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CO-CURE Medical & Research Posts Only Digest - 9 Oct 2006 to 16 Oct 2006 (#2006-47)

There are 21 messages totalling 4078 lines in this issue.

Topics of the week:

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                       This is a special digest of
                  Co-Cure Research & Medical posts only
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Date:    Tue, 10 Oct 2006 10:02:40 -0400
From:    "Peter Kemp  [via Co-Cure Moderators
         <co-cure-mod@listserv.nodak.edu>]" 
Subject: RES,MED: ME Association article on Lyme disease

Permission to repost

Apparently, in the ME Association magazine, ME Essential, under the
title, "Lyme Disease - let's dispel the myths"
Dr Ho-Yen wrote:

Most ME is Lyme Disease
LD is characterised by early and late disease. The clinical syndromes of
early disease are well recognised, such as the characteristic rash
(erythema migrans); whereas late disease has characteristic clinical
syndromes (for example, dermatological, cardiac, rheumatoid), but also
includes a fatigue state. Therefore, it is only the late disease fatigue
state that has common features with ME. Overall, this may represent only
10% of all LD infections. It is certainly not the majority of LD
infections and most ME sufferers do not have LD. In the Highlands of
Scotland, we have the greatest tick populations and it has been my
routine in the investigation of ME patients to have them tested for LD.
In this large series of patients who have had very significant exposure
to ticks, the number of ME patients who have LD as the cause of their
illness is around 5%.
Dr. Ho-Yen appears to be implying that because the Highlands of Scotland
have the greatest tick populations and significant exposure that his
figure of around 5% (ME patients with Lyme disease) is the maximum that
could be expected throughout the UK.
In Scotland, Lyme disease is notifiable but in England and Wales it is
not. Dr. Ho-Yen remarks, "Experts have said that LD is ten times more
common than is reported. This is absolutely true". The Health Protection
Agency (2006) had 595 cases reported in 2005 in England and Wales (488
acquired in the UK). According to Dr. Ho-Yen the actual annual incidence
might have been 5950. In Scotland, where Lyme disease is notifiable,
there were 63 cases in 2005 (Health Protection Scotland, 2006).
The Health Protection Agency (2006) remark on the "Epidemiology of Lyme
Borreliosis":"Cases have been reported from most counties in England
and Wales". They also state:

Over 60% of indigenously acquired infections were acquired in southern
counties of England, comprising the South-West and South-East Health
Regions. These areas include well-known foci of Lyme borreliosis around
the New Forest, Salisbury Plain, Exmoor and Thetford Forest. Other
endemic areas include the Lake District, Yorkshire moors and Scottish
Highlands and Islands.
If Lyme Disease should be found to affect just 5% of people with M.E. or
CFS in the UK then:
UK population = 60,441,457
Incidence of ME/CFS .2 - .4% (NICE, 2006) = 120,883 to 241,766,
5% = 6044 to 12,088
This would be a very significant number of misdiagnosed people who might
be at risk of developing extremely serious symptoms. Wikepedia (2006)
lists the chronic (late) symptoms of Lyme disease:

fatigue, muscle pain (myalgia), joint pain with or without frank
arthritis, neuropathy (numbness, tingling, burning, itching,
oversensitivity), tremor, muscle twitching, Bell's palsy, meningitis,
vision problems (eg. double vision), sensitivity to light, motion,
hyperacusis (severe sensitivity to sound & vibration), vestibular
symptoms (balance; inner/middle ear), seizures, severe startle reaction,
panic attacks, depression, short-term memory loss, sleep disturbance,
hallucinations, cardiac arrhythmias, tachycardia (too-rapid heartbeat),
nausea or vomiting, adrenal disorders, immune suppression
And further add:
Lyme disease may be misdiagnosed as multiple sclerosis, rheumatoid
arthritis, fibromyalgia, chronic fatigue syndrome (CFS), or other
(mainly autoimmune and neurological) diseases, which leaves the
infection untreated and allows it to further penetrate the organism.
Some of these conditions may be misdiagnosed as Lyme disease, although
this is thought to be a rare occurrence. False positive Lyme diagnosis
is most commonly due to false positive serology in a subset of patients
who may suffer from syphillis, rheumatologic diseases, or infectious
mononucleosis. More confounding is that patients may present with Lyme
Disease and a related disease such as MS. This makes diagnosis
exceptionally difficult. It should be noted that this kind of
misdiagnosis is the exception rather than the rule as it is widely held
that Lyme Disease is underdiagnosed and underreported ranging from
factors of 10 to upwards of 40. It is important to remember that chronic
fatigue syndrome (CFS) is by definition a diagnosis of exclusion,
meaning it would be inaccurate to say that a patient does not have Lyme
because he or she has CFS. The substantial overlap in symptomatology
between Lyme and CFS makes this a crucial point.[3]
I am disappointed that the ME Association chose to publish the article
which I believe represents misleading and unbalanced information.
Peter Kemp MA

REFERENCES
Health Protection Agency (2006) Epidemiology of Lyme Borreliosis.
[Online] Available at:
http://www.hpa.org.uk/infections/topics_az/zoonoses/Lyme_borreliosis/enhanced.htm
[Accessed Sept. 7th 2006]
Health Protection Scotland (2006) Notifiable Diseases: Infectious
diseases and food poisoning. [Online] Available at:
http://www.hps.scot.nhs.uk/Search/detail.aspx?id=5945265 [Accessed Sept.
7th 2006]
NICE (2006) The National Institute for Clinical Excellence. Draught for
Consultation. NICE guideline. [Online] Available at:
http://www.nice.org.uk/page.aspx?o=368933 [Accessed Sept. 7th 2006]
Wikipedia (2006) Lyme Disease. [Online] Available at:
http://en.wikipedia.org/wiki/Lyme_disease [Accessed Sept. 7th 2006]


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Date:    Tue, 10 Oct 2006 14:13:14 -0400
From:    "Bernice A. Melsky" 
Subject: RES: Which of the three different tender points assessment methods 
is more useful for predicting the severity of fibromyalgia  syndrome?

Which of the three different tender points assessment methods is more
useful for predicting the severity of fibromyalgia syndrome?

Rheumatol Int. 2006 Oct 7; [Epub ahead of print]

Tastekin N, Birtane M, Uzunca K.

Physical Medicine and Rehabilitation Department, Medical Faculty, Trakya
University, Edirne, Turkey.

PMID: 17028859


Digital palpation, myalgic scoring and dolorimetry are frequently used to
count tender points in fibromyalgia syndrome. We aimed to investigate the
probable relation between tender points count and fibromyalgia impact
questionnaire and to assess which of the tender point counting methods is
the most successful in predicting the severity of the disease.

Tender point areas of 36 patients with fibromyalgia syndrome were assessed
with three methods which are myalgic scoring, digital and dolorimetric
tender points counting methods. Fibromyalgia impact questionnaire was used
to measure the disease severity. The correlation between each of the
assessment methods and fibromyalgia impact questionnaire was investigated.

The mean count of digitally evaluated tender points was 14.86 ± 2.67 and
by dolorimetry was 11.81 ± 4.48. The mean total myalgic score was found
to be 24.61 ± 8.91. All of the tender point evaluation methods correlated
positively with each other (P < 0.01). Fibromyalgia impact questionnaire
score was also correlated with only digital palpation tender point count of
these three evaluation methods (r = 0.427, P < 0.05).

Digital tender point count seemed to be sufficient for assessment, and
there is no need for an additional instrument for tender point evaluation.


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Date:    Wed, 11 Oct 2006 02:23:21 +0200
From:    Jan van Roijen
Subject: not,med: The Young ME Sufferers Trust -Vision

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


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>>     11 October 2006      <<<<
Editorship : j.van.roijen@chello.nl
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~

From:  "Jane Colby" <jane.colby@xxxxxxx.xxx>


May be reposted



NOTICE FROM THE YOUNG ME SUFFERERS TRUST
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~


The new issue of 'Vision' and 'The Brief' are now at
www.tymestrust.org on the magazine page in full colour.

Below is a summary of some of the contents. You'll also find
contributions from the young people. Mark's usual sense of
design (and fun) pervades the whole - many thanks to him.

Under the summary is a short extract from 'Vision', which may be
reprinted for newsletters but not shortened, nor used in part or
changed in any way. Credit must be given to 'Vision 2006-2 by
The Young ME Sufferers Trust'. Please also publish our website,
to facilitate others accessing the full magazine. I hope you will
find it a good read.



VISION (2006-2)

Vision : Project Update

*  Young Hearts Advocacy Project : In schools, surgeries,
     libraries
*  Tymes Trust/Nisai NVA : Up to 2000 free places for over16s
*  The Gibson Inquiry : Dr Ian Gibson gives his views
*  GP Line - Our Experience : Get a special rate through the
    Trust
*  In The Spotlight : Consultant's letter not needed for home
     education
*  Mythtery of Lyme Disease Explained : Lyme scare
    reassurance
*  Healthy Results : Watch our virtual seminar for schools and
    teachers
*  20Q Returns : Melvin the Brain seeks new home to visit
*  Out and About with Kinnerton : He does nick exceedingly good
    cakes...
*  Sally's Open Day : Get a personal invitation for the next one!


THE BRIEF (2006-2)

*  ME and the Enteroviral Link : Jane Colby's paper in Journal of
    Clinical Pathology
*  Facts At Your Fingertips : Close Household Contact Risk
    Factor for CFS; GP Services
*  Focus on School Examinations and ME - Special Assessment
    Arrangements
*  Opathyitis


Extract:  IN THE SPOTLIGHT

Government confirms consultant's report not needed for home
education

Towards the end of 2005, our Founder Patron Lord
Clement-Jones, Chair of Trustees Keith Harley and Executive
Director Jane Colby met with Lord Adonis, Parliamentary
Under-Secretary of State for Schools. We are now pleased to
announce the latest result of that meeting.

Under discussion was the insistence by schools and Local
Education Authorities on a consultant's report before providing
home-based education. It is a misinterpretation of Government
statutory guidance in 'Access to Education for Children and
Young People with Medical Needs' regarding education in the
home.

This misinterpretation comes from an LEA policy (appended, as
an example, to the Access to Education guidance) in which the
child's GP was cut out of the loop. This has led to unacceptable
and repeated delays in suitable provision under the law, as we
predicted when meeting the previous Under-Secretary of State.
A GP is a qualified doctor and the Government own Exemplar
Megan's Journey shows an LEA providing education in the
home for a child with CFS/ME on the GP's recommendation.

LEAs' legal responsibilities include ensuring that pupils are not
at home without access to education for more than 15 days. It is
not possible except in cases of emergency for a child to get to
see a consultant within 15 days, nor, according to the medical
profession, is it normally appropriate.

The relevant paragraph from Jane Colby's review in the Journal
of Clinical Pathology, which you may wish to quote, states: "It is
not commonly known that, although helpful and in some cases
invaluable, there is no requirement for a consultant's
recommendation for a child too unwell to access school to be
provided with an alternative means of education. [..] The GP's
recommendation, as a qualified doctor, is sufficient. After a
meeting with the Trust, Parliamentary Under-Secretary of State
Lord Adonis wrote: 'It is unfortunate if, as calls to The Young ME
Sufferers Trust advice line would appear to indicate, the advice
in Access to Education is sometimes being misinterpreted as
insisting that local authorities obtain a report from a consultant
before action can be taken to provide support to children with
ME who are unable to attend school full time. [On diagnosis] our
guidance is quite clear. We say that ideally an early diagnosis
should be made by a consultant paediatrician but we do not
suggest that this is a requirement.' "

At Lord Adonis' request, the Trust has provided the Government
with real-life examples of good practice.

