Primer for doctors and researchers

2017-05-02T04:58:11Z

Aaron c:Saw that the link to the Stanford study on brain matter abnormalities in CFS just linked to the stanford website teaser. Changed it to the actual study. This is my first edit, let me know there's some master plan I'm not seeing!

[[Chronic Fatigue Syndrome]] (CFS) is also known as [[Myalgic Encephalomyelitis]] (ME) or [[ME/CFS]]. [[Chronic fatigue]] is a symptom of many diseases, illnesses, depression and drug therapies and the term is not interchangeable with the grossly misnamed disease [[CFS]]. There are many clinical and research definitions which create confusion for doctors, researchers, and patients. ''See:'' [http://me-pedia.org/wiki/Definitions_of_ME_and_CFS Defintions of ME and CFS].

== Disease onset and course of illness==
The disease [[ME/CFS]] is diagnosed when a person does not recover from a flu-like illness, [[EBV]], [[Mononucleosis]], [[HHV]], [[Q fever]], [[Virus]] or other infections and meets one or more diagnostic criteria for either ME, CFS or ME/CFS.<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref><ref>[http://me-pedia.org/wiki/Definitions_of_ME_and_CFS Definitions of ME and CFS - MEpedia]</ref> "Occasionally, ME/CFS has been triggered by environmental toxins, the receipt of an immunizing injection, or surviving a major trauma."<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Patient health is never the same and they experience numerous symptoms and disease severity which fluctuate day to day, week to week, month to month, year to year and decade to decade as well as varying symptoms and disease severity among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

=== Pediatric ME/CFS ===
Children are also afflicted with ME/CFS.<ref>[http://www.openmedicinefoundation.org/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/ ME/CFS in Children - by David S. Bell, MD - Open Medicine Foundation]</ref><ref>[https://www.masscfids.org/pediatric-me-cfs-links Pediatric ME/CFS - Massachusetts CFIDS/ME FM Association]</ref> ''See'': [[Pediatric]].

=== Prognosis ===
Prognosis for ME/CFS is generally poor. ''See'': [[Prognosis]]

=== Female to male ratio ===
Like many auto-immune and neuro-immune diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio is 6:1.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/21244747 Chronic fatigue syndrome/myalgic encephalomyelitis: an update. - PUBMed Dec. 2010]</ref> [[Fibromyalgia]] has a F/M 7:1 ratio<ref>[http://emedicine.medscape.com/article/329838-overview#a5 Fibromyalgia:Epidemiology - Medscape]</ref> and some ME/CFS patients have this additional diagnosis.<ref>[http://www.cdc.gov/arthritis/basics/fibromyalgia.htm Fibromyalgia - CDC]</ref><ref>[http://solvecfs.org/what-is-mecfs/ What Is ME/CFS (Fibromyalgia) Solve ME/CFS Initiative]</ref>

==It is not tiredness==

=== Symptoms ===
Symptom presentation varies enormously between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear. There are many symptoms which people with ME/CFS experience, though those listed below are arguably the most common:
*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After physical or mental exertion (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program) there is a payback which can be delayed 24-48 hours and can last 24 hours or more. The patient will experience even greater fatigue as well as exasperate the flu-like symptoms and body pain. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref>[http://solvecfs.org/unraveling-post-exertional-malaise/ Unraveling Post-Exertional Malaise - Solve ME/CFS Initiative By: Jennifer M. Spotila, J.D. - Plus a link to all 4 parts]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://chronicfatigue.about.com/od/cfsglossary/g/malaise.htm Post-Exertional Malaise - About.com Health - FMS/ME/CFS]</ref>

:Regarding PEM the [[CFIDS Association of America]] states: "This is a term which describes a symptom in which exercise or exertion can bring on malaise (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold)."<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html - What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref>

*[[Chronic fatigue]]
*Chronic pain
*[[Cognitive dysfunction]]
*[[Unrefreshing sleep]], and sleep disturbance
*[[Orthostatic intolerance]], such as [[Postural orthostatic tachycardia syndrome]] ([[POTS]]) or [[Neurally mediated hypotension]] ([[NMH]])
*[[Neuroinflammation]]
*Neurological disturbances such as muscle spasms, numbness/tingling, sensory overload

===Biological abnormalities===
Because there is currently no biomedical test for ME/CFS, many have incorrectly assumed that there are no medical abnormalities found in people with the condition. As a result, ME/CFS symptoms are often considered to be medically unexplained, and therefore psychological in origin. While it is true that the condition is poorly understood, many biological abnormalities have been found in a range of different body systems, particularly in the Central Nervous System, Autonomic Nervous System, Immune system, and energy metabolism.<ref name="IOM2015MECFS"/> Unfortunately, none have yet proved to be specific enough to ME/CFS as to be useful as a biomarker of the condition, and many were identified in small studies, which need replication. Whilst there have been abnormalities identified to be associated with the condition, it cannot yet be determined whether these are a cause or consequence of the condition.

