CO-CURE Medical & Research Posts Only Digest - 2 Oct 2006 to 9 Oct 2006 (#2006-46)

There are 25 messages totalling 4750 lines in this issue. Topics of the week:

1. NOT,RES: The Trouble with Medical Journals 2. RES: Brief Report: The Accuracy of Parents for the Thoughts and Feelings of Their Adolescent Suffering from Chronic Fatigue: A Preliminary Study of Empathy 3. RES: Pain thresholds and tender point counts as predictors of new chronic widespread pain in psychologically distressed subjects 4. RES: Conceptual issues in undifferentiated somatoform disorder and chronic fatigue syndrome 5. RES: Cognitive behavioural therapy in chronic fatigue syndrome: a randomised controlled trial of an outpatient group programme 6. RES: Potential Polygenic Influences on Chronic Fatigue Syndrome 7. RES: Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect? 8. RES: Psychological approaches in pain management: what works? 9. RES, NOTICE: Reports From the CAMDA Conference 10. RES,NOT: Review CFS therapies 11. MED: Lyme Disease: Let's Dispel the Myths 12. NOT,MED: IACFS 8th Annual Conference on Chronic Fatigue Syndrome, Fibromyalgia, Gulf War Syndrome, and other related illnesses 13. MED: CFS, possibly the immune dysfunction 14. RES,ACT: Royal Colleges Review of CFS therapies 15. RES: Quality of life and associated clinical distress in fibromyalgia 16. RES: Lessons Learned Combining N-of-1 Trials to Assess Fibromyalgia Therapies 17. RES: New treatment options using 5-HT3 receptor antagonists in rheumatic diseases 18. RES: Fibromyalgia: diagnosis, pathogenesis, and treatment 19. RES: Central pain 20. RES: Reduced Presynaptic Dopamine Activity in Fibromyalgia Syndrome Demonstrated With Positron Emission Tomography: A Pilot Study 21. act,res: is hysteria real?-brain images say yes 22. act,med: Latest APPG Developments (UK) 23. med: Lyme Disease & ME -Followup 24. RES,NOT: Fitness and Exercise in CFS and FM 25. RES: Alpha2 receptors and agonists in pain management

[Return to digest index] --------------------------------------------- This is a special digest of Co-Cure Research & Medical posts only Problems? Write to mailto:mods@co-cure.org --------------------------------------------- ---------------------------------------------------------------------- Date: Tue, 3 Oct 2006 14:52:56 -0400 From: "Jan van Roijen <j.van.roijen@xxxxx.xx> (via Co-Cure Moderators) Subject: NOT,RES: The Trouble with Medical Journals Send an Email for free membership ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ >>>> Help ME Circle <<<< >>>> 3 October 2006 <<<< Editorship : j.van.roijen@chello.nl Outgoing mail scanned by Norton AV ~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~:~ http://www.ireland.com/newspaper/health/2006/0919/1158590761760.html Sun Oct 1, 2006 7:51 pm (PST) Special Reports Health Tue, Sep 19, 06 Add a pinch of salt to medical findings ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Good debate: Don't believe all you read in a medical journal, a former editor tells Claire O'Connell Every day, doctors thumb through medical journals looking for the latest information on treatments. Meanwhile, journalists relate the findings of published studies to millions of people. And the underlying belief is that if it is in a prestigious medical journal, then it must be true. Right? Not always, according to Dr Richard Smith, whose book, The Trouble with Medical Journals, is published today. Smith, a medical doctor and editor with the BMJ (British Medical Journal) for more than 20 years, lifts the lid on shady ethical practices in large medical journals. These include dodgy courtships with the mass media leading to public scares, as well as unsavoury links with the pharmaceutical industry, which he claims uses medical journals to promote its drugs. He also recommends ditching the time-honoured practice of expert peers reviewing papers before they are published. But why should we care about how medical journals work? "The ways that medical journals behave have an important influence on people," Smith says. "They can create a lot of havoc," he adds, citing examples where studies in medical journals sparked media-fuelled scares about emotive issues such as vaccination, alternative treatments for cancer and the contraceptive pill. His book raises the awkward question of whether journals, in their passion for publicity, might be tempted to publish weak but controversial studies to grab media headlines on "things that are likely to appeal to the public's interest [quite a different thing from the public interest]." For example, a dubious study published in The Lancet in 1998 sparked media hype that led to public fears about links between the MMR vaccine and autism. The study was later withdrawn, its author was discredited and numerous larger and more rigorous studies have since shown no link between the MMR jab and autism. But the mud stuck, and uptake of the triple vaccine was substantially reduced. "All medical journals publish rubbish, and quite a lot of it," says Smith, who openly admits transgressions by his own journal. "But luckily, most of it doesn't have the kind of impact that the MMR paper did." However, medical journals have more worrying bedfellows than the media, according to Smith, who left the BMJ in 2004. Top of his list of gripes is how "medical journals have become an extension of the marketing arm of the pharmaceutical industry". Pharmaceutical companies sponsor most of the large clinical drug trials that are published in major medical journals, and the outcomes of such studies are generally good for the sponsor, he says. "When you look at how often those trials come up with anything that's really bad news for the drug companies, the answer is almost never," says Smith. "It's not because the drug companies are fiddling the results, it's just that they are rather clever at the kinds of questions that they ask and the way they analyse the data. So they very rarely come up with anything that's bad news," he says. A favourable clinical trial published in a prestigious journal can have a major impact on drug sales, says Smith. And there is also a pay-off for the journal: if the pharmaceutical company orders reprints of the paper to send to prospective clients, the journal can make hundreds of thousands of dollars in profit, he adds. Such cosy arrangements benefit neither the doctor nor the patient, and Smith believes a more open and accountable approach would be to publish full details of trials on regulated websites and have journals critique them. Smith also dismisses peer review, a vetting system where journal editors choose experts in a particular field (peers) to review submitted papers and recommend whether or not to publish them. Getting a study into a peer-reviewed journal is generally seen as a mark of quality, but Smith disagrees. "I think it would be good for the world at large to realise just what a dodgy process peer review is," he says. "It just doesn't work very well and it's a bit of a lottery." Instead, he believes that new studies should be published online where everyone can access them and spark a public discourse. "I'm all for sticking it up on the web with a big sign saying don't believe this just because it's here, wait and see what response there is." In fact, Smith believes that printed medical journals are generally not the place for original research data, because they offer little of value for doctors. He suggests that journals instead convey the important information in print and put the full research reports on the web for those who are interested. "The whole model of sending a lot of original research to ordinary doctors is bonkers," says Smith. "Most of the scientific articles [in medical journals] are not relevant to the average doctor. "He or she hasn't got time to read them anyway. And most doctors are not equipped to critically appraise the evidence, so there's a tendency to say 'it's in the New England Journal of Medicine so it must be true'." The extensive list of ills in Smith's book, which he wrote during a two-month stay in Venice, came as something of a surprise, even to himself. "I had no idea the book was going to turn out like that - I've become a grumpy old man," he says. "But probably the closer you get to any institution, the more you see the human defects," he adds. Dr Richard Smith will give a public interview hosted by Dick Ahlstrom, science editor of The Irish Times, on Thursday, September 21st at 6pm in the Royal Irish Academy, 19 Dawson Street, Dublin 2. The event is co-organised by the British Council. Places are free but must be reserved in advance by phoning Laura on 01 6090635 or Maura on 01 6090633 (10am-5pm). © The Irish Times [Return to top] ------------------------------ Date: Tue, 3 Oct 2006 15:23:39 -0400 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Brief Report: The Accuracy of Parents for the Thoughts and Feelings of Their Adolescent Suffering from Chronic Fatigue: A Preliminary Study of Empathy Brief Report: The Accuracy of Parents for the Thoughts and Feelings of Their Adolescent Suffering from Chronic Fatigue: A Preliminary Study of Empathy Journal: Journal of Pediatric Psychology Advance Access published online on September 29, 2006, doi:10.1093/jpepsy/jsl032 Authors: Tine Vervoort MSc [1,2,*], Geert Crombez PhD [1], Ann Buysse PhD [2], Liesbet Goubert PhD [1], Tine De Backer MSc [3], and William Ickes PhD[4] Affiliations: [1] Department of Experimental-Clinical and Health Psychology, Ghent University, Belgium; Research Institute for Psychology and Health, The Netherlands [2] Department of Experimental-Clinical and Health Psychology, Ghent University, Belgium [3] Zeepreventorium, De Haan, Belgium [4] Department of Psychology, University of Texas at Arlington, USA [*] To whom correspondence should be addressed. Tine Vervoort, E-mail: Tine.Vervoort@Ugent.be NLM Citation: PMID: 17012438 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. Keywords: adolescents; chronic fatigue syndrome; empathy; parents. [Return to top] ------------------------------ Date: Tue, 3 Oct 2006 15:54:04 -0400 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Pain thresholds and tender point counts as predictors of new chronic widespread pain in psychologically distressed subjects Pain thresholds and tender point counts as predictors of new chronic widespread pain in psychologically distressed subjects. Ann Rheum Dis. 2006 Sep 29; [Epub ahead of print] Gupta A, McBeth J, Macfarlane GJ, Morriss RK, Dickens C, Ray D, Chiu YH, Silman AJ. University of Manchester, United Kingdom. PMID: 17012291 OBJECTIVE: Tender points are a general measure of distress both in community and clinic subjects. It has been suggested that multiple tender points should be regarded as the early stages of somatization of distress. Similarly, there is recent evidence to suggest that chronic widespread pain is one manifestation of the somatization of distress. Given that a high tender point count and chronic widespread pain are clinical hallmarks of the fibromyalgia syndrome, we hypothesized that in psychologically distressed subjects, a high tender point count, or a low pain threshold would predict the development of chronic widespread pain in the future. METHODS: In this population based prospective study, 245 psychologically distressed adults between 25- 65 years, free of chronic widespread pain, were identified, based on a detailed pain questionnaire, and a psychosocial questionnaire comprising the Somatic Symptom Checklist and the Illness Behaviour subscale of the Illness Attitude Scales. These subjects took part in a pain threshold examination with a Fischer pressure algometer. Tender point counts were computed by including all areas with a pain threshold below 4kg/cm2. Individuals were followed up at 15 months, at which time 231 (97% of subjects still living at their baseline address) provided data on pain status, using the same instruments. RESULTS: At follow-up, 26 subjects (11%) developed new chronic widespread pain. Neither baseline pain threshold, nor tender point count, adjusted for age, gender and baseline pain status, predicted the development of new chronic widespread pain. CONCLUSION: Psychologically distressed subjects free of chronic widespread pain are not at an increased risk of its development if they have high tender points or low pain thresholds. Data from this population based prospective study suggest that a low pain-threshold in subjects with chronic widespread pain is likely to be a secondary phenomenon as a result of pain or associated distress rather than being the antecedent of symptoms. [Return to top] ------------------------------ Date: Wed, 4 Oct 2006 17:08:28 -0400 From: Co-Cure Moderator <ray@xxxxx.xxx> Subject: RES: Conceptual issues in undifferentiated somatoform disorder and chronic fatigue syndrome Conceptual issues in undifferentiated somatoform disorder and chronic fatigue syndrome. Journal: Curr Opin Psychiatry. 