END OF EXTRACT


-----------
Jane Colby
Executive Director
The Young ME Sufferers Trust
PO Box 4347
Stock  Ingatestone
Essex  CM4 9TE
Tel 01245 401080
www.tymestrust.org



~~~~~~~~~~


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Date:    Tue, 10 Oct 2006 21:09:23 -0400
From:    "CF-Alliance <cf_alliance@xxxxxx.xxx> (via Co-Cure Moderators" 
Subject: RES:IBS Patients 60% More Likely to Suffer Fibromyalgia, Migraine, Depression

Irritable Bowel, Pain Syndromes Linked:


  IBS Patients 60% More Likely to Suffer Fibromyalgia, Migraine, Depression

  http://www.webmd.com/content/article/128/116870.htm


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Date:    Tue, 10 Oct 2006 21:15:50 -0400
From:    "<SacWriterEditor@xxx.xxx> [via Co-Cure Moderators"
Subject: NOT,RES:IBS w/Diarrhea clinical trial

Novartis is doing a clinical trial of a medication to treat IBS with
diarrhea.  You can sign up at _www.Belly911.com_ (http://www.Belly911.com)

Here in Sacramento, the trial is being done at 1 Scripps Drive.


Karen M. Campbell
Sacramento, Calif.
www.CFSFacts.org_ (http://www.cfsfacts.org/)  -- dispelling the  myths and
providing the facts

OCTOBER IS DISABILITY AWARENESS  MONTH


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Date:    Wed, 11 Oct 2006 19:17:30 -0400
From:    Co-Cure Moderator <ray@xxxxx.xxx>
Subject: NOT,MED: NEJM ON FDA Problems and Possible Solutions [US]

Early Release:

Perspective
Protecting the Health of the Public -- Institute of Medicine
Recommendations on Drug Safety

Journal: N Engl J Med 355;17, www.nejm.org, October 26, 2006, pp. 1753-1755

Authors: B.M. Psaty and S.P. Burke

is available in PDF format for free at
http://content.nejm.org/cgi/reprint/NEJMp068228v1.pdf

[AOL: <a href="http://content.nejm.org/cgi/reprint/NEJMp068228v1.pdf">Here</a>]


Editorial
Blueprint for a Stronger Food and Drug Administration

Journal: N Engl J Med 355;17, www.nejm.org, October 26, 2006, p. 1821

Authors: G.D. Curfman, S. Morrissey, and J.M. Drazen

is available in PDF for free at

http://content.nejm.org/cgi/reprint/NEJMe068237v1.pdf

[AOL: <a href="http://content.nejm.org/cgi/reprint/NEJMe068237v1.pdf">Here</a>]


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Date:    Wed, 11 Oct 2006 17:34:04 -0700
From:    Co-Cure moderators <cocuremoderator@xxxx.xxx>
Subject: MED: Principles of Effective Pain Management at the End of Life

(registration to view this site is required, but it is free)
http://www.medscape.com/viewarticle/545562_1


Principles of Effective Pain Management at the End of Life

Introduction
The end stages of chronic, progressive, life-limiting diseases bring a host of
difficult symptoms and causes of suffering. There are disease-mediated
symptoms, such as pain, dyspnea, fatigue, and loss of mobility, and there are
the accompanying emotional states, such as depression, anxiety, and a sense of
uselessness.[1] These symptoms and states intertwine and interact in a complex
manner, and each one deserves attention.

Of the many symptoms experienced by those at the end of life, pain is one of
the most common and most feared.[2,3] Pain is often undertreated, even when
prevalence rates and syndromes are well understood and the means of relief are
within all practitioners' capabilities to provide, directly or through
consultation. With careful assessment and a comprehensive plan of care that
addresses the various aspects of the patient's needs, pain can be controlled
in the vast majority of cases. Awareness and provision of basic and
specialized interventions can ensure comfort for all patients through the
final stages of a terminal illness. This is equally important in order to
prevent prolonged and pathologic grief in surviving loved ones.

All the members of a palliative care team play important roles in
comprehensive pain management. Both physicians' and nurses' roles begin with
assessment and continue throughout the development of a plan of care and its
implementation. Rehabilitation specialists, clinical pharmacists,
psychologists, social workers, and spiritual counselors also provide important
elements in helping patients optimize their quality of life, stay comfortable,
heal relationships, complete unfinished business, and find peace as they
approach death. To provide optimal pain control, all healthcare professionals
must understand the prevalence of pain at the end of life, the treatments used
to provide relief, and the barriers that prevent good management.

To illustrate some common scenarios, we present 3 different fictional, but
typical, case studies.

Case 1: Eleanor is a frail, 78-year-old woman who lives on her own with
assistance from a homecare nurse and from a daughter who lives nearby. She was
admitted to the hospital with acute respiratory failure due to bronchitis. She
has advanced chronic obstructive pulmonary disease (COPD), with general
fatigue and a poor appetite, and reports severe, debilitating pain in the
midthoracic region from postherpetic neuralgia (PHN). She also struggles with
coronary artery disease and attendant
angina pectoris that is usually relieved with nitrates. Eleanor says that she
has been feeling "pretty low" lately and finds herself becoming irritated at
small events. She characterizes her pain as "bad as it can be" (see Figure 1).
After a 2- to 3-day intensive care unit (ICU) stay, she will soon be ready for
discharge. However, her pain from PHN is still not controlled, and her life
expectancy is most likely limited due to her ongoing comorbidities. She does
not have a written advanced directive. The hospital staff discuss the next
step.


  Figure 1. Pain Thermometer. Originally published in: Herr KA, Garand L.
Assessment and measurement of pain in older adults. Clin Geriatr Med.
2001;17:457-478, vi. Reprinted with permission.

Return to: Principles of Effective Pain Management at the End of Life

 Question 1:
                          Survey - If you were the attending clinician, would
you feel confident that you could address Eleanor's pain management needs
successfully?
                                Your colleagues responded:
                                71% Yes
                                28% No


Prevalence of Pain at the End of Life

Assessing pain in patients approaching the end of life requires a
multifactorial evaluation. It is important to acknowledge and address the
prevalence, high incidence, and serious adverse consequences of pain in the
end-stage conditions that affect patients with advanced medical illness, such
as controlled and uncontrolled cancer; heart disease; HIV disease;
neurodegenerative diseases (eg, ALS and multiple sclerosis); and end-stage
renal and respiratory diseases (see Figures 2
and 3).[4,5] These conditions may also be accompanied by other pain-producing
disorders that may require separate treatments, as in the case above.


Figure 2. Common causes of persistent pain in advanced medical illness.



Figure 3. Consequences of undertreatment of pain.

The prevalence of pain in the terminally ill varies by diagnosis and
demographics. Approximately one third of the people who are actively receiving
treatment for cancer and two thirds of those with
advanced malignant disease experience pain.[6-9] Almost 75% of patients with
advanced cancer who are admitted to the hospital report pain upon
admission.[10] In a study of cancer patients who were very near the end of
life, pain occurred in 54% and 34% at 4 weeks and 1 week prior to death,
respectively.[11] In a recent study by Goudas and colleagues[12] that compiled
the results of 28 epidemiologic surveys, the study authors found that, in one
study of over 35,000 Japanese cancer patients, 68% to 72% of patients in the
terminal stages reported pain. In another study of over 13,000 cancer patients
in US nursing homes, an average of 30% of the patients reported daily pain. In
those patients, pain varied according to age, sex, race, marital status,
physical function, depression, and cognitive status.[12]

In other studies of patients admitted to palliative care units, pain often is
the dominant symptom, along with fatigue and dyspnea.[2] Until recently, it
was widely believed that patients dying from nonmalignant disease did not have
high levels of pain. However, it is now known that patients dying from cardiac
failure, COPD, end-stage renal disease, and other end-stage diseases suffer
similar levels of pain to those found in patients with malignant
disease.[13,14] People at particular risk for undertreatment include the
elderly, minorities, and women.[15,16]

More recently, an attempt has been made to characterize the pain experience of
those with HIV disease, a disorder frequently seen in palliative care
settings. Over 56% of patients with HIV disease report pain, with the most
common symptoms being headache, abdominal pain, chest pain, and
neuropathies.[4,5,17,18] Lower CD4+ cell counts and HIV-1 RNA levels are
associated with higher rates of neuropathy.[17,18] There have been many
reports of undertreatment of patients with HIV disease, including those
patients with a history of addictive disease.[19,20]



 General Principles of Assessing and Managing Pain

Assessment of pain, including a thorough history and comprehensive physical
exam, guides indications for diagnostic studies and the development of the
pharmacologic and nonpharmacologic treatment plan.  The primary source of
information should be a patient's self-report. There are many different pain
rating scales available, ranging from complex multidimensional tools to very
simple numeric and picture scales, which can help patients identify pain and
then document the efficacy of treatment (see Figures 1 and 4 and Table 1 for
links to sample pain scales). When using pain scales, be sure to follow the
directions for administration carefully.


Figure 4. Pain assessment scales. Reprinted with permission. FACES Pain
Scale - Revised: Copyright 2001 International Association for the Study of
Pain (IASP). Originally published in: Hicks CL, von Baeyer CL, Spafford P, van
Korlaar I, Goodenough B. The Faces Pain Scale -- Revised: toward a common
metric in pediatric pain measurement. Pain.  2001;93:173-183. Other scales:
Originally published in: Herr KA, Garand L. Assessment and measurement of pain
in older adults. Clin Geriatr Med. 2001;17:457-478, vi.


Table 1. Pain Scales Online
Description Web Address
Wong-Baker FACES Pain Rating Scale

http://www3.us.elsevierhealth.com/WOW/faces.html

Sample of Wong-Baker FACES Pain Rating Scale, with instructions for
administration available in many languages

http://www3.us.elsevierhealth.com/WOW/facesTranslations.html

Faces Pain Scale - Revised (FPS-R), with instructions for administration
available in many languages

http://painsourcebook.ca/docs/pps92.html

Verbal pain scale
http://www.intelihealth.com/IH/ihtIH/WSIHW000/29721/32087.html

Numerical pain scales

http://www.intelihealth.com/IH/ihtIH/WSIHW000/29721/32087.html

http://www.medtronic.com/neuro/paintherapies/pain_treatment_ladder/drug_infusion/patient_management/drug_pat_mgmt_strat.html

Pain map

http://www.medtronic.com/neuro/paintherapies/pain_treatment_ladder/pdf/prestim_pain_assess.pdf

McGill Pain Questionnaire

http://www.physiobase.com/Protocols/assessmentforms/pain_questionnaire_2.pdf

Short-Form McGill Pain Questionnaire

http://www.med.umich.edu/obgyn/repro-endo/Lebovicresearch/PainSurvey.pdf

 Brief Pain Inventory

http://www.ohsu.edu/ahec/pain/paininventory.pdf

List of pain scales with evaluations

http://www.chcr.brown.edu/pcoc/Physical.htm

Pain scales in 17 languages

http://www.britishpainsociety.org/pain_scales.html

A pain scale that suits a given patient's ability to self-report should be
part of each patient's medical record. Health professionals should teach
patients and their families to use these scales themselves
to help in longitudinal pain assessment and continuity of care. Patients with
terminal illnesses should be encouraged to verbalize their experiences of pain
in their own words. The use of the "pain thermometer" has been validated as a
self-report instrument for pain intensity in patients with mild-to-moderate
cognitive impairment.[5,21,22]

For example, Eleanor describes her PHN as a "burning, needling pain" near her
spine, spreading out across her back on the right, beneath her axilla and
around to her breast. Her pain subsides sometimes, but rarely goes away
altogether. Knowing the character and location of her neuropathic pain allows
her caregivers to pinpoint adjuvant pain relief. In contrast, Eleanor's angina
pain is "a deep heavy ache" in her chest. She notes that it is intermittent
and that it is stressful, because she
never knows quite when to expect it. By asking her to keep track of when her
angina occurs, her caregivers are able to predict more precisely when it may
be triggered, and advise her accordingly, perhaps reducing both severity and
frequency.

A comprehensive evaluation of pain should include an assessment of the pain
intensity, character, frequency, onset, duration, and location as well as a
detailed history of pain, a physical and neurologic examination, a
psychosocial assessment, and a diagnostic evaluation that includes tests to
determine the cause of pain. It is also important to take into account common
comorbidities, such as sleep disturbances and depression, which can affect
pain levels, suffering, and functioning.[21,22]

Patients sometimes complain of pain as a way of expressing other forms of
suffering, anxiety, or depression. When this is the case, psychosocial
evaluation and intervention will be more effective than analgesics. It is well
established that attention and emotion influence pain processing and
perception, and conversely, inadequately managed pain can lead to anxiety and
depression.[7-9] Therefore, comprehensive assessment is required to determine
the optimal plan of care, as specific to pain etiology as possible.

Pain Types

Pain can usually be defined as nociceptive or neuropathic. Patients in the
terminal stage of an illness may often experience different mechanisms of pain
operating simultaneously. It is important to
differentiate among different types of pain because the type of treatment is
largely dictated by the pain mechanism and its original source.[21] In some
conditions, pain appears to be caused by a complex mix of nociceptive and
neuropathic factors. In these cases, an initial nervous system dysfunction or
injury may trigger the neural release of inflammatory mediators and subsequent
neurogenic inflammation -- migraine headaches, for example, are most likely a
mix of neuropathic and nociceptive pain.

Nociceptive Pain

Nociceptive pain is typically the result of a musculoskeletal or visceral
injury or disease and includes somatic and visceral mechanisms. Primary
afferent neurons receive nociceptive input from peripheral nociceptors.
Nociceptors are activated in response to noxious stimuli, which can be
thermal, chemical, or mechanical in character. Somatic pain is characterized
by aching, throbbing, stabbing, and/or a sensation of pressure. Its source is
skin, muscle, or bone. Visceral pain is characterized by gnawing, cramping,
aching, sharp, and/or stabbing sensations, and its source is the internal
organs. Nociceptive pain usually resolves when the initial tissue damage
heals, and tends to respond well to treatment with anti-inflammatory agents
and opioids.[22-24]

Neuropathic Pain

Neuropathic pain is caused by lesions or physiologic changes in the nervous
system, and it is characterized by hypersensitivity either in the damaged area
or in the surrounding normal tissue. The pain is often triggered by an injury
or disease, but there may not be demonstrable damage to the nervous system
other than the subjectively reported sensory disturbance of pain. The pain
frequently has qualities of burning, numbness, tingling, touch sensitivity,
sharp and shooting sensations
(lancinating pain), or electric shocks (see Figure 5). Persistent allodynia,
which is pain resulting from a nonpainful stimulus, such as a light touch, is
a common characteristic of neuropathic pain. Neuropathic pain tends to persist
long after the initiating event has resolved. Neural inflammation can change
the actual structure of neural organization so that stimuli that were once
interpreted as touch become perceived as painful. Typical examples include
painful diabetic neuropathy, HIV/AIDS neuropathy, postherpetic neuralgia, and
cancer-induced as well as post-treatment cancer pain
syndromes, such as postmastectomy syndrome and radiation and chemotherapy
neuropathies.[22,23,25]


Figure 5. Neuropathic Pain Questionnaire Short Form. Originally published in:
Backonja MM, Krause SJ. Clin J Pain. 2003;19:315-316. Reprinted with
permission.

Effects of Unrelieved Pain

There is significant evidence that inadequate pain relief hastens death by
increasing physiologic stress, potentially diminishing immunocompetence,
reducing mobility, increasing proclivities toward
pneumonia and thromboembolism, and increasing the work of breathing and
myocardial oxygen requirements.[26] Pain may lead to a spiritual despair and
significant decrease in emotional well-being because the individual's quality
of life is impaired.[4,5] It is the professional and ethical responsibility of
clinicians to focus on and attend to adequate pain relief for their patients
and to properly educate patients and their caregivers about analgesic
therapies.[27]

Returning to Eleanor, who has COPD, coronary artery disease, and PHN, it is
clear that discussions regarding care preferences (ie, advanced directives)
are optimally done prior to a medical crisis and while there is cognitive
capacity for decision making. However, under the current circumstances, a care
planning meeting with the attending clinician, consultant clinicians (eg,
palliative care/hospice team), and designated responsible family member is of
paramount importance. Either pain must be adequately controlled prior to
discharge with a follow-up plan in place, or transfer to a skilled facility,
such as an inpatient palliative care/hospice unit (where pain management
expertise and focus can rapidly take place). Alternatively, with a prognosis
of 6 months or less, if Eleanor prefers to go home immediately, a hospice
program with the ability to manage her pain condition should be consulted.
Regardless of setting, nonpharmacologic approaches to pain control with
titration of "first-line" agents for neuropathic pain (anticonvulsants,
topical local anesthetic, and opioids) should proceed with close monitoring to
balance therapeutic vs adverse effects.

Case 2: Sharon is a 70-year-old woman in the late stages of Alzheimer's
disease with severe osteoarthritis in her knees and spine. She lives with her
married daughter and 2 grandchildren. Her daughter and a son living nearby
provide her essential care, and, until recently, she has remained active and
ambulatory. She is beginning to experience severe pain from her arthritis,
manifest by grimacing, crying, and moaning. The current caregivers are not
always sure what she is expressing, but they understand that she is in some
distress and are eager to help alleviate it. They meet with their family
doctor to talk about options. Because Sharon is in the far-advanced stage of
Alzheimer's disease, the physician refers her to hospice for comprehensive
care and support of her family. During her initial evaluation, the family
stresses that their primary goal is to make sure that "Mom" is comfortable.
The hospice nurse evaluates Sharon and determines that she responds well to a
variety of nonpharmacologic interventions. Her family members express a
willingness to use a variety of hands-on and nonpharmacologic techniques to
help Sharon live her last days relatively free of pain and suffering.
Meanwhile, she is started on a regimen of around-the-clock acetaminophen (1000
mg 4 times daily) with the option for more potent pharmacologic therapies left
open.

Nonpharmacologic Approaches to Pain Management in Palliative Care

An important aspect of any management strategy is the use of nonpharmacologic
treatments.[23,28] There are a variety of nonpharmacologic approaches to pain
that have been shown to be effective in alleviating pain for patients with
advanced illness. These include physical interventions, such as positioning
and active or passive mobilization (therapeutic exercise); techniques, such as
TENS, massage, and heat/cold; and complementary and alternative medicine
techniques, music, and relaxation/imagery exercises. Table 2 offers a list of
some of the most common nonpharmacologic interventions.

Table 2. Nonpharmacologic Approaches to Pain Management in Palliative Care

Intervention Details

Rehabilitation/physical therapy

          a.. Physical, occupational, and speech therapy are potentially
beneficial in managing pain
          b.. Mobility may be improved by strengthening, stretching, and the
use of assisting devices
          c.. Home settings vary in their utility for a debilitated person, as
does the degree of hands-on physical assistance that friends and family can
provide
          d.. The decision to use these modalities is made on a case-by-case
basis

        Massage a.. Family members can be taught simple, safe techniques of
massage
          b.. Hospice programs can often provide trained, certified massage
therapists who are familiar with the clinical issues faced by cancer and