*[[Neuroinflammation]] Japanese Neuroinflammation study<ref name="NakatomiY2014"/>, Younger's Leptin study <ref name="JohnsonC20150126younger"/>
*Reduced brain white matter study by [[Stanford ME/CFS Initiative]]<ref name="StanfordMed20141028"/> New York Times Article with brain images.<ref name="TullerD20141124brain"/>Three major brain abnormalities.<ref>[http://privatehealthcarereports.com/chronic-fatigue-patients-suffer-3-major-brain-abnormalities-findings-may-lead-to-clearer-diagnosis/ Chronic Fatigue Patients Suffer 3 Major Brain Abnormalities; Findings May Lead To Clearer Diagnosis. - Private Health Care]</ref>
*Immune findings: [[Mady Hornig]] & [[Ian Lipkin]]<ref name="Hornig20150201immune"/>
*[[Metabolic features of chronic fatigue syndrome]] by the Open Medicine Foundation show blood chemical signature.
*Autonomic nervous system:
*[[Natural killer cell]] findings
*Gut dysbiosis
*[[Rituximab]]

===Epidemiology===

Prevalence estimates for ME/CFS range between 0.2-2.5%, depending on the definition of the condition used.<ref name="ICC2011criteria"/> In the US, estimates range between 836,000 and 2.5 million people with the condition, though true numbers are under-reported. It is estimated that 84-91% of people with the condition remain undiagnosed.<ref name="IOM2015MECFS"/>

*Level of disability (Norwegian study HRQoL)<ref name="Hvidberg2015"/> (suggests quality of life is LOWER than for many cancers, heart diseases, brain stroke, diabetes I & II, rheumatoid arthritis, chronic renal failure, sclerosis, schizophrenia, COPD, etc)

===Causes & triggers===
*Outbreaks - see [[List of outbreaks]]
*Possible infectious triggers: [[Enterovirus]]es, [[Herpesvirus]]es including [[Epstein-Barr virus]]<ref name="Hickie2006"/>, Q Fever<ref name="Hickie2006"/>, Ross River Virus<ref name="Hickie2006"/>, (Ebola?)<ref name="Hickie2006"/>
*Non-viral triggers - trauma, chemical

===Persistence hypotheses===
*Immune findings

===Prognosis===
Dr. [[David Bell]], who serves on the Scientific Advisory Board for the [[Open Medicine Foundation]], discusses three stages of the disease in the article [http://www.openmedicinefoundation.org/2016/08/01/prognosis-of-mecfs/ Prognosis of ME/CFS].

==== Three stages ====
*At the '''''first stage''''', there is an acute illness where [[EBV]] is likely responsible for most adolescents but there is no standard viral illness. The initial virus likely fades away in a week and the patient feels better and is ready for regular activities. He adds "in a person with a gradual onset of symptoms, this stage would be different."
*'''''Second stage''''' "occurs when the symptoms do not disappear, but persist for months to years in roughly the same severity. There is little variation day-to-day, and this time is very confusing. Many medical providers are contacted, most giving conflicting opinions varying from psychological disorders to possible exotic infections, but the tests come back normal."
*In the '''''third stage''''' patients will have mild, gradual improvements over years and patients adjust their lives to the symptoms. Patients may look well and recovery is thought to have taken place. Some patients will make a full recovery in 3-4 years but "recovery and improvement are completely different."<ref>[http://www.openmedicinefoundation.org/2016/08/01/prognosis-of-mecfs/ Prognosis of ME/CFS – Open Medicine Foundation By: David S. Bell, MD]</ref>

Dr. Bell has great concern for patients 35 years old who had become ill as teens and has been studying a group that first became ill in 1985. "Some of the young adults rated their health as “good,” while the amount of activity they could perform was minimal. They had become so used to their performance level, they accepted it as their new normal. Unfortunately, many of them, while they described their health as good, they were unable to work full time or carry on other duties." It is now understood that persons with ME/CFS do not have a good long-term prognosis and it is actually poor as "full recovery from untreated CFS is rare."<ref>[http://www.openmedicinefoundation.org/2016/08/01/prognosis-of-mecfs/ Prognosis of ME/CFS – Open Medicine Foundation By: David S. Bell, MD]</ref>