2006 Nov;19(6):613-8. Author: van Staden WC. Affiliation: Department of Psychiatry, University of Pretoria, Pretoria, South Africa. NLM Citation: PMID: 17012941 PURPOSE OF REVIEW: To review the conceptual problems in distinguishing between undifferentiated somatoform disorder and chronic fatigue syndrome, for both may present with fatigue as the main symptom. RECENT FINDINGS: The differences and/or similarities between undifferentiated somatoform disorder and chronic fatigue syndrome have not been studied, conceptually or empirically. The literature fails to present discriminant validity of chronic fatigue syndrome in relation to undifferentiated somatoform disorder. A critical feature is implied in the definition of undifferentiated somatoform disorder but absent from the definitions of chronic fatigue syndrome: some patients experience their fatigue as being exclusively physical and not as mental, which is prima facie peculiar, for fatigue is necessarily a mental experience. One is not able to experience fatigue without a mind (or a brain). This experience is characterized as a 'mindless' fatigue, underpinned by pathological reductionist thinking. By not recognizing this critical feature, diagnostic endeavours may perpetuate the problem as a function of the patient's difficulty. SUMMARY: Proponents of chronic fatigue syndrome should distinguish chronic fatigue syndrome from undifferentiated somatoform disorder, if chronic fatigue syndrome is a distinct entity at all. Further, the 'mindless' quality is a critical feature that needs consideration in refining the concept of undifferentiated somatoform disorder. [Return to top] ------------------------------ Date: Wed, 4 Oct 2006 17:18:56 -0400 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Cognitive behavioural therapy in chronic fatigue syndrome: a randomised controlled trial of an outpatient group programme Cognitive behavioural therapy in chronic fatigue syndrome: a randomised controlled trial of an outpatient group programme. Journal: Health Technol Assess. 2006 Oct;10(37):1-140. Authors: O'Dowd H, Gladwell P, Rogers CA, Hollinghurst S, Gregory A. Affiliation: Pain Management Centre, Frenchay Hospital, Bristol, UK. NLM Citation: PMID: 17014748 OBJECTIVES: To test the hypothesis that group cognitive behavioural therapy (CBT) will produce an effective and cost-effective management strategy for patients in primary care with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME). DESIGN: A double-blind, randomised controlled trial was adopted with three arms. Outcomes were assessed at baseline and 6 and 12 months after first assessment and results were analysed on an intention-to-treat basis. SETTING: A health psychology department for the management of chronic illness in a general hospital in Bristol, UK. PARTICIPANTS: Adults with a diagnosis of CFS/ME referred by their GP. INTERVENTIONS: The three interventions were group CBT incorporating graded activity scheduling, education and support group (EAS) and standard medical care (SMC). OUTCOME MEASURES: The primary outcome measure was the Short Form with 36 Items (SF-36) physical and mental health summary scales. Other outcome measures included the Chalder fatigue scale, Hospital Anxiety and Depression Scale, General Health Questionnaire, physical function (shuttles walked, walking speed and perceived fatigue), health utilities index and cognitive function (mood, recall and reaction times). RESULTS: A total of 153 patients were recruited to the trial and 52 were randomised to receive CBT, 50 to EAS and 51 to SMC. Twelve patients failed to attend for the 12-month follow-up and 19 patients attended one follow-up, but not both. The sample was found to be representative of the patient group and the characteristics of the three groups were similar at baseline. Three outcome measures, SF-36 mental health score, Chalder fatigue scale and walking speed, showed statistically significant differences between the groups. Patients in the CBT group had significantly higher mental health scores [difference +4.35, 95% confidence interval (CI) +0.72 to +7.97, p = 0.019], less fatigue (difference -2.61, 95% CI -4.92 to -0.30, p = 0.027) and were able to walk faster (difference +2.83 shuttles, 95% CI +1.12 to +5.53, p = 0.0013) than patients in the SMC group. CBT patients also walked faster and were less fatigued than those randomised to EAS (walking speed: difference +1.77, 95% CI +0.025 to +3.51, p = 0.047; fatigue: difference -3.16, 95% CI -5.59 to -0.74, p = 0.011). Overall, no other statistically significant difference across the groups was found, although for many measures a trend towards an improved outcome with CBT was seen. Except for walking speed, which, on average, increased by +0.87 shuttles (95% CI +0.09 to +1.65, p = 0.029) between the 6- and 12-month follow-ups, the scores were similar at 6 and 12 months. At baseline, 30% of patients had an SF-36 physical score within the normal range and 52% had an SF-36 mental health score in the normal range. At 12 months, the physical score was in the normal range for 46% of the CBT group, 26% of the EAS group and 44% of SMC patients. For mental health score the percentages were CBT 74%, EAS 67% and SMC 70%. Of the CBT group, 32% showed at least a 15% increase in physical function and 64% achieved a similar improvement in their mental health. For the EAS and SMC groups, this improvement in physical and mental health was achieved for 40 and 60% (EAS) and 49 and 53% (SMC), respectively. The cost-effectiveness of the intervention proved very difficult to assess and did not yield reliable conclusions. CONCLUSIONS: Group CBT did not achieve the expected change in the primary outcome measure as a significant number did not achieve scores within the normal range post-intervention. The treatment did not return a significant number of subjects to within the normal range on this domain; however, significant improvements were evident in some areas. Group CBT was effective in treating symptoms of fatigue, mood and physical fitness in CFS/ME. It was found to be as effective as trials using individual therapy in these domains. However, it did not bring about improvement in cognitive function or quality of life. There was also evidence of improvement in the EAS group, which indicates that there is limited value in the non-specific effects of therapy. Further research is needed to develop better outcome measures, assessments of the broader costs of the illness and a clearer picture of the characteristics best fitted to this type of intervention. [Return to top] ------------------------------ Date: Thu, 5 Oct 2006 12:55:00 -0400 From: Fred Springfield <fredspringfield@xxxxx.xxx> Subject: RES: Potential Polygenic Influences on Chronic Fatigue Syndrome [Note: See http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0606A&L=CO-CURE&P=R2320 for the original article that this letter comments on.] LETTER TO THE EDITOR Potential Polygenic Influences on Chronic Fatigue Syndrome Journal: PEDIATRICS Vol. 118 No. 4 October 2006, pp. 1799-1800 (doi:10.1542/peds.2006-1664) Author: Kenneth N. Schikler, MD, FAAP, FACR Affiliation: Section of Pediatric Rheumatology and Adolescent Medicine Department of Pediatrics University of Louisville School of Medicine Louisville, KY 40202 Center for Pediatric Fatiguing and Painful Conditions Frazier Rehab Institute Louisville, KY 40202 To the Editor. I found the article by van de Putte et al1 to be most interesting and insightful in construct design and in the conclusions drawn from their study of 40 adolescents with chronic fatigue syndrome (CFS), one of the many syndromes that fit into the category of central pain-processing disorders (along with other disturbing conditions such as fibromyalgia, irritable bowel syndrome, and complex regional pain syndrome type I). Their study results led them to conclude that the shared symptom complex of mother and child suggested an interplay between genetic variability and environmental factors. They, in fact, suggested the potential for a polygenic rather than monogenic inheritance pattern and made reference to an article by Torpy et al2 regarding an association of CFS and the serine allele of the CBG gene. This article was obviously prepared and accepted for publication long before the recently published findings of Goertzel et al,3 who found that combinations of single-gene polymorphisms had a 76.3% predictive accuracy for CFS in studying 43 adults and 58 control subjects. The 3 genes with the highest accumulated importance were neuronal tryptophan hydroxylase (TPH2, involved in serotonin metabolism), catechol-O-methyltransferase (COMT, involved in methylation of norepinephrine), and nuclear receptor subfamily 3, group C member 1 glucocorticoid receptor (NR3C1, involved in corticosteroid sensitivity via signal transduction and transcription of RNA polymerase II promoter). This adds supportive evidence to the concept of a polygenic predisposition to the development of CFS and possibly other central pain-perception processes,4 such as fibromyalgia, that have been felt to have alterations in serotonin,5 norepinephrine,6 and response to stress or allostasis.7 REFERENCES 1. van de Putte EM, van Doornen LJ, Engelbert RH, Kuis W, Kimpen JL, Uiterwaal CS. Mirrored symptoms in mother and child with chronic fatigue syndrome. Pediatrics. 2006;117 :2074 2079[Abstract/Free Full Text] 2. Torpy DF, Bachmann AW, Gartside M, et al. Association between chronic fatigue syndrome and the corticosteroid-binding globulin gene ALA SER224 polymorphism. Endocr Res. 2004;30 :417 429[CrossRef][ISI][Medline] 3. Goertzel BN, Pennachin C, de Souza Coehlo L, Gurbaxani B, Maloney EM, Jones JF. Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes predict chronic fatigue syndrome. Pharmacogenomics. 2006;7 :475 483[CrossRef][ISI][Medline] 4. Diatchenko L, Slade GD, Nackley AG, et al. Genetic basis for individual variation in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005;14 :135 143[Abstract/Free Full Text] 5. Russell IJ. Advances in fibromyalgia: possible role for central neurochemicals. Am J Med Sci. 1998;315 :377 384[CrossRef][ISI][Medline] 6. Legangneux E, Mora JJ, Spreux-Varoquaux O, et al. Cerebrospinal fluid biogenic amine metabolites, plasma-rich platelet serotonin and [3H]imipramine reuptake in the primary fibromyalgia syndrome. Rheumatology (Oxford). 2001;40 :290 296 7. Maloney EM, Gurbaxani BM, Jones JF, de Souza Coelho L, Pennachin C, Goertzel BN. Chronic fatigue syndrome and high allostatic load. Pharmacogenomics. 2006;7 :467 473[CrossRef][ISI][Medline] ©2006 by the American Academy of Pediatrics [Return to top] ------------------------------ Date: Thu, 5 Oct 2006 13:12:40 -0400 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect? Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect? Int Clin Psychopharmacol. 2006 Nov;21(6):311-7. Perahia DG, Pritchett YL, Desaiah D, Raskin J. [a]Lilly Research Centre, Windlesham, Surrey, UK [b]The Gordon Hospital, London, UK [c]Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA [d]Lilly Research Laboratorios, Eli Lilly Canada, Toronto, Ontario, Canada. PMID: 17012978 The evidence that the effects of the antidepressant duloxetine on painful physical symptoms in depression and chronic pain disorders are a direct analgesic effect rather than an indirect antidepressant effect is reviewed. Data from placebo-controlled acute studies of duloxetine in major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia syndrome are included in this review. In placebo-controlled studies of duloxetine in patients with major depressive disorder, non-depressed diabetic peripheral neuropathic pain, and fibromyalgia syndrome, duloxetine has a statistically significantly greater effect on pain than placebo. Path analysis suggests that in these patient populations, approximately 50, 90, and 80%, respectively, of the observed effect on pain is a direct analgesic effect rather than an indirect antidepressant effect. In fibromyalgia syndrome studies, duloxetine had similar and substantial effects on pain regardless of whether patients had comorbid major depressive disorder. Pain is a complex experience, involving both the physiological responses of the nociceptive system and the processing of that information in brain regions associated with emotion. While some effects of duloxetine on painful symptoms can be accounted for by its antidepressant action, the data strongly suggest that duloxetine also exerts a substantial direct analgesic effect over and above its antidepressant effects, in patients with major depressive disorder, diabetic peripheral neuropathic pain, and fibromyalgia syndrome. [Return to top] ------------------------------ Date: Thu, 5 Oct 2006 13:15:12 -0400 From: "Bernice A. Melsky" <bernicemelsky@xxxxx.xxx> Subject: RES: Psychological approaches in pain management: what works? Psychological approaches in pain management: what works? Curr Opin Anaesthesiol. 1998 Oct;11(5):547-52. Turk DC, Okifuji A. Department of Anesthesiology, University of Washington, Seattle, Washington, USA. PMID: 17013272 Outcome studies evaluating psychological treatments for pain vary in nature and intensity. Overall, however, treatment programs that include psychological interventions have been shown to be effective in treating postoperative pain, noncardiac chest pain, fibromyalgia syndrome, and chronic back pain. Cost analyses of the treatments indicate not only the clinical efficacy but the cost-effectiveness of psychological interventions. Issues related to subject attrition, noncompliance, and individual differences in treatment response should be addressed in future studies. [Return to top] ------------------------------ Date: Thu, 5 Oct 2006 12:14:50 -0700 From: "Cort Johnson.................via Co-Cure moderator" Subject: RES, NOTICE: Reports From the CAMDA Conference The analyses of the 2003 CDC Wichita data did not stop with the publications in the Pharmacogenomics Journal. While the CDC researchers and others took a stab at the data the CDC gave another group of independent researchers their shot at it. Researchers from Finland, Canada, the U.K., Italy, Australia, Korea and the U.S. presented their findings in a series of papers presented at the CAMDA conference at Durham, North Carolina in June of 2006. The CAMDA conference takes the form of a contest in which the presenters vie to produce the best paper. An enormous amount of very creative work resulted in a presentation of 10 papers and three posters seeking to elucidate biological characteristics unique to CFS, provide a biomarker, and open new avenues CFS research and treatment. These reports are very complex. Some were successes, some were not. The top paper may have found a biomarker for CFS, other found problems in biological pathways, altered gene networks and one or two, indirectly, suggested problems in the methylation pathway. http://www.phoenix-cfs.org/CAMDA%2006.htm Cort [Return to top] ------------------------------ Date: Thu, 5 Oct 2006 12:37:19 +0200 From: "Dr. Marc-Alexander Fluks" <fluks@xxx.xx> Subject: RES,NOT: Review CFS therapies Source: Journal of the Royal Society of Medicine Vol 99, #10, pp 506-520 Date: October 2006 URL: http://www.jrsm.org/cgi/content/full/99/10/506 [Reviews] Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review -------------------------------------------------------------------------- Duncan Chambers(1,*), Anne-Marie Bagnall(2), Susanne Hempel(1), Carol Forbes(1) 1 Centre for Reviews and Dissemination, University of York, York, YO10 5DD, UK 2 School of Health and Community Care, Leeds Metropolitan University, Leeds, LS1 3HE, UK * Correspondence to: Duncan Chambers E-mail: dc510@york.ac.uk SUMMARY Objectives To determine whether any particular intervention or combination of interventions is effective in the treatment, management and rehabilitation of adults and children with a diagnosis of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Design Substantive update of a systematic review published in 2002. Randomized (RCTs) and non-randomized controlled trials of any intervention or combination of interventions were eligible for inclusion. Study participants could be adults or children with a diagnosis of CFS/ME based on any criteria. We searched eleven electronic databases, reference lists of articles and reviews, and textbooks on CFS/ME. Additional references were sought by contact with experts. Results Seventy studies met the inclusion criteria. Studies on behavioural, immunological, pharmacological and complementary therapies, nutritional supplements and miscellaneous other interventions were identified. Graded exercise therapy and cognitive behaviour therapy appeared to reduce symptoms and improve function based on evidence from RCTs. For most other interventions, evidence of effectiveness was inconclusive and some interventions were associated with significant adverse effects. Conclusions Over the last five years, there has been a marked increase in the size and quality of the evidence base on interventions for CFS/ME. Some behavioural interventions have shown promising results in reducing the symptoms of CFS/ME and improving physical functioning. There is a need for research to define the characteristics of patients who would benefit from specific interventions and to develop clinically relevant objective outcome measures. INTRODUCTION Chronic fatigue syndrome (CFS) is a debilitating condition characterized by fatigue on minimal exertion accompanied by a range of other symptoms such as headaches, sleep disturbance, cognitive difficulties and muscle pain.1,2 The severity of the symptoms varies widely both between patients and over time; in severe cases patients may be confined to bed or to a wheelchair. CFS affects both adults and children. The nomenclature of the condition and the overlap between CFS and myalgic encephalomyelitis (ME) has been much debated. For this review we have used the term CFS/ME and included studies of people with a diagnosis of CFS/ME by any criteria. The aetiology of CFS/ME remains uncertain and diagnosis is based on symptoms as reported by the patients. Case definitions developed for research purposes tend to be used to aid diagnosis, the most widely used being the US Centers for Disease Control and Prevention (CDC)2 and the UK (Oxford)1 criteria. Estimates of the prevalence of CFS/ME vary depending on the case definition used. In a study of 2376 primary care patients in England, 2.6% met criteria for CFS/ME but the prevalence fell to 0.5% when those with co-morbid psychological disorders were excluded.3 The UK Department of Health Working Party on CFS/ME4 estimated that a typical general practice with 10 000 patients is likely to have 30-40 patients with CFS/ME and that about half of these would require specialist services. A variety of interventions have been used for the treatment and management of patients with CFS/ME and a number of groups have performed systematic reviews to assess the effectiveness of these interventions. Price and Couper5 assessed the effectiveness of cognitive behaviour therapy (CBT) in adults and concluded that CBT appears to be an effective and acceptable treatment, although only three relevant randomized controlled trials (RCTs) were found. Edmonds and colleagues reviewed RCTs of exercise therapy.6 Based on five RCTs they concluded that exercise therapy is a promising intervention, although they recommended more rigorous studies involving different patient groups and settings and a wider range of outcomes. A systematic review by Ross and colleagues examined how best to measure, monitor and treat disability in patients with CFS/ME.7 Disability was considered primarily in terms of ability to work. Although the authors found some small studies of interventions (including rehabilitation, CBT and graded exercise therapy [GET]) that reported improved employment outcomes, they concluded that no intervention has been proved to be effective in restoring the ability to work More broadly, Mulrow and colleagues examined the definition and management of CFS/ME,8 while a review of all available interventions for the treatment and management of CFS/ME in both adults and children was carried out at the NHS Centre for Reviews and Dissemination (CRD).9 These two reviews only covered the period up to 2001, and many studies of CFS/ME have been published since then. We recently carried out a number of systematic and scoping reviews on CFS/ME to inform the process of guideline development by the UK National Institute for Health and Clinical Excellence (NICE). In this paper we present an updated systematic review of the literature on interventions for the treatment and management of CFS/ME in adults and children. METHODS Literature search The following databases were searched: MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005), PsycINFO (1872 to April 2005), CENTRAL (May 2005), Social Science Citation Index (1945 to 2005), Science Citation Index (1945 to 2005), Index to Scientific and Technical Proceedings (1982 to 2005), PASCAL (May 2005), Inside Conferences (May 2005), AMED (1985 to January 2005), and HEED (June 2005). Individual search strategies were developed for each electronic database and details of these can be obtained from the authors. The search was broad, with the objective of identifying all studies of CFS/ME and related synonyms and covering several research questions. No language restrictions were applied. Additional references were sought by screening reference lists of retrieved articles, textbooks on CFS/ME, and stakeholder submissions from the NICE Guideline Development Group on diagnosis and management of CFS/ME. Inclusion criteria and study selection Two reviewers independently assessed all titles and abstracts identified from the searches for potential relevance to the review questions, and potentially relevant papers were retrieved in full. Two reviewers independently assessed these studies for possible inclusion, using the specified inclusion criteria. A third reviewer resolved differences. The inclusion and exclusion criteria were: Intervention - any intervention or combination of interventions used in the treatment, management or rehabilitation of people with CFS/ME. Population - adults and/or children aged five years or more with a diagnosis of CFS/ME based on any criteria. Outcomes - all outcomes reported in included studies were considered. Study design - only randomized or controlled