Mind Games: ME-dical malPRACTICEs ?
28th May 2010 Bispebjerg Hospital, Copenhagen
1st Danish ME/CFS Association Conference with
The European Society for ME (ESME)
Malcolm Hooper PhD, B Pharm, ARIC, C Chem
Emeritus Professor of Medicinal Chemistry, University of Sunderland, UK
ME (female) 4
vs
CFS (male) 1
With thanks to Michael
Maes for the title
THE BIG DIVIDE
SOMATISATION
ALL IN THE MIND
COMPLEX CHRONIC MULTISYSTEM CONDITION
PSYCHOSOCIAL
BIOMEDICAL BASIS
1. CLAIMS
2. EVIDENCE
3. POLICY
MYALGIC ENCEPHALOMYELITIS IS A
–COMPLEX
- CHRONIC
- MULTI-SYSTEM ILLNESS
[MUS, PUPS, MUPS – ‘UNEXPLAINED’ ILLNESSES- VANISH]
“Everything that cannot be understood does nevertheless not
cease to exist.” Blaise Pascal (1623-1682)
“I might be criticised for presenting alarming material [about
ME] but I have tried to present the truth and this in
perspective” Dr John Richardson (1915-2002 50 years study)
Compiled by Natalie Boulton
www.jivalobo.com/invisibleME
Making the invisible – visible
LISTEN TO PATIENT
VOICES
History- History- History
Listen to Patient and to
Patient’s Parents – especially
the Mother.
John Richardson -1999
John Chia 2010
LINDA – VERY
SEVERE ME - >20
YEARS.
TOUCH, LIGHT,
SOUND - ARE AGONY
PHOTO/ PAINTING BY
HUSBAND GREG
PAIN
PARALYSIS
SYNDROMES OF UNCERTAIN ORIGINS
Merck Manual 1999, 17th Edition
GULF WAR SYNDROME
GWS/I
MILITARY ME
MULTI-SYSTEM & ORGAN
NEUROLOGICAL- ANS, PNS, CNS
CARDIOVASCULAR
IMMUNE SYSTEM
GASTROINTESTINAL
RESPIRATORY
ENDOCRINE SYSTEM
MULTIPLE
CHEMICAL
SENSITIVITY
OPs
ME-CFS
FMS
“Considering the extent of the patients’
complaints and disability, the results of
ROUTINE laboratory tests were
strikingly NORMAL” S Straus
SOMATISATION- PSYCHIATRIC- THEY ARE ALL IN THE MIND
SYMPTOMS
OPs
JOINT PAIN
+
+
+
FATIGUE
HEADACHE
MEMORY
PROBLEMS
SLEEP
DISTURBED
SKIN
PROBLEMS
PROBLEMS
CONCENTRN
DEPRESSION
+
+
+
+
+
+
+
MUSCLE PAIN
DIZZINESS
G.I. - Irr. Bow.
PERIPH
PARESTHES/
TINGLING
CHEM/ENVIR
SENSITIVITY
EYE
PROBLEMS
ANXIETY
TACHY&/OR
CHEST PAIN
BREATHING
PROBLEMS
LIGHT
SENSITIVITY
+ Literature.
GWS
MCS
FMS
CFIDS
MS
AIDS
+
+
+
+
+
+
around
joint area
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+
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+
+
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+
+
+
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+
+
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+
+
+
+
+
+
?? due to
medicines
burning
skin
+
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Reported
_
+
+
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+
+
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+
+
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Reported
+
+
+
+/-
+
+
Reported
+
+
_
Reported = Anecdotal
+
+
Adapted from Jackie Burkhead
ME/CFS AND OTHER OVERLAPPING SYNDROMES.
WHAT’S IN A NAME? ME vs CFS
WHO - ICD 10 - G93.3 (FROM 1969) IS CLEAR
MYALGIC ENCEPHALOMYELITIS IS A NEUROLOGICAL DISORDER
MUSCLE PAIN WITH INFLAMMATION OF THE BRAIN AND SPINAL
CORD
[THE ONLY ALLOWED ALTERNATIVE NAMES ARE
POST-VIRAL FATIGUE SYNDROME, PVFS, CHRONIC FATIGUE SYNDROME, CFS]
Decreasing
ME DESCRIBES A PATHOPHYSIOLOGICAL CONDITION WITH CLEAR
MEANING
objective
FOR CLINICIANS AND ALLIED SCIENTISTS
information
clinical,
PVFS DESCRIBES AETIOLOGY (VIRUS INDUCED) + A SYMPTOM - diagnostic,
FATIGUE
scientific,
aetiological.
