Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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When simplicity may be misleading
- A. Chaudhuri (30 August 2002)
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Sloppy use of terminology or 'rewriting' history?
- Suzy Chapman (30 August 2002)
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Treating Fatigue
- Robert C bransfield@comcast.net (1 September 2002)
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grasping at straws
- andrew e homer (1 September 2002)
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More science and less opinion, please.
- Gurli Bagnall (2 September 2002)
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'A little hubris can be a dangerous thing'
- Paul Lynch (5 September 2002)
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Fatigue a symptom of hypercalcaemia
- Masud S Haq, Mark Spring, Consultant Endocrinologist, Kingston Hospital, Galsworthy Road, Surrey, KT2 7QB (6 September 2002)
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Murky waters?
- Lucy Cavendish-Gray (6 September 2002)
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Medications in assessment and management of fatigue states
- Ananth Puranik, Lindsey Kemp (10 September 2002)
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When Are False Statements Acceptable in Publications?
- Vance W Berger, Jonathan G. Levine (15 September 2002)
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Question marks over evidential basis of claims
- Neil C. Abbot, David J. Newton (17 September 2002)
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Practical Utility of the article 'Fatigue'
- Vasudeo P Paralikar, Meera Oke, Mitchell Weiss, Mohan Agashe, (18 September 2002)
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Review of chronic fatigue syndrome
- Susanne Merz, Lawrence I Mayer, general physician, Partnerskap för Vård AB, Grev Turegatan 40, SE-114 38 Stockholm, Sweden (27 September 2002)
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A. Chaudhuri, Senior Lecturer in Clinical Neurosciences University of Glasgow
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I thank Sharpe and Wilks for providing an account of psychogenic fatigue and chronic fatigue syndrome with a community prevalence figure of 2%. Quite appropriately, the authors have not focussed on neurogenic chronic fatigue (CFS/ME) that has a much lower prevalence (one-tenth, i.e. 0.2%)[1] and is seldom amenable to the approaches advocated for psychogenic chronic fatigue(graded exercises and cognitive behaviour therapy). The authors are correct in stating that fatigue is only a symptom. However, they should have also clarified that psychogenic chronic fatigue is only one of the many causes of chronic fatigue and a proportion of apparently "idiopathic" chronic fatigue is neurogenic where the input of a neurologist will also be necessary. As an example, chronic fatigue is not only the first, but also the only disabling symptom in at least 40% cases of multiple sclerosis (MS)[2]; MS is also one of the two disorders commonly misdiagnosed as functional somatic syndrome[3]. The characteristics of fatigue in appropriately defined CFS/ME are closer to MS than to chronic stress, anxiety or depression.[4] It is only the former group of patients who are more intolerant to the anti-depressants, less responsive to exercise and/or behaviour therapy and in need of chronic pain management requiring anti-convulsants like gabapentin or carbamazepine very similar to the MS patients. Simplicity in writing a review is not a virtue when it is done at the expense of facts. Life is an art of drawing sufficient conclusions from insufficient premises.[5] References 1. A Report of the CFS/ME Working Group. Department of Health (2002). 2.Murray TJ. Amantadine therapy for fatigue in multiple sclerosis. Can J Neurol Sci 12; 251-54 (1985). 3. Couprie W, Wijdicks EFM, Roojimans HGM, van Gijn J. Outcome in conversion disorder: A follow up study. J Neurol Neurosurg Psychiatry 58; 750-52(1995). 4. Chaudhuri A, Behan PO. Neurological dysfunction in chronic fatigue syndrome. J Chr Fatigue Synd 6:51-68 (2000). 5. Butler S. Notebooks (1912). |
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Suzy Chapman, Carer of young person with ME Poole, Dorset