noncancer patients with far-advanced disease

        Transcutaneous/percutaneous electrical nerve stimulation

          a.. Evidence exists to support the use of percutaneous electrical
nerve stimulation for persistent low back pain and knee pain

        Acupuncture

        a.. Popular complementary therapy for patients with cancer and other
end-stage pain
        b.. Many patients with cancer use acupuncture when symptoms persist
with conventional treatments, or as a complement to their ongoing treatments
          c.. Several researchers have found acupuncture to be an effective
antidepressant
          d.. Studies show that acupuncture has a significant positive effect
on COPD, dyspnea associated with end-stage cancer, and asthma

        Cognitive interventions

           a.. Some common cognitive interventions:

            a.. Psychological tools and strategies for the purposes of
self-regulating emotions
            b.. Distraction from noxious sensations and thoughts
            c.. Methods for reducing negative attitudes


          b.. Involving patients in cognitive self-care may improve mood and
increase coping behaviors

           Music therapy
           a.. Music effectively reduces anxiety and improves mood for:

            a.. Medical and surgical patients;
            b.. Patients in intensive care units;
            c.. Patients undergoing procedures; and
            d.. In children as well as adults


          b.. Low-cost intervention
          c.. Often reduces chronic pain
          d.. Improves the quality of life, enhancing a sense of comfort and
relaxation
          e.. Music to caregivers may be a cost-effective and enjoyable
strategy for improving empathy, compassion, and relationship-centered care
without interfering with technical aspects of care


 COPD  chronic obstructive pulmonary disease
The type of intervention, or combination of interventions, depends on the
source and severity of pain as well as the physical condition and receptivity
of the patient. In an investigation of the prevalence of complementary and
alternative medicine use in an end-of-life population, Tilden and
colleagues,[29] through a series of phone interviews with family caregivers of
recently deceased, found that 53.7% of the deceased used some kind of
complementary therapy, were more likely to be younger with college degrees and
higher household incomes, and to have used 1 or more life-sustaining
treatment. Symptom relief was the most frequent reason given for complementary
and alternative medicine use.[29]

Although a study by Weiner and Ernst[30] that reviewed common complementary
and alternative treatment modalities for the treatment of persistent
musculoskeletal pain found that the use of these modalities is increasing in
older adults, the study authors concluded that rigorous clinical trials
examining efficacy are still needed before definitive recommendations
regarding the application of these modalities can be made.

Aside from their objective efficacy, a medical sociologic study by Garnett[31]
on the use of complementary therapies by palliative care nurses sees these
therapies as an "emotional inoculation" that builds resiliency and an
important bond between patient and caregiver. Nonpharmacologic interventions
often comfort the patient while involving and empowering family and other
caregivers. The necessity of feeling effective for caregivers should not be
overlooked -- it can have a direct effect on the experience of the patient as
well as the emotional survival of the family caregiver in particular. A study
by Keefe and colleagues[32] on the self-efficacy of family caregivers of
cancer patients found that caregivers who rated their self-efficacy as high
reported much lower levels of caregiver strain as well as lower negative mood
and higher positive mood. Caregiver self-efficacy in managing the patient's
pain was related to the patient's physical well-being. When the caregiver
reported high self-efficacy, the patient reported having more energy, feeling
less ill, and spending less time in bed.[32]

Rehabilitation and Physical Therapy

Functional rehabilitation and physical therapy techniques in appropriately
selected patients add to quality of life even in the face of limited life
expectancy. Sharon is a typical patient who responds
well to nonpharmacologic pain intervention. A recent study by Montagnini and
colleagues[33] assessing the use of physical therapy in a hospital-based
palliative care setting found that a significant proportion demonstrated
improvement in function after 2 weeks. The study authors found that patients
with a diagnosis of dementia were most likely to show improvement in
functional status and concluded that physical therapy assessment and use were
uncommon in the studied group, but, when implemented, it benefited 56% of the
patients.[33]

Massage

Research suggests that patients with cancer, particularly in the palliative
care setting, are increasingly using aromatherapy and massage. There is good
evidence that these therapies may be helpful for anxiety reduction for short
periods. A study by Soden and colleagues[34] was designed to compare the
effects of 4-week courses of aromatherapy with massage and massage alone on
physical and psychological symptoms in patients with advanced cancer. The
study authors were unable to demonstrate any significant long-term benefits of
aromatherapy or massage in terms of improving pain control, anxiety, or
quality of life, but sleep scores improved significantly in both groups, and
there were statistically significant reductions in depression scores in the
massage group -- suggesting that patients with high levels of psychological
distress respond best to these therapies.[34]

Acupuncture and TENS

These modalities may be effective in selected patients based on meta-analyses
of the literature and findings of National Institutes of Health (NIH)
consensus panels.[35] For percutaneous procedures,
appropriate cautions, skilled certified practitioners, and fastidious aseptic
techniques are required to protect patients and staff from untoward adverse
outcomes. Similarly, for therapies involving electrical stimulation, awareness
of implanted devices (pumps, stimulators, implantable cardioverter
defibrillators, or pacemakers) and precautions to prevent malfunction must be
taken.

Cognitive Interventions

Simple psychological interventions can have a significant impact on pain. As
an example, Paqueta and colleagues[36] explored the idea that everyday emotion
regulation through a self-supporting maintenance or change in positive and
negative emotions can help reduce pain intensity in the hospitalized elderly.
Emotion regulation was found to be prospectively related to pain intensity for
both overall emotion and anxiety-specific regulation. The study authors
suggest that promoting
emotion regulation as a self-management strategy could contribute to
cost-effective pain management in general or targeted elderly populations.[36]

Music Therapy

There is growing interest in the therapeutic use of music. The difficulties
inherent in the medical treatment of this population make the use of music, as
a noninvasive therapeutic modality, attractive.[37] Music is often used to
enhance well-being, reduce stress, and distract patients from unpleasant
symptoms. Although there are wide variations in individual preferences, music
appears to exert direct physiologic effects through the autonomic nervous
system.[38]

Choosing the Best Approach

A combination of treatments is usually most effective when using
nonpharmacologic approaches to pain management. Similar to pharmacotherapy,
multimodal approaches offer the potential benefit of additive and synergistic
effects. Because nonpharmacologic therapies need to be tailored to individual
likes, dislikes, and effectiveness, knowledge of the various modalities,
management of expectations, open-mindedness, and a "trial-and-error" approach
should be embraced.

The hospice nurse was able to offer Sharon's family a variety of hands-on and
alternative modalities that could be used in addition to pharmacologic
interventions to successfully comfort the patient. The nurse found that simple
stretches and strengthening and mobilization exercises were effective for
reducing the stiffness that was associated with Sharon's musculoskeletal
disease. This helped both to relax the patient and prevent the usual anxiety
that is associated with getting her out of bed in the morning and daily
personal care, such as bathing and toileting. A simple TENS unit appeared to
ease the patient's knee pain. The nurse was also able to guide the family in
some interventions that reduced Sharon's anxiety and increased the family's
sense of involvement and effectiveness. They found that songs from her youth
brought Sharon a great deal of pleasure, and her son, a fan of the music,
enjoyed spending listening time with her. Physical contact often calmed
Sharon, and the nurse trained Sharon's granddaughter in simple massage
techniques.

Case 3: Jerry is an 82-year-old man with metastatic colon cancer who has just
returned to his home in an assisted living facility postoperatively after a
bowel resection. He sees a geriatric nurse practitioner, in collaboration with
a family physician, for ongoing primary care. It has become clear that that
there are widespread metastases, and his oncologist agrees that the current
goal of care is
comfort only. Jerry is still ambulatory and in the early stages of his
terminal illness. No further chemotherapy or radiation therapies are
indicated, but the patient reports progressive abdominal pain, and symptoms
suggestive of intermittent bowel obstruction develop. Jerry refuses further
hospitalization and surgery, and prefers noninterventional therapies -- if at
all possible. A consulting pharmacist and medical director from the local
hospice are asked to come in and help the nurse practitioner choose the best
pharmacotherapy for pain and bowel-related signs and symptoms, including types
of drugs, route of drug administration, and the best way to minimize possible
side
effects. The explicit goals of care are a comfortable, dignified death; crisis
prevention; and self-determined life closure (no prolongation of dying by
medical intervention).

Drugs for Pain Relief in Palliative Care

Pharmacologic therapies for pain include nonopioids, opioids, adjuvant
analgesics, disease-modifying therapies, and (in some cases) interventional
techniques. Intractable pain and symptoms that are not responsive to basic
therapeutic techniques, although not common, must be treated appropriately and
aggressively. In some highly selective cases, palliative sedation may be
warranted. A sound understanding of pharmacotherapy for pain treatment allows
the palliative care/hospice team to create a comprehensive plan of care as
well as recognize and assess medication-related adverse effects, understand
drug-drug and drug-disease interactions, and educate patients and caregivers
regarding appropriate medication usage. Recognition of the limits of usual
therapies and the ability to muster expert assistance are important skills.
This will ensure a comfortable process of dying for the well-being of the
patient and for the sake of those in attendance.

Genetic factors, pathologic processes, concurrent medication, and aging will
all influence drug response and disposition. However, there are also a variety
of nonmedical factors that influence responses to drug treatment in patients
with far-advanced disease, including the social, environmental, and
psychological milieu as well as the general vulnerability of this population.
Understanding the clinical pharmacology of the drugs in question is essential
for professional
caregivers.[5] Commonly, there is a need to use drugs for non-FDA-approved
indications or routes of administration, simply because randomized, controlled
clinical trials have not been performed, due (usually) to financial
constraints. Rational polypharmacy (combining drugs with different mechanisms
of action to produce additive or synergistic effects and minimize adverse
effects) is often necessary, but there is a high potential for drug
interactions, so close monitoring is required.

  The principles of effective symptom control are always paramount -- diagnose
the underlying cause of each symptom and tailor the treatment to individual
circumstances and clinical context. Keep in mind that normal pharmacokinetics
and pharmacodynamics may be considerably altered by end-stage disease states.
For example, in patients with chronic liver disease or hepatic metastases,
drugs may bypass hepatic metabolism altogether, increasing bioavailability.
Similarly, renal clearance is
almost always diminished during the dying process, leading to the accumulation
of drug metabolites, some of which (eg, those of morphine) may be
toxic.[5,39,40]

Communicating With Patients, Families, and Other Healthcare Professionals

Communicating clearly about pharmacologic pain control with patients,
families, and other members of the palliative care/hospice team is essential
to providing effective pain management. It is important to be specific about
the types of drugs that are available, how they are likely to affect the
patient, how they are to be administered, and how they may interact with
existing medications. Despite the importance of pain management at the end of
life, there are often substantial roadblocks to overcome in getting patients
the treatment that they need. Professional healthcare workers may have
unsubstantiated but strong beliefs about analgesic use, especially opioid use,
that lead to
underprescribing.[41,42] There are several surveys that show that physicians,
nurses, and pharmacists express concerns about addiction, tolerance, and side
effects of morphine and related compounds.[43] These fears are pervasive among
patients and family members as well. Studies
have suggested that these fears lead to undermedication and increased pain
intensity.[44] Concerns about being a "good" patient or belief in the
inevitability of cancer pain lead patients to hesitate in reporting pain. In
these studies, less educated and older patients were most likely to express
these beliefs.[4]

Often, a physician or other providers may be reluctant to offer the patient
direct and objective information on his or her health, especially toward the
end of life, seeking to "soften the blow" by
keeping the details vague. Most patients, however, prefer complete information
about his or her condition.[45,46] However, patients may wish to defer
decision making to the physician or family members.[45,47] Physicians have a
professional duty to determine patients' medical wishes. Pragmatically, this
responsibility may fall to the nurse or nurse practitioner, and there are
tools, such as simple card sorting, that can be used to facilitate this
exchange,[48] for example, the 5-card Control Preference Scale uses cards to
portray different roles in treatment decision making with a statement and a
picture.[49]

Dispelling Common Myths About Pain Management

Understanding the barriers that are faced when treating pain can lead
professionals to better educate and counsel patients and their families.[32]
Patients should be asked whether they are concerned about addiction and
tolerance (often described as becoming "immune" to the drug).[50] At the end
of life, patients may need to rely on family members or other support persons
to dispense medications. Studies suggest that patients' pain experiences and
family members' perceptions about them don't correlate well, leading to
inadequate provision of analgesia.[51,52] The interdisciplinary palliative
care/hospice team is essential in the communication effort, with nurses,
social workers,
chaplains, physicians, volunteers, and others providing support in exploring
the meaning of pain and barriers to pain relief. Education, counseling,
reframing, and spiritual support are imperative.

Overview of Nonopioid and Opioid Therapy

This section provides a brief overview of both commonly used and newer
pharmaceutical agents available in the United States for the treatment of
persistent pain associated with advanced disease. Pain-relieving drugs can be
categorized as nonopioid analgesics, opioid analgesics, and the adjuvant
analgesics. Detailed knowledge of these classes of agents is necessary to
provide quality palliative care, and although a comprehensive review is beyond
the scope of this article, links to more
detailed lists of all drugs used for pain control throughout the world can be
found in Table 3.

  Table 3. Drugs for Pain Control at the End of Life
        Web Address Content
        http://www.palliativedrugs.com Palliative care formulary online
        http://www.pallmed.net Generic site, with drug-compatibility database
        http://nccam.nih.gov Information on complementary medicines
        http://www.fda.gov/orphan/ Information on orphan drugs

    Source: Doyle D, Hanks G, Cherny NI, Calman K, eds. Oxford Textbook of
Palliative Medicine. 3rd ed. Oxford, United Kingdom: Oxford University Press;
2003.

There are several, possible methods of approaching pharmacologic pain
management for patients with advanced diseases. Patients may require several
different medications to deal with a variety of pain syndromes and disease- or
treatment-related discomfort. For expedient and thorough treatment, it is
often wise to adopt a stepwise approach to the use of pain medications. The
World Health Organization (WHO) has developed a simple, 3-step model for
managing cancer pain that can be applied to many different situations. It has
been modified over time to adapt to the evolving fields of pain and palliative
medicine (see Figure 6). This revised approach recommends that mild pain (1-3
on a numerical analogue scale) should be treated with nonopioid pain
relievers, such as aspirin,
acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs), with or
without adjuvant therapy. Higher pain intensities indicate the use of
nonopioid analgesics along with opiate derivatives, such as codeine,
hydrocodone, or tramadol.[25] If pain is not relieved, then titration of
opioids, such as morphine, hydromorphone, and fentanyl, in combination with
nonopioid analgesics and adjuvants is indicated. Refractory pain syndromes
will often require more invasive techniques, such as spinal opioids, nerve
block, or neurostimulation.[1]


    Figure 6. Modification of WHO 3-Step Ladder. Reprinted with permission
from: Fine PG. Anesth Analg. 2005;100:183-188.

Nonopioid Analgesics

Acetaminophen. Acetaminophen has been determined to be one of the safest
analgesics for long-term use in the management of mild pain or as a supplement
in the management of more intense pain syndromes. It is especially useful in
the management of nonspecific musculoskeletal pain or pain associated with
osteoarthritis, but should be considered an adjunct to any chronic pain
regimen. It is often forgotten or overlooked when severe pain is being
treated, but it can be quite effective as a "coanalgesic." It is important to
take into account acetaminophen's limited anti-inflammatory effect and its
hepatic effects. Reduced doses or avoidance of acetaminophen is recommended
for patients with renal insufficiency or liver failure, particularly in
individuals with significant alcohol use.[53,54]

NSAIDs. NSAIDs reduce the biosynthesis of prostaglandins by inhibiting
cyclooxygenase (COX) and the cascade of inflammatory events that cause,
amplify, or maintain nociception. NSAIDs also appear to directly affect the
peripheral and central nervous systems. COX has been identified in spinal cord
neurons, and may play a role in the development of neuropathic pain, but these
agents do not appear to be useful in the treatment of neuropathic pain.[25]
The "classic" NSAIDs (eg, aspirin or
ibuprofen) are relatively nonselective in their inhibitory effects on the
enzymes that convert arachidonic acid to prostaglandins, so gastrointestinal
ulceration, renal dysfunction, and impaired platelet aggregation are
common.[4] The COX-2 selective NSAIDs rofecoxib (Vioxx) and valdecoxib
(Bextra) are now off the market, and, due to potential problems and concerns
with gastrointestinal bleeding and thrombosis, celecoxib (Celebrex) should be
used with caution in high-risk palliative
care patients.[55]

NSAIDs are useful in treating many pain conditions mediated by inflammation,
including those caused by cancer.[58,59] These agents cause minimal nausea,
constipation, sedation, or effects on mental function, although there is
evidence that their use can impair short-term memory in older patients.[58]
These agents may be very useful for moderate-to-severe pain control, either
alone or as an adjunct to opioid analgesic therapy. Adding NSAIDs to an opioid
regime may allow a reduced opioid dose when sedation, obtundation, confusion,
dizziness, or other central nervous system effects of opioid analgesic therapy
alone become problematic.[59] Extended-release formulations are likely to
increase compliance and adherence.[25] As with acetaminophen, decreased renal
function and liver failure are relative contraindications for NSAID use.
Platelet dysfunction or other potential bleeding disorders also contraindicate
use of the nonselective NSAIDs due to their inhibitory effects on platelet
aggregation, a clear advantage of the coxib class of NSAIDs. If NSAIDs are
