliability studies should be conducted to determine if the definition facilitates consistent diagnosis (Jason et al., 1997). Rowe and Rowe (2002) used 24 key symptoms and found one underlying syndrome factor, suggesting that the syndrome complex can be legitimately designated as a syndrome. In addition, Komaroff and colleagues (1996) compared symptoms and fatigue characteristics of a large sample of adult ME/CFS patients with three other groups (healthy controls, depressed subjects, and patients with multiple sclerosis) to determine the validity of each symptom and its contribution to differential diagnosis. Similar techniques would be useful in validating the pediatric definition. Future research on pediatric ME/CFS should carefully word questions aimed at identifying children's level of fatigue, and the developmental context of the children and adolescents being assessed should be taken into account. As children may present as irritable rather than complain of fatigue, questions that focus on school problems (e.g., learning or memory problems) or other consequences of fatigue may need to be asked in addition to questions regarding fatigue. In addition, as there may be discrepancies between caregiver's reports of the child's functioning and the child's own assessment, a comparison of these two descriptions of symptomatology should be made. Fukuda et al. (1994) recommended subgrouping adult ME/CFS patients and similar efforts would be appropriate in the study of pediatric ME/CFS. In addition, it is clear that the current cohort of individuals diagnosed with ME/CFS is a diverse group with varying disease course and disability patterns, offering limited understanding of the etiology or pathology of the illness and its components when considered together (Jason et al., 2005). Patterns of illness course and duration are difficult to decipher when using the current diagnostic criteria to identify individuals with this illness. Similar to disorders such as cancer, it is highly likely that a number of distinct types of ME/CFS exist and that the current method of grouping all individuals who meet diagnostic criteria together complicates the identification of biological markers in these subgroups. The arguments against articulating a definition of ME/CFS specifically for pediatric patients revolve primarily around the harm of an inaccurate diagnosis. These arguments include the uncertainty in diagnosing children due to difficulty in obtaining an accurate self-report from young children. In addition, premature diagnosis may prevent recognition of a treatable condition. Finally, some researchers and clinicians doubt that ME/CFS exists as a clinical entity in children, particularly young ones. However, a consistent case definition is needed to facilitate research on pediatric ME/CFS and to assist in the identification of homogenous groups. While some researchers have suggested that children and adolescents have a higher rate of recovery from ME/CFS when compared to adults, there is still a subgroup of pediatric cases whose illness persists for extended periods of time (Arav-Boger & Spirer, 1995; Smith & Carter, 2003). A consistent case definition would facilitate longitudinal investigations into the prognosis of CFS and help identify risk factors which may predict poorer prognosis, so that these higher risk children and adolescents receive earlier intervention. The summary of symptoms in Table 1 could be referenced by pediatricians, school nurses, and even school teachers and staff responsible for Individual Education Plan development and implementation. In addition, the criteria list could be useful to the young person, parents or others advocating for the youth with ME/CFS in need of accommodations since it would give legitimacy to the child's symptoms. The rapid, accurate identification of cases of ME/CFS followed by comprehensive and appropriate support and treatment might increases chances of recovery for all children and adolescents with this debilitating illness. AUTHOR NOTE The authors appreciate the support from the Board members of the International Association for Chronic Fatigue Syndrome. In addition, they thank the following people who have provided them constructive feedback: Pat Fero, Jill McLaughlin, Eleanor Stein, Mary Schweitzer, Michael Yogman, Kathleen Gale, Connie Vander Eb, and John Herd. NOTE 1. The acronym ME/CFS refers to Myalgic Encephalomyelitis and Chronic Fatigue Syndrome, according to the Canadian Case Definition. The patient community has felt that the term chronic fatigue syndrome trivializes the seriousness of this illness, as the illness is typified by many severe symptoms in addition to fatigue, and fatigue is generally regarded as a common symptom experienced by many otherwise healthy individuals in the general population. The term Myalgic Encephalomyelitis had been used prior to the use of the term chronic fatigue syndrome (Acheson, 1959). Some individuals have preferred to use the term Myalgic Encephalopathy rather than Myalgic Encephalomyelitis, as the former term does not suggest brain inflammation. TABLE TABLE 1. Definition of ME/CFS for Children --------------------------------------------------------------------------------- I. Clinically evaluated, unexplained, persistent or relapsing chronic fatigue over the past 3 months that: A. Is not the result of ongoing exertion B. Is not substantially alleviated by rest C. Results in substantial reduction in previous levels of educational, social and personal activities D. Must persist or reoccur for at least three months --------------------------------------------------------------------------------- II. The concurrent occurrence of the following classic ME/CFS symptoms, which must have persisted or recurred during the past three months of illness (symptoms may predate the reported onset of fatigue). A. Post-exertional malaise and/or post-exertional fatigue. With activity (it need not be strenuous and may include walking up a flight of stairs, using a computer, or reading a book), there must be a loss of physical or mental stamina, rapid/sudden muscle or cognitive fatigability, post-exertional malaise and/or fatigue and a tendency for other associated symptoms within the patient's cluster of symptoms to worsen. The recovery is slow, often taking 24 hours or longer. B. Unrefreshing sleep or disturbance of sleep quantity or rhythm disturbance. May include prolonged sleep (including frequent naps), disturbed sleep (e.g., inability to fall asleep or early awakening), and/or day/night reversal. C. Pain (or discomfort) that is often widespread and migratory in nature. At least one symptom from any of the following: Myofascial and/or joint pain (Myofascial pain can include deep pain, muscle twitches, or achy and sore muscles. Pain, stiffness, or tenderness may occur in any joint but must be present in more than one joint and lacking edema or other signs of inflammation.) Abdominal and/or head pain (May experience eye pain/sensitivity to bright light, stomach pain, nausea, vomiting, or chest pain. Headaches often described as localized behind the eyes or in the back of the head. May include headaches localized elsewhere, including migraines.) D. Two or more neurocognitive manifestations: Impaired memory (self-reported or observable disturbance in ability to recall information or events on a short-term basis) Difficulty focusing (disturbed concentration may impair ability to remain on task, to screen out extraneous/excessive stimuli in a classroom, or to focus on reading, computer/work activity, or television programs) Difficulty finding the right word Frequently forget what wanted to say Absent mindedness Slowness of thought Difficulty recalling information Need to focus on one thing at a time Trouble expressing thought Difficulty comprehending information Frequently lose train of thought New trouble with math or other educational subjects E. At least one symptom from two of the following three categories: 1. Autonomic manifestations: Neurally mediated hypotension, postural orthostatic tachycardia, delayed postural hypotension, palpitations with or without cardiac arrhythmias, dizziness, feeling unsteady on the feet-disturbed balance, shortness of breath. 2. Neuroendocrine manifestations: Recurrent feelings of feverishness and cold extremities, subnormal body temperature and marked diurnal fluctuations, sweating episodes, intolerance of extremes of heat and cold, marked weight change-loss of appetite or abnormal appetite, worsening of symptoms with stress. 