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Authors Mayou and Farmer or their editor, M Sharpe, have yet to respond to significant concerns about the use of terminology in their article in the Clinical Review series: ABC of psychological medicine: Functional somatic symptoms and syndromes, (3 August) [1] May I remind readers that under the heading 'some common symptoms and syndromes' the authors list 'Chronic fatigue (myalgic encephalomyelitis)'. Since it is not at all clear from this, or from a further reference to 'chronic fatigue' towards the end of the article, would the authors or their editor please clarify via Rapid Responses exactly what they mean here? Are they referring to 'chronic fatigue' or 'chronic 'fatigue syndromes' or 'chronic fatigue syndrome'. If the latter, is this 'chronic fatigue syndrome' as in CFS, or as in ICD-CFS? Dr Chaudhuri and others writing in this thread have already reminded the authors that 'myalgic encephalomyelitis' and ICD-CFS are listed by the WHO as 'neurological disorders' in the International Classification of Diseases (ICD 10.). In January 2000, a writer to Rapid Responses had cause to raise a question concerning editorial policy. Editor, Richard Smith replied thus: "We've adopted this policy in order to leave a trail of errors and corrections. They may well prove to be important at some future time. There is something unnerving - and totalitarian - about "rewriting" history." Without doubt an admirable sentiment in any field. The current issue's contribution to Clinical Review: ABC of psychological medicine, is 'Fatigue', by M Sharpe. I quote: "The term myalgic encephalomyelitis (or encephalopathy) has been used in Britain and elsewhere to describe a poorly understood illness in which a prominent symptom is chronic fatigue exacerbated by activity. This is a controversial diagnosis that some regard as simply another name for chronic fatigue syndrome and that others regard as a distinct condition. This article will focus on chronic fatigue syndrome." What exactly is going on here? A few weeks ago we were given 'chronic fatigue (myalgic encephalomyelitis) in an article on 'functional somatic symptoms and syndromes - a few weeks later, we are offered the above statement (and this in a series of articles due to be published together, later this year by the BMJ, in book form). It is about as clear as mud! At best, this looks like sloppy, imprecise and inconsistent use of medical terminology. But given that the WHO have ICD-CFS and myalgic encephalomyelitis listed as 'neurological disorders' in the ICD, is the 'fuzzy' classification of 'myalgic encephalomyelitis' in these two articles an attempt at 'rewriting' history too? I don't doubt that the latest article in this series will generate a good deal of comment, but in the meantime, why have the authors or the editor of 'Functional somatic syndromes and symptoms' not been prepared to address our concerns? And are the BMJ happy with such sloppy use of medical terminology in their journal, and are they equally happy that WHO ICD classifications are disregarded - is this happening with other conditions or just myalgic encephalomyelitis? Suzy Chapman 1 Clinical Review: ABC of psychological medicine: Functional somatic symptoms and syndromes, Mayou and Farmer http://bmj.com/cgi/content/full/325/7358/265 BMJ 2002;325:265-268 (3 August 2002). |
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Robert C bransfield@comcast.net, Associate Director of Psychiatry Riverview Medical Center, Red Bank, NJ, USA 225 Hwy # 35, Red Bank, NJ, USA, 07701
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Dear Editor, I am pleased to see Shape and Wilks draw attention to this often overlooked subject. I am currently performing a prospective study treating fatigue with modafinil, as measured by the Modified Fatigue Impact Scale (MIFS). The data from the first 48 patients demonstrates 83.3% of the patients improved an average of 19 points on the MFIS (84 point scale). A retrospective chart review of 237 patients treated with modafinil for fatigue and associated symptoms using the Clinical Global Impression Severity Scale shall soon be submitted for publication. Based upon my data, modafinil is a cortical activator that is effective, safe, well tolerated and not abused in the treatment of the often associated symptoms of fatigue, excessive daytime sleepiness, certain cognitive impairments, executive dysfunction and disorders of motivation that are associated with a broad range of psychiatric and general medical illnesses. Sincerely,
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andrew e homer, patient Cr2 0df
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I have had M.E. since i came down with some sort of unidentified polio/flu-like virus in 1983. I am now 52 and previous to 1983 was in good health. The symptoms I suddenly came down with then in an acute form, I still have now in a less acute form. Muscle aches, pins and needles and chronic fatigue brought about by exercise or stress. The main problem with beleiving that psychological treaments are effective, (which they may be in a minor form as with most illness), is that it implies that the cause is in some way psychological. Therefore this diverts attention from investigating the real causes of CFS/M.E. and therefore is thus potentially harmful and does not help the plight of those millions who are suffering. Andrew |
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Gurli Bagnall, Patients' Rights Campaigner