'''Few Return to Pre-illness State of Functioning'''

In about 40% of people with ME/CFS, the condition will improve over time, though recovery rates from the condition are generally quite low (less than 10%). The condition may also take a relapsing/remitting course, so individuals who appear to have recovered, may actually be in remission. For 5-20% of people, the condition is degenerative. Some studies suggest that prognosis is better for those with less severe symptoms, and who developed the condition at a younger age (childhood-young adulthood), though these findings are not consistent. It is clear that few people will return to their pre-illness state of health and functioning.<ref name="CairnsR2005prog"/><ref name="JoyceJ1997prog"/><ref name="Johnson20130706"/>

===Treatments===
There are currently no [[FDA]] approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood.<ref name="IACFSME2014primer"/> There are many [http://me-pedia.org/wiki/Welcome_to_MEpedia#Potential_treatments potential treatments], though their evidence-base is limited, as most research into treatments has gone into psychological approaches to treatment.

Two treatments that have garnered much attention are [[Ampligen]] and [[Rituximab]]. Many people have reported enormous benefit from Ampligen, some doctors have been prescribing it for ME/CFS for decades. Attempts to obtain FDA approval for Ampligen in the US have failed so, despite its usefulness, it is unavailable to many. Rituximab, a lymphoma drug, has shown promising results in initial trials in Norway, and there are groups crowdsourcing funding for further trials in other countries. [[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[Low dose naltrexone]] ([[LDN]]) in ME/CFS.<ref> http://www.psy.uab.edu/younger/research.html</ref>

===Exercise as treatment===

Two common treatment recommendations for ME/CFS are [[Graded Exercise Therapy]] ([[GET]]) and [[Cognitive behavioral therapy]] ([[CBT]]). These treatments are based on the hypothesis that the condition might have begun with a viral infection but has been perpetuated by [[deconditioning]] from lack of activity, and fear and avoidance of activity. GET & CBT are aimed at addressing these hypothesized causes by challenging the unhelpful thoughts that result in avoidance of activity and reconditioning through a gradual increase in exercise. These treatments are controversial and are at odds with much of the research literature, which suggests that exercise may actually be harmful to people with ME/CFS. A large patient survey of treatment responses found that 74% of people who had tried GET, reported that their symptoms subsequently worsened,<ref name="MEASSUK20150529survey"/> which is consistent with other patient surveys.<ref name="Phoenix20160222Norway2012"/>

The [[PACE trial]], published in 2011, is the largest GET trial ever conducted. It has received much publicity as a result of its recovery rate claims, though it has come under strong criticism from within both the scientific and patient community for significant flaws in its design, and for overstating (and in some cases misrepresenting) outcomes in both the initial trial, and follow-up studies.<ref> http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00551-9/fulltext</ref> The study was the subject of a series of investigative pieces by journalist [[David Tuller]] in late 2015, that were highly critical of the trial.<ref name="viroblogMECFS"/> A petition signed by almost 12,000 ME/CFS patients and allies,<ref name="MEACTIONpacepetition"/> and an open letter signed by 42 ME/CFS experts from around the world,<ref name="openletrLANCET2"/> were sent to The Lancet, both calling for the data to be reanalyzed. Twenty-four ME/CFS organizations from 14 different countries have written to Queen Mary University London requesting that the trial data be released for reanalysis.<ref name="MEACTION20160313openletr"/> To date, the authors of the trial and editor of The Lancet have refused such requests. Despite such criticism, the [[PACE trial]] continues to influence both government and the medical profession's approach to the treatment of ME/CFS in many countries.

One of the reasons that exercise may be harmful to people with ME/CFS, is the presence of Post-Exertional Malaise (PEM), which is an exacerbation of symptoms following physical, mental or even emotional exertion. Studies have revealed immunological, muscular, neurological, autonomic and cardiovascular abnormalities in response to exercise in people with ME/CFS. As these results are not also found in healthy sedentary controls, the adverse effects of exercise cannot be said to be due to [[deconditioning]].<ref name="TwiskF2015"/><ref> reference needed - Workwell Foundation studies</ref><ref> reference needed - the Lights epigenetic changes post-exercise</ref>

People with ME/CFS should approach exercise with caution, as there is much potential for harm.

Anaerobic threshold, use of HR monitors for activity and pacing. Analeptic, not aerobic.
Energy envelope/pacing - people do better if stay within their envelope than to push to increase activity

===Severely ill patients===
Considerable variation exists in the severity of the condition. The [[International Consensus Criteria]] lists the following severity levels (it should be noted that even "mild" ME/CFS consists of significant debility):

*Mild = 50% reduction in pre-illness activity levels
*Moderate = mostly housebound
*Severe = mostly bedridden
*Very Severe = totally bedridden, and needing help with basic functions.