3. Immune manifestations: Recurrent flu-like symptoms, non-exudative sore or scratchy throat, repeated fevers and sweats, lymph nodes tender to palpitation - generally minimal swelling noted, new sensitivities to food, odors, or chemicals. --------------------------------------------------------------------------------- III. Exclusionary conditions: A. Any active medical condition that may explain the presence of chronic fatigue, such as: 1. Untreated hypothyroidism 2. Sleep apnea 3. Narcolepsy 4. Malignancies 5. Leukemia 6. Unresolved hepatitis 7. Multiple Sclerosis 8. Juvenile rheumatoid arthritis 9. Lupus erythematosus 10. HIV/AIDS 11. Severe obesity (BMI greater than 40) 12. Celiac disease 13. Lyme disease B. Some active psychiatric conditions that may explain the presence of chronic fatigue, such as: 1. Childhood schizophrenia or psychotic disorders 2. Bipolar disorder 3. Active alcohol or substance abuse - except as below: a) Alcohol or substance abuse that has been successfully treated and resolved should not be considered exclusionary. 4. Active anorexia nervosa or bulimia nervosa - except as below: a) Eating disorders that have been treated and resolved should not be considered exclusionary. 5. Depressive disorders --------------------------------------------------------------------------------- IV. May have presence of concomitant disorders that do not adequately explain fatigue, and are, therefore, not necessarily exclusionary. 1. Psychiatric diagnoses such as: a) School phobia b) Separation anxiety c) Anxiety disorders d) Somatoform disorders e) Depressive disorders 2. Other conditions defined primarily by symptoms that cannot be confirmed by diagnostic laboratory tests, such as: a) Multiple food and/or chemical sensitivity b) Fibromyalgia 3. Any condition under specific treatment sufficient to alleviate all symptoms related to that condition and for which the adequacy of treatment has been documented. 4. Any condition, that was treated with definitive therapy before development of chronic symptomatic sequelae. 5. Any isolated and unexplained physical examination, laboratory or imaging test abnormality that is insufficient to strongly suggest the existence of an exclusionary condition. --------------------------------------------------------------------------------- REFERENCES Acheson E.D. (1959). The clinical syndrome variously called benign myalgic en- cephalomyelitis, Iceland Disease, and epidemic neuromyasthenia. American Jour- nal of Medicine, 26, 569-95. American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author. Arav-Boger, R., & Spirer, Z. (1995). Chronic Fatigue Syndrome: Pediatric aspects. Israel Journal of Medical Sciences, 31, 330-334. AYME Functional Ability Scale (2005). Association of Young People with ME. See http://ayme.org.uk/print.php?sid=10&id=11 Bandura, A. (1988). Perceived self-efficacy: Exercise of control through self belief. In: Annual Series of European Research in Behaviour Therapy. In J.P. 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Interventions for the treatment and management of chronic fatigue syndrome: A systematic review. JAMA, 286, 1360-1368. [APPENDIX A. Pediatric Health Questionnaire] -------- (c) 2006 The Haworth Press, Inc. [Return to top] ------------------------------ Date: Sun, 11 Mar 2007 20:22:35 -0000 From: Tom Kindlon <tomkindlon@OCEANFREE.NET> Subject: RES: An internet survey of 2,596 people with fibromyalgia An internet survey of 2,596 people with fibromyalgia Robert M Bennett , Jessie Jones , Dennis C Turk , I. Jon Russel and Lynne Matallana BMC Musculoskeletal Disorders 2007, 8:27 doi:10.1186/1471-2474-8-27 http://www.biomedcentral.com/1471-2474/8/27/abstract Published 9 March 2007 Abstract (provisional) The complete article is available as a provisional PDF http://www.biomedcentral.com/content/pdf/1471-2474-8-27.pdf The fully formatted PDF and HTML versions are in production. Background This study explored the feasibility of using an Internet survey of people with fibromyalgia (FM), with a view to providing information on demographics, sources of information, symptoms, functionality, perceived aggravating factors, perceived triggering events, health care utilization, management strategies, and medication use. Methods A survey questionnaire was developed by the National Fibromyalgia Association (NFA) in conjunction with a task force of "experts in the field". The questionnaire underwent several rounds of testing to improve its face validity, content validity, clarity and readability before it was mounted on the internet. The questionnaire consisted of 121 items and is available online at the website of the National Fibromyalgia Foundation. Results The questionnaire was completed by 2,569 people. Most were from the United States, with at least one respondent from each of the 50 states. Respondents were predominantly middle-aged Caucasian females, most of whom had FM symptoms for 4 years or more. The most common problems were morning stiffness, fatigue, nonrestorative sleep, pain, concentration, and memory. Aggravating factors included: emotional distress, weather changes, insomnia, and strenuous activity. Respondents rated the most effective management modalities as rest, heat, pain medications, antidepressants, and hypnotics. The most commonly used medications were: acetaminophen, ibuprofen, naproxen, cyclobenzaprine, amitriptyline, and aspirin. The medications perceived to be the most effective were: hydrocodone preparations, aprazolam, oxycodone preparations, zolpidem, cyclobenzaprine, and clonazepam. Conclusions This survey provides a snap-shot of FM at the end of 2005, as reported by a self-selected population of people. This descriptive data has a heuristic function, in that it identifies several issues for further research, such as the prescribing habits of FM health care providers, the role of emotional precipitants, the impact of obesity, the significance of low back pain and the nature of FM related stiffness. [Return to top] ------------------------------ Date: Sun, 11 Mar 2007 18:36:59 -0400 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: Variability of criteria used to diagnose myofascial trigger point pain syndrome-evidence from a review of the literature Variability of criteria used to diagnose myofascial trigger point pain syndrome-evidence from a review of the literature. Clin J Pain. 2007 Mar-Apr;23(3):278-86. Tough EA, White AR, Richards S, Campbell J. Peninsula Medical School, Universities of Exeter and Plymouth, UK. PMID: 17314589 OBJECTIVES: The aim of the literature review was to investigate the criteria adopted by "experts" to diagnose myofascial trigger point (MTrP) pain syndrome. Experts were defined as being either researchers investigating MTrP pain syndrome or the "authority" the researchers cited as a source of reference for MTrP pain syndrome diagnosis. METHODS: We searched electronic databases to identify relevant empirical research (excluding studies not in English and those relating to dental pathology). Of 607 possibly relevant publications 93 met our inclusion criteria. We recorded (1) the individual criterion and criteria combinations used to diagnose MTrP pain syndrome; (2) the cited "authoritative" publications and (3) the criteria recommended by the authoritative publications as being essential for MTrP pain syndrome diagnosis. RESULTS: The review identified 19 different diagnostic criteria. The 4 most commonly applied criteria were: "tender spot in a taut band" of skeletal muscle, "patient pain recognition," "predicted pain referral pattern," and "local twitch response." There was no consistent pattern to the choice of specific diagnostic criteria or their combinations. However, one pair of criteria "tender point in a taut band" and "predicted or recognized pain referral" were used by over half the studies. The great majority of studies cited publications by Travell and more recently Simons as a principal authoritative source for MTrP pain syndrome diagnosis, yet most of these studies failed to apply the diagnostic criteria as described by these authorities. DISCUSSION: We conclude that there is as yet limited consensus on case definition in respect of MTrP pain syndrome. Further research is needed to test the reliability and validity of diagnostic criteria. Until reliable diagnostic criteria have been established, there is a need for greater transparency in research papers on how a case of MTrP pain syndrome is defined, and claims for effective interventions in treating the condition should be viewed with caution. [Return to top] ------------------------------ Date: Sun, 11 Mar 2007 18:40:25 -0400 From: "Bernice A. Melsky" <bernicemelsky VERIZON.NET> Subject: RES: The myofascial trigger point region: correlation between the degree of irritability and the prevalence of endplate noise The myofascial trigger point region: correlation between the degree of irritability and the prevalence of endplate noise. Am J Phys Med Rehabil. 