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Apart from a patient's question, “Is it all due to a virus?” raised under the heading “Identifying unhelpful beliefs”, no other reference was made to infection in the article entitled “Fatigue”. One wonders, therefore, why David Wilks, consultant in infectious diseases at Western General Hospital, Edinburgh, would contribute to this scientifically unsubstantiated article. It seems somewhat arrogant and indeed, dangerous, for Sharpe and Wilks to take such a dogmatic stance while still having to acknowledge that “…fatigue remains poorly understood and has hitherto probably been not been (sic) given adequate attention by doctors.” The implication is, perhaps, that only the authors and others who belong to the same school of thought, have a “unique understanding” of fatigue. What a pity they didn’t share the secret and back it up with scientific evidence. Very relevant to this article, is the case of Ray Nimmo who, in June of this year, was awarded the sum of 40,000 pounds. Mr. Nimmo consulted his doctor in 1984 with a dental infection. An allergic reaction to the antibiotic led to severe abdominal pain and a prescription for the benzodiazepine, Xanax, to deal with his “muscle spasm”. The pain continued and other similar drugs were prescribed, resulting in years of side effects including suicidal depression, agoraphobia, insomnia, panic attacks and, of course, addiction. Given these side effects, fatigue no doubt figured quite substantially as well. Now that his doctor has had to pay out compensation, it is to be hoped he will, in future, be less dogmatic about pushing inappropriate treatments and pinning psychiatric labels where they do not belong. The general media considered the story of Ray Nimmo highly newsworthy. It was picked up by several newspapers and Mr. Nimmo was interviewed on both radio and TV. The case is expected to trigger a number of similar law suits in the UK. It is hardly unreasonable to have expected this very relevant news item to have have picked up by the BMJ, but for some strange reason, it wasn’t. Indeed the BMJ, is most reluctant to even mention the word “benzodiazepine”. But then it is part of an inglorious and shameful aspect of medicine, involving in particular, the branch of it to which Sharpe belongs. Given that millions during the last 30 years in the UK have been affected as Nimmo was, would Michael Sharpe please be kind enough to explain why the lay community should trust a medical opinion when it makes no sense whatsoever? After all, the medical profession has shown itself to be every bit as fallible as the rest of society. Gurli Bagnall, Patients’ Rights Campaigner, New Zealand. 1.Why doctors must be wary of prescribed drug case, Butterworths Legal News, July 22, 2002. 2. Benzodiazepine guidelines routinely ignored, Transcript, You and Yours, BBC Radio 4, July 16, 2002. 3. Landmark Clinical Negligence Victory, Transcript, BBC Look North, June 28, 2002. 4. £40,000 for Valium dad, The Sun, June 28, 2002. 5. Interview with BBC Radio Humberside, Transcript, June 27, 2002. 6. 'Valium ruined my life' claimant wins £40,000 damages from ex-GP, Yorkshire Post, June 27, 2002. 7. 'GPs made me into zombie', Scunthorpe Telegraph, June 25, 2002. 8. Keeble Hawson wins £40,000 settlement, June 24, 2002. 9. Valium addict wins pay-out of £40,000, The Observer, June 23, 2002. Breaking news story about the owner of this site. 10. Log on to drug help, Scunthorpe Evening Telegraph, Monday, May 28, 2001. |
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Paul Lynch, Retired
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The Authors have, once again, failed to agknowledge the evidence of abnormalities found in ME and ICD-CFS. Therefore, I quote for the record. (1) Despite beliefs and assertions to the contrary, in ME there is evidence of inflammation of the central nervous system (CNS); that is what helps to differentiate ME from other forms of CFS. There are many references in the medical literature to inflammation of the CNS in ME and in ICD- CFS but such CNS inflammation is not found in all variants of CFS. It is incorrect to deny the existence of CNS inflammation in ME / ICD-CFS. In some cases of ME, as in multiple sclerosis, there is evidence of oligoclonal bands in the cerebrospinal fluid. It is accepted by the most experienced ME clinicians that some degree of encephalitis has occurred both in patients with ME and in those with post-polio syndrome: the areas chiefly affected include the upper spinal motor and sensory nerve roots and the spinal nerve networks traversing the adjacent brain stem (which is always damaged). In nearly every patient there are signs of disease of the central nervous system. Recent research continues to support neurological involvement. There is a substantial literature on the neuroendocrine dysfunction which has been demonstrated in ME / ICD-CFS, particularly the known dysfunction of the hypothalamic-pituitary-adrenal axis (HPA axis), leading to a disordered stress response. There is mounting international evidence that ME / ICD-CFS is an autoimmune