effective, but there is need for prolonged use or there is a history of
gastrointestinal complications, proton pump inhibitors can be given to lower
the risk of gastrointestinal bleeding.[60]

Opioid Analgesics

Opioid analgesics are the most useful agents for the treatment of pain
associated with advanced disease. They reduce pain-producing signals and
perception throughout the nervous system, regardless of the pathophysiology of
the pain.[61] Opioids exist in 3 classes -- pure agonists, mixed
agonist-antagonist, and pure antagonists.[39] They are classified according to
their interaction with the 3 major opioid receptor types. Pure agonists, which
interact with (mu) receptors in the brain and spinal cord, are generally
preferred for managing moderate-to-severe pain, and have been shown to reduce
pain in a number of neuropathic pain syndromes, contrary to previous
thinking.[62]
Opioids can also be used to treat dyspnea and as an anesthetic adjunct. There
are few, if any, indications for the mixed agonist-antagonist agents. The pure
antagonists are used to treat acute overdose and, in selected cases, as a
means of treating or preventing opioid-induced bowel dysfunction. The opioids
used most commonly in palliative care are morphine, hydromorphone, fentanyl,
oxycodone, and methadone. A sustained-release form of oxymorphone is in the
approval stage and may add to this growing formulary.

The only absolute contraindication to the use of an opioid is a history of a
hypersensitivity reaction (eg, rash, wheezing, and edema). Allergic reactions
are almost exclusively limited to the morphine
derivatives, and the prevalence of true allergic reactions to synthetic
opioids is much lower. There is significant inter- and intraindividual
variation in clinical responses to the various opioids, so dose
titration is the best approach to initial management. Idiosyncratic responses
may require trials of different agents in order to determine the most
effective drug and route of delivery for any given patient.  Table 4 lists
more specific suggestions regarding optimal use of opioids.

  Table 4. Choosing an Opioid: A Matrix of Factors Leading to a "First Best
Choice"
        General Pharmaco-Medical Considerations
        Pharmaco-Clinical Considerations
        Pharmacogenetic Considerations
        Pharmacoeconomi Considerations
        Allergies/sensitivities (e.g., morphine and its derivatives)
        Prior experience (subjective responses and preferences)
        Adherence (compliance) issues
        Social circumstances (cognitive capacity, reliable caregiver, etc.)
Cytochrome P-450 enzyme system genotypes (e.g., "slow metabolizers" at CYP 2D6
ineffectively convert the pro-drug codeine to the active drug morphine)
Insurance coverage and formulary restrictions
        Drug-disease interactions (e.g., renal insufficiency; pulmonary
disease)
        Administration or absorption preferences and limitations (e.g., oral
vs. transdermal formulation; once-a-day dosing vs. multiple dosings per day;
G-tube "sprinkle" formulations) Future possibilities of genotyping to match
patient-specific opioid phenotypes to physiochemically different opioids
Indirect costs (e.g., care-giver time, utilization of clinical services,
treatment of "side effects" such as constipation, etc.)
        Drug-drug interactions (e.g., CNS depressants; MAOI's; SSRI's; shared
metabolic pathways [i.e., inducers and inhibitors of at CYP2D6 and CYP3A4])
Monitor efficacy (e.g., activity, sleep, mood, pain intensity scores)
        Monitor changes in clinical condition (e.g., resolution or progression
of disease; new disease; change in medications) Monitor adverse effects (e.g.,
sedation, nausea, bowel function, ataxia,
cognitive effects, "tolerance"/hyperalgesia)

    Originally published in: Fine PG. Opioid-induced hyperalgesia and opioid
rotation. J Pain Palliat Care Pharmacother. 2004;18:75-79. Reprinted with
permission from Haworth Press, Inc.

Opioid analgesics may accumulate toxic metabolites over time, especially when
drug clearance and elimination decrease as disease progresses and organ
function deteriorates.[63] Use of meperidine is specifically discouraged for
chronic pain management due to its neurotoxic metabolite, normeperidine. [25]
Use of propoxyphene (eg, Darvocet-N 100) is also discouraged due to the active
metabolite norpropoxyphene, its weak analgesic efficacy, and the significant
acetaminophen dose found in some formulations.[64] The mixed
agonist-antagonist agents, typified by butorphanol, nalbuphine, and
pentazocine, are not recommended for the treatment of chronic pain. They have
limited efficacy, and their use may cause an acute abstinence syndrome in
patients using pure agonist opioids.[39,65]

Morphine. Morphine, the prototype agonist, is considered the "gold standard"
of opioid analgesics and is used as a measure for dose equivalence.[39,64]
Although some patients cannot tolerate morphine due to pruritus, headache,
dysphoria, or other adverse effects, common initial dosing effects, such as
sedation and nausea, often resolve within a few days.[4] It is best to
anticipate these adverse effects, especially constipation, nausea, and
sedation, and prevent or treat appropriately (see below).
Morphine-3-glucuronide, a metabolite of morphine, may contribute to myoclonus,
seizures, and hyperalgesia, particularly when patients cannot clear the
metabolite due to renal impairment.[63,66] Side effects and metabolite effects
can be differentiated over time: Side effects generally occur soon after the
drug is absorbed, whereas metabolite effects are generally delayed by several
days. If adverse effects exceed the analgesic benefit of the drug, convert to
an equianalgesic dose of a different opioid. Because cross-tolerance is
incomplete, reduce the calculated dose by one third to one half and titrate
upward based on the patient's pain intensity scores.[4]

  Morphine's bitter taste may be prohibitive, especially if
"immediate-release" tablets are left in the mouth to dissolve. In this case,
several options are available. One available type of long-acting morphine
comes in a capsule that can be opened, releasing small pellets that can be
mixed in applesauce or other soft food.[67] Oral morphine solution can be
swallowed, or small volumes (0.5-1 mL) of a concentrated solution (eg, 20
mg/mL) can be placed in the mouth of patients whose
voluntary swallowing capabilities are significantly limited.[68]

  Fentanyl. Fentanyl is a lipophilic opioid that can be administered
parenterally, spinally, transdermally, transmucosally, and nebulized for the
management of dyspnea.[4] Because of its potency, dosing is usually conducted
in micrograms. It should be noted that on July 15, 2005, the
FDA issued a public health advisory to alert healthcare professionals,
patients, and their caregivers of reports of death and other serious side
effects from overdoses of fentanyl in patients using transdermal fentanyl
(Duragesic) for pain control.[69] Careful fentanyl dosing is particularly
important in older patients; a recent study of transdermal fentanyl in
postoperative patients found that absorption was significantly delayed in men
64-82 years of age compared with men 25-38
years of age.[70]

  In consideration of the aforesaid cautions, transdermal fentanyl, often
called the fentanyl patch, is particularly useful when patients cannot
swallow, do not remember to take medications, or experience adverse effects
from other opioids.[71] Opioid-naive patients should begin with titrated
immediate-release opioids to establish the needed 24-hour dose of opioid
before determining that the lowest available dose, currently a 12-mcg/hour
patch, can be tolerated. Patients should be monitored by a responsible
caregiver for the first 24-48 hours of therapy until steady-state blood levels
are reached. Transdermal fentanyl may not be appropriate for patients with
fever, diaphoresis, cachexia, morbid obesity, and ascites, all of which may
have a significant impact on the absorption, blood levels, and clinical
effects of the drug.[72,73]

  Some patients experience reduced analgesic effects within 48 hours of
applying a new patch. If so, determine whether a higher dose can be tolerated
with increased duration of effect or whether a more frequent (every 48 h)
patch change is the better alternative. Under most circumstances, breakthrough
pain medications should be available to patients using continuous-release
opioids, such as the fentanyl patch. There are several, novel transdermal
fentanyl delivery systems under
development, including ones that allow bolus dosing. There are insufficient
data or experience to make recommendations about their relative safety or
efficacy at this time.

  Oral transmucosal fentanyl citrate (Actiq) is composed of fentanyl on an
oral applicator ("lollipop") to provide rapid absorption of the drug. This
formulation of fentanyl is particularly useful for breakthrough pain.

  Oxycodone. Oxycodone is a synthetic opioid available in a long-acting
formulation (OxyContin), as well as immediate-release tablets (alone or with
acetaminophen) and liquid. It is approximately as lipid-soluble as morphine,
but has better oral absorption.[74] Side effects appear to be similar to those
experienced with morphine, but one study comparing the 2 formulations in
patients with advanced cancer found that oxycodone was less likely to cause
nausea and vomiting.[75] Despite significant media attention to oxycodone and
its role in opioid abuse, there is no basis to infer that it is inherently
"more addicting" than other opioids used in palliative care. Because of this
attention, however, several states have restricted the numbers of tablets that
can be distributed to an individual in a month.

  Methadone. Methadone has several characteristics that make it useful in the
management of severe, chronic pain.[39,76,77] Methadone has a half-life of
24-36 hours with a much longer terminal half-life, allowing for prolonged
dosing intervals. Methadone is an N-methyl-D-aspartate (NMDA) receptor
antagonist, which may be of particular benefit in neuropathic pain.[78,79]
Methadone is much less costly than comparable doses of proprietary
continuous-release formulations, making it potentially more available for
patients without sufficient financial resources for more expensive drugs.

  Despite these advantages, much is unknown about the appropriate dosing ratio
between methadone and morphine, as well as the safest and most effective time
course for conversion from another opioid to methadone.[4] Current data
suggest that the dose ratio increases as the previous dose of oral opioid
equivalents increases, and, although the long half-life is an advantage, it
also increases the potential for drug accumulation prior to achieving
steady-state blood levels.[80] There may
be a risk of oversedation and respiratory depression after 2-5 days of
treatment with methadone. Close monitoring of these potentially adverse or
even life-threatening effects is required.[25,39] Myoclonus has been reported
with methadone use, and recent studies suggest that high doses
of methadone may lead to life-threatening QT interval prolongation (although
it is not clear whether this is due to the methadone or preservatives in the
parenteral formulation).[4]

  Patients currently receiving methadone as part of a maintenance program for
addictive disease often develop cross-tolerance to opioids and require higher
doses than opioid-naive patients.[81] Prescribing methadone for addictive
disease requires a special license in the United States, so prescriptions for
methadone to manage pain in palliative care should specify "for pain."

  Hydromorphone. Hydromorphone (Dilaudid) is a synthetic opioid that can be a
useful alternative to morphine. It is available in oral tablets, liquids,
suppositories, and parenteral formulations, but the only long-acting
formulation was recently recalled by the FDA due to interactions with alcohol
that could lead to excessively rapid drug release.[39,82] As a synthetic
opioid, hydromorphone can be useful if there is inadequate pain control or
when patients experience true allergic responses to morphine or intolerable
side effects occur. The metabolite hydromorphone-3-glucuronide may lead to the
same opioid neurotoxicity seen with morphine metabolites: myoclonus,
hyperalgesia, and seizures.[83] This is particularly likely in patients with
renal dysfunction.[84,85]

  Other Opioids. Codeine, hydrocodone, levorphanol, oxymorphone, and tramadol
are other opioids available in the United States for treatment of pain. See
Table 5 for equianalgesic comparisons.

  Table 5. Pure mu-Agonists Used for Pain in the United States*

http://www.medscape.com/viewarticle/545562_7





  Routes for Administering Opioids
  The oral route is generally preferred when patients are capable and enteral
absorption is not problematic. In the palliative care setting, alternative
routes of administration must be available for patients who can no longer
swallow or when other dynamics preclude the oral route. These include
transdermal, transmucosal, rectal, vaginal, topical, epidural, and
intrathecal. In a study of cancer patients at 4 weeks, 1 week, and 24 hours
before death, over half of the patients required more
than 1 route of opioid administration. As patients approached death and oral
use diminished, the use of intermittent subcutaneous injections and
intravenous or subcutaneous infusions increased.[11]

  Enteral feeding tubes can be used to access the gut when patients can no
longer swallow. The rectum, stoma, or vagina can be used to deliver
medication, although fecal contents, mucosal dryness, thrombocytopenia, or
painful lesions may preclude the use of these routes. For morphine,
commercially prepared suppositories, compounded suppositories, or microenemas
can be used to deliver the drug directly to the rectum or stoma.[86]
Sustained-release morphine tablets have been used rectally, with resultant
delayed time to peak plasma level and approximately 90% of the bioavailability
achieved by oral administration. Because the vagina has no sphincter, a tampon
covered with a condom or an inflated urinary catheter balloon may be used to
prevent early discharge of the drug.[87] Although useful, the rectal or
vaginal routes may be unacceptable to many patients and their caregivers,
especially when the patient is obtunded or unable to assist.[5]

  Parenteral administration in palliative care is usually limited to
subcutaneous and intravenous delivery because repeated intramuscular opioid
delivery is excessively noxious. The intravenous route provides rapid drug
delivery but requires vascular access, which may not be easily obtained or
maintained in a home or long-term care setting. In the absence of intravenous
access, it must be remembered that subcutaneous boluses, although effective,
have a slower onset and lower peak effect when compared with intravenous
boluses.[4] Subcutaneous infusions as much as 10 mL/hour are usually absorbed,
although most patients tolerate 2-3 mL/hour with least difficulty.[88,89]

  Intraspinal routes, including epidural or intrathecal delivery, may allow
administration of drugs, such as opioids, local anesthetics, and/or
a-adrenergic agonists. A recent randomized, controlled trial demonstrated
benefit for cancer patients experiencing pain.[90] However, the equipment used
to deliver these medications is complex, requiring specialized knowledge for
healthcare professionals and potentially greater caregiver burden. Risk of
infection and other complications along with upfront and maintenance costs are
significant concerns when contemplating high-technology procedures. Selection
should be based on greater than 6 months life expectancy for implanted
programmable pumps, and adequate organizational infrastructure to manage these
devices should be in place.

  Adjuvant Therapies
  The term "adjuvant analgesics" is often used synonymously with
"coanalgesics," "pain-modifying drugs," and similar descriptives. A wide
variety of nonopioid medications from several pharmacologic classes have been
demonstrated to reduce pain caused by various pathologic conditions (eg,
tricyclic antidepressants) or to modify the ongoing disease process in a way
that specifically reduces pain (eg, bisphosphonates). Under most
circumstances, these drugs are indicated for the treatment of severe
neuropathic pain or bone pain, and opioid analgesics are used
concurrently to provide adequate pain relief. Typical adjuvants include
tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitor (SNRI)
antidepressants, anticonvulsants, corticosteroids, and other disease-modifying
drugs, such as bisphosphonates for metastatic bone pain. See Table 6 for a
listing of current adjuvant therapies for neuropathic pain.

  Table 6. Adjuvant Therapies for Neuropathic Pain*
        Category/Agents Comments
        Corticosteroids
        Dexamethasone
        Prednisone
        Prednisolone a.. Shown to reduce spontaneous discharge in injured
nerves
          b.. Dexamethasone has the least mineralcorticoid effect (long
duration of action for once-daily dosing)
          c.. May be dosed orally, intravenously, subcutaneously, or
epidurally
          d.. May produce psychosis, proximal muscle wasting

        Anticonvulsants:
        Carbamazepine
        Gabapentin
        Valproate
        Phenytoin
        Clonazepam
        Tiagabine
        Levetiracetam
        Lamotrigine
        Topiramate
        Zonisamide
        Oxcarbazepine

Pregabalin
a.. Older agents are used extensively, but potential for adverse events
requires careful monitoring. Clinical experience is extensive for
carbamazepine, but propensity for bone marrow suppression (ie, leukopenia)
limits its use in patients with cancer

b.. Lamotrigine has demonstrated efficacy in HIV sensory neuropathy, painful
diabetic neuropathy, and poststroke pain, but requires slow titration. Also
associated with Stevens-Johnson syndrome
and severe rash

c.. The role of newer agents (ie, levetiracetam, oxcarbazepine, tiagabine,
etc) has not been established
d.. Gabapentin approved for PHN=20
e.. Pregabalin approved for painful diabetic neuropathy.

        Tricyclic antidepressants:
        Amitriptyline
        Nortriptyline
        Desipramine
        Imipramine
        Clomipramine
a.. Use is associated with significant tolerability issues
b.. Nortriptyline has lesser anticholinergic/anti-alpha-adrenergic effects,
and therefore has better
tolerability, especially in elderly persons
c.. Should be administered at night to reduce daytime sedation and support
good sleep hygiene

        Local anesthetics
        Mexiletine
        Lidocaine IV
a.. Oral lidocaine analogs are effective in some patients, but long-term use
may lead to clinically significant adverse events
b.. Infusional lidocaine is gaining greater acceptance; may be particularly
effective for visceral or central pain
c.. A lidocaine challenge can assess whether a patient's pain is responsive;
ie, 1-3 mg/kg IV or SC over 30-60 min. If challenge is effective or partially
effective, continuous infusion consists of 1-2
mg/kg/hr
d.. Perioral numbness suggests toxicity. Infusion should be halted and
restarted at a slower rate upon resolution

        Anticancer therapies
        Radiation therapy
a.. Local, half-body, or whole-body radiation therapy can enhance efficacy of
analgesia by directly affecting tumor and other causes of pain

        Surgery
a.. Curative excision or palliative debulking of tumor may relieve pain
directly, decrease symptoms of obstruction or compression, and improve
prognosis


    *Adapted and reprinted with permission from: Fine PG, Miaskowski C, Paice
JA. Meeting the challenges in cancer pain. J Support Oncol.
2004;2(suppl4):5-22

  Antidepressants. The analgesic effect of tricyclic antidepressants appears
to be related to inhibition of norepinephrine and serotonin reuptake, making
these neurotransmitters more available within central nervous system pain
inhibitory pathways. There are many significant, controlled clinical trials
for several pain conditions, and a recent consensus panel listed tricyclic
antidepressants as 1 of 5 first-line therapies for neuropathic pain.[91,92]
The significant side effects, especially in older patients, limit the use of
these agents in palliative care, but their sleep-enhancing and mood-elevating
effects may be beneficial enough to outweigh their disadvantages.[93] The
newer mixed SNRIs-selective serotonin reuptake inhibitors (SSRIs), such as
venlafaxine (Effexor) and duloxetine (Cymbalta), may offer some of the
advantages of tricyclic antidepressants without the anticholinergic side
effects.[39]

  Anticonvulsants. The older anticonvulsants, such as carbamazepine and
clonazepam, relieve pain by blocking sodium channels.[93] These compounds are
very useful in the treatment of neuropathic pain, especially pain with
episodic, lancinating qualities. Gabapentin seems to have several different
mechanisms of action, although calcium ion channel blockade is thought to be
its main pain-inhibiting mechanism.[94,95]

  The analgesic doses of gabapentin reported to relieve pain in
non-end-of-life pain conditions ranged from 900 mg/day to 3600 mg/day in
divided doses.[4] A common reason for inadequate relief is failure to titrate