clinical trials were eligible for inclusion. Data extraction Data were extracted from study reports by one reviewer and the results were checked by a second reviewer. Any discrepancies were resolved by reference to the original study, with a third reviewer being consulted if necessary. Only between-group comparisons were considered. Validity assessment The criteria for validity assessment described by Bagnall et al.9 and based on the CRD recommendations10 were used to allocate a validity score, ranging from 0 to 20, to each study. Assessment of validity was based on method of randomization and allocation concealment (randomized studies only); baseline comparability of groups; adjustment for confounding factors and appropriateness of the control group (controlled studies only); blinding; completeness of follow-up; handling of drop-outs and missing data; objectivity of outcome assessment; appropriateness of statistical analysis; whether the groups were treated identically apart from the named intervention; and sample size/statistical power. Validity was assessed by one reviewer and checked by another. Disagreements were resolved by discussion and reference to a third reviewer if necessary. Data synthesis Data were grouped by intervention into pre-specified broad categories and synthesized qualitatively. In evaluating the effects of interventions, a study was classified as showing some effect (positive or negative) of treatment if any of the outcomes measured showed a significant (P<50.05) difference between the treatment and control groups. Studies were classified as showing an overall effect of treatment if there was a significant difference between the treatment and control groups for more than one clinical outcome. Studies of pre-specified subgroups of patients (children and those with severe CFS/ME) were considered separately. RESULTS The overall literature search identified 10,768 items, of which 70 met the inclusion criteria for the review (Figure 1). Two studies included in the review by Bagnall et al. were excluded from the updated review, one because it included patients with chronic mononucleosis11 and one because a full report was subsequently published.12 Fifteen papers that were ordered as potentially meeting inclusion criteria had not arrived at the time of writing.13-27 One paper in the Russian language was identified as potentially meeting inclusion criteria but has not been translated.28 The paper is about a yeast extract supplement but it is unclear whether patients all had CFS. Of the studies included in the review, 59 were RCTs and the remainder non-randomized controlled trials (Table 1). Of the newly included studies (Table 2), 15 showed some beneficial effect of the intervention and eight showed an overall beneficial effect. Validity scores ranged from 2 to 19 for the included RCTs and from 0 to 14 for the controlled trials. Controlled trials generally scored less well than RCTs on all validity criteria. A high degree of heterogeneity in interventions and outcomes was evident. The evidence supporting the effectiveness of CBT has been strengthened by one recent good quality RCT in children and adolescents29 which found an overall positive effect of the intervention. CBT was associated with a significant positive effect on fatigue, symptoms, physical functioning and school attendance. Most other new studies of CBT and modified CBT have also favoured the treatment for one or more outcomes but these were either lower quality RCTs or non-randomized studies. GET has recently been studied in two moderate quality RCTs.30,31 These studies have broadened the evidence base for GET because, unlike earlier studies, they involved non-UK settings and patients who met the 1994 CDC case definition criteria for CFS/ME. As with CBT, the overall results of studies to date suggest that this intervention may have positive effects on the symptoms of CFS/ME. Improvements in measures of physical function were also found in all five RCTs of GET published to date.30-34 No severely affected patients were included in the studies of GET. Two new studies of immunological therapies (a controlled trial of inosine pranobex35 and a relatively low quality RCT of staphylococcus toxoid36) were added to the updated review. Both of these treatments showed benefits for some outcomes but were also associated with relatively high levels of adverse events. Overall there is still insufficient evidence about the effectiveness of therapies of this type. Treatment of CFS/ME with pharmacological therapies has given disappointing results in most cases. A recent large RCT of the acetylcholinesterase inhibitor galantamine hydrobromide37 found no significant differences between groups and 120 of 434 patients (27.6%) withdrew from the trial. An RCT of hydrocortisone published in 200238 found a significant difference between groups for fatigue, but this study scored poorly for validity. Two other recent studies of steroid treatment39,40 found no significant effect, in line with the mixed results reported in 2002. The only new study of complementary/alternative therapies was an RCT of homeopathic treatment41 that showed significant differences favouring the treatment group for one of five measures of fatigue and one of five measures of functional limitations. This trial used rigorous methodology but there is also a published study showing no effect of homeopathic treatment42 and further studies are clearly required. A supplement of acetyl-L-carnitine and propionyl-L-carnitine showed an overall positive effect in one moderate quality RCT published in 2004.43 Other supplements (essential fatty acids44 and magnesium45) have also given promising results in single studies, although a later study of essential fatty acids failed to replicate the results of the first study.46 The trial of magnesium supplementation has apparently not been replicated. The evidence base for supplements and miscellaneous interventions for CFS/ME remains very limited. There is limited evidence about adverse effects associated with behavioural interventions. Withdrawals from treatment in RCTs suggest that there may be an issue but the evidence is often difficult to interpret because of poor reporting. In one RCT of CBT,47 two patients attributed a deterioration in their symptoms to the effects of the treatment. Another RCT of CBT reported high withdrawal rates in all three intervention groups, but the reasons for withdrawal were not reported.48 In the study of GET by Fulcher and White,32 one patient in each group withdrew because of worsening symptoms. In the RCT of patient education to encourage GET,33 21 of 148 patients (14.1%) entering the trial withdrew; 19 of these were in the groups randomized to GET, but the reasons for withdrawal were not reported clearly enough to be sure how many were attributable to adverse events. Eleven patients withdrew because of adverse events in a RCT of GET with or without fluoxetine,34 but it is not clear which intervention group they were in. New studies of behavioural interventions included in the update (Table 2) did not report any withdrawals caused by adverse events, although again the reasons for withdrawal were often not reported. Several studies of immunological/antiviral, pharmacological and nutritional interventions have reported withdrawals because of adverse effects, including recent studies of Staphylococcus toxoid,36 galanthamine hydrobromide37 and hydrocortisone/fludrocortisone.39 Recent studies of CBT29 and modified CBT49 in children and young people both reported that school attendance was significantly better in the treatment group compared with controls. One study supported the effectiveness of immunoglobulin treatment in children50 but this intervention may also have harmful effects. DISCUSSION Statement of principal findings A number of RCTs suggest that behavioural interventions, including elements of CBT, GET and rehabilitation, may reduce symptoms and improve physical functioning of people with CFS/ME. Immunological and anti-viral treatments may have beneficial effects but are also associated with harmful side-effects. Most pharmacological treatments have not shown beneficial effects. Strengths and weaknesses of the study Review methodology Our review was supported by a search of the literature that was designed to be as comprehensive as possible, with the objective of identifying all published studies of interventions for CFS/ME and related conditions that met pre-specified inclusion criteria. We searched for conference abstracts and dissertations as well as standard journal articles, and we attempted to locate unpublished reports and ongoing clinical trials. Publication bias needs to be considered in any systematic review; studies with statistically significant or unexpected results are more likely to be published than those showing non-significant results. Various statistical tests to assess publication bias are available, notably funnel plots, but the reliability of these is questionable and they are no longer recommended by the Cochrane Collaboration. We decided not to assess publication bias statistically for this reason and because of the wide range of interventions and outcomes included in the review. However, the fact that only one included study51 reported a negative effect of the intervention suggests that a degree of publication bias may be present in the CFS/ME literature. A fundamental problem in evaluating interventions for CFS/ME is that the wide variety of outcome measures used in the included studies makes it difficult to compare the effects of interventions across studies. Even when studies evaluated the same outcome, they used a variety of scales and measures to do so. This heterogeneity made it impossible to combine studies by meta-analysis. Standardized measures of treatment effect (effect sizes) can be calculated when studies measure the same outcome in different ways but the data required for this (sample size, mean treatment effect and standard deviation in each group) were not reported in many included studies. We have summarized our results (Table 1) in a way designed to convey as much information as possible in a relatively small space, but this presentation has limitations. Achievement of statistically significant differences between groups may be influenced by sample size in the study and results may be statistically but not clinically significant. Our measure of â€˜overall effectâ€™ represents an attempt to deal with this issue by showing which studies reported a statistically significant treatment effect on two or more clinical outcomes. A summary of the results of all included studies showing the magnitude of treatment effects is available from the authors and will be included in an updated version of the report by Bagnall and colleagues9 that will be available from the Centre for Reviews and Dissemination (http://www.york.ac.uk/inst/crd/index.htm). Included studies As noted above, development of standardized and objective outcome measures and agreement on their use in studies remain largely unmet goals. There is also a lack of longterm follow-up data for most interventions, although a five-year follow-up of the RCT of CBT by Deale and colleagues showed maintained benefit of the intervention for several outcomes52 and a two-year follow-up of one RCT of GET was published in 2004.53 The studies included in our review also show a lack of uniformity in terms of case definitions for CFS/ME, study inclusion and exclusion criteria and the basic information provided about the participants. For example, baseline functional status and duration of illness are not always reported. It is therefore difficult to assess the generalizability of the findings of many of these studies. Although we have discussed all the studies evaluating