disorder, with similarities to systemic lupus erythematosus. Evidence of antilamin antibodies has been found in the blood of ME / ICD- CFS patients: antibodies against this protein are proof of autoimmunity and of damage to brain cells. The occurrence of autoantibodies to an intra -cellular protein like lamin B1 provides laboratory evidence for an autoimmune component in ME / ICD-CFS. In the UK, patients with autoimmune features and neurological signs and symptoms are usually the most sick and as such they are excluded from studies of "CFS" or chronic fatigue undertaken by psychiatrists, so the results of UK studies from which such patients are excluded are not representative of the true situation. A particularly important piece of research in these patients has demonstrated sensitivity of the vascular endothelium to acetylcholine (a major neurotransmitter and vascular dilator) and this finding may have implications for many other cholinergic pathways (which are extensive throughout the body). In ME / ICD-CFS there is evidence of disruption in ion channels in the cell membranes; changes in ion channel function from time to time offer a rational basis to explain the fluctuating symptoms, and such ion channel changes are known to be induced by physical activities, stress and fasting. If sodium channels are blocked in the open mode, this causes entry of sodium into neural tissues and muscles. This ingress of sodium is followed by water, which in turn leads to swelling of the neural tissues, a phenonmenon observed both electron microscopically and by laser scanning microscopy. Acquired ion channel abnormalities in the myocardium could explain the pathogenesis of Syndrome X and may form the basis of cardiac dysfunction in both Syndrome X and in ME / ICD-CFS. Australian researchers have found that total body potassium (TBK) is significantly lower in patients with ME / ICD-CFS; they suggest that abnormal potassium handling by muscles in the context of low overall body potassium may contribute to muscle fatigue in this disorder. Burnett reports that there is a reduced flux of potassium across the cell membrane (which fits in with a channelopathy) and that patients will feel more ill the lower the potassium levels. TBK results for ME / ICD-CFS patients have also been shown by others to be significantly lower than those for controls; this fits with other metabolic abnormalities in these patients, such as impaired water metabolism. There is convincing evidence that patients with ME / ICD-CFS reach exhaustion more rapidly that normal subjects: the use of 31 P-nuclear magnetic resonance (31 P-NMR) has now provided positive evidence of defective oxidative capacity in such patients. These findings show that there is a continued loss of post-exertional muscle power (giving an additional loss of power), with delayed recovery for at least 24 hours, whereas sedentary controls recovered full muscle power after 200 minutes. A genetic component to ME / ICD-CFS is strongly suggested by HLA phenotyping analysis in the laboratory of Paul Terasaki at UCLA School of Medicine. Terasaki is one of the world’s leading experts in HLA typing and he found 46% of ME / ICD-CFS patients were HLA-DR4 positive. However, in a small study of only 58 patients, Wessely (a UK psychiatrist – see below) found no association between HLA genotype and CFS and claims there is no significant difference in HLA frequencies between patients and controls. In the February 2000 issue of The American Journal of Medicine, Anthony Komaroff (Assistant Professor of Medicine at Harvard and a world expert on this disorder) summarised key points in an Editorial: "Many controlled studies have compared patients with age-matched and gender-matched healthy control subjects. Objective biological abnormalities have been found significantly more often in patients with the syndrome than in the comparison groups. The evidence indicates pathology of the central nervous system and immune system. What is the evidence of central nervous system pathology? Magnetic resonance imaging has revealed areas of high signal in the white matter. Single photon emission computed tomography (SPECT) signal abnormalities also are found more often in patients, abnormalities like those seen in patients with encephalopathy due to the acquired immunodeficiency syndrome (AIDS) and unlike the findings in patients with depression. Autonomic nervous system testing has revealed abnormalities of the sympathetic and parasympathetic systems that are not explained by depression or physical deconditioning. Studies of hypothalamic and pituitary function have revealed neuroendocrine abnormalities not seen in healthy control subjects and opposite to those found in depression. There is considerable evidence from different investigators, using different technologies and studying different groups of patients, of a state of chronic immune activation. In summary, there is now considerable evidence of an underlying biological process in most patients (which) is inconsistent with the hypothesis that (the syndrome) involves symptoms that are only imagined or amplified because of underlying psychiatric distress. It is time to put that hypothesis to rest". ...It is essential to be ever mindful of the fact that it is unsafe to assume that the most prolific published author on a subject is necessarily the unquestioned expert on that subject. This is especially true in relation to ME / ICD-CFS. 1): 'What is ME? What is CFS? INFORMATION FOR CLINICIANS AND LAWYERS' December 2001. EP Marshall, M. Williams, A. Hooper. http://www.btinternet.com/~severeme.group/papers/whatisME_whatisCFS.htm http://www.meactionuk.org.uk/What_is_ME_What_is_CFS.pdf |