upward after prescribing the usual starting dose of 100 mg by mouth 3 times
daily. Additional evidence supports the use of gabapentin in neuropathic pain
syndromes seen in palliative care, such as thalamic pain, pain due to spinal
cord injury, cancer pain, and restless legs syndrome and HIV-associated
sensory neuropathies.[23,95,96] Withdrawal from gabapentin should be gradual
to prevent possible seizures.[97] Lamotrigine has been effective in
HIV-associated neuropathy, diabetic neuropathy, and poststroke pain. It
requires slow titration and may have
prohibitive side effects, such as Steven-Johnson syndrome and severe rash.[23]
Newer anticonvulsants that have been used successfully in treating
neuropathies include levetiracetam, tiagabine, and oxcarbazepine, but no
randomized, controlled clinical trials are available.[23]

  Corticosteroids. Corticosteroids are particularly useful for neuropathic,
visceral, and bone pain syndromes, including plexopathies and pain associated
with stretching of the liver capsule due to
metastases.[98,99] Dexamethasone produces the least amount of
mineralocorticoid effect, making it the least toxic choice. Dexamethasone is
available in oral, intravenous, subcutaneous, and
epidural formulations. The standard dose is 16-24 mg/day and can be
administered once daily due to the long half-life of this drug, but divided
doses are usually used to mitigate high-dose toxic effects, such as psychosis
and severe blood sugar abnormalities in diabetic patients. Doses as high as
100 mg may be given with severe pain crises, similar to the doses used in
acute neurologic emergencies. Intravenous bolus doses should be administered
over several minutes to reduce untoward reactions, such as burning sensations.

  Local Anesthetics. Local anesthetics are useful for relieving neuropathic
pain. They can be given orally, topically, intravenously, subcutaneously, or
spinally.[23,100] Mexiletine has been reported to be useful when
anticonvulsants and other adjuvant therapies have failed. Doses start at 150
mg/day and increase to levels as high as 900 mg/day in divided doses.[101,102]
Pretreatment electrocardiogram evaluation is recommended to evaluate for
conduction blocks that can be exacerbated by oral local anesthetics. Local
anesthetic gels and patches have been used to prevent the pain that is
associated with needlestick and other minor procedures. Both gel and patch
(Lidoderm) versions of lidocaine have been shown to reduce the pain of
postherpetic neuralgia.[103] Intravenous lidocaine at 1-5 mg/kg (maximum, 500
mg) administered over 1 hour, followed by a continuous infusion of 1-2
mg/kg/hour, has been reported to reduce intractable neuropathic pain in
patients in inpatient palliative care and home hospice settings.[23] Epidural
or intrathecal
lidocaine or bupivacaine delivered with an opioid can reduce neuropathic
pain.[104]

  Bisphosphonates. Bisphosphonates inhibit osteoclast-mediated bone resorption
and alleviate pain related to metastatic bone disease and multiple myeloma,
reduce the incidence of pathologic fractures, and are used to treat
tumor-related hypercalcemia.[105] In patients with breast cancer and multiple
myeloma, zoledronic acid has demonstrated improved safety and efficacy
compared with pamidronate.[106,107] Similarly, there appears to be more
sustained pain relief with zoledronic acid compared with other bisphosphonates
in patients with metastatic prostate cancer.[108] Clinical trials in patients
with lung and renal cell carcinoma have also shown therapeutic benefit from
regular infusions of zoledronic acid.[109]

  Calcitonin. Subcutaneous calcitonin may be effective in the relief of
neuropathic or bone pain, although studies are inconclusive.[110] The nasal
form of this drug may be more acceptable in end-of-life care when other
therapies are ineffective. Usual doses are 100-200 IU/day subcutaneously or
nasally.

  Chemotherapy and Radiation Therapy. Palliative chemotherapy is the use of
antitumor therapy to relieve the symptoms that are associated with malignancy.
Patient goals, performance status, sensitivity of the tumor, and potential
toxicities must be considered.[4] Examples of symptoms
that may improve with chemotherapy include relief of chest wall pain from
reduced tumor ulceration through the use of hormonal therapy in breast cancer.
Similarly, newer agents, such as docetaxel, reduce pain and improve quality of
life in hormone-refractory prostate cancer, and topotecan and epidermal growth
factor receptor inhibitors accomplish similar results for patients with lung
cancers.[111-113]

  Radiation therapy is also a highly useful adjunct to control pain from bone
metastasis and pressure-inducing and ulcerative malignancies. Single-fraction
and hypofractionated regimens are proving to be effective in very sick
patients and those with limited life expectancy in whom the opportunity costs
of multiple treatment sessions are untenable.[114,115] These therapies are
often underutilized in hospice/palliative care, and they should be considered
for any patient with a life expectancy of more than a few weeks.[116]

  Other Adjunct Analgesics. Topical capsaicin has been shown to be useful in
relieving the pain that is associated with postmastectomy syndrome,
postherpetic neuralgia, and postsurgical neuropathic pain in cancer.[98] A
burning sensation experienced by patients is a common reason for discontinuing
therapy.

  Baclofen, a skeletal muscle relaxant, is also useful for the relief of
spasm-associated pain, and it may be helpful in the treatment of intractable
hiccups, which can be painful and cause sleep
disturbance.[117] Doses begin at 10 mg/day, increasing every few days.
Feelings of weakness and confusion or hallucinations often occur with doses
above 60 mg/day. Slow downward titration is necessary to prevent
withdrawal-related seizures.

  Calcium channel blockers are believed to provide pain relief in certain pain
syndromes as well. For instance, nifedipine 10 mg orally may be useful to
relieve ischemic or neuropathic pain syndromes.[118,119] There are few
randomized, controlled clinical trials to support these mostly anecdotal
findings.

  Beginning Therapy, Adding or Changing Drugs, and Breakthrough Pain

  Application of practical and mechanism-based approaches, coupled with
context-appropriate follow-up, will optimize drug and other palliative
therapies. The "best first choice" and subsequent timing of opioid rotation
will depend on patient-specific medical, psychological, and social
considerations and a sound knowledge of opioid pharmacotherapy. Titration and
combining drugs that may provide additive or synergistic effects should
proceed along rational lines, based on the
pharmacokinetics and monitored pharmacodynamics of the drugs. Frail patients
and those with pain crises may require observation in a monitored setting in
order to provide safe and effective relief within an acceptable time frame.

  Transitory flares of pain, or "breakthrough pain," can be expected both at
rest and during movement. If breakthrough pain lasts longer than a few
minutes, rescue doses of the patient's current analgesics may provide
relief.[25] In patients without parenteral access, oral transmucosal fentanyl
may be useful for rapid episodic pain relief or during a brief but painful
dressing change. Adults should start with the 200-mcg dose and monitor
efficacy, advancing to higher dose units as needed.[120] Clinicians must be
aware that, unlike other breakthrough pain drugs, the around-the-clock dose of
opioid does not predict the effective dose of oral transmucosal fentanyl. Pain
relief can usually be expected in about 5-10 minutes after beginning use.
Patients should use oral transmucosal fentanyl citrate over a period of 15
minutes because more active sucking will result in more swallowing and less
transmucosal absorption.

  Because misunderstandings lead to undertreatment, all clinicians involved in
the care of patients with chronic pain must be able to differentiate the
clinical conditions of tolerance, physical dependence, and addiction that come
with the use of opioids. It is also critically important to be aware that
titration of opioid analgesics to affect pain relief is rarely associated with
induced respiratory depression and iatrogenic death. The most compelling
evidence suggests that inadequate
pain relief hastens death by increasing physiologic stress, decreasing
immunocompetence, diminishing mobility, increasing the potential for
thromboembolism, worsening respiratory effort and thus placing the patient at
risk for pneumonia, and increasing myocardial oxygen requirements. In a recent
survey of high-dose opioid use (> 299 mg of oral morphine equivalents) in a
hospice setting, there was no relationship between opioid dose and
survival.[121]

  Minimizing and Managing Adverse Effects
  There are a variety of adverse effects that drugs for pain can cause
patients in palliative care. The normal side effects associated with pain
relief medications are often exacerbated by changes in metabolism caused by
end-stage disease, polypharmacy associated with old age, and other factors.
Below are some of the more common adverse effects seen for these patients, and
an overview of possible approaches to preventing or alleviating them.

  Constipation. Patients in palliative care frequently experience
constipation, in part due to opioid therapy.[44] Always begin a prophylactic
bowel regimen when commencing opioid analgesic therapy. Avoid bulking agents,
such as psyllium, because these tend to increase desiccation time in the large
bowel, and debilitated patients can rarely take in sufficient fluid to
facilitate the action of bulking agents. Instead use cost-effective and
palatable products, such as senna tea and fruit.[39] If this is ineffective at
creating regular laxation, then prescription therapies are indicated (eg,
bisacodyl, senna derivatives, etc). Tables listing recommended regimens are
readily available in
clinical guidelines and texts.

  Sedation. Excessive sedation may occur with the initial doses of opioids. If
sedation persists after 24-48 hours and other correctable causes have been
identified and treated, the use of psychostimulants may be beneficial. These
include dextroamphetamine 2.5-5 mg by mouth every
morning and midday or methylphenidate 5-10 mg by mouth every morning and 2.5-5
mg midday (although higher doses are frequently used, and use later in the day
may be required for wakefulness throughout the evening hours, if desired).[4]
Adjust both the dose and timing to prevent nocturnal insomnia, and monitor for
undesirable psychotomimetic effects (such as agitation, hallucinations, and
irritability). Once-daily dosing of modafinil, a newer agent approved to
manage narcolepsy, has been reported to relieve opioid-induced sedation.[122]

  Respiratory Depression. Respiratory depression is rarely a clinically
significant problem for opioid-tolerant patients who are in pain.[39] When
respiratory depression occurs in a patient with advanced disease, the cause is
usually multifactorial.[123,124] When depressed consciousness occurs along
with a respiratory rate less than 8/minute or hypoxemia (O2 saturation less
than 90%) associated with opioid use, slow, cautious titration of naloxone
should be instituted (0.4 mcg every 3-5 minutes while providing respiratory
support and supplemental oxygen). Excessive administration may cause abrupt
opioid reversal with pain and autonomic crisis.

  Nausea and Vomiting. Nausea is common and vomiting is an occasional adverse
effect associated with opioids due to activation of the chemoreceptor trigger
zone in the medulla, vestibular sensitivity, and delayed gastric emptying, but
habituation occurs in most cases within several days.[125] Assess for other
treatable causes. In severe cases or when nausea and vomiting are not
self-limited, pharmacotherapy is indicated. Usually, low doses of an H1
blocker (eg, diphenhydramine) are all that is required while the patient
habituates to this unpleasant side effect. If there is no relief within a few
days, a different opioid is recommended; also consider transdermal rather than
enteral therapy.

  Myoclonus. Myoclonic jerking can occur with high-dose opioid therapy.[39] If
myoclonus develops, switch to an alternate opioid, especially if using
morphine. Evidence suggests that this symptom is
associated with metabolite accumulation, particularly in the face of renal
dysfunction.[4] A lower relative dose of the substituted drug may be possible,
due to incomplete cross-tolerance. Clonazepam 0.5-1 mg by mouth every 6-8
hours, to be increased as needed and tolerated, may be
useful in treating myoclonus in patients who are still alert, able to
communicate, and take oral preparations.[126] Lorazepam can be given
sublingually if the patient is unable to swallow. Otherwise, parenteral
administration of diazepam is indicated if symptoms are distressing. Grand mal
seizures associated with high-dose parenteral opioid infusions have been
reported and may be due to preservatives in the solution.[127]
Preservative-free solutions should be used when administering high-dose
infusions.

  Pruritus. Pruritus can occur with most opioids, although it appears to be
most common with morphine. Fentanyl and oxymorphone may be less likely to
cause histamine release. Most antipruritus therapies cause sedation, so the
patient must see this as an acceptable trade-off.
Antihistamines (such as diphenhydramine) are the most common first-line
approach to this opioid-induced symptom when treatment is indicated.
Ondansetron and paroxetine have been reported to be effective in relieving
opioid-induced pruritus, but no randomized, controlled studies exist.[128,129]

  After examination and consultation, it is determined that Jerry can continue
to live in the assisted living facility, attended to by home-based hospice
staff. Treatment proceeded with subcutaneous
administration of octreotide and hydromorphone to relieve bowel symptoms and
provide analgesia on an as-needed basis. In this way, the unpleasantness of
nasogastric suctioning, nausea, and vomiting was avoided, and the patient was
able to die in a manner consistent with his preferences.

  Summary
  In summary, effective pain management in advanced medical illness and at the
end of life is a critical component of quality medical care to ensure a
dignified, safe, and comfortable dying. To quote Sir William Osler, the
"father" of modern medicine, "The study of morbid anatomy combined with
careful clinical observations has taught us to recognize our limitations and
to accept the fact that a disease itself may be incurable and that the best we
can do is to relieve symptoms and make the patient comfortable.[130]"

  Principles to help improve this important domain of clinical care can be
summarized with the following key points regarding pharmacotherapy for the
relief of pain in far-advanced illness.

  Principles of Effective Pain Management

    a.. Determine the etiology of pain and the social and prognostic
circumstances that will affect the pain experience and pain therapy.

    b.. Focus on discernible clinical end points:


      a.. Pain reduction
      b.. Functional capacities
      c.. Mood
      d.. Sleep
      e.. Relationships
      f.. Pleasure in living


    c.. Match the mechanism of pain with the class of drug whenever possible;
initiate therapy and adjust dose according to therapeutic response, side
effects, and known pharmacokinetics of the drug.


    d.. Anticipate and monitor for adverse effects:


      a.. Prevent side effects
      b.. Actively treat side effects


    e.. Acetaminophen should be the first consideration in the treatment of
mild-to-moderate pain of musculoskeletal origin.


    f.. Use adjunctive drug therapies, especially for neuropathic pain.


    g.. Opioid analgesic drugs are often necessary to relieve
moderate-to-severe pain, and long-acting or sustained-release analgesic
preparations should be used for continuous pain.


    h.. Breakthrough pain should be identified and treated by the use of
fast-onset, short-acting preparations.


    i.. Lastly, and perhaps most importantly, know your limits. When a patient
is not responding to therapy, be prepared to consult with someone who has more
training, expertise, and experience.


  Original content for this activity was supported by VistaCare and National
Hospice and Palliative Care Organization.

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  Copyright 2006 Medscape.


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

Date:    Thu, 12 Oct 2006 11:56:18 +0200
From:    "Dr. Marc-Alexander Fluks" <fluks@xxx.xx>
Subject: RES,NOT: Parents' empathy for YPWCs

Source: Journal of Pediatric Psychology
        Preprint
Date:   September 29, 2006
URL:    http://jpepsy.oxfordjournals.org/archive/


Brief Report: The Accuracy of Parents for the Thoughts and Feelings of Their
Adolescent Suffering from Chronic Fatigue: A Preliminary Study of Empathy
----------------------------------------------------------------------------
Tine Vervoort(*,1,2) MSC, Geert Crombez(1,2) PHD, Ann Buysse(1) PHD, Liesbet
Goubert(1,2) PHD, Tine De Backer(3) MSc, and William Ickes(4) PHD

1 Department of Experimental-Clinical and Health Psychology, Ghent University,
  Belgium,
2 Research Institute for Psychology and Health, The Netherlands,
3 Zeepreventorium, De Haan, Belgium,
4 Department of Psychology, University of Texas at Arlington, USA
* All correspondence concerning this article should be addressed to Tine
  Vervoort, Department of Experimental-Clinical and Health Psychology,
  Ghent University, Henri Dunantlaan 2, B-9000 Ghent, Belgium.
  E-mail: Tine.Vervoort@Ugent.be.


Objective
This study examined the actual and estimated empathic accuracy (EA) of the
parents of adolescents with chronic fatigue syndrome (CFS).

Methods
The actual EA of both parents (n=24) was assessed in relation to the thoughts
and feelings of their child (n=14) about CFS and about other life events.
Adolescents were also asked to estimate the parents' EA.

Results
For the actual EA, both parents were significantly less accurate regarding
the adolescent's thoughts and feelings about CFS than about other life
events. Fathers were just as empathically accurate as mothers. For the
estimated EA, however, results indicated that adolescents perceived their
mother to be more empathically accurate than their father. Actual EA and
estimated EA about CFS were negatively correlated for fathers, not for
mothers.

Conclusions
Results are discussed in terms of the importance of assessing EA in relation
to other dimensions of empathic understanding and distress in the observer.

Key words
adolescents; chronic fatigue syndrome; empathy; parents.


Introduction

The ability of parents to accurately judge their child's pain and illness
experiences is considered to have adaptive benefits for the child by
fostering tailored care and help (Craig, 2004; Goubert et al., 2005).
However, studies indicate that the accuracy of parental judgments regarding
children's pain and illness experiences is low. Overall, parents
underestimate their child's pain and illness experiences. Waters,
Stewart-Brown and Fitzpatrick (2003) found that when adolescents' reports
were compared with the estimates of their parents, parents were more likely
to estimate less pain, fewer (mental) health problems, and a lesser impact
of their health on family activities. Also, Chambers, Reid, Craig, McGrath
and Finley (1998) found that parents displayed low levels of accuracy in
identifying when their children were experiencing clinically significant
pain.

Despite numerous findings of parental inaccuracy, our understanding of
parental accuracy and its underlying processes remains limited, and is
probably hampered by several issues. Throughout the literature, accuracy has
been defined differently, for example, as level of agreement (Chambers et
al., 1998), intersubjective understanding (Sillars, Koerner, & Fitzpatrick,
2005), or accurate interpretation of infant signals (Ainsworth, 1989). All
of these definitions share an implicit emphasis on the ability of parents to
accurately empathize with their child, that is, to accurately infer the
content of the thoughts and feelings of their child. Most studies, however,
have focused upon the accuracy of symptom report, and not upon the accuracy
of the thoughts and feelings related to illness. It is also not known
whether inaccuracy is specific to understanding the illness experiences of
their child, or whether it extends to other substantial aspects of the daily
life experiences of their child. Furthermore, the focus of studies regarding
the parental assessment of childhood illness is almost exclusively on the
mother-child relationship. The possible differential effects of mother and
father are ignored (Phares, Lopez, Fields, Kamboukos, & Duhig, 2005).
Finally, it is unclear whether actual levels of parental accuracy reflect
estimated or perceived levels of parental accuracy by the adolescent.
Investigating both may shed light on the extent to which parental accuracy
is communicated and translated into parenting behavior towards the child.

To date, no study has explored these issues in parents of ill children.
There is, however, a growing research literature on empathic accuracy (EA)
in the context of other close relationships in adults (Ickes, 2003). This