2007 Mar;86(3):183-9. Kuan TS, Hsieh YL, Chen SM, Chen JT, Yen WC, Hong CZ. Department of Physical Medicine and Rehabilitation, College of Medicine, National Cheng Kung University, Tainan, Taiwan. PMID: 17314703 OBJECTIVE: This study was designed to investigate the correlation between the irritability of the myofascial trigger point (MTrP) and the prevalence of endplate noise (EPN) in the MTrP region of human skeletal muscle. DESIGN: Twenty normal subjects with latent MTrPs and 12 patients with active MTrPs in the upper trapezius muscles were recruited for this study. The patients reported the subjective pain intensity of the active MTrP (0-10). The MTrP and an adjacent non-MTrP site were confirmed and marked for the measurement of pressure pain threshold (with a pressure algometer) and the prevalence of EPN (with electromyographic recordings). RESULTS: The prevalence of EPN in the MTrP regions was significantly higher (P < 0.01) in the active MTrPs than in the latent ones. However, no EPN could be found in the non-MTrP region near either the active or the latent MTrPs. The pain intensity and the pressure pain threshold were highly correlated with the prevalence of EPN in the MTrP region (r = 0.742 and -0.716, respectively). CONCLUSIONS: The irritability of an MTrP is highly correlated with the prevalence of EPN in the MTrP region of the upper trapezius muscle. The assessment of EPN prevalence in an MTrP region may be applied to evaluate the irritability of that MTrP. [Return to top] ------------------------------ Date: Mon, 12 Mar 2007 09:39:33 +0100 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: Pediatric CFS - Psychosocial and Physical Impact Source: Journal of Chronic Fatigue Syndrome Vol. 13, No. 2/3, 2006, pp. 55-74 Date: 2006 URL: http://jcfs.haworthpress.com Ref: See also, http://listserv.nodak.edu/cgi-bin/wa.exe?S2=co-cure&I=1&a=2007&b=2007&f=fluks&s=Pediatric+CFS Psychosocial and Physical Impact of Chronic Fatigue in a Community-Based Sample of Children and Adolescents ------------------------------------------------------------------------------- Susan R. Torres-Harding, PhD Karen Jordan, PhD Leonard A. Jason, PhD Renee Arias, BA Susan R. Torres-Harding, Leonard A. Jason, and Renee Arias are affiliated with the Center for Community Research, DePaul University, Chicago, IL. Karen Jordan is Associate Professor, Louisville School of Medicine, Louisville, KY. Address correspondence to: Leonard A. Jason, PhD, Center for Community Re- search, DePaul University, 990 West Fullerton Avenue, Room 3100, Chicago, IL 60614 (E-mail: Ljason depaul.edu). SUMMARY Background Few studies have examined the problem of chronic fatigue in children and adolescents and its potential impact on functioning. Chronic fatigue may have a negative impact on school functioning, family activities, psychological well-being, physical functioning, and severity of medical symptomatology. Objectives This study compared psychosocial, family, and physical functioning between a randomly selected community based sample of 36 children and adolescents with chronic fatigue and a group of 21 children and adolescents without fatigue. Methods Children and parents completed a comprehensive medical history questionnaire and questionnaires assessing psychological functioning, family functioning, and school attendance. Results Results indicated that children with chronic fatigue tended to have more difficulties in overall physical and psychological functioning, as measured by the Child Health Questionnaire and the Child Behavior Checklist. In addition, children in the chronic fatigue group experienced disruptions in a range of activities and reported more severe physical symptomatology when compared to children without fatigue. Conclusions Findings suggest that children and adolescents with chronic fatigue may have a range of associated difficulties, including limitations in physical and psychosocial functioning and a negative impact on the ability to engage in normative activities. KEYWORDS. Chronic fatigue, children, adolescents, psychosocial functioning, physical functioning INTRODUCTION Fatigue has been found to be a significant problem in adult populations, but has less frequently been studied in children. Fatigue is a common symptom among pediatric populations, particularly adolescents (1). Children and adolescents are generally less at risk for fatigue than adult populations; however, when fatigue has been found in pediatric populations, it has been associated with negative consequences, including increased psychiatric comorbidity, decreases in functioning, and school disruption (2). Some researchers have investigated the occurrence of chronic fatigue syndrome (CFS) in children, a chronic condition characterized by severe disabling fatigue. When using criteria developed by Fukuda et al. (3), this condition also encompasses a variety of additional symptoms, including sore throat, headache, joint pain, muscle pain, lymph node pain or tenderness, unrefreshing sleep, post-exertional malaise, memory and concentration impairment. However, the application of the Fukuda case definition to pediatrics is controversial because these criteria were developed for adults, and some have questioned its applicability to children (4,5). For this reason, some researchers have focused on children with chronic fatigue, or severe fatigue lasting 6 months or more, to determine whether children and adolescents with longer-lasting fatigue that does not resolve on its own might be more indicative of difficulties in this population (1). It is possible that children and adolescents with chronic fatigue, even if they do not fully meet the Fukuda criteria for chronic fatigue syndrome, might still be experiencing significant difficulties and disruption in functioning due to the presence of chronic fatigue. The prevalence of children and adolescents with either general fatigue (lasting more than a few days) or prolonged fatigue (fatigue lasting one month or more) range from .06% (6) to 16% (7). The prevalence of pediatric chronic fatigue, or fatigue lasting 6 months or more, has been estimated at between .01% and 4% (8, 9). Farmer et al. (10) conducted a postal study of a twin registry in Great Britain consisting of 3,051 pairs of twins, and they found that 4.4% were identified as having more than a few days of disabling fatigue. In this sample, the mean duration of fatigue was 9 months for boys and 14 months for girls. Steele et al. (6) conducted a random digit-dialing telephone survey of chronic fatigue in the San Francisco urban area with 8,004 households and found unexplained prolonged fatigue (fatigue lasting for 1 month or more) in .06% of the children and adolescents under the age of 18. Peterson et al. (7) found that, among a randomized cluster sample of 1,155 Swedish schoolchildren ages 6-13 years, the prevalence of fatigue at least once a week was 31%, and 16% felt tired almost every day, with older school children reporting more recurrent fatigue. In a randomly-selected community-based epidemiological study conducted in Wichita, Kansas, with 34,018 households, the prevalence of adolescents having chronic fatigue (fatigue lasting 6 months or more) was 1,298 per 100,000, or .01% (8). Finally, in a second large-scale community-based epidemiological study conducted in the US among a socioeconomically and ethnically diverse random community sample of 18,675 households, 4% of children and adolescents exhibited either fatigue or school learning/memory problems (9). In studies of children with fatigue or chronic fatigue, it has been found that school difficulties and school failure are a significant problem. Nagane (2) found, in a study of 32 healthy Japanese children age 9-10, that children with greater fatigue had lower scores on some items of academic achievement and sports ability. This study suggested that fatigue may be a risk factor for reduced mental and physical activity in school children. Carter et al. (1), in their study of 31 adolescents (average age 14.3) of unexplained chronic fatigue lasting 6 months or more referred to a pediatric infectious disease clinic, found that 55% of these participants had missed 20 to 60 days of school during the most recent school year because of their fatigue. Further, 35% of these participants indicated declines in academic performance due to their illness, and 52% experienced declines in extracurricular activities. These individuals also reported impairment in their social activities (55%), problems with social relationships (35%) and feeling as if their family members treated them differently (39%). Smith, Martin-Herz, Womack, and Marsigan (11) also found that adolescents referred for evaluation of chronic fatigue to a specialty clinic reported a greater level of absenteeism from school, with those individuals with unexplained chronic fatigue reporting an average of 44 school days missed within the past 6 months. Farmer et al. (10) identified 96 children and adolescents from a community-based twin registry with disabling fatigue, and they found that the boys missed a mean of 10 days of school during the past school term, and the girls missed a mean of 15 days per school term. Finally, Van Hoof, De Becker, Lapp, and DeMeirlier (12) conducted a qualitative study in 27 adolescents diagnosed with CFS, and these adolescents reported a range of school difficulties, including prolonged absenteeism, difficulty with completing courses and the need for accommodations in order to complete exams, conflicts and lack of support at school, impaired social interaction