CHRONIC FATIGUE DESCRIBES A SYMPTOM – SUBJECTIVE – PROVIDES
NO
OBJECTIVE CLINICAL SIGNS FOR DIAGNOSIS- MAKES MISCHIEF POSSIBLE
NOT ENCEPHALOPATHY (NOT CLASSIFIED) –MYALGIC ENCEPHALOMYELITIS
FUNCTIONAL SOMATIC SYNDROMES: ONE OR MANY? Wessely et al
Lancet 1999;354:936-9 PSYCHOSOCIAL SCHOOL PARADIGM
Gastroenterology – IBS, Non-ulcer dyspepsia
Gynaecology – PMS, chronic pelvic pain
Rheumatology – Fibromyalgia
Cardiology – Atypical or non-cardiac pain
CANNOT EXPLAIN
BYCONVENTIONAL
PARADIGMS
CONVENTIONAL
THERAPY INEFFECTIVE
Respiratory medicine – hyperventilation
Infectious Disease – PVFS- ME-CFS
MORE COMON IN
WOMEN THAN MEN
Neurology – Tension headache
Dentistry – TMJ dysfunction, Atypical facial pain
ENT – Globus syndrome
SHARE NON-SPECIFIC
SYMPTOMS
ALLERGY - MCS
SYNDROMES RESPOND TO SAME THERAPIES, CBT/GET, PACING,
PARTLY SUPPORTED– PATIENT SELECTION/DEFINITION CRUCIAL.
MISREPRESENTATION AND WORSE
FITNESS FOR WORK - OUP-2004 REPRINT £50-00 IN ASSOCIATION WITH
RCP FACULTY OF OCCUPATIONAL MEDICINE
WESSELY et al p.132 - incl, Maurice LIPSEDGE Consultant Psychiatrist KCL.
BRIEF INFECTION (USUALLY VIRAL) >>>
VULNERABLE PERFECTIONIST PERSONALITY + PRESSURE AT WORK
EMPLOYEE SICKNESS ABSENCES>>>
FATIGUE >>>>
PROLONGED BED REST >>>>
MALADAPTIVE BELIEFS >>>
CHRONIC INVALIDISM>>>
Twisk & Maes 2009;
Wessely & Wood ,
1999! supply
EVIDENCE
SHOWING SOME OF
THESE CLAIMS TO
BE IN ERROR.
TERMINATION OF SERVICE ON MEDICAL GROUNDS.
ALL LAZY CHILDREN - INACTIVE >>>>
+/- PENSION !
STEPHEN RALPH -12/6/04 - www.meactionuk.org.uk
Efficacy of CBT & GET - FROM
THE “HORSES MOUTH”.
“They reduce disability, & enhance
control over symptoms”.
“Modestly effective”.
“Not remotely curative”.
“These interventions are not the
answer to CFS”.
Professor Simon Wessely, Journal American Medical Association Vol. 286, #11 Sept. 19, 2001
Read your own papers please! Twisk & Maes 2009 make same point
A Psychiatric Condition?
CHAPTER 7
Psychiatry and
neuropsychiatry
7.6 “Nearly all studies find
that between one-quarter to
one-third of those who fulfil
criteria for CFS do not fulfil
ANY criteria for psychiatric
disorder.
Any
simple
equation of CFS with
psychiatric disorder is thus
erroneous”.
SOMATIC MEDICINE ABUSES PSYCHIATRY – AND NEGLECTS CAUSES
An almost TOTAL lack of SCIENTIFIC support
Reclassifying BODILY symptoms as MENTAL problems…where
CONVENTIONAL medicine is at a loss for an explanation.
LACK OF firm KNOWLEDGE is converted into SPECULATIVE ASSERTIONS
without any CRITICAL voices being heard. PD, MS, Diabetes
Causal explanation for illnesses .. go with predominantly somatic symptoms [that]
lack any basic similarity to known mental disorders.
An evasive argument…with its lamentably poor record of research into causes,
particularly where environmental factors are concerned.
Industrial interests are actively influencing the course of what is ostensibly a
scientific discussion.