research focuses on the ability of one person (the perceiver) to accurately
infer the specific content of another person's (the target person's)
thoughts and feelings. Ickes and colleagues (2001) have developed a paradigm
to measure EA. EA is a measure of how accurately perceivers can infer 'on
line' the specific content of other people's thoughts and feelings while
viewing a videotape of the target person in a naturally occurring
conversation with another interaction partner. Accuracy is defined in terms
of the degree to which the content of a perceiver's inference matches the
corresponding content of the target person's actual thought or feeling. To
the best of our knowledge, the EA method has been used widely in adults, but
only once in healthy adolescents (Sillars et al., 2005).

In the present study, this paradigm was used to investigate the EA of
parents with respect to their child with chronic fatigue syndrome (CFS). CFS
is characterized by severe, disabling fatigue, together with a variety of
other symptoms such as muscle pain, sore throat, headache, and concentration
problems (Fukuda et al., 1994). We explored whether parental actual and
estimated EA for the thoughts and feelings of adolescents with CFS varied as
a function of (a) the topic of the adolescent's thoughts and feelings
('illness experience' vs. 'other life events'), (b) the parental perceiver
(mother vs. father), and (c) whether estimated EA reflects actual EA.


METHOD

Participants

Twenty-one adolescents with CFS and their parents were contacted by mail and
invited to participate. They were contacted either through the tertiary care
unit of a regional children's medical centre or through a self-help group
for CFS. Eligibility criteria included: (a) the adolescent was
Dutch-speaking and between the ages of 12 and 20 years; and (b) the
adolescent had been diagnosed with CFS by a physician specialized in CFS.
Fourteen adolescents (response rate 66.6%; 4 boys and 10 girls; mean age ¼
18.1 years, SD=2.4; with four adolescents in the 12-16 year range; mean
duration of CFS=45.8 months, SD=28.9), 2 from the self-help group and 12
from the tertiary care unit, agreed to participate. All 14 adolescents met
inclusion criteria. For four adolescents, the father or the mother was
unable to take part, mainly because of relational problems. The mean age of
the mothers (n=13) and the fathers (n=11) was 46.1 years (SD=4.5) and 49.0
years (SD=5.8), respectively. Most parents (n=12) were married or
co-habiting. Two had parents who were divorced. 79.2% of the parents had a
higher education beyond the age of 18 years. Because both parents did not
always participate, degrees of freedom varied across statistical analyses.


Procedure

A letter explaining the purpose of the study was sent to the adolescents
with CFS and their parents. Next, a researcher phoned all adolescents and
parents to discuss participation. When they agreed to take part, adolescents
and their parents were invited to the tertiary care unit or to a lab at
Ghent University where the study was conducted. Informed consent was
obtained from all parents and adolescents. The procedures used in this study
were approved by the university's institutional review board.


Measures

EA Paradigm
The EA paradigm was used to assess the EA of both the mothers and the
fathers for their child with CFS. The EA paradigm has been shown to be both
valid and reliable (Ickes, 2001, 2003). The measurement of EA involved three
separate phases: collection of the videotape data, collection of the thoughts
and feelings, and the computation of the EA scores.

Collection of the videotape data.

The adolescent was taken into the observation room by the experimenter while
the parents waited in an adjacent room. The experimenter explained to the
adolescent that two interviews of 8 min each, one about CFS and one about
other life events, would be conducted and videotaped. The order of the 2
interviews was counterbalanced across participants. The camera was always
focused on the adolescent's whole body from the same angle and distance. The
adolescents were asked to talk freely about their experiences with 'CFS'
(during the interview about 'CFS') or to talk freely about 'other life
events' (during the interview about 'other life events'). The interviewer
maintained a non-directive and neutral stance as much as possible while
(nonverbally) showing interest and support. When the adolescent stopped
talking during the interview for more than 3 s, the interviewer gave verbal
encouragement by asking one of four standard questions (e.g., for the
interview about 'CFS'; 'Can you describe the impact of CFS upon your
life' or for the interview about 'other life events'; 'Can you tell me
something about your hobbies'). This semi-structured interview technique
differed from the original EA procedure (i.e., videotaping of unstructured
conversation between two interacting partners) as described by Ickes (2001).
After each interview, the adolescents were asked to rate the degree to which
they felt they had been talking about their illness. Ratings were made on an
11-point scale (from 0=not at all to 10=very much).

Collection of the thought/feeling data.
After collecting the videotape data, the adolescents and their parents were
seated in separate areas of a test room and asked to view the videotapes.
Each videotape was stopped by the experimenter every 30 s. At each of these
'stop points' (16 per videotape), the adolescents were asked to provide a
written record of the specific thought or feeling they had experienced at
that point in time, and the parents provided a written inference about the
content of the specific thought or feeling reported by their child at that
point in time. Family members were asked not to discuss their experiences
with each other until the study was complete. They were all encouraged to
write down either their actual thoughts and feelings (adolescent) or their
inferred thoughts and feelings (parents) in a way that would provide the
most accurate and complete report possible.

Computation of empathic accuracy scores.
The EA of each parent was computed by comparing the actual and inferred
thought/feeling entries. EA is an index of the degree to which the content
of the parent's thought/feeling inferences matched the actual content of the
corresponding thoughts and feelings reported by the adolescent (Ickes,
2001). Both the adolescent-generated thought/feeling entries and the
parent-generated thought/feeling entries were typed into word processor
files. Five independent coders compared each of the adolescent's reported
thoughts and feelings with the parent's corresponding inference and rated
their similarity on a 3-point scale, with 0 meaning 'essentially different
content,' 1 meaning 'similar, but not the same, content,' and 2 meaning
'essentially the same content.'

For each video interview, four indexes of EA were computed (EA scores for
'CFS' and 'other life events' for both the mother and the father). To
compute these indices, we first summed the ratings assigned by the five
coders across the 16 thought=feeling inferences within each interview
('CFS' and 'other life events') for each perceiver (mother and father).
These summed values were divided by the total number of coders (5) and by
32, the maximum number of accuracy points that could be obtained in each
phase (i.e., 16 inferences x 2 points possible per inference) to derive
percentage-analogue accuracy scores having a potential range of 0 (no
accuracy) to 100 (perfect accuracy). In the present study, the internal
consistency (Cronbach's alpha) of the five coders' EA ratings was high
(.88), justifying aggregation of ratings across the five coders. The four EA
indices were used as dependent measures in the analyses reported below.


Self-report of Empathic Accuracy

After obtaining the actual EA data, the experimenter asked the adolescent to
respond to two questions with regard to each theme that had been videotaped.
They were asked to estimate how accurate they imagined their mother/father
had inferred their thoughts and feelings with respect to the interviews
about 'CFS' and separately for 'other life events'. Ratings were made on
an 11-point scale (from 0=not at all to 10=very much) and provided indices
of the adolescent's estimated parental EA for both topics.


RESULTS

Manipulation Check

As expected, adolescents reported that they talked significantly less about
their illness in the interview about 'other life events' (M=4.3, SD=2.6)
than in the interview about 'CFS' (M=8.2, SD=1.9), [t(12)=-4.81, p<.0005],
confirming that our manipulation of topic of the interview was effective.


Estimated Empathic Accuracy

Means and standard deviations of estimated EA are displayed in Table I. A 2
(perceiver: mother or father) x 2 (topic: 'CFS' or 'other life events')
within-factor ANOVA was performed for the measure of adolescent- estimated
parental EA. There was a significant main effect of perceiver, [F(1,8)=5.22,
p<.05]: Adolescents estimated that their mother (M=6.8, SD=1.9) was more
likely to have been empathically accurate than their father (M=5.1, SD=1.8).
According to the criteria of Cohen (1988), this effect size is large
(unbiased d=.99, Hedges, 1981). There was no main effect of topic
[F(1,8)=1.84, n.s.] (unbiased d=.30), nor an interaction between topic and
[F(1,8)<1, n.s.).


Actual Empathic Accuracy

Table I displays the summary statistics for actual EA. A 2 (perceiver:
mother or father) x 2 (topic: 'CFS' or 'other life events') ANOVA conducted
for the measure of the parents' actual EA scores revealed no effect of
perceiver and no interaction between topic and perceiver (Fs < 1). However,
there was a significant main effect of topic [F(1,8)=13.65, p<.05]: Actual
EA scores were lower with respect to the adolescents' 'CFS'-relevant
thoughts and feelings (mean for mothers=31.9%; mean for fathers=28.8%) than
with respect to the adolescents' 'other life events'-relevant thoughts and
feelings (mean for mothers=41.2%; mean for fathers=43.0%). The effect size
for this effect was large for both the mother (unbiased d=.71) and the
father (unbiased d=1.22).


Correlations between Estimated and Actual EA

Pearson correlation coefficients between the actual EA and the estimated EA
by the adolescents (for both topic and both perceivers; i.e., four
correlation coefficients) were computed. Results revealed a significant
negative correlation between the actual EA of the father for the thoughts
and feelings of their child related to CFS and the corresponding estimated
EA by the adolescent (r=-.63, p<.05). All other correlations yielded no
significant effects.


DISCUSSION

A first aim of the current study was to determine whether parental actual
and estimated EA for the thoughts and feelings of their child differs with
respect to the topic of the adolescent's experiences. A second aim was to
examine whether mothers and fathers are similarly or differentially accurate
(actual and estimated) in inferring their child's thoughts and feelings. A
final aim of this study was to explore whether the EA estimated by perceiver
the adolescent reflects the actual EA of the mother or father, respectively.

An important general finding was that both parents were less accurate with
respect to 'CFS' thoughts and feelings than for those pertaining to
'other life events'. There are several possible reasons for this finding.
First, the nature of the illness is 'mysterious' (Richards, 2000), and its
effects upon the adolescent are not always visible and observable, making it
difficult to infer such thoughts and feelings. Second, although it is common
to socially share many emotional experiences, individuals with chronic
illnesses may sometimes be reluctant to share their illness experiences
because they fear burdening others with their problems (Herbette & Rime,
2004), or because they want to present themselves as competent and not
different from healthy peers (Morley, Doyle, & Beese, 2000). Third, research
on EA within close relationships has shown that perceivers are sometimes
motivated to be empathically inaccurate in cases when accurate knowledge of
the other person's thoughts and feelings might be personally distressing
(Simpson, Blackstone, & Ickes, 1995). In the present case, it is possible
that parents were less accurate about their child's CFS-related thoughts and
feelings as a means of avoiding distress and the frustration of not being
able to provide sufficient help. Crombez and Eccleston (2002) have proposed
a similar explanation for the often-found underestimation of pain in
children by their parents.

We also found that, although the adolescents believed that their mothers
were more empathically accurate than their fathers, the results of the EA
paradigm showed that the fathers and mothers were equally accurate in
inferring the specific content of their child's thoughts and feelings. The
finding that fathers were, overall, as empathically accurate as mothers,
despite being perceived as less empathically accurate, is in line with other
findings. These indicate that there are no overall gender differences in EA
(Ickes, Gesn, & Graham, 2000), although women are generally being perceived
as much more empathically accurate than men (Ickes, 2003). Possibly, the
ability to be empathically accurate might be differentially used by fathers
and mothers, giving rise to the adolescents' belief that their mothers are
more empathically accurate than their fathers. Fathers might be less
communicative and less inclined to act upon their knowledge compared to
mothers, especially with regard to illness-related issues of their child
(Seiffge-Krenke, 2002). Also, parental acknowledgment of illness-related
thoughts and feelings of the child might, as suggested above, create
distress. This might enhance the tendency for fathers to seek the benefit of
withdrawal, whereas mothers might seek the benefit of engagement (Buysse et
al., 2000). Our finding that paternal actual EA for CFS-related thoughts and
feelings of the child is significantly negatively correlated with
corresponding estimated EA by the adolescent further corroborates this idea.

To our knowledge, this is the first study investigating EA in parents of
chronically ill adolescents. This EA approach offers new avenues for
research. In particular, investigating EA in relation to observational
measures of child-parent interactions is encouraged, to disentangle the
different components (i.e., cognitive, affective and behavioral) of empathic
understanding and its implications for child and family functioning (see
e.g., Sillars et al., 2005). Furthermore, efforts should be dedicated to
investigating why some parents are more empathically accurate than others. A
recently described model of empathy for pain, (Goubert et al., 2005)
emphasizes the importance of investigating the impact of bottom-up factors
(i.e., features of the child such as verbal and nonverbal expressions),
top-down factors (i.e., features of the parents' knowledge and other
dispositions such as prior personal experiences), and contextual factors
(such as the child's age or developmental status) upon empathic
understanding. There are, however, some limitations to the study. First,
this study was cross- sectional. We were not able to infer causal
relationships. Second, the results need replication, because of the small
sample size. Low statistical power could have resulted in the detection of
large rather than medium or small effect sizes. Third, extended measures of
perceived empathy are needed, beyond our one-item scale. Single-item scales
are less reliable and decrease the statistical power to detect differences.
Fourth, our sample comprised many more females than males, which might have
impacted upon the results of this study. Finally, as we did not use a
comparison group, it is not clear whether these results are specific to CFS
or may be true for other chronic illnesses or the general population.


Acknowledgments

T.V. is a Doctoral student of the Fund for Scientific Research - Flanders
(Belgium) (FWO). L.G. is Post-doctoral fellow of the Fund for Scientific
Research - Flanders (Belgium) (FWO).

Conflict of Interest: None declared.

Received November 23, 2005; revisions received May 8, 2006 and August 18,
2006; accepted September 7, 2006


Table

Table I. Means (M) and standard deviations (SD) for the actual (range 0-100) and estimated
      (range 0-10) empathic accuracy (EA) for topic ('CFS' vs.'other life events') and
      perceiver (mother vs. father)
---------------------------------------------------------------------------------------------
        Actual EA                                   Estimated EA
        -----------------------------------------   -----------------------------------------
        CFS                   Other life events     CFS                   Other life events
        -------------------   -------------------   -------------------   -------------------
        n   M (SD)            n   M (SD)            n   M (SD)            n   M (SD)
---------------------------------------------------------------------------------------------
Father  11  28.18 (13.23)     10  43.00 (9.61)      11  4.90 (1.87)       10  5.30 (1.70)
Mother  13  31.92 (15.23)     12  41.17 (8.62)      13  6.38 (1.98)       12  7.17 (1.80)
---------------------------------------------------------------------------------------------


References

Ainsworth, M. D. S. (1989). Attachments beyond infancy. American
  Psychologist, 44, 709-716.
Buysse, A., De Clercq, A., Verhofstadt, L., Heene, E., Roeyers, H., & Van
  Oost, P. (2000). Dealing with relational conflict: A picture in
  milliseconds. Journal of Social and Personal Relationships, 17, 574-597.
Chambers, C. T., Reid, G. J., Craig, K. D., McGrath, P. J., & Finley, G. A.
  (1998). Agreement between child and parent reports of pain. Clinical
  Journal of Pain, 14, 336-342.
Cohen, J. (1988). Statistical power analysis for the behavioural sciences.
  San Diego, CA: McGraw-Hill. Craig, K. D. (2004). Social communication of
  pain enhances protective functions: A comment on Deyo, Prkachin and Mercer.
  Pain, 107, 5-6.
Crombez, G., & Eccleston, C. (2002). To suppress or express may be function
  of others' distress. Behavioral and Brain Sciences, 25, 457-458.
Fukuda, K., Straus, S. E., Hickie, I., Sharpe, M. C., Dobbins, J. G., &
  Komaroff, A. (1994). The international Chronic Fatigue Syndrome Study
  Group. The chronic fatigue syndrome: A comprehensive approach to its
  definition and study. Annals of Internal Medicine, 121, 953-959.
Goubert, L., Craig, K. D., Vervoort, T., Morley, S., Sullivan, M. J. L.,
  Williams, A., et al. (2005). Facing others in pain: The effects of
  empathy. Pain, 118, 285-288.
Hedges, L. V. (1981). Distribution theory for Glass's estimator of effect
  size and related estimators. Journal of Educational Statistics, 6, 107-128.
Herbette, G., & Rime´, B. (2004). Verbalization of emotion in chronic pain
  patients and their psychological adjustment. Journal of Health Psychology,
  9, 661-676.
Ickes, W. (2001). Measuring empathic accuracy. In J. A. Hall, & F. J.
  Bernieri (Eds.), Interpersonal sensitivity: Theory and measurement (pp.
  219-241). Mahwah NJ: Erlbaum.
Ickes, W. (2003). Everyday mind reading: Understanding what other people
  think and feel. Amherst, NY: Prometheus Books.
Ickes, W., Gesn, P. R., & Graham, T. (2000). Gender differences in empathic
  accuracy: Differential ability or differential motivation. Personal
  Relationships, 7, 95-109.
Morley, S., Doyle, K., & Beese, A. (2000) Talking to others about pain:
  Suffering in silence. In M. Devor, M. C. Rowbotham, & Wiesenfeld-Hallin, Z.
  (Eds.), Proceedings of the ninth world congress on pain, progress in pain
  research and management (Vol. 16, pp. 1123-1129). Seatlle, WA: IASP.
Phares, V., Lopez, E., Fields, S., Kamboukos, D., & Duhig, A. M. (2005). Are
  fathers involved in pediatric psychology research and treatment? Journal of
  Pediatric Psychology, 30, 631-643.
Richards, J. (2000). Chronic fatigue Syndrome in children and adolescents: a
  review article. Clinical Child Psychology and Psychiatry, 5, 31-51.
Seiffge-Krenke, I. (2002). 'Come on, say something, Dad!': Communication
  and coping in fathers of diabetic adolescents. Journal of Pediatric
  Psychology, 27, 439-450.
Sillars, A., Koerner, A., & Fitzpatrick, M. A. (2005). Communication and
  understanding in parent­ adolescent relationships. Human Communication
  Research, 31, 102-128.
Simpson, J. A., Blackstone, T., & Ickes, W. (1995). When the head protects
  the heart: Empathic accuracy in dating relationships. Journal of Personality
  and Social Psychology, 69, 629-641.
Waters, E., Stewart-Brown, S., & Fitzpatrick, R. (2003). Agreement between
  adolescent self-report and parent reports of health and well-being: Results
  of an epidemiological study. Child Care Health and Development, 29, 501-509.

--------
(c) 2006 Oxford University Press
(c) 2006 Society of Pediatric Psychology


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

Date:    Thu, 12 Oct 2006 17:49:56 +0200
From:    Jan van Roijen <j.van.roijen@xxxxx.xx>
Subject: act,med: FDA & Pharmaceutical Industry

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


Send an Email for free membership
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http://www.newstarget.com/z019717.html


NewsTarget.com printable article