At least 25% of people with ME/CFS are bedbound or housebound, often for years or even decades, so are largely an invisible population.<ref name="IOM2015MECFS"/> So invisible in fact, that they have rarely been included as part of research because their level of debility precludes them from traveling to laboratories for required testing. The [[Open Medicine Foundation]]'s [http://www.openmedicinefoundation.org/mecfs-severely-ill-big-data-study/ Severely Ill Big Data Study] will be the first in-depth study of people with a severe form of ME/CFS.

Notable patients with severe ME/CFS include [[Whitney Dafoe]], [[Karina Hansen]], [[Lynn Gilderdale]], [[Laura Hillenbrand]], [[Tom Kindlon]], [[Vanessa Li]], [[Doctor Speedy]], [[Naomi Whittingham]].

Though uncommon, there have been instances of deaths which have been attributed to the condition (see [[Sophia Mirza]]).

== Notable studies ==
*[[Pathways to prevention report]] (P2P)
*[[Institute of Medicine report]]
*[[PACE trial]] is a highly criticized UK trial designed by psychiatrists to promote [[GET]] and [[CBT]] as therapy which is deemed harmful and useless for ME/CFS patients by many clinicians, researchers, patients, and advocates.

==History==
*[[Osler's Web]] is a book on the early history of CFS.
*[[Thirty Years of Disdain]] picks up on the ME/CFS history where Osler's Web leaves off.
*[[List of news articles on ME and CFS]]
*[[Sophia Mirza]]'s life ended due to CFS.
*[http://me-pedia.org/wiki/Disabled_in_Tory_Britain#PACE_trial UK agencies involved in the implementation of the PACE trial. Disabled in Tory Britain - PACE trial]

==Learn more==
*[http://iacfsme.org/portals/0/pdf/Primer_Post_2014_conference.pdf IACFS/ME Primer for Clinical Practitioners - 2014 Edition]<ref name="IACFSME2014primer"/>
*[http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf Myalgic Encephalomyelitis - Adult & Pediatric - International Consensus Criteria Primer for Medical Practitioners]<ref name="ICP2011primer"/>
*[http://www.meassociation.org.uk/2014/07/our-purple-booklet-clear-clinical-guidance-and-the-latest-research-all-wrapped-up-in-52-pages/ ME Association clinical guidance]<ref name="MEASSUKprimer2013"/>
*[http://treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf ME/CFS Treatment Resource Guide for Practitioners by A Martin Lerner, MD]<ref name="LernerPrimer2011"/>
*[http://www.tandfonline.com/doi/full/10.1080/21641846.2016.1160598 The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem], 2016.<ref name="Edwards2016"/>
*[[Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]] (CDC Video, 2016)
*[[Notable studies]]

==See also==
*[[Primer for the public#Disease_names_and_acronyms_around_the_world|Primer for the public (''Disease names and acronyms around the world'' section)]]
*[[Primer for patients]]
*[[Forgotten Plague]] Documentary
*[[Fibromyalgia]]
*[[David Tuller]] writes and speaks at length and in detail about the PACE Trial.

==References==
<references>



<ref name="Edwards2016">{{Citation
| last1 = Edwards | first1 = JCW | authorlink1 = Jonathan Edwards
| last2 = McGrath | first2 = S | authorlink2 = Simon McGrath
| last3 = Baldwin | first3 = A | authorlink3 = Adrian Baldwin
| last4 = Livingstone | first4 = M | authorlink4 = Mark Livingstone
| last5 = Kewley | first5 = A | authorlink5 = Andrew Kewley
| title = The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 4 | issue = 2 | pages = 63–69
| date = 2016-04-02
| doi = 10.1080/21641846.2016.1160598
| url = http://www.tandfonline.com/doi/full/10.1080/21641846.2016.1160598
}}</ref>