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Masud S Haq, Specialist Registrar Endocrinology Kingston Hospital, Galsworthy Road, Surrey, KT2 7QB, Mark Spring, Consultant Endocrinologist, Kingston Hospital, Galsworthy Road, Surrey, KT2 7QB
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Dear Editor We were interested to read the comprehensive article regarding chronic fatigue(1). In addition to the appropriate screening measures recommended in a patient with fatigue, we would strongly suggest, as endocrinologists and general physicians, that serum calcium measurement is added to the other screening tests mentioned. Hypercalcaemia has many causes and is a relatively common condition(2) that may present with many of the symptoms associated with chronic fatigue such as depression, musculo-skeletal pain, tiredness and lethargy. Measurement of serum calcium is inexpensive and freely available with reliable bioassay techniques. Finally, hypercalcaemia is an important diagnosis that may represent underlying malignancy or benign conditions such as primary hyperparathyroidism or sarcoidosis that are easily amenable to treatment. 1. Sharpe M, Wilks D. Fatigue. BMJ 2002; 325: 480-483. (31 August) 2. Heath D, Marx S. Calcium disorders. Butterworths International Medical Reviews. Clinical Endocrinology Vol 2. Butterworth Scientific, London. Masud Haq Mark Spring Conflict of interest: none |
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Lucy Cavendish-Gray, Former lecturer, Special Educational Needs Canterbury, Kent
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Suzy Chapman (eBMJ, 30 August) questions terminology used in the Clinical review series: ABC of psychological medicine, and remarks that it is about as clear as mud [1]. Perhaps I can offer some clarification. Sharpe gives us inclusion criteria for chronic fatigue syndrome and goes on to comment that: "The term myalgic encephalomyelitis (or encephalopathy)…is a controversial diagnosis that some regard as simply another name for chronic fatigue syndrome and that others regard as a distinct condition. This article will focus on chronic fatigue syndrome." Sharpe fails to explain whether he chooses, in his article, to focus on chronic fatigue syndrome because he, himself, regards myalgic encephalomyelitis (or encephalopathy) as another name for chronic fatigue syndrome, or because he regards it as a distinct condition. No matter, for in a previous article in this series, 'ABC of psychological medicine: Functional somatic symptoms and syndromes' [2] under the heading 'Some common functional symptoms and syndromes' is listed: Chronic fatigue [sic](myalgic encephalomyelitis). It is not at all clear in this article on 'Functional somatic symptoms and syndromes' whether the term 'chronic fatigue' is here being used synonymously with 'chronic fatigue syndrome', but since 'myalgic encephalomyelitis' is given in brackets afterwards, then I think it safe to assume that this must have been the editor's intention, since no one would want to confuse a portmanteau term like 'chronic fatigue' with the disorder 'myalgic encephalomyelitis'. What 'myalgic encephalomyelitis' or, for that matter, 'chronic fatigue (syndrome)' are doing listed in an article on 'functional somatic symptoms and syndromes' in the first place, and why the BMJ persists in colluding with this, remains a mystery [3][4]. I do hope this has helped. Lucy Cavendish-Gray 1 Sloppy use of terminology or 'rewriting' history? Suzy Chapman (eBMJ Rapid Response: 30August 2002) Clinical review: ABC of psychological medicine: Fatigue Michael Sharpe and David Wilks BMJ 2002; 325: 480-483 (30 August) 2 Clinical review: ABC of psychological medicine: Functional somatic symptoms and syndromes, Richard Mayou, Andrew Farmer BMJ 2002; 325: 265-268 (3 August) 3 Multiple chemical sensitivity (MCS): Review by Margaret Williams (August 2002): "Exquisite Chemical Sensitivity Mechanism in MCS", by Professor Marty Pall, Journal of the Federation of American Societies for Experimental Biology 4 Rethinking Somatization: Review by Margaret Williams (September 2002) Robert Bennett (ref: The Scientific Basis for Understanding Pain in Fibromyalgia. Immune Support.com, 28 August 2002) from a paper called “Rethinking Somatization” published in the Annals of Internal Medicine in May 1997 by Ian McWhinney et al (ref: Rethinking Somatization. McWhinney IR, Epstein RM, Freeman TR: Ann Intern Med 1997:126:747-750) |
