CO-CURE Medical & Research Posts Only Digest - 9 Oct 2006 to 16 Oct 2006 (#2006-47)
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. [Return to top] ------------------------------ 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 : firstname.lastname@example.org Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ From: "Jane Colby" <email@example.com> 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 ~~~~~~~~~~ [Return to top] ------------------------------ Date: Tue, 10 Oct 2006 21:09:23 -0400 From: "CF-Alliance <firstname.lastname@example.org> (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 [Return to top] ------------------------------ 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 [Return to top] ------------------------------ Date: Wed, 11 Oct 2006 19:17:30 -0400 From: Co-Cure Moderator <email@example.com> 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>] [Return to top] ------------------------------ Date: Wed, 11 Oct 2006 17:34:04 -0700 From: Co-Cure moderators <firstname.lastname@example.org> 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. 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. 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. In a recent study by Goudas and colleagues 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. In other studies of patients admitted to palliative care units, pain often is the dominant symptom, along with fatigue and dyspnea. 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. 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. 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. 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, 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. Although a study by Weiner and Ernst 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 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 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. 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 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. 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 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. 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. 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 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. 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. 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. 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. 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. These fears are pervasive among patients and family members as well. Studies have suggested that these fears lead to undermedication and increased pain intensity. 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. 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, for example, the 5-card Control Preference Scale uses cards to portray different roles in treatment decision making with a statement and a picture. 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. Patients should be asked whether they are concerned about addiction and tolerance (often described as becoming "immune" to the drug). 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. 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. 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. 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. 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. 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. 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. Extended-release formulations are likely to increase compliance and adherence. 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. 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. Opioids exist in 3 classes -- pure agonists, mixed agonist-antagonist, and pure antagonists. 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. 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. Use of meperidine is specifically discouraged for chronic pain management due to its neurotoxic metabolite, normeperidine.  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. 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. 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. 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. 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. Fentanyl. Fentanyl is a lipophilic opioid that can be administered parenterally, spinally, transdermally, transmucosally, and nebulized for the management of dyspnea. 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. 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. 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. 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. 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. 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. 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. 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). 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Anticonvulsants. The older anticonvulsants, such as carbamazepine and clonazepam, relieve pain by blocking sodium channels. 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. 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. 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. Newer anticonvulsants that have been used successfully in treating neuropathies include levetiracetam, tiagabine, and oxcarbazepine, but no randomized, controlled clinical trials are available. 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. 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. Epidural or intrathecal lidocaine or bupivacaine delivered with an opioid can reduce neuropathic pain. 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. 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. Clinical trials in patients with lung and renal cell carcinoma have also shown therapeutic benefit from regular infusions of zoledronic acid. Calcitonin. Subcutaneous calcitonin may be effective in the relief of neuropathic or bone pain, although studies are inconclusive. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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). 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. Respiratory Depression. Respiratory depression is rarely a clinically significant problem for opioid-tolerant patients who are in pain. 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. 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. 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. 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. 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. 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." 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. 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[Return to top] ------------------------------ Date: Thu, 12 Oct 2006 11:56:18 +0200 From: "Dr. Marc-Alexander Fluks" <email@example.com> 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 [Return to top] ------------------------------ Date: Thu, 12 Oct 2006 17:49:56 +0200 From: Jan van Roijen <firstname.lastname@example.org> Subject: act,med: FDA & Pharmaceutical Industry ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 12 October 2006 <<<< Editorship : email@example.com Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ 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. `````````````````````````````````````````````````````````````````````````````` All content posted on this site is commentary or opinion and is protected under Free Speech. Truth Publishing LLC takes sole responsibility for all content. Truth Publishing sells no hard products and earns no money from the recommendation of products. Newstarget.com is presented for educational and commentary purposes only and should not be construed as professional advice from any licensed practitioner. Truth Publishing assumes no responsibility for the use or misuse of this material. For the full terms of usage of this material, visit www.NewsTarget.com/terms.shtml ~~~~~~ [Return to top] ------------------------------ Date: Thu, 12 Oct 2006 14:31:23 -0700 From: "Greg Crowhurst <firstname.lastname@example.org>..........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 [Return to top] ------------------------------ Date: Thu, 12 Oct 2006 23:50:38 -0400 From: Co-Cure Moderator <email@example.com> 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 [Return to top] ------------------------------ Date: Fri, 13 Oct 2006 00:32:37 -0400 From: Co-Cure Moderator <firstname.lastname@example.org> 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>] [Return to top] ------------------------------ Date: Fri, 13 Oct 2006 00:37:34 -0400 From: Co-Cure Moderator <email@example.com> 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>] [Return to top] ------------------------------ Date: Fri, 13 Oct 2006 05:51:56 -0400 From: "Bernice A. Melsky" <firstname.lastname@example.org> 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. [Return to top] ------------------------------ Date: Fri, 13 Oct 2006 17:39:52 +0200 From: Jan van Roijen <email@example.com> Subject: not,res: Holiday Cards -Research Support ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 13 October 2006 <<<< Editorship : firstname.lastname@example.org 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 ~~~~~~~~~~ [Return to top] ------------------------------ Date: Sat, 14 Oct 2006 11:18:48 -0400 From: Fred Springfield <email@example.com> 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. [Return to top] ------------------------------ Date: Sat, 14 Oct 2006 11:22:17 -0400 From: Fred Springfield <firstname.lastname@example.org> 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. email@example.com 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. [Return to top] ------------------------------ Date: Sat, 14 Oct 2006 11:33:16 -0400 From: "Bernice A. Melsky" <firstname.lastname@example.org> 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. [Return to top] ------------------------------ Date: Sun, 15 Oct 2006 12:32:02 -0400 From: "Bernice A. Melsky" <email@example.com> 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, firstname.lastname@example.org. 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. [Return to top] ------------------------------ Date: Mon, 16 Oct 2006 19:00:45 +0200 From: Jan van Roijen <email@example.com> Subject: not,res: IiME ME Conference 2007 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 16 October 2006 <<<< Editorship : firstname.lastname@example.org 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: "email@example.com" <firstname.lastname@example.org> 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/> <MycoplasmaRegistryemail@example.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. <MycoplasmaRegistryfirstname.lastname@example.org> <MycoplasmaRegistryemail@example.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. * * * * * * * * * * * * * * * * * * * * * * * * * * * [Return to top]
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