a particular intervention together, the treatment offered to patients receiving a particular type of therapy in practice may vary considerably, particularly for behavioural interventions. For example, in the CBT study by Stulemeijer et al.,29 participants in the intervention group received ten individual therapy sessions over five months in a hospital child psychology department, whereas in the study by Whitehead et al.54 the intervention was a form of 'brief CBT' delivered by general practitioners. Further standardization of methods for delivering behavioural interventions in research and practice would be desirable. Strengths and weaknesses in relation to other studies This updated systematic review confirms and extends the conclusions of previous reviews in this area.5,6,8,9 Evidence reviews also informed guidelines for the treatment or management of CFS/ME published in Australia55 and the Royal College of Paediatrics and Child Health (RCPCH) guidelines covering children and young people.56 The Australian guidelines concluded that CBT and GET 'may be effective for some people with CFS' (based on level 1 and 2 evidence, respectively). This is similar to the conclusions of our review. The recommendations for children and young people were largely developed by consensus because of a lack of specific evidence for this age group. GET and CBT were recommended for consideration based on extrapolation from studies in adults. The effectiveness of CBT for adolescents is supported by a recent high-quality RCT,29 although this had only 69 participants. Meaning of the study and implications for clinicians/policy makers Our results demonstrate that there are a considerable number of studies evaluating interventions for the treatment and management of CFS/ME and that many of them have used robust research methods; the majority of the included studies were RCTs and many of these were of high methodological quality (Table 1). However, RCTs generally scored poorly for concealment of treatment allocation and many failed to use an intention-to-treat analysis. These issues should be addressed in designing future clinical trials of interventions for CFS/ME. In view of the chronic nature of CFS/ME, future trials should be designed, as far as practicable, to collect long-term data on effectiveness and adverse events. A number of issues may limit the uptake and availability of effective interventions for CFS/ME. Behavioural interventions require the participation of trained therapists and this may raise issues both of cost and the availability of personnel. This is particularly true for CBT, which is regarded as a valid therapy option for a range of conditions. Improving the organization and delivery of psychological therapies has been identified as a priority for the UK National Health Service.57 Unanswered questions/further research Homeopathy and supplements (essential fatty acids and magnesium) have shown beneficial effects but only in one or two trials and further rigorous trials of these interventions would be helpful. Similarly, very few studies have assessed the effectiveness of interventions for children and young people and for severely affected patients. No rigorous evaluations of pacing were identified. A large trial known as PACE (Pacing, Activity and Cognitive behaviour therapy: a randomized Evaluation), involving patients attending specialist CFS/ME clinics across the UK, is underway and is due for completion in 2009. This trial is designed to compare specialist medical care against specialist medical care with the addition of adaptive pacing therapy, CBT or GET. Patient perceptions and preferences regarding interventions have been investigated but are not generally reported in studies of effectiveness. Some studies of behavioural interventions have reported significant rates of withdrawal from treatment or loss to follow-up, as high as 20-40% in some studies.48,54 Withdrawals not related to adverse events may reflect patient dissatisfaction with treatment. Our review did not find any new evidence of adverse effects (sufficient to cause withdrawal from treatment) associated with GET or CBT. However, reasons for withdrawals were often poorly reported and should be investigated in more detail in future studies. The protocols for many clinical studies require patients to attend a clinic for treatment and/or assessment. These conditions may exclude people severely affected with CFS/ME from taking part and hence bias the sample towards those with less severe symptoms. Surveys by patient organizations highlight the fact that those with the worst symptoms often receive the least support from health and social services.58 The balance between effectiveness and adverse effects of interventions may be different in more severely affected compared with less severely affected patients and methods of delivery/doses may need to be different. Research to evaluate the effectiveness of interventions for severely affected patients should be considered a priority. The FINE (Fatigue Intervention by Nurses Evaluation) trial is designed to evaluate a pragmatic rehabilitation therapy delivered by nurses in patients' homes, and hence accessible to severely affected patients.59 This trial is expected to end in 2008. Footnotes Acknowledgments We thank Vickie Orton for carrying out the literature searches and Paul Wilson for helpful comments. Authors' contributions Carol Forbes prepared the project proposal and managed the project. All authors participated in designing the study, selection of studies for the review, data extraction, data analysis and interpretation, and writing the paper, and approved the final manuscript. Guarantor Duncan Chambers is guarantor for this paper. Ethical approval Was not required. Funding/Support This project was funded by the National Institute for Health and Clinical Excellence who commissioned the National Collaborating Centre for Primary Care (part of the Royal College of General Practitioners) to produce guidelines for â€˜The Diagnosis and Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy) in Adults and Childrenâ€™. The work forms part of the independent synthesis of research evidence to support the development of these guidelines. The views expressed in this publication are those of the authors and not necessarily those of the NCC-PC, RCGP or the Institute. The funding source had no influence on study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and the decision to submit the paper for publication. Competing interests None declared. FIGURE CAPTIONS Figure 1 (A) QUORUM statement checklist of the systematic review. Figure 1 (B) QUORUM statement flow diagram of the systematic review. RCT, randomized controlled trial; CCT, controlled clinical trial TABLES Table 1 Summary of results of studies included in the review. Controlled studies are shaded in the table, all other studies are RCTs ------------------------------------------------------------------------------------- Treatment Number of Outcomes Any Overall Validity score patients investigated effect effect (Maximum 20) ------------------------------------------------------------------------------------- Behavioural CBT⁶⁰ 60 PH; PS; QOL + + 18 CBT⁴⁸ 270 PH; PS; QOL + + 16 CBT⁴⁷ 60 PH; PS; QOL + + 15 CBT²⁹ 69 PH; QOL + + 16 CBT + DLE⁶¹ 90 PH; PS; LAB; QOL + = 13 Rehab⁶² 47 PH; QOL + + 9 Rehab⁶³ 130 PH; PS; QOL + + 8 Rehab⁶⁴ 97 PH; PS; QOL + = 7 CBT⁵⁴ 65 PH; PS; QOL = = 3 CBT/rehab⁴⁹ 56 PH; QOL + = 2 CBT⁶⁵ 44 PH; PS; QOL = = 1 GET & Fluoxetine³⁴ 136 PH; PS; QOL + = 17 GET³² 66 PH; PS; LAB; QOL + + 17 GET³³,53 148 PH; PS; QOL + + 17 GET³¹ 61 PS; PH; LAB + + 9 GET³⁰ 49 PH + + 9 Immunological Immunoglobulin⁵⁰ 71 PH + + 16 Immunoglobulin⁶⁶ 30 PH; LAB; QOL = = 15 Immunoglobulin⁶⁷ 49 PS; QOL + = 13 Immunoglobulin⁶⁸ 99 PH; PS; LAB; QOL = = 13 Staphylococcus 98 PH + + 14 toxoid³⁶ Staphylococcus 28 PS; QOL + = 9 toxoid⁶⁹ Alpha interferon⁷⁰ 30 LAB; QOL + = 11 Interferon⁷¹ 20 PH = = 6 Acyclovir⁵¹ 27 PH; PS; LAB; QOL - = 15 Ampligen⁷² 92 RU; PH; PS + + 12 Terfenadine⁷³ 30 PH; QOL = = 12 Gancyclovir⁷⁴ 11 PH = = 4 Inosine pranobex³⁵ 16 PH; LAB; QOL + = 6 Pharmacological Hydrocortisone⁷⁵ 32 PH; QOL + = 18 Hydrocortisone⁷⁶ 70 PH; PS; QOL = = 14 Hydrocortisone³⁸ 120 PH; LAB + = 2 Hydrocortisone and 80 PH; PS; LAB; QOL = = 14 fludrocortisone³⁹ Fludrocortisone⁷⁷ 100 PH; PS; LAB; QOL = = 18 Fludrocortisone⁷⁸ 25 PH; PS; QOL = = 16 Topical nasal 28 PH = = 3 corticosteroids⁴⁰ Moclobemide⁷⁹ 90 PH; PS; LAB; QOL = = 19 Fluoxetine⁸⁰ 107 PH; PS; QOL = = 12 Selegiline⁸¹ 25 PH; PS; QOL + = 11 Galantamine 434 PH; PS = = 15 hydrobromide³⁷ Galanthamine 49 PH; PS; QOL = = 9 hydrobromide⁸² Oral NADH⁸³ 26 QOL + + 12 Pharmacological Oral NADH⁸⁴ 20 PH = = 3 Clonidine⁸⁵ 10 PS = = 12 Phenelzine⁸⁶ 24 PH; PS; QOL = = 10 Sulbutiamine⁸⁷ 326 PH; QOL = = 10 Dexamphetamine⁸⁸ 20 PH; QOL + = 8 Growth hormone⁸⁹ 20 PH = = 5 Melatonin⁹⁰ 30 PH; PS + + 5 Complementary/Alternative Homeopathy⁴¹ 103 PH + = 17 Any homeopathic 64 QOL = = 6 remedy⁴² Massage therapy⁹¹ 20 PH; PS; LAB + + 9 Osteopathy⁹² 58 PH; PS; QOL = = 0 Supplements General supplements⁹³ 53 PH = = 10 General supplements⁹⁴ 42 PH; QOL = = 10 General supplements⁹⁵ 12 PH = = 6 Essential fatty 63 LAB; QOL + + 17 acids*^44 Essential fatty 50 PS; QOL = = 16 acids*46 Magnesium⁴⁵ 34 PH; PS; LAB; QOL + + 15 Liver extract⁹⁶ 15 PH; PS; QOL = = 10 Acetyl-L-carnitine and 90 PH; PS + + 10 propionyl-L-carnitine⁴³ Pollen extract⁹⁷ 22 PH; PS; QOL; LAB = = 9 Acclydine and amino 90 PH; LAB + = 3 acids⁹⁸ Medicinal mushrooms⁹⁹ 70 PH = = 3 Other interventions Combination¹⁰⁰ 72 PH + + 19 Combination¹⁰¹ 71 QOL = = 3 Combination¹⁰² 52 PS; QOL + = 2 Low sugar, low yeast 57 PH; PS = = 11 diet (Hobday et al., unpublished data) Buddy/mentor¹⁰³ 12 PH; PS; QOL + = 4 Group therapy¹⁰⁴ 14 PH; QOL = = 1 ------------------------------------------------------------------------------------- +, positive effect of treatment; -, negative effect of treatment; =, no effect of treatment; rehab, rehabilitation; DLE, dialyzable leukocyte extract Outcome codes: PH, physical; PS, psychological; LAB, laboratory and physiological; QOL, quality of life and general health; RU, resource use. Outcomes which showed a significant difference between intervention and control groups are highlighted in bold * Essential fatty acids (both studies) were 36mg gamma-linoleic acid (GLA), 17mg eicosapentanoic acid (EPA), 11mg docosahexanoic acid (DHA), 255mg linoleic acid (LA), plus 10 IU vitamin E Table 2 Results of new studies included in the updated review ------------------------------------------------------------------------------------------------------------------------------ Intervention Author (Year), Results number of ----------------------------------------------------------------------------------------------- participants Physical Psychological Physiological Quality of life Drop-outs/ Validity and general Adverse effect score ------------------------------------------------------------------------------------------------------------------------------ Behavioural CBT Whitehead (2002) Fatigue: no Anxiety and Disability: no At 6 months, 8 3 ^54 n=65 significant Depression: no significant in treatment difference significant difference group and 11 between difference between groups in control group groups between groups were lost to follow-up Rehabilitation Cox (2002) Physical Emotional Maintaining 6 months after 7 (NB ^64 n=97 functioning distress: no activity and discharge, 14 controlled and fatigue: significant accommodating treatment group trial) no significant differences to illness: and 16 in control differences between groups significant group did not between groups difference in return favour of questionnaires treatment group (P<0.03) Rehabilitation Cox (1999)⁶³ Physical/ Perceived ability, Illness 5 withdrew from 8 (NB n=130 