and fewer friends after becoming ill, and participation in fewer extracurricular activities because of illness. Further, some researchers have suggested that children and adolescents with chronic fatigue may be at more risk for poor psychological and psychosocial functioning. Carter et al. (1) found that, on the Child Behavior Checklist (CBCL), fatigued adolescents had more internalizing symptoms when compared to healthy controls and had fewer externalizing symptoms when compared to depressed adolescents. Fatigued adolescents exhibited lower scores on the majority of the Children's Depression Inventory scales and the overall score when compared to depressed adolescents and exhibited higher overall depression and anhedonia than healthy controls. Thus, the fatigued adolescents appeared to have poorer overall psychological functioning when compared to controls, but this did not always fall into the clinical ranges of these subscales, and these difficulties appeared to be less when compared to depressed adolescents. Carter et al. (1) indicated that their results suggest pediatric patients with chronic fatigue are at risk for psychological disturbances. It is possible that psychological difficulties may result when a child has difficulty coping with their fatigue illness, or may result from the stress of having chronic medical problems. Similarly, Farmer et al. (10) found that the parents of 96 children with chronic fatigue experienced impaired relationships with family and friends and limitations in leisure activity participation. Further, they found that individuals with disabling fatigue were more likely to develop symptoms of depression during their fatigue episodes, with 38% of boys and 39% of girls in their sample experiencing DSM-IV criteria for depression (10). Limitations in energy may have a significant impact in psychological functioning due to its impact on school, academic, or social functioning. While there have been limited studies that have examined the problem of fatigue and chronic fatigue in children and adolescents, findings from research cited above indicate that chronic fatigue may potentially be disruptive, particularly to school functioning. It is possible that children with chronic fatigue are experiencing an overall higher level of physical impairment and other physical symptoms which may occur as a result of the fatigue. Examining the effects of chronic fatigue is particularly important to determine the impact of this symptom on everyday physical functioning. Further, information regarding the associations with chronic fatigue may be helpful for family care specialists and pediatricians who often must evaluate the causes and significance of unexplained chronic fatigue in their patients. This study examined the effect of chronic fatigue on school functioning, family functioning, and overall physical and emotional impairment in a randomly selected community based sample of children with fatigue or other health difficulties and in a group of children without fatigue. It was hypothesized that children and adolescents with chronic fatigue would exhibit increased difficulties in various areas of life functioning when compared to a control group of children without chronic fatigue. METHODS Procedure The data from this study are derived from a larger epidemiological prevalence study of chronic fatigue in a randomly selected, community-based sample of adults and children (13,14). This larger study of CFS entailed a cross-sectional screening telephone survey of a random sample of 28,673 households. Procedures described in Jason et al. (13) were used to select one adult from each household. Birth dates for each adult were gathered, and the person with the most recent birth date was interviewed. A random sample of adults (18 years or older) was screened for inclusion into the larger study, and as part of the screening process, information regarding the fatigue and illness status of all children in the household were collected. This pediatric study was carried out in three stages. Stage 1. First, a brief screening questionnaire was added to the adult screening questionnaire protocol several months after adult data collection had commenced. This screening questionnaire took approximately one to two minutes to administer. This brief questionnaire was developed for this study and assessed for either the presence of severe fatigue and/or disruption in school activities. This second question regarding school activities was asked because previous research has suggested that children may not report fatigue as their principal symptom or may exhibit fatigue through irritability or in other ways (15). The questionnaire also assessed symptoms that commonly occur in CFS, as defined by Fukuda et al. (3), as well as additional symptoms proposed by Bell (16). Stage 2. Children and adolescents were invited to participate in the second and third phases of the study if they had no exclusionary medical conditions, at least 4 of the additional CFS symptoms (sore throat, headache, lymph node pain, joint pain, muscle pain, post-exertional malaise, unrefreshing sleep, and memory/concentration problems), and significant fatigue or problems with memory or learning at school. Further, a control group was randomly selected from among those children who screened negative for study inclusion in stage 1. The second phase of the study included a psychological examination with the children and adolescents. The structured clinical interview for the DSM-IV, Childhood version (KID-SCID, 17) was administered by one of three master's level clinicians. The KID-SCID utilizes multiple information (i.e., parent and child) to determine the presence of a psychiatric diagnosis. Stage 3. Following completion of the psychological examination, children and adolescents received a medical evaluation to rule out medical conditions leading to fatigue and to determine whether an individual met criteria for a diagnosis of CFS. The medical evaluation included an extensive medical history questionnaire which assessed the child's medical history, current symptoms, and fatigue symptomatology. Also, a full medical evaluation was conducted by a pediatrician, and laboratory testing was performed. The laboratory testing included a urinalysis, complete blood count with differential, erythrocyte sedimentation rate, chemistry panel, thyroid function tests, and an HIV test. A chest x-ray was performed if one had not been conducted within 8 months of the physical examination date, and a tuberculosis skin test (PPD) was conducted. The medical examination and laboratory testing were administered to rule other potential diseases, as recommended by Fukuda et al. (3). Finally, the results obtained from the all testing performed (medical, psychiatric, etc.) were reviewed by an independent physician review panel who were blind to the experimental status (experimental vs. control) of each study participant. The team of four physicians determined the final diagnosis for each participant after completion of all phases of the study. Final diagnoses included a diagnosis of CFS, meaning that the participant met the criteria for CFS as defined by Fukuda et al. (3). Alternately, individuals were also diagnosed with Idiopathic Chronic Fatigue (ICF), defined as those children experiencing unexplained fatigue that did not fully meet criteria for CFS as defined by Fukuda et al. (3) or as having Chronic Fatigue Explained, meaning that the individual was experiencing significant fatigue, but that their fatigue was fully explained by a medical or psychiatric diagnosis. Finally, individuals could be classified as No Fatigue, meaning that the child was not currently experiencing significant problems with fatigue. Participants: Fifty-seven children and adolescents participated in stages 2 and 3. Because only 2 children were identified with CFS, it was decided that children would be grouped into two categories. Those who exhibited CFS, ICF, or Chronic Fatigue Explained were classified into the "Chronic Fatigue" group. Individuals who did not exhibit chronic fatigue were classified into the "No Fatigue" group. The current study examined those individuals who had chronic fatigue (CFS, ICF, or Chronic Fatigue Explained) and those individuals without ongoing fatigue difficulties (No Fatigue). In addition, this investigation examined among all respondents the association between whether one had chronic fatigue or not, and the other psychosocial and disability-related measures to determine whether chronic fatigue might also be associated with these variables. The final sample of 57 participants was 54.4% female and 45.6% male. Regarding ethnicity, 22.8% were African-American, 24.6% were Caucasian, 49.1% were Latino, and 3.5% were of another ethnicity. The average age of the sample was 11.4, with the age range of the sample from 5 to 18 years old. Using chi-square analyses, no statistically significant differences were found between the two groups (Chronic Fatigue vs. No Fatigue) for