<ref name="ICP2011primer">{{citation
| last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers
| last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande
| last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick
| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell
| last7 = Staines | first7 = D | authorlink7 = Donald Staines
| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles
| last9 = Speight | first9 = N | authorlink9 = Nigel Speight
| last10 = Vallings | first10= R | authorlink10= Rosamund Vallings
| last11 = Bateman | first11= L | authorlink11= Lucinda Bateman
| last12 = Bell | first12= DS | authorlink12= David Bell
| last13 = Carlo-Stella | first13= N | authorlink13= Nicoletta Carlo-Stella
| last14 = Chia | first14= J | authorlink14= John Chia
| last15 = Darragh | first15= A | authorlink15= Austin Darragh
| last16 = Gerken | first16= A | authorlink16= Anne Gerken
| last17 = Jo | first17= D | authorlink17= Daehyun Jo
| last18 = Lewis | first18= DP | authorlink18= Donald Lewis
| last19 = Light | first19= AR | authorlink19= Alan Light
| last20 = Light | first20= KC | authorlink20= Kathleen Light
| last21 = Marshall-Gradisnik | first21= S | authorlink21= Sonya Marshall-Gradisnik
| last22 = McLaren-Howard | first22= J | authorlink22= John McLaren-Howard
| last23 = Mena | first23= I | authorlink23= Ismael Mena
| last24 = Miwa | first24= K | authorlink24= Kunihisa Miwa
| last25 = Murovska | first25= M | authorlink25= Modra Murovska
| last26 = Stevens | first26= SR | authorlink26= Staci Stevens
| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners
| date = 2012
| isbn = 978-0-9739335-3-6
| url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf
}}</ref>

<ref name="IACFSME2014primer">{{citation
| last1 = International Association for Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (IACFS/ME)
| last2 = Friedberg | first2 = Fred | authorlink2 = Fred Friedberg
| last3 = Bateman | first3 = Lucinda | authorlink3 = Lucinda Bateman
| last4 = Bested | first4 = Alison C | authorlink4 = Alison Bested
| last5 = Davenport | first5 = Todd | authorlink5 = Todd Davenport
| last6 = Friedman | first6 = Kenneth J | authorlink6 = Kenneth Friedman
| last7 = Gurwitt | first7 = Alan R | authorlink7 = Alan Gurwitt
| last8 = Jason | first8 = Leonard A | authorlink8 = Leonard Jason
| last9 = Lapp | first9 = Charles W | authorlink9 = Charles Lapp
| last10 = Stevens | first10= Staci R | authorlink10= Staci Stevens
| last11 = Underhill | first11= Rosemary A | authorlink11= Rosemary Underhill
| last12 = Vallings | first12= Rosamund | authorlink12= Rosamund Vallings
| title = 2014 Primer for Clinical Practitioners (CFS/ME)
| journal = IACFS/ME
| date = Jul 2014
| url = http://iacfsme.org/portals/0/pdf/Primer_Post_2014_conference.pdf
}}</ref>

<ref name="LernerPrimer2011">{{citation
| last1 = Lerner | first1 = AM | authorlink1 = A Martin Lerner
| title = ME/CFS Treatment Resource Guide for Practitioners
| date = 2011
| url = http://treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf
}}</ref>

<ref name="MEASSUKprimer2013">{{citation
| last1 = Shepherd | first1 = C | authorlink1 = Charles Shepherd
| last2 = Chaudhuri | first2 = A | authorlink2 = Abhijit Chaudhuri
| title = ME/CFS/PVFS An Exploration of the Key Clinical Issues ('Purple Booklet')
| date = 2013
| url = http://www.meassociation.org.uk/wp-content/uploads/2011/01/pruple-booklet-front-cover.jpg
}}</ref>

<ref name="CairnsR2005prog">{{citation
| last1 = Cairns | first1 = R | authorlink1 = Ruth Cairns
| last2 = Hotopf | first2 = M | authorlink2 = Matthew Hotopf
| title = A systematic review describing the prognosis of chronic fatigue syndrome
| journal = Occupational Medicine | volume = 2005;55 | page = 20–31
| doi = 10.1093/occmed/kqi013
| url = http://occmed.oxfordjournals.org/content/55/1/20.full.pdf
}}</ref>

<ref name="JohnsonC20150126younger">{{citation
| last1 = Johnson | first1 = Cort | authorlink1 = Cort Johnson
| title = Getting “Younger”: Leptin, Chronic Fatigue Syndrome and Fibromyalgia]
| date = 26 Jan 2015
| url = http://www.cortjohnson.org/blog/2015/01/26/getting-younger-leptin-chronic-fatigue-fibromyalgia/
}}</ref>