functional anxiety, depression, management: experimental controlled status, fatigue, emotional distress: significant group, 18 from trial) pain, symptoms: significant difference in control group significant difference between favour of difference groups for treatment between groups emotional group (P<0.03) for fatigue distress (P<0.03) symptoms (P<0.02) and pain (P<0.05) Rehabilitation Taylor (2004) Symptoms: Quality of life: No withdrawals 9 ^62 n=47 significant significant interaction interaction (P<0.05) (P<0.05) CBT Stulemeijer Physical School 6 patients 16 (2005)²⁹ n=69 functioning, attendance: dropped out fatigue, significant during treatment. symptoms: difference in 7 were missing significant favour of from CBT group difference in treatment and 2 from control favour of CBT group (P=0.04) group at final group (P<0.003) assessment Modified CBT Viner (2004) CFS severity: Global wellness, No withdrawals 2 (NB ^49 n=56 better result in school controlled intervention attendance: trial) group, significance significantly not reported better in treatment group (P<0.05) GET Moss-Morris CGI, fatigue: 3/25 dropped out 9 (2005)³⁰ n=49 significant of treatment and difference in 3/24 did not return favour of questionnaires at treatment group 12 weeks (P<0.03) GET Wallman (2004) Fatigue: Depression, Resting and One excluded 9 ^31 n=61 significantly anxiety: target heart after randomization better in significantly rate and blood because BMI too treatment group better in pressure, high to participate (P=0.027) treatment group exercise test in exercise test. (P=0.027) values: None reported comparisons during the study not made between groups Immunological Inosine Diaz-Mitoma Symptoms, Cognitive Immune function: Global 1 withdrawal in 6 pranobex (2003)³⁵ n=16 fibromyalgia function: no significant severity, each group. tender points: significant improvements activities of Transient no significant differences in treatment daily living, elevation of difference between groups group (P<0.03) Karnofsky serum uric acid between groups Performance (presumably in differences treatment between groups group) Staphylococcus Global impression, 10 dropouts 14 toxoid Zachrisson symptoms, pain: during study. (2002)³⁶ n=98 statistically 13 patients significant in the treatment difference in group and 7 in favour of treatment the placebo group group for CGI experienced side (P<0.001) and effects. 'feeling good' item on fibromyalgia impact questionnaire Pharmacological Galantamine Blacker (2004) Global Cognitive 130 patients 15 hydrobromide ^37 n=434 impression, function: no withdrew. 389 fatigue, significant patients reported symptoms: no difference adverse events, of significant between groups which 88 withdrew differences between groups Hydrocortisone Cleare (2002) Fatigue: Hormone levels: 2 ^38 n=120 'significantly' greater increase in greater cortisol response improvement in to HCRH in treatment group treatment group (P not reported) (significance not reported) Hydrocortisone Blockmans Fatigue: no Anxiety and Blood pressure: SF-36, 9 in treatment 14 and (2003)³⁹ n=80 significant depression: no no significant wellbeing: no group and 11 in fludrocortisone differences significant differences significant placebo group between groups differences between groups differences dropped out. Only between groups between groups one dropped out due to adverse events Topical Kakumanu (2001 Fatigue, Daily activity: 3 nasal ^40 n=28 daytime no significant corticosteroids sleepiness, improvement with muscle pain: treatment no significant improvement Oral NADH Santaella Symptoms: no 11 dropped out 3 (2004)⁸⁴ n=20 significant of 31 initially difference randomized. No between groups adverse events were reported in treatment group Dexamphetamine Olson (2003) Fatigue, sleep: SF36 scores: Reduced food 8 ^88 n=20 significant no significant consumption difference in difference reported by 5 favour of between groups patients in treatment group treatment group, for fatigue one in placebo (P<0.02) group Clonidine Morriss (2002) Cognitive One patient 12 ^85 n=10 function: no withdrew after significant GP prescribed effects fluoxetine Melatonin vs Williams Symptoms, Anxiety, 12 of initial 5 phototherapy (2002)⁹⁰ n=30 fatigue: depression: 42 patients improved sleep significant withdrew, 10 (P=0.03), effects of due to time and vitality treatment social demands (P=0.016) and of the study mental health (P=0.046) with melatonin, worsening of bodily pain (P=0.044) Complementary/Alternative Fatigue, 11 withdrew from 17 Homeopathy Weatherley- functional treatment arm Jones (2004) limitations: (5 did not ^41 n=103 significant complete differences in treatment) and 8 favour of placebo arm (6 treatment group did not complete for fatigue treatment) (P=0.04) and some physical dimensions of the Functional Limitations Profile (P value not reported) Supplements Vermeulen Global 8 patients 10 Acetyl-L- (2004)⁴³ n=90 improvement, Attention, withdrew to carnitine and fatigue, concentration: side effects propionyl-L- pain: 'significant' and 8 withdrew carnitine significant improvements due to lack of improvement in all groups efficacy. in general fatigue in PLC (P=0.004) and combined group (P<0.001); significant improvement in mental fatigue in ALC group (P=0.015) Acclydine De Becker Global IGF-1 levels: 3 (NB and amino (2001)⁹⁸ n=90 improvement, significantly controlled acids symptoms: more trial) improvements improvement in seen in intervention intervention than placebo group above group control group (P<0.0002) but groups were not compared statistically Pollen Ockerman Fatigue, Depression: Erythrocyte 1 withdrawal 9 extract (2000)⁹⁷ n=22 sleep, comparisons fragility: due to moving symptoms: were not made comparisons away. 'Slight comparisons between groups were not made intestinal were not between groups inconvenience' made between was the only groups side effect for a few days in 1 or 2 patients RM-10: Rothschild Symptoms: 2 dropped out 3 medicinal (2002)⁹⁹ n=70 improved of treatment mushrooms more in the group, not treatment reported for group placebo group. 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A feasibility study comparing two treatment approaches for chronic fatigue syndrome in adolescents. Arch Dis Child2005; 90:369-72 28. Dotsenko VA, Mosiichuk LV, Paramonov AE. [Biologically active food additives for correction of the chronic fatigue syndrome]. Vopr Pitan 2004;73:17-21 29. Stulemeijer M, de Jong LW, Fiselier TJ, Hoogveld SW, Bleijenberg G. Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial. BMJ2005; 330:14 30. Moss-Morris R, Sharon C, Tobin R, Baldi JC. A randomized controlled graded exercise trial for chronic fatigue syndrome: outcomes and mechanisms of change. J Health Psychol2005; 10:245-59 31. Wallman KE, Morton AR, Goodman C, Grove R, Guilfoyle AM. Randomised controlled trial of graded exercise in chronic fatigue syndrome. Med J Aust2004; 180:444-8 32. Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ1997; 314:1647-52 33. Powell P, Bentall RP, Nye FJ, Edwards RH. Randomised controlled trial of patient education to encourage graded exercise in chronic fatigue syndrome. BMJ2001; 322:387-90 34. Wearden AJ, Morriss RK, Mullis R, et al. Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiatry1998; 172:485-90 35. Diaz-Mitoma F, Turgonyi E, Kumar A, Lim W, Larocque L, Hyde BM. Clinical improvement in chronic fatigue syndrome is associated with enhanced natural killer cell-mediated cytotoxicity: the results of a pilot study with Isoprinosine. J Chronic Fatigue Syndr2003; 11:71-93 36. Zachrisson O, Regland B, Jahreskog M, Jonsson M, Kron M, Gottfries CG. Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome-a randomised controlled trial. European Journal of Pain: EJP 2002;6:455-66 37. Blacker CVR, Greenwood DT, Wesnes KA, et al. Effect of galantamine hydrobromide in chronic fatigue syndrome: A randomized controlled trial. JAMA2004; 292:1195 38. Cleare A. Hydrocortisone treatment in CFS. Int J Neuropsychopharmacol 2002; 5(Suppl 1):S35 39. Blockmans D, Persoons P, Van Houdenhove B, Lejeune M, Bobbaers H. Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study. Am J Med2003; 114:736-41 40. Kakumanu S, Mende C, Lehman E, Yeageer M, Craig T. The effect of topical nasal corticosteroids in patients with chronic fatigue syndrome and rhinitis. J Allergy Clin Immunol2001; 107:S153 41. Weatherley-Jones E, Nicholl JP, Thomas KJ, et al. A randomised, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome. J Psychosom Res 2004;56:189-97 42. Awdry R. Homeopathy may help ME. Int J Alternat Complement Med1996; 14:12-6 43. Vermeulen RC, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med2004; 66:276-82 44. Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand 1990;82:209-16 45. Cox IM, Campbell MJ, Dowson D, Davies S, Walden RJ. Magnesium and chronic fatigue syndrome. Lancet1991; 337:1295 46. Warren G, McKendrick M, Peet M. The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA. Acta Neurol Scand1999; 99:112-6 47. Sharpe M, Hawton K, Simkin S, et al. Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. BMJ1996; 312:22-6 48. Prins JB, Bleijenberg G, Bazelmans E, et al. Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial. Lancet2001; 357:841-7 49. Viner R, Gregorowski A, Wine C, et al. Outpatient rehabilitative treatment of chronic fatigue syndrome (CFS/ME). Arch Dis Child 2004;89:615-9 50. Rowe KS. Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents. J Psychiatr Res1997; 31:133-47 51. Straus SE, Dale JK, Tobi M, et al. Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial. N Engl J Med1988; 319:1692-8 52. Deale A, Husain K, Chalder T, Wessely S. Long-term outcome of cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome: a 5-year follow-up study. Am J Psychiatry2001; 158:2038-42 53. Powell P, Bentall RP, Nye FJ, Edwards RH. Patient education to encourage graded exercise in chronic fatigue syndrome. 2-year followup of randomised controlled trial. Br J Psychiatry2004; 184:142-6 54. Whitehead L, Campion P. Can general practitioners manage Chronic Fatigue Syndrome? A controlled trial. J Chronic Fatigue Syndr 2002;10:55-64 55. Royal Australasian College of Physicians. Chronic fatigue syndrome. Clinical practice guidelines-2002. Med J Aust2002; 176:S19-55 56. Royal College of Paediatrics and Child Health. Evidence Based Guideline for the Management of CFS/ME (Chronic Fatigue Syndrome/Myalgic Encephalopathy) in Children and Young People. London: Royal College of Paediatrics and Child Health; 2004 57. Department of Health. Organising and Delivering Psychological Therapies. London: Department of Health;2004 58. Action for M.E. Severely Neglected: M.E. in the UK-Membership Survey London: Action for M.E.;2001 59. Wearden AJ, Riste L, Dowrick C, et al. Fatigue Intervention by Nurses Evaluation- the FINE trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. BMC Medicine2006; 4:9 60. Deale A, Chalder T, Marks I, Wessely S. Cognitive behavior therapy for chronic fatigue syndrome: a randomized controlled trial. Am J Psychiatry 1997;154:408-14 61. Lloyd AR, Hickie I, Brockman A, et al. Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial. Am J Med1993; 94:197-203 62. Taylor RR, Braveman B, Hammel J. Developing and evaluating community-based services through participatory action research: two case examples. Am J Occup Ther2004; 58:73-82 63. Cox DL. An Evaluation of an Occupational Therapy Inpatient Intervention for Chronic Fatigue Syndrome [Ph.D]. London: King's College London, 1999 64. Cox DL. Chronic fatigue syndrome: An evaluation of an occupational therapy inpatient intervention. Br J Occup Ther2002; 65:461-68 65. Friedberg F, Krupp LB. A comparison of cognitive behavioral treatment for chronic fatigue syndrome and primary depression. Clin Infect Dis1994; 18 (Suppl 1):S105-10 66. Peterson PK, Shepard J, Macres M, et al. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med1990; 89:554-60 67. Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome. Am J Med1990; 89:561-8 68. Vollmer-Conna U, Hickie I, Hadzi-Pavlovic D, et al. Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome. Am J Med1997; 103:38-43 69. Andersson M, Bagby JR, Dyrehag LE, Gottfries CG. Effects of staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome. European Journal of Pain: EJP 1998;2:133-42 70. See DM, Tilles JG. a-Interferon treatment of patients with chronic fatigue syndrome. Immunol Invest1996; 25:153-64 71. Brook MG, Bannister BA, Weir WR. Interferon-alpha therapy for patients with chronic fatigue syndrome. J Infect Dis1993; 168:791-2 72. Strayer DR, Carter WA, Brodsky I, et al. A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome. Clin Infect Dis1994; 18(Suppl 1):S88-95 73. Steinberg P, McNutt BE, Marshall P, et al. Double-blind placebo- controlled study of the efficacy of oral terfenadine in the treatment of chronic fatigue syndrome. J Allergy Clin Immunol1996; 97:119-26 74. Lerner AM, Zervos M, Chang CH, et al. A small, randomized, placebo-controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome [comment]. Clin Infect Dis2001; 32:1657-8 75. Cleare AJ, Heap E, Malhi GS, Wessely S, O'Keane V, Miell J. Lowdose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet1999; 353:455-8 76. McKenzie R, O'Fallon A, Dale J, et al. Low-dose hydrocortisone for treatment of chronic fatigue syndrome: A randomized controlled trial. JAMA1998; 280:1061-66 77. Rowe PC, Calkins H, DeBusk K, et al. Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial. JAMA2001; 285:52-9 78. Peterson PK, Pheley A, Schroeppel J, et al. A preliminary placebo- controlled crossover trial of fludrocortisone for chronic fatigue syndrome. Arch Intern Med1998; 158:908-14 79. Hickie IB, Wilson AJ, Wright J, Bennett BK, Wakefield D, Lloyd AR. A randomized, double-blind, placebo-controlled trial of moclobemide in patients with chronic fatigue syndrome. J Clin Psychiatry 2000;61:643-48 80. Vercoulen J, Swanink CMA, Zitman FG, et al. Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome. Lancet1996; 347:858-61 81. Natelson BH, Cheu J, Hill N, et al. Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome. Neuropsychobiology1998; 37:150-4 82. Snorrason E, Geirsson A, Stefansson K. Trial of a selective acetylcholinesterase inhibitor, galanthamine hydrobromide, in the treatment of chronic fatigue syndrome. J Chronic Fatigue Syndr1996; 2:35-54 83. Forsyth LM, Preuss HG, MacDowell AL, Chiazze L Jr, Birkmayer GD, Bellanti JA. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol1999; 82:185-91 84. Santaella ML, Font I, Disdier OM. Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. P R Health Sci J.2004; 23:89-93 85. Morriss RK, Robson MJ, Deakin J. Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal. Psychopharmacology (Berl)2002; 163:166-73 86. Natelson BH, Cheu J, Pareja J, Ellis P, Policastro T, Findley TW. Randomized, double-blind, controlled placebo phase in trial of low dose phenelzine in the chronic fatigue syndrome. Psychopharmacology (Berl) 1996;124:226-30 87. Tiev KP, Cabane J, Imbert JC. Treatment of chronic postinfectious fatigue: randomized double-blind study of two doses of sulbutiamine (400-600 mg/day) versus placebo. Rev Med Interne1999; 20:912-8 88. Olson LG, Ambrogetti A, Sutherland DC. A pilot randomized controlled trial of dexamphetamine in patients with chronic fatigue syndrome. Psychosomatics2003; 44:38-43 89. Moorkens G, Wynants H, Abs R. Effect of growth hormone treatment in patients with chronic fatigue syndrome: A preliminary study. Growth Horm IGF Res 1998;8:131-33 90. Williams G, Waterhouse J, Mugarza J, Minors D, Hayden K. Therapy of circadian rhythm disorders in chronic fatigue syndrome: no symptomatic improvement with melatonin or phototherapy. Eur J Clin Invest 2002;32:831-7 91. Field TM, Sunshine W, Hernandez-Reif M, et al. Massage therapy effects on depression and somatic symptoms in chronic fatigue syndrome. J Chronic Fatigue Syndr1997; 3:43-51 92. Perrin RN, Edwards J, Hartley P. An evaluation of the effectiveness of osteopathic treatment on symptoms associated with Myalgic Encephalomyelitis. A preliminary report. J Med Eng Technol 1998;22:1-13 93. Brouwers FM, Van Der Werf S, Bleijenberg G, Van Der Zee L, Van Der Meer JW. The effect of a polynutrient supplement on fatigue and physical activity of patients with chronic fatigue syndrome: a double-blind randomized controlled trial. QJM2002; 95:677-83 94. Martin RWY, Ogston SA, Evans JR. Effects of vitamin and mineral supplementation on symptoms associated with chronic fatigue syndrome with Coxsackie B antibodies. J Nutr Med1994; 4:11-23 95. Stewart W, Rowse C. Supplements help ME says Kiwi study. J Altern Complement Med1987; 5:19-20 96. Kaslow JE, Rucker L, Onishi R. Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome. Arch Intern Med 1989;149:2501-3 97. Ockerman PA. Antioxidant treatment of chronic fatigue syndrome. Clinical Practice of Alternative Medicine2000; 1:88-91 98. De Becker P, Nijs J, Van HE, McGregor N, De MK. A double-blind, placebo-controlled study of acclydine in combination with amino acids in patients with chronic fatigue syndrome. AHMF Proceedings, "Myalgic Encephalopathy/Chronic Fatigue Syndrome The Medical Practitioners' Challenge in 2001".2001 99. Rothschild PR, Huertas JG. Ambulatory naturopathic treatment of chronic fatigue immune deficiency syndrome (CFIDS) with RM-10 caplets. Progress in Nutrition2002; 4:77-96 100. Teitelbaum JE, Bird B, Greenfield RM, Weiss A, Muenz L, Gould L. Effective treatment of chronic fatigue syndrome and fibromyalgia- A randomized, double-blind, placebo-controlled, intent-to-treat study. J Chronic Fatigue Syndr2001; 8:3-28 101. Marlin RG, Anchel H, Gibson JC, Goldberg WM, Swinton M. An evaluation of multidisciplinary intervention for chronic fatigue syndrome with long-term follow-up, and a comparison with untreated controls. Am J Med 1998;105:110S-14S 102. Goudsmit E. Learning to Cope with Post-Infectious Fatigue Syndrome, a Follow-up Study. Brunel,1996 103. Schlaes J, Jason L. A buddy/mentor program for PWCs. CFIDS Chronicle 1996:21-5 104. Soderberg S, EvengÃ¥rd B. Short-term group therapy for patients with chronic fatigue syndrome. Psychother Psychosom 2001;70:108-11 -------- (c) 2006 The Royal Society of Medicine [Return to top] ------------------------------ Date: Thu, 5 Oct 2006 13:42:35 -0700 From: Co-Cure moderators <cocuremoderator@xxxxx.xxx> Subject: MED: Lyme Disease: Let's Dispel the Myths >From ME Essential, Issue 100. October 2006 pages 20 and 21. Lyme Disease - let's dispel the myths LD specialist Dr. Darrel Ho-Yen urges caution over the bug that can be confused with ME The Internet has fuelled hysteria about Lyme disease. Lyme disease (LD) was discovered in 1975, with the first human case due to Borrelia burgdorferi being identified in 1983. Whereas many may know that I wrote the first book on ME, Better Recovery from Viral Illnesses, in 1985, and that this book is now in its fourth edition, many may not know that my first scientific publication on Lyme disease was in 1989, and that our laboratory in Inverness provides a Lyme testing service for Scotland. More importantly, I receive many emails, letters and telephone calls on LD from all over the world. Such communications have one thing in common: patients are worried about LD. Such anxieties and concerns are based on what they have heard or read and what they are being told by friends and relatives. These myths are many and varied: The Internet has the best information on Lyme disease This seems a very reasonable statement as the Internet has access to the most experts worldwide. The difficulty is separating the right information from the wrong. There needs to be judgement on what is being said. Unfortunately, looking for the right information can be like looking for a needle in a haystack. It may be difficult to find. In many cases, information on LD and ME is wrong. Doctors are ignorant of LD This appears to be an outrageous statement but has elements of truth in it. LD is a recently identified illness and is described as "an emerging infection." This means that many doctors have not studied this infection at medical school and that more information is emerging on this disease. This is not uncommon in medicine and indeed is to be expected. It also has to be balanced by the fact that not all areas of Britain have equal prevalence of LD. There are many urban areas where LD is very uncommon whereas in rural areas there is greater awareness and knowledge. Again, this is not a judgement on the medical profession but simply a reflection of reality. Those doctors in rural areas have to diagnose and manage LD. Most ME is Lyme Disease LD is characterised by early and late disease. The clinical syndromes of early disease are well recognised, such as the characteristic rash (erythema migrans); whereas late disease has characteristic clinical syndromes (for example, dermatological, cardiac, rheumatoid), but also includes a fatigue state. Therefore, it is only the late disease fatigue state that has common features with ME. Overall, this may represent only 10% of all LD infections. It is certainly not the majority of LD infections and most ME sufferers do not have LD. In the Highlands of Scotland, we have the greatest tick populations and it has been my routine in the investigation of ME patients to have them tested for LD. In this large series of patients who have had very significant exposure to ticks, the number of ME patients who have LD as the cause of their illness is around 5%. Antibiotics can cure LD This is a very attractive proposition. The truth of the matter is that in LD, early disease is amenable to antibiotic treatment and is curative. Unfortunately, late disease does not have the same response to antibiotics. In other countries, this has meant that prolonged treatment with antibiotics (often a year or longer) has been recommended. The very need for such prolonged treatment with antibiotics suggests that the success rate is not good. Indeed, it is difficult to separate the natural improvement that occurs with chronic disease from the effects of antibiotic treatment. Antibiotic treatment has limited success in late LD patients with symptoms comparable to that of ME. Instead, such patients should be managed, as is explained in my book, Better Recovery from Viral Illnesses, fourth edition, www.dodonabooks.co.uk All laboratories produce dependable results All NHS laboratories in Britain have to be accredited by Clinical Pathology Accreditation (UK) Ltd. If there is a diagnosis of LD without such accreditation, the diagnosis is suspect. Many patients are also seeking diagnosis by European or American Laboratories, and many such laboratories do not have appropriate accreditation. It is important to recognise that accreditation allows the user to have confidence in the report. Unaccredited laboratories can produce suspect results and may be influenced by the patient paying for the test. Within the accredited laboratory, all of its procedures have to be reproducible and subject to internal and external quality assurance. This guarantees that quality of the product to the user. Anyone receiving a diagnosis of LD should ensure that this is from an accredited laboratory. Misleading expert comment Experts have said that LD is ten times more common than is reported. This is absolutely true. Unfortunately, this statement is usually applied to all LD infections: from asymptomatic, flu-like illness to the well-defined clinical presentations. The number of patients that fall into the group of late LD with a comparable illness such as ME is small. LD accounts for 5% of ME patients in an