gender, age, or ethnicity. Measures CFS Medical Questionnaire: Parent and Child Report. This questionnaire assessed the study participants' demographic information and complete medical history, including current and past symptomatology, history of service utilization, results of past medical and psychiatric evaluations, history and course of illness, and effects of illness on overall functioning. This questionnaire was developed for use specifically within this research investigation. It was administered to both the parent and the child. The Structured Clinical Interview for the DSM-IV, Childhood Version (KID-SCID) (17) is a semi-structured psychiatric interview that assesses for the presence of psychiatric disorders in children and adolescents age 5 to 18. The KID-SCID obtains information from multiple informants (i.e., parent and child), and this information is then used by the clinician to arrive at the appropriate diagnosis. This interview has demonstrated good interrater reliability in the Disruptive Behavior module, .842 for ODD and CD, and 1.0 for ADHD (18). In addition, this instrument has demonstrated good test-retest reliability, with Kappa scores consisting of .84 for Attention Deficit/Hyperactivity Disorder, .84 for Conduct Disorder, .63 for Oppositional Defiant Disorder, 1.0 for Social Phobia, .66 for Separation Anxiety Disorder, and .44 for Posttraumatic Stress Disorder (19). The Fatigue Scale (21). This scale was used to assess fatigue severity. This scale was originally used in a hospital-based case control study (20) and was further refined by Chalder et al. (21). Despite its brevity, the scale was found to be reliable and valid, and it had good face validity and reasonable discriminant validity. The fatigue scale consists of 11 items, and includes items such as "Do you have problems with tiredness?" "Do you feel weak?" and "Do you have difficulty concentrating?" with responses rated on a four-option continuum. Total fatigue severity scale scores range from 0 to 33, with higher scores signifying more fatigue. Child Health Questionnaire (22). This instrument measure the physical and psychosocial well-being of children 5 years of age and older. Several versions for parent and child are available. In the current study, Parent Form 50 (PF50) was administered to all parents; and the Child Form 87 (CH87) was administered to all children age 10 and older. The PF50 and the CF87 each yield the following subscales: Physical functioning (measure and extent of physical limitations due to health-related problems); Role/Social Physical (limitations in daily functioning as a result of physical health); General Health Perceptions (subjective assessment of overall health and illness); Bodily Pain (intensity and frequency of pain and discomfort); Role/Social-Emotional (limitations in activities as a result of emotional problems); Role/Social-Behavior (limitations in activities as a result of behavior problems); Self-Esteem (satisfaction with academic, athletic abilities, appearance, social functioning, and overall life satisfaction); Mental Health (measures the frequency of both positive and negative mental states); General Behavior (frequency of behavior problems and ability to get along with others); Family-Limitations in Activities (degree of disruption in usual family activities); Family-Cohesion (degree to which family members 'get along'); and Changes in Health (change in health over previous year). In addition, the PF-50 also includes the following two subscales: Parent Impact-Time (limitations in personal parental time as a result of child's medical, psychological, or psychosocial difficulties) and Parent Impact-Emotional (amount of parental distress as a result of child's medical, psychological, or psychosocial difficulties). Finally, the PF-50 combined the Role/Social-Emotional and Role/Social-Behavior scales into one scale, Role/Social-Emotional/Behavioral. The CHQ demonstrates adequate reliability and validity and has been used with children with a range of physical and psychiatric difficulties (22,23). For US representative samples, the Parent Form 50 exhibits high inter-item consistency, with 91% of the items exceeding the minimum criteria for item internal consistency (>=.40). The average success rate for tests of item discriminant validity was 95%. Similarly, in a representative sample of children in the US, 94% of the items met the minimum criteria for item internal consistency (>=.40), and the average success rate for test of item discriminant validity was 92%. Test-retest reliabilities for the CHQ fall between .54-.73 for the parent version, and .18-.77 for the child version (23). Child Behavior Checklist and Youth Self-Report (24,25). The Child Behavior Check List (CBCL) and Youth Self-Report (YSR) measure internalizing and externalizing problems in children. The CBCL is a questionnaire containing 120 items that is completed by parents of children age 4 to 18 years. The YSR is a self-report measure containing 119 items that is completed by adolescents age 11 to 18 years. The CBCL and the YSR each yield nine subscales: Withdrawn, Somatic Complaints, Anxious/Depressed, Social Problems, Thought Problems, Attention Problems, Delinquent Behavior, Aggressive Behavior, Sex Problems. In addition, there are two composite scales (Internalizing and Externalizing) and three competence scales (Activities, Social, and School). The CBCL and YSR both demonstrate adequate reliability and validity. Internal consistency reliabilities for the CBCL range from .56 to .92, and inter-rater reliability coefficients range from .26 to .86 (26). For the YSR, internal consistency reliabilities range from .59 to .90, and test-retest reliabilities range from .47 to .81 when re-tested over a 1-week interval (26). Finally, the CBCL and YSR demonstrate satisfactory concurrent and discriminant validity (26). Family Environment Scale: Parent and Child Version (27). The Family Environment Scale (FES) is a self-report questionnaire that measures a broad array of family environment dimensions. There are parent and child versions available for this scale. This scale consists of 90 true-false items that assess ten dimensions of family environment: Cohesion, Expressiveness, Conflict, Independence, Achievement, Intellectual-Cultural Orientation, Active-Recreational Orientation, Moral-Religious Emphasis, Organization, and Control. This scale has exhibited appropriate internal consistencies, ranging from .61-.78 for all of the FES subscales. Further, two-month and four-month test-retest reliabilities were also in the acceptable range, with two-month test-retest reliabilities ranging from .68-.85, and four-month test-retest reliabilities ranging from .54-.91 (27). Finally, this instrument has demon- strated appropriate convergent and discriminant validity with other scales measuring family interaction and family environment variables (27,28). Statistical Analyses Because the majority of variables were not normally distributed, Mann-Whitney tests, the non-parametric alternative to the t-test, were used to compare results between the chronic fatigue and no fatigue on the majority of the subsequent analyses. However, when data was normally distributed, the t-test statistic was used as indicated below. Because of the large number of separate analyses conducted, a p-value of .01 or below was set as the threshold for statistical significance in order to minimize Type I error. RESULTS First, analyses were conducted that examined the differences between the chronic fatigue and no fatigue groups on the subscales of the Child Health Questionnaire. Using the Mann-Whitney non-parametric test statistic, separate analyses compared the two groups on each of the parent and child subscales. On the Parent Form-50, children in the chronic fatigue group had significantly poorer scores on the following subscales: physical functioning (p<.01); behavior (p<.01); mental health (p<.01); general health (p<.01); parent impact-emotional (p<.01); parent impact-time (p<.001); and family activities (p<.01). On the Child Form-87, there were no statistically significant differences between the chronic fatigue group and the no fatigue group, when using the Mann-Whitney test statistic. These results are summarized in Table 1. Next, comparisons between the two groups on the CBCL subscales and the YSR subscales were conducted. On the CBCL, children in the chronic fatigue group were rated as having significantly poorer functioning on the following subscales: Somatic problems (p<.01); Anxious/Depressed (p<.01); Thought Problems (p<.01); and Attention Problems (p<.01). On the competence scales, children with chronic fatigue scored more poorly on the Activities subscale (p<.01)). On the composite scores, children with chronic fatigue scored more poorly on the Total Score (p<.001) and the Internalizing (p<.01) composite scales. None of the group means fell into the clinical range (i.e., 65 and above), with the exception of the Somatic Problems subscale for the chronic fatigue