What makes an individual human being ill cannot be determined by statistics
Lack of knowledge is a considerable handicap in the treatment of chronic diseases
Per Dalen (Psychiatrist) http:art-bin.com/art/dalen_en.html
Mercury, Lyme’s disease, placebo effect, toxicology, epidemiology
N McLaren THE (BIO)PSYCHOSOCIAL MODEL and FRAUD
This model is based on fraud and ignorance and a complete misunderstanding of
the origins of the idea. It is a myth.
“I see psychiatry under attack from all quarters. Some people see a great future
for us. I don’t share that view. I believe there is a serious risk that psychiatry as
we know it will no longer exist in as little as fifteen years. The reason is simply a
lack of anything approximating an adequate intellectual framework for our
efforts.”
The myth of the biopsychosocial model.
Australian and New Zealand Journal of Psychiatry 2006; 40 (3), 277-278
http://www.futurepsychiatry.com/ Chapters 7 and 9
This model was the basis for the rejection of the Class Action brought by
GWVs and persists still- see Phil Trans Royal Soc 2006;631:689-695.
THE DECEPTION !
MYALGIC ENCEPHALOMYELITIS – CHRONIC FATIGUE SYNDROME AT G93.3
[NEUROLOGICAL DISORDERS]
CHRONIC
FATIGUE SYNDROMES
SYNDROME
CHRONIC FATIGUE
[MENTAL & BEHAVIOURAL DISORDERS – F48.0]
NEUROLOGY
G93.3
PSYCHIATRY/PSYCHOLOGY
F48.0
DUAL CLASSIFICATION IS NOT ALLOWED UNDER RUBRICS OF WHO
NIH-CFS DEBATE, 2007 -19 YEARS AFTER DECISION
Dr Donna Dean
1. ME/CFS carries significant STIGMA for PATIENTS
2. MEDICAL COMMUNITY bears some responsibility for invalidating ME/CFS
as a REAL condition.
3. PATIENT ADVOCACY bears come some responsibility – working at crosspurposes even among themselves.
4. NIH Panel MEMBERSHIP is SIGNIFICANTLY BIASED towards the
BEHAVOURAL side of research.
Prof Anton Komaroff
“None of the participants in creating the 1988 CFS case definition and name
ever expressed any concern that it might TRIVIALISE the illness. We were
insensitive to that possibility and WE WERE WRONG.
THE NAME DIVIDES – The medical community that has tried to abandon the use
of ME, replacing it by CFS. Patients INSIST on using ME.
BIGGEST DIVIDE: PSYCHIATRY, ALL IN THE MIND.
SOMATISATION/SOMATOFORM DISORDER vs BIOLOGICAL- ORGANIC ILLNESS.
25% ME GROUP [THE SEVERELY AFFECTED-1/3/O4
RANDOM SAMPLE -437 = 66% OF MEMBERSHIP
COMMENTS ON TREATMENTS GIVEN
H%
UNH%
PERSON-CENTRED COUNSELLING
54
46
PSYCHOTHERAPY
10
90
CBT*
7
93
GET*
5
95
PACING*
70
30
ALTERNATIVE THERAPIES
60
40
SYMPTOMATIC CARE MANAG
73
30
PAIN MANAGEMENT
75
25
* £8.2 MILLION GOVERNMENT FUNDING HAS BEEN COMMITTED TO
CLINICS OFFERING ONLY THESE TREATMENTS. WHY?
Hooper, Williams with Members of the ME Community – 2010. Download www.
meactionuk.org
1. Interventions – CBT, GET, Pacing, Stand Med Care
2. NO OBJECTIVE CRITERIA WERE USED- Exercise or Biological (White- Chief
Investigator of the Trial, lead among Principal Investigators White, Sharpe,
Chalder. In 2004, White showed raised levels of TNF-a sustained at least 3 days
after exercise. He needs to read his own papers! )
CFS – CBT - GET
CBT IS NOT HARMLESS – TO IGNORE SYMPTOMS IS TO INVITE SERIOUS
CLINICAL PROBLEMS- MISSED DIAGNOSES- MISDIAGNOSES see BYRON
HYDE’S LATEST BOOK.
GET IS POSITIVELY DANGEROUS LEADING TO EXTENSIVE RELAPES
AND EVEN DEATH!