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Ananth Puranik, Consultant Psychiatrist Priority House, West Kent NHS and Social Care Trust. ME16 9PH, Lindsey Kemp
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EDITOR -We read with interest Drs Sharpe and Wilks article on fatigue (BMJ ABC of Psychological Medicine 31st August 2002). Despite careful scrutiny of the text we can see no reference of medication being a common and iatrogenic contributor to fatigue. A review of the BNF shows fatigue listed as a potential side effect in medications such as SSRIs, digoxin, prednisolone and amiodarone to name a few. The side effects of medication may often be an issue that patients feel is not taken seriously and in the interests of doctor patient relations the trade off between treatment benefits and side effects may have to be made explicit. As pointed out in the article fatigue can have a disabling impact on the quality of life of the sufferer and therefor needs to be taken into consideration in the patients overall management. In the treatment of depression tiredness may remain as a residual, treatment resistant symptom despite improvement in sleep, appetite and mental state. The fact that tiredness is not relieved despite adequate treatment of the underlying condition may leave the physician feeling frustrated and inadequate and the patient feeling less than satisfied. We feel it is of value in all consultations around fatigue to take a full history and consider a review of all medications taken by the patient both those prescribed and those bought over the counter when considering such symptoms as fatigue. 1 Sharpe, M and Wilks, D ABC of psychological medicine; Fatigue BMJ 2002;325:480-3 (31 August) 2 British National Formulary 43; March 2002 Ananth Puranik, consultant psychogeriatrician Priority House, Maidstone ME16 9PH Lindsey Kemp, consultant in psychiatric rehabilitation
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Vance W Berger, Mathematical Statistician National Cancer Institute, Jonathan G. Levine
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Sharpe and Wilks [1] did a nice job of explaining the ABCs of fatigue, and overall we found this to be a good article. Had we been reviewers, we might have recommended it for publication. But certainly not as is, because there is a false statement in the article that should have been corrected. Specifically, it is stated that “Like blood pressure, subjective fatigue is normally distributed in the population”. In fact, it is not. We make this bold claim not because we possess any special knowledge of the true distribution of fatigue in the population. Nor do we base this claim on an inspection of the graph of fatigue in the population presented in [1], although it is clearly skewed (indicating non- normality). Rather, we make the claim because while a statement that data have a normal distribution may seem innocuous, in fact it actually means something. The implications include a specific probability for each of the infinitely many intervals on the real line and the exclusion of each of the infinitely many distributions that is not normally distributed. In the space of all distributions, the normal distributions occupy literally zero per cent (technically, the normal distributions together have Lebesgue measure zero). At least the proverbial needle has some positive measure relative to the haystack within which it hides. How can the infinitely many statements represented by a claim of normality all be credible when they are based on a small finite amount of data? Even a complete census of the population, with perfect measurement of fatigue without any error, and perfect compliance, would still not suffice to allow for a credible statement of normality. Furthermore, any census conducted by Sharpe and Wilks [1] was incomplete, in that they missed at least two people (us). Of course, how the population is defined is not quite clear, so it may be defined in some way as to exclude us from it. Ultimately one can only assume, not prove, that a random variable has a normal distribution. Assumptions such as normality, equality of variances, additivity, linearity, and monotonicity are covert methods of augmenting the information contained in the data with prior knowledge or beliefs. If the assumptions derive from actual knowledge of the phenomenon under study, then this augmentation may be appropriate. If the assumptions derive from wishful thinking, or the researcher’s desire to have a smaller variance estimate or a more powerful test, then assumptions amount to a disservice to science. In extreme cases, assumptions can drown out the information contained in the data. It is clear that like blood pressure, fatigue has a distribution. Perhaps this is what Sharpe and Wilks [1] meant. It is also