Originally published July 21 2006


FDA's own scientists report pattern of intimidation,
censorship and scientific fraud that undermines public safety
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~



In a truly astonishing survey just released by the Union of
Concerned Scientists, the Food and Drug Administration's own
scientists describe the agency as an environment of
intimidation, censorship and scientific fraud. A survey of 997
FDA scientists revealed that forty percent feared "retaliation" for
voicing safety concerns over prescription drugs in public. Over
one-third of the scientists didn't even feel safe expressing safety
concerns inside the agency, behind closed doors!

Intimidation and censorship have been well documented at the
FDA, and this survey adds further weight to the evidence that the
FDA has been utterly co-opted by the pharmaceutical industry
and now serves Big Pharma's commercial interests rather than
anything resembling a commitment to honest science or public
safety. Time and time again, it has been the courageous actions
of independent FDA scientists, taking a stand despite intense
intimidation and censorship from the agency's top officials, who
have warned the U.S. public about dangerous prescription drugs
like Vioxx.

Literally tens of millions of Americans have been harmed by
FDA negligence over the last decade, and well over one million
have been killed by FDA-approved prescription drugs -- many of
which were approved based on fraudulent scientific data the
FDA conveniently chose to overlook. Through its abandonment
of public safety and scientific integrity, the FDA has now
become the single greatest threat to the health and safety of the
American people, dwarfing any threat posed by terrorists.


The FDA's nuclear bomb

Imagine a nuclear bomb detonating over Seattle, Washington. A
hundred thousand citizens might be instantly killed, and two
million (or more) could be seriously injured from the fallout. As
horrific as that image may seem, this is what happens in
America every single year from prescription drugs under the
watch of the FDA. Allowing the FDA to continue operating as it
does today kills as many Americans as detonating a nuclear
weapon over a major U.S. city each year.

And yet most lawmakers and government officials pretend the
big threat to the safety of Americans is found somewhere else,
in a foreign land, rather than right here at home. If anyone in the
Bush Administration really cared about protecting the lives of
Americans, they would summon the military to surround the FDA
and start arresting the criminal-minded officials who run the
agency. It is time to hold FDA decision makers accountable for
the chemical warfare they have waged against the American
public, and at the same time set free the honest FDA scientists
so they can tell the truth without fear of being silenced.


Scientific fraud is routine at the FDA

Because right now, many of those scientists are being routinely
intimidated to alter their conclusions in order to fit the political
agenda of top FDA officials. A shocking 18.4 percent of
scientists surveyed report that they "...have been asked, for
non-scientific reasons, to inappropriately exclude or alter
technical information or their conclusions in a FDA scientific
document."

In this environment of such scientific fraud, reported first-hand by
FDA scientists, to imagine that our system of drug approvals
has anything to do with "evidence-based medicine" is nothing
short of preposterous. All the billions of dollars in advertising,
propaganda, donations to politicians and bribery of doctors can't
cover up the sobering truth: The drug industry today is a massive
criminal enterprise operating in broad daylight, and the FDA is
its chief enforcer. It has nothing to do with honesty, integrity or
even health, but everything to do with generating obscene
profits, exploiting patients and controlling information through
intimidation.

Sixty-one percent of the respondents, the survey results show,
knew of cases where "Department of Health and Human
Services or FDA political appointees have inappropriately
injected themselves into FDA determinations or actions."

Is it really any surprise? The politicians are running the FDA, and
crimes against the American people (which would be
considered terrorism or treason if committed by anyone else)
are routinely overlooked.


Lame proposals for reform don't cut it

Across the nation, to anyone who has been paying attention,
we're beyond the point of realizing that something needs to be
done about the FDA. But every proposal I've seen so far falls
short of solving the problem. They're little more than a collection
of wimpy wrist slaps that try to force the FDA to act with integrity
while ignoring the culture of corruption and criminal-minded
behavior that characterizes the agency's top officials.

These prescriptions for reforming the FDA mirror conventional
medicine's flawed philosophy, by the way, by focusing on
treating symptoms while ignoring the root causes of disease. At
the FDA, the continued pattern of scientific fraud, intimidation
and censorship is only a symptom of a deeper, fundamental
problem: The fact that top FDA officials are, in fact, corrupt,
criminal-minded bureaucrats who are responsible for the deaths
of countless Americans. You can't cure this cancer by treating its
symptoms; you have to get rid of the cause of the cancer.

We don't merely need reform, we need prosecutions. We need
to hold these FDA officials accountable for their crimes against
the children, adults and senior citizens of this country who have
been needlessly harmed (and killed) by prescription drugs that
the FDA absolutely knew were dangerous.

We are not talking about crimes of money here. This isn't some
Martha Stewart insider stock trading scandal, or even an
Enron-class hoodwinking of shareholders. The damage done by
the FDA is way beyond the realm of finances. Our family
members are dead due to FDA negligence. Our brothers and
sisters, daughters and sons, and even many of our parents have
been outright killed by a homicidal system of medicine that
maximizes Big Pharma profits at the expense of human life... a
system whose key architect is the unapologetically corrupt Food
and Drug Administration.


Who will declare the Emperor has no clothes?

Almost no politician, it seems, has the courage to stand up and
speak the truth about the FDA. Drug company money for
reelection campaigns is simply too valuable. Sen. Charles
Grassley, however, is an exception to the rule. He continues to
speak out against the FDA and push for serious reform.
Likewise, Rep. Ron Paul, a lifelong champion of freedom in all
its forms, continues to support the Health Freedom Protection
Act, a bill that would help end FDA tyranny and restore health
freedom to the people.

As Americans, we must declare an end to FDA tyranny and
demand our own Nuremberg-style trials for disgraced FDA
officials. I'm sure Dr. David Graham and other key FDA
scientists would be more than willing to testify at such a trial, if
the nation could ever find the courage to subject the FDA to the
scrutiny of real justice.

Personally, I don't understand why Americans continue to
tolerate tyranny in medicine. They witness the events of
September 11 and rally for war on somebody -- anybody -- but
when our own drug companies kill a hundred times as many
Americans right here at home, all they do is sign up in droves for
the latest Medicare discount drug sham. It's almost as if the
more drugs are prescribed, the more the American people are
losing consciousness, and they are left as mind-numbed
zombies who can only follow orders, but can never question the
reality spoon-fed to them by a Big Pharma-controlled news
media.

Because we know the "official" information sources these days
are mostly spouting utter nonsense. In this FDA survey, for
example, only 47 percent of the scientists think the "FDA
routinely provides complete and accurate information to the
public." Think about that for a minute. It means that 53 percent
believe the FDA provides inaccurate information to the public!

And yet mainstream news sources continue to parrot FDA
warnings, press releases and press conferences as if the
agency possessed something resembling authority. In reality, it
has no authority whatsoever, only tyranny. It rules through
intimidation and censorship, not good science and public
education. As a result, it has no genuine authority, and no one
who is aware of the facts of the situation assigns any kind of
credibility to the agency. The FDA is simply one more rogue
extension of a federal government that has become a
considerable threat to the very people it was supposed to
protect and serve.

Prescription drug deaths: The silent holocaust

So why isn't the public up in arms? Why aren't we rallying for war
against the FDA? Because the deaths are silent. There's no
footage for the evening news: No explosions, no missile attacks,
and no crumbling high-rise buildings... just millions of Americans
dying in their hospital beds after succumbing to prescription
drugs the FDA assured them were perfectly safe. It's a silent
chemical holocaust. And there's nothing to film for the evening
news... nothing the viewers will want to see or admit to, anyway.
But you can visualize it in this way. Imagine if the FDA owned a
B2 stealth bomber armed with nuclear weapons manufactured
by pharmaceutical companies. Imagine that each year, it flew the
stealth bomber over a major U.S. city and dropped a nuclear
bomb directly onto the civilian population. Consider the number
of deaths and injuries that would follow. That's what's happening
right now in terms of the number of people killed each year by
FDA negligence.

With FDA-approved toxic chemicals now the dominant form of
so-called medicine in the United States, we are nuking our own
population with chemicals that will ultimately harm them or kill
them. To call this "scientific medicine" stretches the very
definition of absurdity.

I have to wonder: Would the people demand reform if the FDA
actually conducted nuclear bombing raids on U.S. cities? Would
lawmakers finally stand up and say the FDA should stop
bombing our cities? Or would the FDA brush off the critics and
simply slap a black-box warning label on the side of the B2
stealth bomber that said, "Warning: This bomb may kill you," and
then continue the bombing runs?

As long as powerful corporations keep making money, it
appears that nothing can stop this chemical warfare being
waged against the American people. No number of deaths is
too high, it seems, for a conspiracy of medicine that trades lives
for dollars with each passing minute. Shame on the FDA, Big
Pharma and every single person who continues to draw a
paycheck (or a cash bribe) from these organizations of evil. To
continue working for these organizations is to actively contribute
to a system that exploits living persons, that has no regard for
the value of a human life, and that drains the health and cash of
our fellow human beings in order to maximize profits for
corporate shareholders.

So I have a question. Why do we still tolerate the actions of this
Food and Drug Administration when it is so blatantly engaged in
crimes against humanity? Why isn't the FBI conducting armed
raids on the agency right now and marching these criminals
away in handcuffs?

And when do the FDA trials start? Because when they begin, I
want a front row seat.




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

Date:    Thu, 12 Oct 2006 14:31:23 -0700
From:    "Greg Crowhurst <gregcrowhurst@xxxxx.xx.xx>..........via Co-Cure moderators"
Subject: MED, ACT: Caring for someone with severe ME/CFS

I am compiling a carer's diary, trying to show the reality and the issues of
caring for someone with  severe ME/CFS. Part one is available to view on
YouTube :

http://www.youtube.com/watch?v=LGsHr3x9pVE

Greg Crowhurst


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

Date:    Thu, 12 Oct 2006 23:50:38 -0400
From:    Co-Cure Moderator <ray@xxxxx.xxx>
Subject: NOT,MED: Safety-related drug labeling changes for September 2006 [US]

MedWatch - The FDA Safety Information and Adverse Event Reporting Program

Safety-related drug labeling changes for September 2006 have been posted
on the MedWatch website. The September 2006 posting includes 39 drug
products with safety labeling changes to the BOXED WARNING,
CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, or ADVERSE REACTIONS sections.

The Summary page --

http://www.fda.gov/medwatch/SAFETY/2006/sep06_quickview.htm

-- provides drug names and a listing of the sections changed.

The Detailed view --

http://www.fda.gov/medwatch/SAFETY/2006/sep06.htm

-- includes sections/subsections changed and a description of new or
modified safety information in the Boxed Warning, Contraindications, or
Warnings sections. The full labeling may be accessed by clicking on the
drug name in the detailed view.

The following drugs had modifications to the BOXED WARNING,
CONTRAINDICATIONS, and/or WARNINGS sections:

Seroquel (quetiapine fumarate) Tablets
Cordarone (amiodarone HCl) Tablets
Lopressor (metoprolol tartrate tablets and injection, USP)
Lopressor HCT (metoprolol tartrate, USP and hydrochlorothiazide, USP)
Tablets
Abilify (aripiprazole) Tablets and Oral Solution
Avastin (bevacizumab) for Intravenous Use
Concerta (methylphenidate hydrochloride) Extended-Release Tablets
Cymbalta (duloxetine hydrochloride) Delayed-Release Capsules
Effexor (venlafaxine hydrochloride) Tablets
Effexor XR (venlafaxine hydrochloride) Extended- Release Capsules
Ethrane (enflurane, USP) Liquid for Inhalation
Lamictal (lamotrigine) Tablets
Lamictal (lamotrigine) Chewable Dispersible Tablets
Magnevist (brand of gadopentetate dimeglumine) Injection
Neumega (oprelvekin)
Ortho Evra (norelgestromin/ethinyl estradiol transdermal system)
Prozac (fluoxetine capsules and oral solution, USP)
Symbyax (olanzapine and fluoxetine HCl capsules)
Zarontin (ethosuximide) Capsules

The following drugs had modification to patient information labeling
[either Medication Guide or Patient Package Insert]:

Cordarone (amiodarone HCl) Tablets
Lamictal (lamotrigine) Tablets
Lamictal (lamotrigine) Chewable Dispersible Tablets


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

Date:    Fri, 13 Oct 2006 00:32:37 -0400
From:    Co-Cure Moderator <ray@xxxxx.xxx>
Subject: NOT,MED: Pharmacotherapy for CFS

Pharmacotherapy for CFS
by Loretta Spotila, PhD

10-04-2006

This article is reproduced from The Science & Research of CFS, a special
issue of the CFIDS Chronicle, with kind permission of the CFIDS Association
of America. For a summary of this 65-page publication's many other superb
expert reports on worldwide CFS-related research findings, theories, and
best treatment practices, browse through the table of contents at the CFIDS
Association Website. Copies are available for $12, and online access to a
number of articles is free of charge.

Relatively few research studies or clinical trials have been done on
prescription drugs, supplements or herbal remedies for treating Chronic
Fatigue Syndrome. In fact, no prescription drugs have been developed
specifically to treat CFS. Here, we review the research done thus far and
the best options for patients.
Note - this review also includes the following charts and related reports,
which are cited in the text:

* "Medications for Treating CFS"  a chart listing commonly prescribed drugs

* "What's Been Studied?"  a chart reviewing studies of prescription and
nonprescription therapies for CFS patients

* "Galantamine Hydrobromide Tested for Sleep and Cognition"

* "On the Frontier: Two Studies Suggest Oral NADH May Be Helpful in
Treating CFS"

There is no known cause and no known cure for Chronic Fatigue Syndrome
(CFS). Despite the complexity and mystery of this disease, there are a
number of therapies available that target one or more of the
endocrinological, neurological, immunological or psychological effects of CFS.

Read the complete article at
http://www.immunesupport.com/library/showarticle.cfm?ID=7360

[AOL: <a
href="http://www.immunesupport.com/library/showarticle.cfm?ID=7360">Here</a>]


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Date:    Fri, 13 Oct 2006 00:37:34 -0400
From:    Co-Cure Moderator <ray@xxxxx.xxx>
Subject: MED: Help for Choosing a Pain Management Physician or Clinic & More

Help for Choosing a Pain Management Physician or Clinic & More
by the American Pain Foundation

10-04-2006


If your current treatment is not working, or if your pain is getting worse,
it's probably time to see a pain specialist. Pain management doctors have
completed additional training in pain medicine, giving them a specialized
understanding of the diagnosis and treatment of disorders that cause all
types of pain. Pain specialists use a variety of treatment options to
manage pain, and strive to improve patients' quality of life.
Below is a list of organizations that may be useful to contact as you look
for pain doctors in your area:


The full text of this article is available at
http://www.immunesupport.com/library/showarticle.cfm?ID=7358

[AOL: <a
href="http://www.immunesupport.com/library/showarticle.cfm?ID=7358">Here</a>]


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Date:    Fri, 13 Oct 2006 05:51:56 -0400
From:    "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx>
Subject: RES: Effects of balneotherapy on serum IL-1, PGE(2 )and LTB  (4) levels in fibromyalgia patients

Effects of balneotherapy on serum IL-1, PGE(2 )and LTB (4) levels in
fibromyalgia patients.

Rheumatol Int. 2006 Oct 11; [Epub ahead of print]

Ardic F, Ozgen M, Aybek H, Rota S, Cubukcu D, Gokgoz A.

Department of Physical Medicine and Rehabilitation, Faculty of Medicine,
Pamukkale University, Denizli, Turkey.

PMID: 17033835


The purpose of this study was to investigate the clinical effects of
balneotherapy in the treatment of Fibromyalgia Syndrome (FMS) and to
determine if balneotherapy influences serum levels of inflammation markers,
IL-1, PGE(2 )and LTB(4).

24 primary fibromyalgia female patients diagnosed according to American
College of Rheumatology criteria were included to the study. Their ages
ranged between 33 and 55 years. FMS patients were randomly assigned in two
groups as, group 1 (n = 12) and group 2 (n = 12). Group 1 received 20-min
bathing, once in a day for five days per week. Patients participated in the
study for 3 weeks (total of 15 sessions) in Denizli. Group 2 did not
receive balneotherapy. FMS patients were evaluated by tenderness
measurements (tender point count and algometry), Visual Analogue Scale,
Beck's Depression Index, Fibromyalgia Impact Questionnaire. Ten healthy
women recruited group three as the controls. Serum PGE(2), LTB(4) and
IL1-alpha levels were measured in all three groups. The biochemical
measurements and clinical assessments were performed before and at the end
of general period of therapy.

Statistically significant alterations in algometric score, Visual Analogue
score, Beck's Depression Index and PGE(2) levels (P < 0.001), numbers of
tender points (P < 0.01) and Fibromyalgia Impact Questionnaire score (P <
0.05) were found after the balneotherapy between group 1 and 2. Mean PGE(2)
level of FMS patients were higher compared to healthy control group (P <
0.0001) and decreased after the treatment period, only in group 1 (P <
0.05). As in the group 2 and 3, detectable IL-1 and LTB(4) measurements
were insufficient, statistical analysis was performed, only in group 1.
After balneotherapy IL-1 and LTB(4) significantly decreased in group 1 (P <
0.05).

In conclusion, balneotherapy is an effective choice of treatment in
patients with FMS relieving the clinical symptoms, and possibly influencing
the inflammatory mediators.


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Date:    Fri, 13 Oct 2006 17:39:52 +0200
From:    Jan van Roijen <j.van.roijen@xxxxx.xx>
Subject: not,res: Holiday Cards -Research Support

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


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>>    13 October 2006      <<<<
Editorship : j.van.roijen@chello.nl
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~

From: GAILRONDA@aol.com




Holiday Cards to Support Research
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~


The National CFIDS Foundation i selling beautiful holiday cards
to support research as well as to inform people about this
devastating illness.  The card's greeting say "Season's
Greetings" and, in smaller type, "May the new year bring good
health and happiness!".  The card offers an informative
explanation of ME/CFIDS on the back of the full color
photograph.

The full color picture on heavy card stock is a photograph of
Hurricane Ridge on the Olympic Peninsula of Washington State
taken by Diane R. Rose.  She has had CFIDS/ME for 15 years.
Nine years ago, her illness became so debilitating she could no
longer keep her high tech career.  She turned her photography
hobby into a part-time business that offers her flexibility to work
around her illness.

The prices for the holiday cards include shipping costs and all
international orders must be placed online.  A picture of the card
can be viewed at our website: http://www.NCF-NET.org.



For better health,

Gail Kansky
President, National CFIDS Foundation, Inc.
103 Aletha Rd.
Needham, MA 02492-3931