BRYNMOOR JOHN MP ME + EXERCISE DIED ON WESTMINSTER BRIDGE
IMMEDIATELY AFTERWARDS.
SHORTENED LIFE EXPECTANCY/DEATH – HEART FAILURE 20.1% (58.7)[83.1];
CANCER 19.4% (47.8)[72.0]; SUICIDE 20.1% (39.3)[48.0]
CHRONIC FATIGUE SYNDROME – DEFINITIONS DETAILS
1994 Case Definition: Fukuda et al Ann Int Med Dec 1994 – this the most widely
used clinically/Research. Oxford also still employed by some.
Characterised by:
 Medically unexplained
 Of new onset
 At least 6 months duration
 Not the result of ongoing exertion
 Not substantially relieved by rest
 Substantial reduction in previous activities
OXFORD
1. Disabling fatigue of
uncertain cause.
2. Psychiatric disorders not
necessarily excluded.
3. Any identifiable
biomedical illness excludes.
With 4 of the following:
SELECTS ONLY
 impaired memory/concentration
PSYCHIATRIC PATIENTS
 Sore throat
NOT ME-CFS.
 Tender cervical lymph nodes
 Myalgia
 Headaches of new type
 Unrefreshing sleep
 Post-exertional malaise (Some with ME-CFS)
 Multi joint pain without swelling or redness
1994 FUKUDA CDC classification found wanting symptoms [number (%)]
Sore Throat
Concentration/Memory Problems
Glands
Muscle Pain
Joint Pain
Headaches
Sleep
Post Exercise Fatigue
CFS/ME
n=48
25
(52%)
48
(100%)
27
(56%)
45
(94%)
37
(77%)
28
(58%)
43
(90%)
48
(100%)
OP
n=25
12
(48%)
24
(96%)
6
(24%)
6
(24%)
19
(76%)
17
(68%)
18
(72%)
24
(96%)
Kennedy, Spence et al Ann Epidemiol. 2004;14:95-100
GW
n=24
11
(46%)
24
(100%)
9
(38%)
9
(38%)
23
(96%)
21
(88%)
23
(96%)
23
(96%)
CANADIAN CONSENSUS PANEL CRITERIA FOR M.E. - 2003
MAJOR COMMON FEATURES
FATIGUE
POST-EXERTIONAL MALAISE & FATIGUE
SLEEP DISORDERS
PAIN
NEUROLOGICAL /COGNITIVE MANIFESTATIONS (2 or more)
AT LEAST ONE SYMPTOM FROM 2 OF FOLLOWING CATEGORIES
AUTONOMIC - NMH, POTS, Delayed Postural Hypotension, Low plasma and/or
RBC volume, Vertigo, Light Headedness, Extreme pallor, Intestinal or Bladder,
disturbances with IBS or Bladder dysfunction, Cardiac Arrhythmias, Vasomotor
Instability, Respiratory Irregularities
NEUROENDOCRINE - Thermostatic instability- heat/cold intolerance, Anorexia
or Abnormal Appetite, Marked weight change, hypoglycaemia, loss of adaptability
/tolerance to stress and slow recovery from stress, emotional lability
IMMUNE - tender lymph nodes, sore throat, flu-like symptoms, general, general
malaise, development of new allergies or change in status of old ones,
hypersensitivity to medications and/or chemicals.
CANADIAN CRITERIA, 2003, SUB-GROUPS ESSENTIAL AND CHARACTERISED.
Jason et al, 2005 showed need for sub-groups
Roberto Patarca-Montero. JCFS 2000:7(4):1 “the sorting of patients into
subpopulations….is helping in the design and interpretation of clinical trials
for therapeutic interventions aimed at particular disease manifestations”.
De MEIRLEIR –FROM RNase L etc IDENTIFIES 3 MAJOR SUB-GROUPS 19992005.
KERR et al 2005, 2007, 2010 - GENETICS - 8 CLINICAL PHENOTYPES, SNPs
NEWTON et al. 2007 2 SUB-GROUPS - 75% ME-CFS patients have
DYSAUTONOMIA WITH THEIR FATIGUE
ALL HAVE DIFFERENT TESTING & TREATMENT IMPLICATIONS
ME CLASSIFICATION AND NOMENCLATURE
WHAT ME IS NOT!