clear that, contrary to what Sharpe and Wilks [1] said, neither of these distributions is normal, although either may be close enough to normality that using the normal model would not result in tremendous differences from exact models. What troubles us most is that with no support, or, in this case, even against clear evidence to the contrary, some researchers will continue to claim that the distributions are normal, and some journals will publish articles with these false statements. So the question concerns the salient features of this particular false statement that make it publishable. One could argue that the statement of fatigue being normally distributed had no impact on the remainder of the article, so its truth is not necessary. This would suggest that non-essential statements may be false. Or one could argue that similar statements have been made in other articles. This would suggest that statements may be false as long as there is a precedent for making this particular false statement. An extension of the first argument would be that it is acceptable to publish a false medical claim as long as this is done in an article that is not about medicine. For example, one could publish an article in the statistics literature, in which a new method is developed, and demonstrated on a fictitious medical example. But because the example is not crucial to the main contribution, the first argument would suggest that the authors could legitimately claim that the fictitious medical example is actually real. An extension of the second argument would then be that once this false statement is published, it can be published again, this time in the medical literature. To find either argument compelling is to enter into a slippery slope towards a society in which one cannot trust what one reads. Or have we already taken that plunge? Here are two votes to hold publications to a higher standard, in which all claims (including statistical) are correct. References [1]. Sharpe M, Wilks D, ABC of Psychological Medicine: Fatigue, BMJ 2002;325:480-483. |
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Neil C. Abbot, Director of Operations MERGE (ME Research Group for Education and Support), The Gateway, North Methven St, Perth PH1 5PP, David J. Newton
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Sharpe and Wilks' review [1] contains an "evidence-based summary" with the statement, "graded exercise and cognitive behavioural therapies are effective in treating chronic fatigue syndrome". However, rigorous examination of the literature indicates that this remark is not itself evidence-based, a serious criticism since evidence-based summaries in the BMJ carry weight and are widely quoted. For the record, two research groups have now conducted systematic reviews of putative treatments for chronic fatigue syndrome [2,3]. They have identified 3 eligible randomised controlled trials (RCTs) of graded exercise therapy (GET) and 5 RCTs of cognitive behavioural therapy (CBT). The total number of available trials is small, numbers are relatively low (6/8 trials have n<40 in the active groups), and two of the 5 CBT trials do not show an overall significant effect (Table). No trial contains a "control" intervention adequate to determine specific "efficacy": in only 2 trials are the treatment arms compared with an 'active', though not indistinguishable, intervention. Yet, the chart in the clinical review [1] refers to the "efficacy" of CBT, showing data from one trial (Prins et al, 2001) in which the comparison groups were guided support (social worker) for 11 sessions (against 16 sessions of CBT) and no intervention. A number of non-specific effects could have accounted for these results, and the fact that the drop-out rate in the active arm was 40% may point in this direction, as discussed in one of the reviews [2]. Again, the heterogeneity of the trials, the potential effect of publication or funding bias for which there is some evidence [4], and professional doubts about the evidence base for some behavioural therapies themselves [5] give grounds for caution. Indeed, if a similar evidence base existed for, say, Shamanic healing - which has no professional proponents - it would arouse little clinical interest. Neither of the review groups has commended GET or CBT as particularly effective
for chronic fatigue syndrome patients. Whiting et al. [2] state, "all conclusions
about effectiveness should be considered together with the methodological inadequacies
of the studies. Interventions that have shown promising results include CBT
and GET"; and Mulrow et al. [3] state, "….it is unlikely that
the beneficial effects of such general treatments are specific or limited only
to patients with CFS. In other words, although these therapies may help some
people with CFS, their effectiveness does not help establish an underlying aetiology
or cause of CFS". References
Table: Randomised controlled trials of CBT and GET identified by recent
systematic reviews.