area where there is great tick exposure. In future, if there is better diagnosis of LD, the amount of patients could double. However, the important consideration is how these patients should be managed. Summary LD is a new, emerging infection. Much is being written and discovered about this infection, and most of it is exciting and very helpful. Unfortunately, the Internet and certain groups have emphasised 10% of the information on LD rather than the 90%. It is important that all ME patients have a balanced approach to information on LD, especially as the management of late LD patients is similar to that of ME patients in which there are no obvious infectious disease causes. The answer is in making a balanced judgement, taking responsibility for your illness and sticking to guidelines. To blame others for not getting a diagnosis or appropriate management may not be helpful. In the end, it is a matter of what makes you better. *Dr. Darrel Ho-Yen is head of microbiology at the Raigmore Hospital, Inverness. (Further facts) (Picture of an engorged tick "The culprit" a tick) Fears over Lyme Disease as ticks flourish From the Daily Mail, September 1st. Rising temperatures have sparked a boom in the number of ticks carrying a dangerous blood-borne disease, experts have warned. The increase in levels of the insect has put people in danger of contracting Lyme Disease, which if left undiagnosed can trigger serious heart and joint problems. The rise was noticed after scientists were instructed by the Government to investigate why increasing numbers of farm animals were developing a virus transmitted by the parasites. They found there had been an apparent rise in ticks in recent months in Britain and warned this also had alarming implications for humans. Last year there were 600 laboratory confirmed cases of Lyme Disease in England and Wales, however some believe as many as 2,000 people may now be catching it every year. People are particularly at risk when in forests or in long grass where they are more likely to be bitten by the insects. The Department for Environment, Food and Rural Affairs (Defra) commissioned Professor Sarah Randolph from the Zoology Department at Oxford University to investigate what was triggering the rise. Although her work will not be completed for another year, she already has results back from 136 locations across the country. Based on the findings so far, she concluded: "Evidence does seem to indicate an increase in tick numbers. Everyone does seem to be concerned with an increase in incidence of certain diseases. Then there is also the very important issue of ticks' hosts which are mostly deer in the UK and also sheep and cattle." The disease is caused by a bacteria which ticks carry and is transmitted into the person when it begins to draw blood. Lyme Disease was discovered following a cluster of cases in the 1970s among young people living in Old Lyme in Connecticut, USA. However it is thought to have been around in Europe since the 1880s. It often begins with flu-like symptoms and then several days or weeks later 60 per cent of people notice an expanding rash. At this stage it can be treated with antibiotics, but if it is allowed to progress it can become very difficult to beat. It can then lead to long-term fatigue, plus create problems in the heart, joints and nervous system. ME Essential October 2006. [Return to top] ------------------------------ Date: Thu, 5 Oct 2006 20:47:16 -0400 From: "Marly Silverman <beatcfsfms@xxxxx.xxx> via Co-Cure Moderator" Subject: NOT,MED: IACFS 8th Annual Conference on Chronic Fatigue Syndrome, Fibromyalgia, Gulf War Syndrome, and other related illnesses [Note: For those who may wish to print this notice, a properly type-set version exists in PDF format at http://www.co-cure.org/conf8.pdf ] P.A.N.D.O.R.A. Hope. The only antidote! © PATIENT ALLIANCE FOR NEUROENDOCRINEIMMUNE DISORDERS ORGANIZATION FOR RESEARCH AND ADVOCACY - 501 c 3 - ID # 550795076 C/O VINA + COMPANY, 255 Alhambra Circle, Suite 715, Coral Gables, Florida 33134 Phone: 305-441-1591 Volunteer Help line: 954-783-6771 - www.pandoranet.info October 5, 2006 AN OPEN INVITATION TO OUR COMMUNITY Dear Friends, From January 10-14, 2007, we are co-hosting, with the International Association of Chronic Fatigue Syndrome (IACFS), their 8th Annual Conference on Chronic Fatigue Syndrome, Fibromyalgia, Gulf War Syndrome, and other related illnesses -www.iacfs.net to be held at the ocean-front Bahia Mar Resort in Fort Lauderdale. Some highlights of the 2007 international patient and professional conference are: * Presentation of the 2007 Advocates Extraordinaire/Sand Castles Scholarship Awards" a special leadership and advocacy agenda. Goals of this program are to: * Refresh skills of strong active advocates and encourage new ones to join our ranks. * Enable patients, family members, and/or caregivers become successful advocates on behalf of our community as well as an opportunity for sharing, supporting an embracing each other as a big family. * Presentations by special advocates, encouraging them to share their success stories (and hurdles) with others in our community: * Provision of a unique time to network within our international community * Allow members of the many nonprofit organizations and well organized groups, who have similar goals, the opportunity to get acquainted in a more intimate environment; share resources; and foster lifelong friendships, respect, and encouragement. * Exchange and debate ideas to strengthen cause and overall mission. * Support of the International Association for Chronic Fatigue Syndrome (IACFS) which is among the few professional medical associations that share a most important component of our entire community's mission - that research for chronic fatigue syndrome and fibromyalgia be placed in the forefront. * Establishment of a strong scientific research environment to foster greater opportunities and find cures for the illnesses for which we are advocating: * Meet the many researchers; physicians; and federal, state, and local health agencies, including the Centers of Disease Control and Prevention and the National Institute of Health, the Office of Research on Women's Health and many more. * Enhancing and creating "unity in action" by displaying a strong community front to strengthen our overall community advocacy and educational efforts. Save the dates January 10-14, 2007. Share P.A.N.D.O.R.A.'s flyer with friends, family, medical and allied health care professionals, and potential exhibitors and sponsors. A visit to South Florida in January, when most of the country is shivering from the cold, will be a wonderful winter respite. The weather will be fabulous, and Florida's sandy beaches will be extremely inviting during the days of the conference. I look forward to Well-Coming© you in Florida at the IACFS 2007 conference! In Good Health and In Beauty, Marly C. Silverman Founder P.A.N.D.O.R.A., Inc. Co-Chair - IACFS Patient Conference Planning Committee Built on Hope - Strong on Advocacy - Finding a Cure through Research [Return to top] ------------------------------ Date: Thu, 5 Oct 2006 21:45:50 -0400 From: Rika Kageyama via Co-Cure Moderator <ray@xxxxx.xxx> Subject: MED: CFS, possibly the immune dysfunction Dear all on the Co-Cure, This is Rika Kageyama from Tokyo, Japan. I was diagnosis with the CFS in 1989 (onset 1979), developed the RP (relpasing polychondritis) in 1995, the Lymph-TB in 2002 and currently the Colon-TB. Quite a department store of immune related disease. I will share my recent episode here. Currently I have been taking the prednisolne for 17.5mg/day (started from a mild dosage, 20mg/day, but I flared the RP symptoms when reduced the dosage. So, we have been stay on the dosage, 17.5mg/day). I am taking the prednisolone for long term. As long as I also cope with my TB (extra-plumonary, currently "colon TB"), I don't know what will happen in my future. My trachea symptoms have been progressed very gradually (dropping the oxygen saturation level very-very gradually. Luckily, I still have around 95). No obvious narrowing or abnormal for the visible tests though. The problem is that (some might remember but) I can not cure my TB due to the chemical allergy against the anti- TB agents. (I can not use four of four anti TB agents to cure as the CDC has recommended). Obviously, my TB is recurring. I have to use the prednisolone to control my RP symptoms. I believe my symptoms are not severe as I have to take the immuno supressants, such as immuran and azatioprin, or methotrexate. So, for the moment, I don't worry about the worst scenario. But, I do know it is the problem of "time". I have been under the very odd (troublesome) situation. Still need more investigation about the relationship between "my" CFS (chronic fatigue syndrome - real disease) and "my" RP. (Possibly, about "my" TB, also). I was told by my rheumatologist at the university hospital that I have to be hospitalized again for the investigation as soon as my colon TB will be subsided (Probably, in the spring in next year). Regarding the RP (relapsing polychondritis), my hospital is the university hospital at the University of Tokyo. My physician (Rheumatologist) is Prof. Kazuhiko Yamamoto. I will let you know when I learn something from the further investigation at the university. (I don't know if they will let me know some important thing though! Well, at least they will publish something for public or in journals). I believe the university and its hospital has broad minded for all of the patients and researchers in the world. My situation is much serious than I expected and their situation is more troublesome than they thought. I share this because, to me, all I have experienced have been the immune related diseases (CFS, RP, TB). My sed-rate, CRP have been normal as usual. Hugs to all, Rika Kageyama From Tokyo, Japan *CFS 1979 *RP 1995 *TB (extra-pulmonary) 2002- [Return to top] ------------------------------ Date: Thu, 5 Oct 2006 23:05:23 -0700 From: "Mary Schweitzer..........via Co-Cure moderators" Subject: RES,ACT: Royal Colleges Review of CFS therapies I want to thank Dr. Fluks for the copy of the Royal Colleges review of ME/CFS therapies by Duncan Chambers, Anne-Marie Bagnall, Susanne Hempel, and Carol Forbes. I found it strange that the authors wrote so positively of cognitive behavior therapy (CBT) and graded exercise therapy (GET): "As with CBT, the overall results of studies to date suggest that [GET] may have positive effects on the syptoms of CFS/ME" when in the same paragraph they admit that "Most ... studies of CBT and modified CBT have also favoured the treatment for one or more outcomes but these were either lower quality [random control trials] RCTs or non-randomized studies ... No severely affected patients were included in the studies of GET." They mentioned only two studies of immune therapies, both "associated with relatively high levels of adverse events." And then, "Treatment of CFS/ME with pharmacological therapies has given disappointing results in most cases.' Finally, their "statement of principal findings": "A number of [random control trials] RCTs suggest that behavioural interventions, including elements of CBT, GET and rehabilitation, may reduce symptoms and improve physical functioning of people with CFS/ME. Immnological and anti-viral treatments may have beneficial efects but are also associated with harmful side-effects. Most pharmacological treatments have not shown beneficial efects." That was not how I read their own measurement of success or failure (a ranking where 0 is a total failure and 20 is total success) in the table included with the study. There were eight studies using cognitive behavior therapy (CBT). The quality scores ranged from 1 to 18, with an average of 10.5 and a median o