NOT a Fatigue Syndrome/Neurasthenia. ICD-10 G.93.3 NOT F.48.0
NOT Chronic Fatigue - many causes, Amer Med Assoc 1990
NOT Burnout – cortisol responses differ Mommersteeg et al
NOT DECONDITIONING - Burnett, Newton.
NOT CFS - Spence et al, Olano et al
NOT Clinical Depression fails clinical tests –Richardson et al and many others
SUMMARY OF BIOMEDICAL EVIDENCE
Twisk &
Maes, 2009
SF-36 SCORES MEAN OF GENERAL POPULATIONS
ME/CFS, OP & GULF WAR
PF
SF
RP
RE
MH
VT
BP
GH
PF= Physical Functioning (10); SF = Social Functioning (2); RP= Role Limitations Physical
Problems (4); RE= Role Limitations Emotional Problems (3); MH=Mental Health (5); VT=
Vitality/Energy (4); BP = Pain (2); GH = General Health (5)
OTHER CHRONIC ILLNESSES - SCORE < 72 HEART FAILURE, DIABETES,
RECENT MI, COPD, DEPRESSION. Haley 2004 Lloyd Inquiry
WESSELY et al UNABLE TO DISTINGUISH BETWEEN SICK AND ‘WELL’
GWVs - JOEM 2003;45:668-675.
MAJOR CHAPTERS ON VIRUSES
Cardiovascular Consequences
Central Nervous System
Glandular Effects
Pregnancy
Neoplasms
Toxins OCs mimic ME
Treatment Considerations
THIS IS A MAJOR CLINICAL
WORK THAT REPRESENTS A LIFE
TIME OF DEDICATED STUDY AND
PATIENT CARE.
Brain blood flow by PET Scans
differentiates ME/CFS from depression
ISBN 0-7890-1127 Haworth Medical Press, 2001
1992- Byron Hyde, Jay
Goldstein, Paul Levine (Eds)
74 Chapters covering all aspects
of ME-CFS
Modern Techniques- SPECT ,
PET, MRI (MRS)
Numerous Clinical Studies
Multi system effects
Effective Treatments
Chia JKS. The Role of Enteroviruses in Chronic Fatigue Syndrome- A
Review J Clin Pathol 2005;58:1126-32
Enteroviruses are well known causes of acute respiratory and gastrointestinal
infections, with tropism for the central nervous system, muscle, and heart. Initial
reports of chronic enteroviral infections causing debilitating symptoms in patients
with CFS were met with skepticism, and largely forgotten for the past
decade…….Recent evidence not only confirmed the earlier studies but also
clarified the pathological role of viral RNA through antiviral treatment.
Ribavirin, interferon-a [JR –pooled immunoglobulins early, choline + ascorbic
acid.]
THE HEART AND ENTEROVIRUSES
Reetoo KN, Osman SA, Illavia SJ, Cameron-Wilson CL, Bantavala JE, Muir P.
Quantitative analysis of viral RNA kinetics in coxsacchie B3- induce murine
myocarditis….with persitence of residual viral RNA throughout and beyond the
inflammatory phase. J Gen Virol 2000;81:2755-62
Lane RJM, Soteriou BA, Zhang H, Archard LC. Enterovirus related metabolic myopathy:
a postviral fatigue syndrome. J Neurol Neurosurg Psychiatry 2003;74:1382-6.
Peckerman A, Lamanca JJ, Dahl KA, ChemitigantiR, Qureseishi B, Natelson BH.
Abnormal Impedance Cardiography predicts Symptom Severity in Chronic Fatigue
Syndrome. Am J Med Sci 2003;326:55-60.
Twisk & Maes, 2009.
Pall 2007
Klimas et al
Spence et al
This is the first time that raised levels of the gold standard measure of
in vivo oxidative stress (isoprostanes) and their association with CFS
symptoms have been reported.
McArdle et al FRBM 2005;39:651-7
Showing free radical (reactive
oxygen species) increasing with
exercise.
Chronic Fatigue Syndrome: assessment of increased oxidative stress and altered
muscle excitability in response to incremental exercise. Jammes et al J Intern
Med 2005;257:299-310
In CFS there is
– increased oxygen uptake by exercising muscle
- exercise-induced oxidative stress was enhanced.
hsCRP correlates beset with clinical status of ME patients –
Spence et al unpublished data
This is why GET is damaging to people with ME/CFS
They start with a high ROS load which is rapidly increased.