<ref name="Hickie2006">{{citation
| last1 = Hickie | first1 = Ian | authorlink1 = Ian Hickie
| last2 = Davenport | first2 = Tracey | authorlink2 = Tracey Davenport
| last3 = Wakefield | first3 = Denis | authorlink3 = Denis Wakefield
| last4 = Vollmer-Conna | first4 = Ute | authorlink4 = Ute Vollmer-Conna
| last5 = Cameron | first5 = Barbara | authorlink5 = Barbara Cameron
| last6 = Vernon | first6 = Suzanne D | authorlink6 = Suzanne Vernon
| last7 = Reeves | first7 = William C | authorlink7 = William Reeves
| last8 = Lloyd | first8 = Andrew | authorlink8 = Andrew Lloyd
| last9 = Dubbo Infection Outcomes Study Group
| title = Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study
| journal = BMJ | volume = 2006; 333:575
| date = 14 Sep 2006
| pmid = 16950834 | doi = 10.1136/bmj.38933.585764.AE
| url = http://www.bmj.com/content/333/7568/575.long
}}</ref>

<ref name="Hornig20150201immune">{{citation
| last1 = Hornig | first1 = Mady | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = José G | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = Nancy G | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = Susan | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = Donna | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = Lucinda | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = Daniel L | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = C Gunnar | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = Andrew F | authorlink9 = Andrew Schultz
| last10 = Che | first10= Xiaoyu | authorlink10= Xiaoyu Che
| last11 = Eddy | first11= Meredith L | authorlink11= Meredith Eddy
| last12 = Komaroff | first12= Anthony L | authorlink12= Anthony Komaroff
| last13 = Lipkin | first13= W Ian | authorlink13= Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1
| date = 1 February 2015
| url = http://advances.sciencemag.org/content/1/1/e1400121
}}</ref>

<ref name="Hvidberg2015">{{citation
| last1 = Hvidberg | first1 = Michael Falk | authorlink1 = Michael Falk Hvidberg
| last2 = Brinth | first2 = Louise Schouborg | authorlink2 = Louise Schouborg Brinth
| last3 = Olesen | first3 = Anne V | authorlink3 = Anne V Oleson
| last4 = Petersen | first4 = Karin D | authorlink4 = Karin Peterson
| last5 = Ehlers | first5 = Lars | authorlink5 = Lars Ehlers
| title = The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS)
| journal = PLoS One
| date = 6 Jul 2015
| doi = 10.1371/journal.pone.0132421
| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132421
}}</ref>

<ref name="ICC2011criteria">{{citation
| last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers
| last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande
| last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick
| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell
| last7 = Staines | first7 = D | authorlink7 = Donald Staines
| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles
| last9 = Speight | first9 = N | authorlink9 = Nigel Speight
| last10 = Vallings | first10= R | authorlink10= Rosamund Vallings
| last11 = Bateman | first11= L | authorlink11= Lucinda Bateman
| last12 = Baumgarten-Austrheim | first12= B | authorlink12= Barbara Baumgarten-Austrheim
| last13 = Bell | first13= DS | authorlink13= David Bell
| last14 = Carlo-Stella | first14= N | authorlink14= Nicoletta Carlo-Stella
| last15 = Chia | first15= J | authorlink15= John Chia
| last16 = Darragh | first16= A | authorlink16= Austin Darragh
| last17 = Jo | first17= D | authorlink17= Daehyun Jo
| last18 = Lewis | first18= DP | authorlink18= Donald Lewis
| last19 = Light | first19= AR | authorlink19= Alan Light
| last20 = Marshall-Gradisnik | first20= S | authorlink20= Sonya Marshall-Gradisnik
| last21 = Mena | first21= I | authorlink21= Ismael Mena
| last22 = Mikovits | first22= JA | authorlink22= Judy Mikovits
| last23 = Miwa | first23= K | authorlink23= Kunihisa Miwa
| last24 = Murovska | first24= M | authorlink24= Modra Murovska
| last25 = Pall | first25= ML | authorlink25= Martin Pall
| last26 = Stevens | first26= SR | authorlink26= Staci Stevens
| title = Myalgic encephalomyelitis: International Consensus Criteria
| journal = Journal of Internal Medicine | volume = 270 | issue = 4 | page = 327–338
| date = 22 August 2011
| pmid = 21777306 | doi = 10.1111/j.1365-2796.2011.02428.x
| url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02428.x/full
}}</ref>

<ref name="IOM2015MECFS">{{citation
| last1 = Institute of Medicine (USA)
| title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness
| publisher = The National Academies Press | location = Washington, DC, USA
| date = 10 February 2015
| isbn = 978-0-309-31689-7
| url = http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx
}}</ref>

<ref name="Johnson20130706">{{citation
| last1 = Johnson | first1 = Cort | authorlink1 = Cort Johnson
| title = ME/CFS Prognosis
| journal = Health Rising
| date = 6 July 2013
| url = http://www.cortjohnson.org/about-chronic-fatigue-syndrome-mecfs/prognosis/
}}</ref>