group. When examining the results of the Youth Self-Report subscales, adolescents did not differ on any of the YSR individ- ual subscales, not did they differ on the composite scales. None of the YSR subscale or composite scores fell into the clinical range (i.e., 65 and above). The results are summarized in Table 1. Next, t-test analyses were used to compare mean subscale scores on the Family Environment Scale for the two groups. The only statistically significant different found between the families of children with chronic fatigue and families of children with no fatigue were found on the parent report (t(51)= 3.236, p<.01) of the Active-Recreational subscale and on the child report of the Control subscale (t(51)=-3.798, p<.01). These results are summarized in Table 1. Regarding missed days of school, separate t-test analyses were conducted to compare number of missed days of school reported by the parent and the child. Parents in the chronic fatigue group reported an average of 1.02 days missed during the past month, as compared to .17 days reported missed in the no fatigue group. Also, parents of children with chronic fatigue reported an average of 3.40 days missed in the past 6 months and 6.94 days missed in the past year, and parents of children with no fatigue reported an average of .94 days missed during the past month and 3.22 days in the past year. Children in the chronic fatigue group self-reported that they missed 1.67 days during the past month, as compared to .40 days reported in the control group. Using the Mann-Whitney non-parametric test, there were no statistically significant differences found in the number of days of school reported over the past month by both the parent and the child, nor was there a difference in number of days missed in the past 6 months or past year as reported by the parents. Next, parent and child rating of overall activity level were compared between the chronic fatigue and no fatigue group using separate Mann-Whitney tests. These analyses found that both the parent ratings (p <.01) and the child rating (p<.01) of activity levels in the chronic fatigue group were significantly lower when compared to the no fatigue group. Finally, the severity of physical symptoms reported by parent and child were compared between the chronic fatigue group and the no fatigue group using the Mann-Whitney test-statistic. Separate analyses were conducted for each of the following symptoms: fatigue, sore throat, lymph node pain, eye pain/light sensitivity, stomach pain, muscle pain, joint pain, headache, memory/attention problems, dizziness/ fainting after standing quickly, dizziness/fainting after hot shower, dizziness/fainting when turning head fast, dizziness/fainting when bending over, sleep problems, sick/worse/exhausted after physical exertion, fever/chills/night sweats, and depression. Children in the chronic fatigue group reported significantly higher levels of memory and attention problems (p<.01) and sleep problems (p<.001), when compared to those in the no fatigue group. Parents of children in the chronic fatigue group reported that their children were experiencing more severe levels of fatigue (p<.01), eye pain/light sensitivity (p<.01), headache (p<.01), memory and attention problems (p<.001), and depression (p<.01). No other analyses were statistically significant. DISCUSSION As hypothesized, children with chronic fatigue tended to exhibit difficulties in psychosocial and physical functioning when compared to a control group of children with no fatigue. The presence of chronic fatigue (fatigue lasting 6 months or more) was associated with impairments in overall functioning on the Child Health Questionnaire. On this questionnaire, parents of children in the chronic fatigue group reported more severe difficulties with in a variety of areas, including physical functioning, general health perceptions, mental health, family activities, and impact on parental time and parental emotions. In contrast, children in the chronic fatigue group did not report poorer functioning on any of the CHQ subscales when compared to the no fatigue group. It should be noted that, when examining the mean scores between the two groups, the majority of the statistically different subscale mean scores did not fall below one standard deviation of the subscale mean for the general population (22). For the chronic fatigue group, only the subscales of Parent Impact-Time, Parental Impact-Emotional, and the Mental Health on the parent report fell more than one standard deviation away from the respective subscale means for the general US population. The presence of chronic fatigue may negatively impact a child's overall mental health for many reasons. Not being able to engage in the same normative activities as their peers, such as being able fully participate in school, participate in active recreation with their friends, attend peer or class functions, and even feeling singled out or different because of their illness, may have a particularly devastating impact on a child's sense of identity and subsequently lead to feelings of sadness or anxiety. Regarding the other CHQ subscales, although functioning was poorer when compared to the no fatigue group, the chronic fatigue group appeared to be only mildly impaired. Similarly, there were many differences found on the CBCL between the chronic fatigue and no fatigue group, and it appeared that children in the chronic fatigue group had more difficulties with internalizing behavior. However, as with the CHQ, very few of these subscales scores fell within the clinical range (i.e., above 65). Only the somatic problems subscale was considered to be in the clinical range (i.e., above 65). Some (26) have noted that children with physical disorders commonly score higher on this particular subscale than children without physical or medical disorders, so whether this mean score is truly indicative of abnormal functioning in the chronic fatigue group is unclear. This results are similar to findings reported by Carter et al. (1), who found that, when comparing a group of healthy controls, depressed adolescents, and adolescents with unexplained chronic fatigue, the latter group had scores that fell somewhere between the healthy controls and the depressed adolescents. Thus, while there appear to be somewhat more difficulty on this psychological measure, the changes within the chronic fatigue group may in fact be milder than the difficulties reported in children with primarily psychiatric difficulties. Significant differences were found between when examining overall activity levels and reported physical symptoms of children with chronic fatigue, in that children with chronic fatigue appeared to be more physically limited when compared to those in the no fatigue group and also exhibited more severe physical symptoms. However, as with the other psychosocial measures, these differences tended to be mild when examining the overall means reported for the overall activity level and the reported physical symptoms. For the rating of overall activity levels, the chronic fatigue group mean was at 85 on a scale from 0-100. On this scale, a score of 85 corresponded roughly to a level of disability where the children either exhibited no or mild symptoms at rest, symptoms present primarily after physical exertion, activity restriction was minimal, and the child was still able to go to school full-time. Likewise, when examining the severity of the physical symptoms scored on Likert-type scale from 0-7, the means of those symptoms which were significantly different in the chronic fatigue group tended to fall within 2.32 and 3.14, whereas the means of those in the control group tended to fall below one. A severity score of approximately 2 -3 corresponded to a descriptor of 'mild' on the severity Likert-type item scale. Thus, the symptom severity reported by the chronic fatigue group appeared to be mild. In terms of associations with the family environment, few differences were found. Only the active recreation subscale was reported to be significantly different by parents when compared between the two groups. Also, children with chronic fatigue were more likely to report higher levels of the control dimension. It might be expected that families of children with chronic fatigue would indeed engage in less active recreation due to the limited ability or negative potential effects of engaging in active family past-times. Regarding the perception of increased family control reported by children with chronic fatigue, it is possible that this perception of more rules and regulations in the family could have occurred because the children are having more difficulty meeting their family roles and responsibilities. Likewise, these additional rules and responsibilities might be perceived as more burdensome by children who are experiencing problems with chronic fatigue. In general, these findings are consistent with those reported above that the presence of chronic fatigue appeared to be associated with