~~~~~~~~~~


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Date:    Sat, 14 Oct 2006 11:18:48 -0400
From:    Fred Springfield <fredspringfield@xxxxx.xxx>
Subject: RES: Treatment of patients with the chronic-fatigue syndrome

[Treatment of patients with the chronic-fatigue syndrome]
[Article in Dutch]

Journal: Ned Tijdschr Geneeskd. 2006 Sep 23;150(38):2067-8.

Authors: Jonker K, van Hemert AM.

Affiliation: Parnassiagroep-PsyQ, afd Somatiek en Psyche, Den Haag.

NLM Citation: PMID: 17036854


In the last few years, the chronic-fatigue syndrome has been recognised as
an important health problem. In a recent report, the Health Council of the
Netherlands suggested that the capacity for treatment be increased.
Cognitive behavioural therapy and graded exercise training are treatment
options of first choice.

A recently published, uncontrolled evaluation of a Dutch clinical
rehabilitation programme based partly on these methods proved to be
successful. Unfortunately, due to the uncontrolled character of the study,
it remains unclear which elements in the treatment were responsible for the
success. Which patients should be included in a costly clinical
rehabilitation programme also remains unclear.

More in general, there is room for empirical studies of treatment
allocation, not in the least because of the frequently occurring
comorbidity. Good progress has been made in the treatment of the
chronic-fatigue syndrome, but we are still far removed from evidence-based,
stepped care, treatment programmes.


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Date:    Sat, 14 Oct 2006 11:22:17 -0400
From:    Fred Springfield <fredspringfield@xxxxxx.xxx>
Subject: RES: Favourable results of a rehabilitation programme with  cognitive behavioural therapy and graded physical activity in patients  with the chronic-fatigue syndrome

[Favourable results of a rehabilitation programme with cognitive
behavioural therapy and graded physical activity in patients with the
chronic-fatigue syndrome]
[Article in Dutch]

Journal: Ned Tijdschr Geneeskd. 2006 Sep 23;150(38):2088-94.

Authors: Torenbeek M, Mes CA, van Liere MJ, Schreurs KM, ter Meer R,
Kortleven GC, Warmerdam CG.

Affiliation: Het Roessingh, Centrum voor Revalidatie, divisie
Pijnrevalidatie, Enschede. m.torenbeek@roessingh.nl

NLM Citation: PMID: 17036861


OBJECTIVE: To determine whether a specific course of interdisciplinary
rehabilitation might lead to clinically significant changes in fatigue,
experienced disability and physical function in patients with the
chronic-fatigue syndrome (CFS). DESIGN: Prospective and uncontrolled.

METHOD: 'Het Roessingh', a rehabilitation centre in Enschede, the
Netherlands, has developed an interdisciplinary clinical rehabilitation
programme for patients with CFS in cooperation with the 'Nijmeegs
Kenniscentrum Chronische Vermoeidheid' [Chronic-Fatigue Knowledge Centre]
in Nijmegen, the Netherlands. In this programme, physical, mental and
social activities are gradually increased on the basis of cognitive
behavioural principles and graded activity. Of the 127 successive persons
who enrolled for the therapy during the period from August 2000 to December
2004, 99 fulfilled the inclusion criteria; they had a median duration of
symptoms of 6 years. The results of treatment were evaluated by a
measurement with the 'Checklist individuele spankracht' [Checklist
individual muscle tone] before and after treatment and the scores on the
'Patientspecifieke beperkingen' [Patient-specific disability] and the Short
form-36. The measured data were complete in 74 patients.

RESULTS: Before rehabilitation, the levels of fatigue, disability and
distress were high. After treatment, the studied population showed
significant improvement in fatigue, experienced disability and physical
function. The magnitude of the improvement was generally 'average'. At the
end of treatment, 70% of the patients were clinically less fatigued, 68%
experienced less disability and 55% functioned better physically. In 34%
the level of fatigue was normalised after treatment, but 9.5% of the
patients was more fatigue.

CONCLUSION: The rehabilitation programme offered for CFS led to significant
improvements in function and fatigue.


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Date:    Sat, 14 Oct 2006 11:33:16 -0400
From:    "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx>
Subject: RES: The treatment of fibromyalgia with cranial electrotherapy stimulation

The treatment of fibromyalgia with cranial electrotherapy stimulation.

J Clin Rheumatol. 2001 Apr;7(2):72-8.

Lichtbroun AS, Raicer MM, Smith RB.

Robert Wood Johnson Medical School, East Brunswick, NJ (ASL); Real World
Health, Wall, NJ (M-MCR); Electromedical Products International, Mineral
Wells, TX (RBS).

PMID: 17039098


In cranial electrotherapy stimulation (CES), microcurrent levels of
electrical stimulation are passed across the head via electrodes clipped to
the ear lobes. After successful clinical use of CES with fibromyalgia
patients in our clinic, it was decided to test these results with a
double-blind, placebo-controlled study in which 60 randomly assigned
patients were given 3 weeks of 1-hour-daily CES treatments, sham CES
treatments, or were held as wait-in-line controls for any placebo effect in
the sham-treated patients.

Treated patients showed a 28% improvement in tender point scores, and a 27%
improvement in self-rated scores of general pain level. The number of
subjects rating their quality of sleep as poor dropped from 60% at the
beginning of the study to 5%. In addition, there were significant gains in
the self-rated feelings of well-being and quality of life, plus gains in
six stress-related psychological test measures. No placebo effect was found
among the sham-treated controls.

A theoretical role of CES in affecting the brain's pain message mechanisms
and/or neurohormonal control systems is discussed.

It is concluded that CES is as effective as the drug therapies in several
trials, with no negative side effects, and deserves further consideration
as an additional agent for the treatment of fibromyalgia.


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Date:    Sun, 15 Oct 2006 12:32:02 -0400
From:    "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx>
Subject: RES: Use of ziprasidone in patients with fibromyalgia: a case  series

Use of ziprasidone in patients with fibromyalgia: a case series.

Rheumatol Int. 2006 Oct 13; [Epub ahead of print]

Calandre EP, Hidalgo J, Rico-Villademoros F.

Instituto de Neurociencias, Universidad de Granada, Avenida de Madrid 11,
18012, Granada, Spain, calandre@gmail.com.

PMID: 17039363


Atypical antipsychotics may be useful in chronic pain treatment. The
objective of the present study was to assess the effect of ziprasidone in
fibromyalgia management.

Ziprasidone was administered to 32 fibromyalgia patients at a dose of 20
mg/day, subsequently adjusted according to clinical response and
tolerability. Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep
Quality Index (PSQI), a Clinical Global Impression improvement scale
(CGIi), and a scale evaluating the severity of fibromyalgia symptoms were
administered at 4 week intervals for 12 weeks. Drug adverse reactions were
recorded.

Ten patients withdrew from the study. The CGIi showed 32% of responders.
FIQ and PSQI scores showed a non-statistically significant decrease. The
conditions of stiffness, anxiety and sadness improved significantly. Most
frequent side effects included sleep disturbances, headache, tremor, and
rigidity.

Although ziprasidone does not seem an especially useful adjunct drug in
fibromyalgia, it could be tried on patients who are markedly anxious and/or
depressed.


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Date:    Mon, 16 Oct 2006 19:00:45 +0200
From:    Jan van Roijen <j.van.roijen@xxxxx.xx>
Subject: not,res: IiME ME Conference 2007

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


Send an Email for free membership
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~
       >>>> Help ME Circle  <<<<
 >>>>    16 October 2006      <<<<
Editorship : j.van.roijen@chello.nl
Outgoing mail scanned by Norton AV
~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~

http://www.investinme.org/IIME%20International%20ME%20Conference%202007%20Conference%20Details.htm


Invest in ME - ME Conference


The 2nd INTERNATIONAL IiME M.E. Conference 2007

2nd-3rd May 2007 in London, UK



The ME Conference 2007 Details
````````````````````````````````````````````

The ME Conference aims to educate and provide current
information to healthcare professionals (GPs, paediatricians,
nurses) to researchers and to the media and politicians who are
involved in establishing news or debate regarding healthcare.

The series of lectures, held over two days with one day focusing
on treatments and care and the other day focusing on medical
information and research, will provide a broad range of valuable
information for all.

The conference will provide a chance to hear the latest news on
ME from the most prominent speakers within the ME community
- in ME Awareness Month 2007.



Conference topics
`````````````````````````

* Epidemiology
* Diagnosis
* Treatments and Protocols for ME
* Research
* Care
* Law



Conference Speakers
``````````````````````````````
We welcome applications to speak at the conference from
physiciands, researchers, academics, healthcare workers and
others who have knowledge of Myalgic Encephalomyelitis.




Amongst the speakers at the conference Invest in ME are
pleased to announce the following presenters -

Dr. Arbhijit Chaudhuri
``````````````````````````````
Consultant Neurologist at the Essex Centre of Neurological
Science

Professor Kenny De Meirleir
``````````````````````````````````````
Professor of Physiology and Internal Medicine at Free University
of Brussels in Belgium

Dr. Ian Gibson MP
````````````````````````
MP for Norwich North and chair of the Proposed Inquiry into ME

Professor Malcolm Hooper
````````````````````````````````````
Emeritus Professor of Medicinal Chemistry, University of
Sunderland

Dr. Byron Hyde
````````````````````
Nightingale Research Foundation

Dr. Jonathan Kerr
`````````````````````````
Sir Joseph Hotung Senior Lecturer in Inflammation, St George's
University of London

Dr. Sarah Myhill
``````````````````````
GP and Secretary of the British Society of Allergy,
Environmental  and Nutritional Medicine
Professor Basant Puri
``````````````````````````````
Consultant at Hammersmith Hospital

Dr. Vance Spence
`````````````````````````
Chairman ME Research UK






Conference Format
```````````````````````````
Delegates are welcome to both days of the conference (see
registration details by clicking the button at the right).

Day 1 is aimed at healthcare staff, ME patients, support groups,
politicians and the media  wishing to view current issues with
ME. It is an ideal opportunity for staff working in PCTs or
hospitals to work together with patient organisations to better
understand these issues.

Day 2 is aimed at GPs, medics, physicians, students, nurses
and other healthcare staff associated with treatment of ME.



CPD Accreditation
``````````````````````````
As with the May 2006 conference we are again seeking CPD
(Continuous Professional Development) accreditation by the
Royal Colleges.


Register
````````````
By clicking the buttons at the side you will be able to branch to
the specific area of interest regarding the conference. There are
both downloadable and online registration forms and details of
the presenters.

Please note - this conference is a TICKET-ONLY event. Tickets
must be purchased and received before the event.


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

Date:    Mon, 16 Oct 2006 15:35:13 GMT
From:    "mycoreg@xxxx.xxx" <mycoreg@xxxx.xxx>
Subject: not,res,med,act:"Chlamydia&Mycoplasma infections in humans"Meeting'07 Italy

topics:Chronic Fatigue Syndrome(CFS),multiple sclerosis, rheumatic =

infections,encephalitis,atherosclerosis,cardiovascular =

diseases,respiratory diseases,urogenital infections,ocular lymphomas =


* * * * * * * * * * * * * * * * * * * * * * * * * * *
MYCOPLASMA REGISTRY REPORTS
for gulf war syndrome & chronic fatigue syndrome
=A9 2006 Sean Dudley & Leslee Dudley. All rights reserved.
<http://groups.yahoo.com/group/MycoplasmaRegistry/>
<MycoplasmaRegistry-subscribe@yahoogroups.com>
* * * * * * * * * * * * * * * * * * * * * * * * * * *

International Meeting on 

"Chlamydia and Mycoplasma Infections in humans"
http://mycoplasmas.cvm.iastate.edu/IOM/ferrara.html

DATE - April 19-20, 2007 

LOCATION -  Palazzo Renata di Francia, via Savonarola, Ferrara, 

University of Ferrara Italy, Ferrara, Italy
SUPPORTED - in part FEMS.
LANGUAGE -  English
CD - with the major topic discussed will be offered. 


AIM - this international meeting is to provide knowledge and skills 

for particular aspects of biology, pathogenesis, clinical aspects, 

diagnostic advances, treatment and vaccine perspectives of Chlamydia 

and Mycoplasma human infections. 


SPECIAL TOPICS WILL BE -
atherosclerosis
cardiovascular diseases 

respiratory diseases
urogenital infections
rheumatic infections in adult and paediatric individuals. 

Neurological diseases (and other diseases of particular interest including )
multiple sclerosis 

encephalitis 

Chronic Fatigue Syndrome (CFS) 

ocular lymphomas  

in whom the role of these pathogens seems to be called in cause, will 

be particularly stressed.

SPEAKERS - will mainly include the major international experts on the 

matter. Persons who have accepted to participate this event are: 

M. Leinonen (Oulu, Finland)
D. Taylor-Robinson (London UK) 

Dr. C. Hermann (Konstanz, Germany)
S. Sriram, (Nashville, Tennessee)
J. Nijs (Brussel, Belgium)
F. Blasi (Milan, Italy)
A. Blanchard and C. B=E8bear (Bordeaux, France)
K. Waites (Birmingham, USA) 

A. Dautry Varsat (Paris, France)

This meeting will be an important opportunity for the sharing of 

experience, the acquisition of new information and the kindling of 

collaborative endeavours. Considerable space will also be devoted to 

oral and poster presentations. This meeting will be registered in the 

Italian and European ECM program. Ferrara, medieval city on Po River, 

rich of history and art and famed for its architectural design, will 

provide an attractive setting for this important meeting.

SCHEDULE:
Wednesday, April 18 2006, evening: Opening ceremony
Thursday, April, 19 2006: Scientific Sessions (full day)
Friday, April 20, 2006: Scientific sessions and Closing Ceremony

ADDITIONAL INFORMATION:
Carlo Contini, MD
Professor of Infectious Diseases
Institute of Infectious Diseases
Dept Clin & Exp Medicine
University of Ferrara
Ferrara, Italy
Tel+39 532 291310
Fax +30 532 291391

* * * * * * * * * * * * * * * * * * * * * * * * * * *
FREE BROCHURE: "How to Get an Accurate Polymerase Chain Reaction
(PRC) Blood Test for Mycoplasmal and Other Infections-with a List of
International Laboratories" =A9 2006 by Sean and Leslee Dudley is sent
automatically and immediately to all new subscribers. It is updated
with current information and the new version is posted to the
Mycoplasma Registry Reports & News list each month.
<MycoplasmaRegistry-subscribe@yahoogroups.com>
<MycoplasmaRegistry-owner@yahoogroups.com>
FAIR USE: In accordance with Title 17 U.S.C. Section 107, this
material is distributed without profit to those who have expressed a
prior interest in receiving the included information for research and
educational purposes. The Mycoplasma Registry has no affiliation with
the originator of this article nor is the Mycoplasma Registry
endorsed or sponsored by the originator. If you wish to use
copyrighted material from this site for purposes of your own that go
beyond 'fair use', you must obtain permission from the copyright
owner.
* * * * * * * * * * * * * * * * * * * * * * * * * * *


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