<ref name="JoyceJ1997prog">{{citation
| last1 = Joyce | first1 = J | authorlink1 = J Joyce
| last2 = Hotopf | first2 = M | authorlink2 = Matthew Hotopf
| last3 = Wessely | first3 = Simon | authorlink3 = Simon Wessely
| title = The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review
| journal = QJM | volume = 90 | issue = 3
| date = 1 March 1997
| pmid = 9093600 | doi = 10.1093/qjmed/90.3.223
| url = http://qjmed.oxfordjournals.org/content/90/3/223.long
}}</ref>

<ref name="MEACTIONpacepetition">{{citation
| last1 = #MEAction | authorlink1 = #MEAction
| title = Petition: Misleading Claims Should Be Retracted
| journal = #MEAction
| date = Oct 2015
| url = http://my.meaction.net/petitions/pace-trial-needs-review-now
}}</ref>

<ref name="MEACTION20160313openletr">{{citation
| last1 = #MEAction | authorlink1 = #MEAction
| title = 24 organisations in 14 countries tell QMUL: Release the PACE data
| date = 13 Mar 2016
| url = http://www.meaction.net/2016/03/13/24-organisations-in-14-countries-tell-qmul-release-pace-data/#comment-2518
}}</ref>

<ref name="MEASSUK20150529survey">{{citation
| last1 = ME Association (UK) | authorlink1 = ME Association
| date = 29 May 2015
| title = Our CBT, GET and Pacing Report calls for major changes to therapies offered for ME/CFS
| url = http://www.meassociation.org.uk/2015/05/23959/
}}</ref>

<ref name="NakatomiY2014">{{citation
| last1 = Nakatomi | first1 = Yasuhito | authorlink1 = Yasuhito Nakatomi
| last2 = Mizuno | first2 = Kei | authorlink2 = Kei Mizuno
| last3 = Ishii | first3 = Ishii | authorlink3 = Akira Ishii
| last4 = Yasuhiro | first4 = Wada | authorlink4 = Yasuhiro Wada
| last5 = Masaaki | first5 = Tanaka | authorlink5 = Masaaki Tanaka
| last6 = Shusaku | first6 = Tazawa | authorlink6 = Shusaku Tazawa
| last7 = Kayo | first7 = Onoe | authorlink7 = Kayo Onoe
| last8 = Sanae | first8 = Fukuda | authorlink8 = Sanae Fukuda
| last9 = Joji | first9 = Kawabe | authorlink9 = Joji Kawabe
| last10 = Kazuhiro | first10= Takahashi | authorlink10= Kazuhiro Takahashi
| last11 = Yosky | first11= Kataoka | authorlink11= Yosky Kataoka
| last12 = Susumu | first12= Shiomi | authorlink12= Susumu Shiomi
| last13 = Kouzi | first13= Yamaguti | authorlink13= Kouzi Yamaguti
| last14 = Masaaki | first14= Inaba | authorlink14= Masaaki Inaba
| last15 = Hirohiko | first15= Kuratsune | authorlink15= Hirohiko Kuratsune
| last16 = Yasuyoshi | first16= Watanabe | authorlink16= Yasuyoshi Watanabe
| title = Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study
| journal = Journal of Nuclear Medicine | volume = 2014 Jun;55(6) | page = 945-50
| date = 24 Mar 2014
| pmid = 24665088 | doi = 10.2967/jnumed.113.131045
| url = http://jnm.snmjournals.org/content/55/6/945.long
}}</ref>