a negative impact on the family. When examining the number of days of school missed, children and parents in the chronic fatigue group reported slightly more days of school missed when compared to the no fatigue group, but this difference was not statistically significant. The total number of missed school days reported by children and parents was fewer than days missed than reported in other research studies. In the chronic fatigue group, parents reported that their children missed an average of 1 day within the last month, 3 days within the past 6 months, and 7 days within the past year. However, other researchers have reported much higher mean number of days of school missed within the past year. For example, Carter et al. (1) reported that the majority of participants with unexplained chronic fatigue missed between 20 to 60 days of school during the past year; and Smith, Martin-Herz, Womack, and Marsigan (11) reported a mean of 44 school days missed within the past 6 months in their sample of chronically fatigued adolescents. Van Hoof et al. (12) reported that only 22% of the adolescents with CFS in their sample attended school full-time. In contrast, Farmer et al. (10) found that the boys missed a mean of 10 days of school during the past school term, and the girls missed a mean of 15 days per school term, and these days of missed school are similar to the results found in the current study. This discrepancy in results might be due to the fact that the individuals in the Carter et al. (1), Smith et al. (11), and Van Hoof et al. (12) studies were samples of adolescents referred to specialty and tertiary care clinics, whereas, children and adolescents in the current investigation and in the Farmer et al. (10) were samples drawn from the community. It is likely that young people drawn from tertiary care clinics were more severely ill when compared to a community-based sample of children and adolescents who may not have sought help from a medical professional on their own. In the current sample, it is possible that the number of days missed was not statistically different than healthy children because these children were less severely ill when compared to clinic-referred samples. In general, when comparing the parent versus child report on these various measures, many more significant differences arose on parent report, and few differences were found on the child report of functioning. Thus, the parents' assessment of their child's functioning may be particularly valuable in identifying changes in their child's behavior. Some of the difficulty in identifying and classifying the presence of chronic fatigue in children may be due to the fact that, as with adults, fatigue is a vague, poorly defined physical and emotional state, and children in particular may have difficulty in accurately reporting the presence of fatigue and the effects of fatigue on life. They may be less able to accurately verbally describe their emotional and physical well-being because of their cognitive developmental level (15). Parents, by contrast, may be better at noticing subtle changes in their children's behavior, and thus, active involvement with the parents of children with fatigue seems warranted in order to more fully assess the presence of chronic fatigue and understand the impact that fatigue may be having in their child's life. Taken together, the results suggest that children in the chronic fatigue group experienced a range of impairment at both the individual and family level. However, most of the reported physical and psychological impairments were mild and were not at the same level of severity as would be expected in a psychiatrically ill or a hospital-based population. It is possible that the mild impairments found in this study are due to the fact that the children in adolescents in this study were drawn from a community based study, while samples in other studies were drawn from clinic-referred samples. Also, as noted above, the children and adolescents in the CF group engaged in fewer overall activities as measured by the Activities competence scale on the CBCL and a general activity scale, and engaged in fewer family activities, as measured by the FES. While these children are not so ill that they miss more days of school when compared to a healthy sample, there appears to be a reduction in activities that occurs such that they may need to spend all of their energy on school attendance and may not have any energy available for other normative, out of school activities. This is consistent with Van Hoof et al. (12), who found that adolescents with CFS reported not only school failure or prolonged absenteeism, but a range of school-related problems including reductions in social and extra-curricular activities. Further, it is unknown whether these children might request help from their physicians or mental health professionals, as the children in general still appeared to be functioning with the average or non-clinical range, so these effects of chronic fatigue may be harder to detect on an individual basis. In contrast, clinic-referred samples may represent those children from the community whose chronic fatigue is the most severe and disruptive to school functioning, which may have caused them to seek out medical help. In addition, it is unknown whether the presence of even these mild difficulties might place a child 'at risk' for future difficulties, as the long-term consequences are unknown. Research from the CFS literature, which investigates the course of CFS in children and adolescents suggest that young people with CFS recover much more quickly than adults with the disorder. It is possible that, in contrast to their adult counterparts, these mild difficulties may reflect the resilience experienced by children and adolescents that has been often reported in the CFS literature. It is unknown whether individuals in the current sample, many of whom are much less severely affected than those fully meeting the stringent Fukuda et al. (3) case definition for CFS, would be expected to show a relatively good prognosis in recovering from their fatigue difficulties. It is also unknown whether these children and adolescents recover from fatigue and other symptoms on their own. However, it is also possible that the individuals in the current sample, even though they experience less severe fatigue difficulties when compared to children diagnosed with CFS, might still be more at risk for developing more serious fatigue problems or even CFS in the future. Limitations of this study include the fact that, due to the small sample size, the chronic fatigue group as a whole was examined in the statistical analyses, and other variables that might help predict differences in physical and psychological status, such as age or ethnicity, could not be entered as covariates. Further, because the data was correlational in nature, it is unclear whether having chronic fatigue causes impairments in a range of physical, psychosocial, and psychological functioning, whether deficits in everyday functioning contribute to the experience or persistence of chronic fatigue, or whether impairment and the presence of chronic fatigue are due to other factors that were not measured as part of this study. Research utilizing larger samples sizes and longitudinal data would allow for the inclusion of other factors that may be related to the presence of chronic fatigue, and may help provide support for the results found in this investigation. Finally, research with pediatric samples having CFS rather than just CF might more strongly differentiate this ill group from healthy controls, particularly if more appropriate ways are developed to better diagnosis CFS in pediatric samples (see article in this volume on the new pediatric case definition). In summary, these results suggest that children and adolescents with chronic fatigue, defined as severe fatigue lasting 6 months or longer, may exhibit a range of associated difficulties, including limitations in physical and emotional functioning and a negative impact on parental and family functioning. However, the functional limitations found in the current investigation appear to be mild in severity, and it is currently unknown whether this group of children and adolescents with chronic fatigue might be at risk for other, longer-term fatigue difficulties. Longitudinal studies of the course of fatigue symptomatology in a community sample of children and adolescents are needed to better understand the prognosis and long-term consequences of chronic fatigue. TABLE TABLE 1. Results of comparisons between chronic fatigue and no fatigue group on psychosocial and behavioral rating scales, using the Mann-Whitney test statistic. ------------------------------------------------------------------------------------ Child Health Questionnaire Parent Report Child Report ----------------------- ------------------------ Chronic No Chronic No Fatigue Fatigue Sig. Fatigue Fatigue Sig. n=36 n=21 n=30 n=13 Physical Functioning 