Outcomes: P = physical; Psy = psychological; Lb = laboratory; Qol = quality
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Vasudeo P Paralikar, Psychiatrist Regional Mental Hospital,Yeravada, Pune, India, Meera Oke, Mitchell Weiss, Mohan Agashe,
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Dear Editor, I must congratulate you and the authors for their highly useful article. It is excellent for its practical utility in primary care, and especially in developing countries like India. The controversies in rapid responses are all scholarly and of high research interest; but the section is ABC of Psychological Medicine to which it does more than adequate justice. Another important reason for which the article is useful, is the magnitude of the problem. If the psychogenic fatigue is more than 10 times prevalent than the esoteric and rare syndromes, it must be dealt with adequately. And the disability is the same whether psychogenic or otherwise. The high controversy generated and seen in the rapid responses, is evidence of the fact stated in the book by Wessely et al on Disorders of Chronic Fatigue that 'fatigue is like Central Africa of Medicine; no sane doctor would like to enter it'. The guidelines about attending to the beliefs of the patient cannot be overemphasized. In our ongoing study on cultural disorders of fatigue and weakness using explanatory model interview catalogue, we have found that an elaborate expression by the patient of his own views of the illness experience, its stigma, the perceived causes, and experiences regarding the past treatment all are important in shaping his views and behaviour. Only the clear understanding by the patient of his own suffering in his context helps the patient to realize the role of stresses and of psychological factors in his illness and recovery. The origin may not only be in the 'psyche', but in the relevant and important social and cultural themes! With Regards, Vasudeo Paralikar |
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Susanne Merz, medical writer Jungfrudansen 34, SE-171 56 Solna, Sweden, Lawrence I Mayer, general physician, Partnerskap för Vård AB, Grev Turegatan 40, SE-114 38 Stockholm, Sweden
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EDITOR - Sharpe and Wilks (1) claim to review chronic fatigue syndrome (CFS) as defined by the US Centers for Disease Control criteria of 1994 (CDC94) (2). a. Despite that claim, Sharpe and Wilks' key recommendations for the treatment of CDC94-CFS rely on studies based on other definitions of CFS: definitions which are inconsistent with and describe quite different groups of patients than CDC94 (3). Specifically: I. On the strength of the review (4), Sharpe and Wilks recommend graded exercise therapy (GET) for CDC94-CFS. But NONE of the GET-studies in that review used CDC94. II. On the strength of the same review (4), Sharpe and Wilks recommend cognitive behaviour therapy (CBT) for CDC94-CFS. But of the six CBT- studies in that review, four didn't use CDC94 at all (4), one claimed to study CDC94-CFS but in fact never did (5), and one studied CDC94-CFS but failed to show any benefit from CBT (4). These facts call into question Sharpe and Wilks' recommendations (I)-(II) for the treatment of CDC94-CFS. b. CDC94-CFS is a diagnosis of exclusion. So how should patients with unexplained substantial chronic fatigue be worked up? Sharpe and Wilks suggest that workup by the primary physician is sufficient in most cases, with referral to a specialist only if a specific etiology is suspected. There are two problems with that strategy: (i) Unexplained substantial chronic fatigue has exceedingly many exceedingly rare differential diagnoses (3) whose COMBINED probability is substantial: a nightmare situation for the primary physician. (ii) Failure to discover the correct one of these differential diagnoses can cause an even worse nightmare for the patient. Therefore, if Sharpe and Wilks' workup strategy fails to find the underlying etiology, the patient with unexplained substantial chronic fatigue should be referred to a multidisciplinary coordinated team of specialists familiar with both the common and the exceedingly many exceedingly rare differential diagnoses. Only if that team also fails to find the underlying etiology should a diagnosis of CDC94-CFS be considered (3). No competing interests. References 1. Sharpe M, Wilks D. Fatigue. BMJ 2002;325:480-3. 2. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A and the International Chronic Fatigue Syndrome Study Group. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994;121:953-959. 3. Merz S. Chronic fatigue syndrome. More and more differential diagnoses suggest a new view of this syndrome. Läkartidningen 2002;99:3282-7. 4. Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow C, Ramirez G. Interventions for the treatment och management of chronic fatigue syndrome. A systematic review. JAMA 2001;286:1360-1368. 5. Vermeulen RCW, Scholte HR, Bezemer PD. Cognitive behaviour therapy for chronic fatigue syndrome. Letter. Lancet 2001;358:238. |
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