<ref name="openletrLANCET2">{{citation
| last1 = Davis | first1 = Ronald W | authorlink1 = Ronald Davis
| last2 = Edwards | first2 = Jonathan C W | authorlink2 = Jonathan Edwards
| last3 = Jason | first3 = Leonard A | authorlink3 = Leonard Jason
| last4 = Levin | first4 = Bruce | authorlink4 = Bruce Levin
| last5 = Racaniello | first5 = Vincent R | authorlink5 = Vincent Racaniello
| last6 = Reingold | first6 = Arthur L | authorlink6 = Arthur Reingold
| last7 = Ablashi | first7 = Dharam V | authorlink7 = Dharam Ablashi
| last8 = Baraniuk | first8 = James N | authorlink8 = James Baraniuk
| last9 = Barcellos | first9 = Lisa F | authorlink9 = Lisa Barcellos
| last10 = Bateman | first10= Lucinda | authorlink10= Lucinda Bateman
| last11 = Bell | first11= David S | authorlink11= David Bell
| last12 = Bested | first12= Alison C | authorlink12= Alison Bested
| last13 = Broderick | first13= Gordon | authorlink13= Gordon Broderick
| last14 = Chia | first14= John | authorlink14= John Chia
| last15 = Chu | first15= Lily | authorlink15= Lily Chu
| last16 = Enlander | first16= Derek | authorlink16= Derek Enlander
| last17 = Fletcher | first17= Mary Ann | authorlink17= Mary Ann Fletcher
| last18 = Friedman | first18= Kenneth | authorlink18= Kenneth Friedman
| last19 = Kaufman | first19= David L | authorlink19= David Kaufman
| last20 = Klimas | first20= Nancy | authorlink20= Nancy Klimas
| last21 = Lapp | first21= Charles W | authorlink21= Charles Lapp
| last22 = Levine | first22= Susan | authorlink22= Susan Levine
| last23 = Light | first23= Alan R | authorlink23= Alan Light
| last24 = Marshall-Gradisnik | first24= Sonya | authorlink24= Sonya Marshall-Gradisnik
| last25 = Medveczky | first25= Peter G | authorlink25= Peter Medveczky
| last26 = Nahle | first26= Zaher | authorlink26= Zaher Nahle
| last27 = Oleske | first27= James M | authorlink27= James Oleske
| last28 = Podell | first28= Richard N | authorlink28= Richard Podell
| last29 = Shepherd | first29= Charles | authorlink29= Charles Shepherd
| last30 = Snell | first30= Christopher R | authorlink30= Christopher Snell
| last31 = Speight | first31= Nigel | authorlink31= Nigel Speight
| last32 = Staines | first32= Donald | authorlink32= Donald Staines
| last33 = Stark | first33= Philip B | authorlink33= Philip Stark
| last34 = Stein | first34= Eleanor | authorlink34= Eleanor Stein
| last35 = Swartzberg | first35= John | authorlink35= John Swartzberg
| last36 = Tompkins | first36= Ronald G | authorlink36= Ronald Tompkins
| last37 = Underhill | first37= Rosemary | authorlink37= Rosemary Underhill
| last38 = Vallings | first38= Rosamund | authorlink38= Rosamund Vallings
| last39 = Van ElZakker | first39= Michael | authorlink39= Michael Van ElZakker
| last40 = Weir | first40= William | authorlink40= William Weir
| last41 = Zinn | first41= Marcie L | authorlink41= Marcie Zinn
| last42 = Zinn | first42= Mark A | authorlink42= Mark Zinn
| title = An open letter to the Lancet - again
| date = 10 Feb 2016
| website = Virology Blog
| url = http://www.virology.ws/2016/02/10/another-request-for-data-from-the-pace-trial/
}}</ref>

<ref name="StanfordMed20141028">{{citation
| last1 = Montoya | first1 = José G | authorlink1= Jose Montoya
| title = Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome
| journal = Radiology | volume = 274 | issue = 2
| date = Feb 2015
| url = http://pubs.rsna.org/doi/abs/10.1148/radiol.14141079
}}</ref>

<ref name="TullerD20141124brain">{{citation
| last1 = Tuller | first1 = David | authorlink1 = David Tuller
| title = Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder
| journal = New York Times | volume = Well Blogs
| date = 24 Nov 2014
| url = http://well.blogs.nytimes.com/2014/11/24/brains-of-people-with-chronic-fatigue-syndrome-offer-clues-about-disorder/
}}</ref>

<ref name="TwiskF2015">{{citation
| last1 = Twisk | first1 = Frank NM | authorlink1 = Frank Twisk
| last2 = Geraghty | first2 = Keith J | authorlink2 = Keith Geraghty
| title = Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome
| journal = Jacobs Journal of Physiology | volume = 2015, 1(2): 007
| date = 11 Jul 2015
| url = http://www.jacobspublishers.com/images/Physiology/J_J_Physiology_1_2_007.pdf
}}</ref>

<ref name="Phoenix20160222Norway2012">{{citation
| title = Norwegian patient survey: Experiences of therapeutic approaches (2012)
| journal = Phoenix Rising Forum
| date = 22 Feb 2016
| url = http://forums.phoenixrising.me/index.php?threads/norwegian-patient-survey-experiences-of-therapeutic-approaches-2012-update.43193/
}}</ref>

<ref name="viroblogMECFS">{{citation
| title = List of ME/CFS articles published at Virology Blog
| url = http://www.virology.ws/mecfs/
}}</ref>
</references>
[[Category:Primers]]

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