84.84 94.44 ** 83.46 88.60 Role/Social-Physical 82.83 95.03 81.85 92.31 General Health Perceptions 59.00 73.96 ** 61.47 69.10 Bodily Pain 72.42 83.00 65.33 79.23 Parental Impact-Time 64.31 92.78 *** - - Parental Impact-Emotional 52.27 75.42 ** - - Role/Social-Emotional/Behavior 77.44 94.44 - - Role/Social-Emotional - - 73.70 87.18 Role/Social-Behavior - - 86.30 98.29 Self-Esteem 68.54 79.00 74.49 82.19 Mental Health 64.73 81.00 ** 61.35 73.77 Behavior Scale 63.21 78.25 ** 75.65 76.13 Family Activities 72.35 88.33 ** 67.64 77.56 Family Cohesion 58.94 70.50 63.17 71.15 ------------------------------------------------------------------------------------ Achenbach Behavior Rating Child Behavior Youth Self-Report Scales-CBCL and YSR Checklist (CBCL) (YSR) ----------------------- ------------------------ n=36 n=21 n=21 n=9 Total T score 61.36 49.62 *** 56.71 46.89 Internalizing T score 62.97 51.24 ** 55.43 46.44 Externalizing T score 53.82 46.62 54.67 46.89 Withdrawn T score 60.73 53.86 57.71 52.56 Somatic Problems T score 66.64 57.95 ** 58.62 52.22 Anxious/Depressed T score 61.36 53.71 ** 58.76 51.22 Social Problems T score 59.82 54.76 55.19 52.67 Thought Problems T score 60.58 53.52 ** 53.29 53.33 Attention Problems T score 63.12 54.14 ** 55.33 51.89 Delinquent Behavior T score 56.81 53.76 58.57 55.44 Aggressive Behavior T score 56.55 52.19 58.95 51.33 Sex Problems T score (ages 4-11) 52.27 51.27 - - Self-Destructive T score (boys) - - 58.25 52.75 Activities T score 38.55 45.62 ** 40.64 39.61 Social T score 39.27 44.29 41.14 43.63 School T score 41.43 44.58 - - Total Competence T score 37.20 44.58 ** 49.74 46.00 ------------------------------------------------------------------------------------ Family Environment Scale Parent version Child version ----------------------- ------------------------ n=36 n=21 n=34 n=21 Expressiveness T score 50.78 45.29 50.82 50.62 Independence T score 46.00 49.57 48.71 48.33 Achievement T score 50.97 53.67 50.24 46.81 Control T score 54.25 55.67 56.50 48.14 *** Cohesion T score 50.38 55.48 49.35 52.19 Conflict T score 50.78 45.43 42.41 41.19 Intellectual/Cultural T score 49.84 53.38 51.65 54.19 Active Rec. T score 43.41 51.67 ** 42.21 48.29 Moral Religious T score 56.31 59.38 49.29 50.38 Organization T score 53.34 54.48 49.68 50.95 ------------------------------------------------------------------------------------ ** = significant at the p<.01 level *** = significant at the p<.001 level REFERENCES 1. Carter BD, Edwards JF, Kronenberger W, Michalczyk L, Marshall GS. Case control study of chronic fatigue in pediatric patients. Pediatrics 1995; 95 (2): 179-186. 2. Nagane M. Relationship of subjective chronic fatigue to academic performance. Psychol Reports 2004; 95: 48-52. 3. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The Chronic Fatigue Syndrome: A comprehensive approach to its definition and study. Ann Int Med 1994; 121: 953-959. 4. Jones JF. Chronic fatigue syndrome in adolescents - an opinion. Journal of Chronic Fatigue Syndrome 1997; 3(2): 53-8. 5. Plioplys AV. Chronic fatigue syndrome should not be diagnosed in children. Pediatrics 1997; 100: 270-1. 6. Steele L, Dobbins JG, Fukuda K, Reyes M, Randall B, Koppelman M, Reeves WC. The epidemiology of chronic fatigue in San Francisco. Am J Med 1998; 105(3A): 83S-90S. 7. Peterson S, Bergstrom E, Brulin C. High prevalence of tiredness and pain in young schoolchildren. Scandinavian J Pub Health 2003; 31: 367-374. 8. Jones JF, Nisenbaum R, Soloman L, Reyes M, Reeves WC. Chronic fatigue syndrome and other fatiguing illnesses in adolescents: A population-based study. J Adol Health 2004; 35: 34-40. 9. Jordan KM, Ayers PA, Jahn SC, Taylor KK, Huang CF, Richman JA, Jason LA. Prevalence of fatigue and chronic fatigue syndrome-like illness in children and adolescents. J of CFS 2000; 6: 3-21. 10. Farmer A, Fowler T, Scourfield J, Thapar A. Prevalence of chronic disabling fatigue in children and adolescents. Brit J Psych 2004; 184: 477-481. 11. Smith MS, Martin-Herz SP, Womack WM, Marsigan JL. Comparative study of anxiety, depression, somatization, functional disability, and illness attribution in adolescents with chronic fatigue or migraine. Pediatrics 2003; 111(4): e376-381. 12. Van Hoof ELS, De Becker PJ, Lapp C, De Meirleir KL. How do adolescents with chronic fatigue syndrome perceive their school environment? A qualitative study. J Child Health Care: in press. 13. Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S. A community-based study of chronic fatigue syndrome. Arch Intern Med 1998; 159(18): 2129-2137. 14. Jordan KM, Jason LA, Mears CJ, Katz BZ, Rademaker A, Huang CF, Richman J, McCready W, Ayers PM, Taylor KK. Prevalence of pediatric chronic fatigue syndrome in a community-based sample. JCFS 2006; 13(2/3): 75-77. 15. Jordan KM, Landis DA, Downey MC, Osterman SL, Thurm AE, Jason LA. Chronic Fatigue Syndrome in children and adolescents: A review. J Adolesc Health 1998; 22: 4-18. 16. Bell DS. Diagnosis of Chronic Fatigue Syndrome in children and adolescents: Special considerations. JCFS 1995; 1 (3/4): 29-66. 17. Hein D, Matzner F, First M, Spitzer R, Williams J, Gibbon M. Structured Clini- cal Interview for the DSM-IV Childhood Diagnoses. New York: Department of Psychiatry, Columbia University Medical School; 1998. 18. Matzner F. Videotapes as Training Tools for the Development of the KID-SCID. Scientific Proceedings, American Academy of Child and Adolescent Psychiatry, 42nd Annual Meeting; 1994. 19. Matzner F, Silva R, Silvan M, Chowdhury M, Nastasi L. Preliminary test-retest reliability of the KID-SCID. Scientific Proceedings, American Psychiatric Association Meeting; 1997. 20. Wessely S, Powell R. Fatigue syndromes: a comparison of chronic "postviral" fatigue with neuromuscular and affective disorders. J Neurol Neurosurgery Psych 1989; 52: 940-948. 21. Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP. Development of a fatigue scale. J Pychosom Res 1993; 37(2): 147-153. 22. Landgraf JM, Abetz L, Ware JE. The CHQ User's Manual. Second Printing. Boston, MA: HealthAct; 1999. 23. Schmidt LJ, Garratt AM, Fitzpatrick R. Child/parent-assessed population health outcome measures: A structured review. Child: Care Health Dev 2002; 28: 227-237. 24. Achenbach TM. Manual for the Child Behavior Checklist and 1991 Profile. Burlington, VT: University Associates in Psychiatry; 1991. 25. Achenbach TM. Manual for the Youth Self-Report and the 1991 Profile. Burlington, VT: University Associates in Psychiatry; 1991. 26. Sattler JM. Assessment of Children: Behavioral and Clinical Applications. San Diego: Jerome M. Sattler, Publisher, Inc; 2002. 27. Moos RH, Moos BS. Family Environment Scale Manual: Development, Applications, Research (Third Edition). Palo Alto, CA: Mindgarden, Inc; 2002. 28. Sanford K, Bingham CR, Zucker RA. Validity issues with the family environ- ment scale: Psychometric resolution and research application with alcoholic families. Psychol Assessment 1999; 11: 315-325. -------- (c) 2006 The Haworth Press, Inc. [Return to top] ------------------------------ Date: Mon, 12 Mar 2007 22:14:18 +0100 From: "Dr. Marc-Alexander Fluks" <fluks COMBIDOM.COM> Subject: RES,NOT: Did Charles Darwin suffer from CFS ? Source: Metro U.K. Date: March 12, 2007 URL: http://www.metro.co.uk/news/article.html?in_article_id=40772&in_page_id=34 Ref: The Emma Wedgwood diaries can be viewed at http://darwin-online.org.uk/EmmaDiaries.html Darwin wife's diaries go online ------------------------------- The diaries of the wife of naturalist Charles Darwin have been published online. Emma Darwin's diaries cover six decades of the couple's life together and provide an insight into the daily life of the Victorian scientist and his family. The 60 pocket books were previously known only to a handful of academics familiar with the Darwin archive at Cambridge University Library. Appointments, family visits and illnesses are all noted in the books. The first diary is dated 1824 when the then Emma Wedgwood was 16 years old. She married Charles, her first cousin, in 1839 and kept a diary until the last year of her life. The diaries reveal how the Darwins entertained visiting scientists - with guests sometimes numbering 10 or 15. The complete works of Charles Darwin, who showed how natural selection could explain evolution, were published online last year. Project director Dr John van Wyhe said: "The diaries are extremely fascinating and provide so many details about the private life of this famous man who changed the world. "They also fill in the gaps where we didn't know where Darwin was or what he was doing because we find Emma has written 'Charles to London' or 'Charles returned'. The diaries also bring to life the domestic side of Darwin as a father and as a husband. Having these diaries online is the next big step towards making the complete collection that exists available to everyone and not just to academics in big libraries." -------- (c) 2007 Metro U.K. [Return to top] ------------------------------
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