Part of strong evidence for ENCAPHALOMYELITIS vs NOT -OPATHY debate
P
U
P
P
E
T
XMRV SUMMARY SLIDE – ITS MAKES SENSE!
C
O
M
P
L
E
X
I
L
L
N
E
S
S
Cancer (Prostate,)
Thyroid, NHL- Hyde
Inflammation
Cardiovascular Disease
Vance Spence et al
ME
MANY
SYMP
XMRV
Genetics – Kerr et al, Gow et al
TOMS
RNaseL Immune Dysregulation
–Autoimmunity De Meirleir et al
Virus Susceptibility
Enteroviruses Coxsacchie B
Herpes EBV etc Richardson,
Chia, Lerner
M
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T
E
R
M
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N
Y
S
T
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S
POLTICAL CONTROL OF HEALTH COSTS OF CHRONIC CONDITIONS
AND CONCERNS OF INSURANCE INDUSTRY ABOUT COSTS REQUIRE
M.E. TO BE DISMISSED BY FALSE EVIDENCE AND PATIENTS TO BE
IGNORED.
POLICY-BASED EVIDENCE [PACING, CBT, GET] WITH NO CREDIBLE
INTELLECTUAL OR CLINICAL FOUNDATION
VS
EVIDENCE-BASED POLICY [BIOMEDICAL WITH SOUND SCIENTIFIC
FOUNDATION PROVIDING TARGETED HEALTH CARE &TREATMENT
FAILURE OF NATIONAL AND INTERNATIONAL HEALTH AND INSURANCE
AGENCIES
GP HOME VISITS
Never
Periodically
Regularly
53%
38%
9%
VISIT THE SICK – DO NO HARM –MEDICAL NEGLIGENCE/DERELICITON OF DUTY
American Psychiatric Association’s Diagnostic and Statistical Manual for
MENTAL DISORDERS, DSM –V. PROPOSED REVISION OF DSM 4
Excuse? RATIONALISE REVISION OF 1CD-10 TO ICD-11 categories of
Mental Disorders with DSM.
NEW CATEGORY! COMPLEX SOMATIC SYMPTOM DISORDER, CSSD.
A. Somatic Symptoms- multiple & Distressing or ONE severe symptom
B. Misattributions, Excessive concerns or pre-occupation with
symptoms and Illness.
At least 2 of
+ High level of health-related anxiety
+ Normal bodily symptoms are viewed as threatening and harmful.
+ Tendency to Assume Worst – catastrophising!
+ Belief in medical seriousness of their symptoms – despite contrary
evidence
+ Health concerns assume a central role in their lives.
Examples Abound – Severe and persistent Gastric upset and pain – occasionally
blood, vomiting- sometimes relieved by eating but some foods cause more pain.
Feel weak and tired, worried. What is it?
M.E. (G93.3) is NOT a Mental and Behavioural Disorder (F48.0) –
repeat 3 times – morning, noon and night !- until THIS FALSE BELIEF clears.
IT IS FALSE ILLNESS BELIEF TO ASSERT M.E.HAS A PSYCHOGENIC ORIGIN
IT IS MEDICAL MALPRACTICE AND NEGLIGENCE [CRUEL AND PERVERSE]
1. NOT TO READ AND FULLY CONSIDER ALL THE BIOMEDICAL EVIDENCE
ABOUT M.E. ( >4000 PEER-REVIEWED PAPERS). DATA, DATA, DATA- READ –
MARK – LEARN – INWARDLY DIGEST – ACT IN THE LIGHT OF THIS KNOWLEDGE
2. TO DENY APPROPRIATE TESTS TO CONFIRM THE ILLNESS. NICE GUIDELINE
IS USELESS, Gibson Report. Testing is not advised/ proscribed
3. TO USE SUCH WILFUL IGNORANCE TO LIMIT AND DENY APPROPRIATE
TREATMENTS & INSURANCE BENEFITS.
1. THE NAME MUST BE CHANGED- DROP CFS AND ANY REFEENCE TO FATIGUE
SYNDROME(S). KEEP ICD 11 G93.3 EXCLUDE FROM F48.0 & DSM V
2. EXPLORE OTHER POSSIBILITIES BASED ON BIOMEDICAL EVIDENCE eg.
RETROVIRAL DISEASES Chap 0.?
THANK YOU FOR LISTENING