Complementary therapies

Complex societal factors unrelated to evidence of efficacy influence the increasing use of complementary and alternative therapies, which can be viewed as one form of health consumerism. The “therapeutic footprint” is a conceptual model that “plots” medical therapies and complementary and alternative therapies in relationship to one another and to their levels of risk and supporting evidence, acknowledging that medical therapies also entail risks. Philosophies about management of risk and adverse effects differ between complementary and alternative therapies and standard medical care, due to fundamental differences between professionalism within medicine and the demands of health consumerism. In standard medical care, patients’ risks are mediated prior to treatment via the doctor–patient relationship and informed consent. With complementary and alternative therapies, protection mechanisms for consumers come into effect mainly after a problem has occurred. Understanding this difference helps doctors whose patients are using complementary or alternative therapies to define the boundaries between these therapies and professional medicine and provide appropriate disclosure of risks. Discussing complementary and alternative therapies and how they differ from standard medical care can provide opportunities to explore patients’ concerns and improve the therapeutic relationship.

Christine R Sanderson BM BS, MPH, FRACP · Bogda Koczwara BM BS, FRACP, MBioethics · David C Currow BMed, MPH, FRACP

Although viewed with scepticism by the medical and scientific community, complementary and alternative medicine (CAM) is being used by about 50% of Australians. Integrative medicine is a holistic approach to cancer care, with some CAM of proven effectiveness being used as adjuvants to conventional medical treatments. However, there is little evidence of a systematic process of evaluation or dialogue between mainstream cancer medicine and CAM providers in Australia. Collaboration, guidance and support for relevant research in this area are needed. The key elements of a process of furthering integrative medicine include improving knowledge about CAM; addressing uncertainties about CAM efficacy and safety; improving communication about CAM between medical practitioners and patients, and between medical practitioners and CAM practitioners; introducing regulatory frameworks and credentialing of CAM practitioners; and addressing ethical issues.

Monica C Robotin FRACS, MBA · Andrew G Penman MACP, MPH

We report a fatal case of acute selenium poisoning in a 75-year-old man. After reading on the Internet about a possible role of selenium in prostate cancer, the patient ingested 10 g of sodium selenite. Despite intensive care treatment, he suffered a cardiac arrest and died 6 hours after ingestion. This case illustrates the risks of failing to critically evaluate Internet information and exposes the myth that natural therapies are inherently safe. Clinical recordAfter a single test showing a raised level of prostate-specific antigen, a 75-year-old man became concerned about prostate cancer. Without confirmation of the diagnosis, he researched prostate cancer on the Internet and discovered that selenium may have a role in its prevention and treatment. He purchased sodium selenite powder and tablets from two separate pharmacies for supplementation. He presented to the emergency department with vomiting and diarrhoea at 10:30 am, 3.5 hours after ingesting 10 g of sodium selenite (purity, 96%). He had significant abdominal pain, poor perfusion, and hypotension, with a pulse rate of 76 beats per minute, blood pressure of 75/45 mmHg, and prolonged QT interval. Arterial blood gas examination (breathing 60% O2) showed pH, 7.325 (reference range [RR], 7.35–7.45); PO2, 122 mmHg (RR, 85–100 mmHg); Pco2, 22.4 mmHg (RR, 35–45 mmHg); and HCO3 concentration, 11 mmol/L (RR, 22–28 mmol/L). He also had hypokalaemia (serum potassium concentration, 3.4 mmol/L [RR, 3.5–5.0 mmol/L]). A blood specimen collected at this time later showed a serum selenium level of 68.0 μmol/L (RR, 0.6–2.3 μmol/L). The patient was transferred to the intensive care unit, where fluid resuscitation was continued, and a dobutamine infusion was begun. He remained hypotensive (blood pressure, 85/50 mmHg) but conscious. At 12:10, he developed significant ventricular tachycardia, interspersed with normal complexes with ST depression. Repeat blood gas tests showed worsening acidosis and hypokalaemia. Magnesium (10 mmol) and potassium (25 mmol) were administered intravenously over 40 minutes. Dysrhythmia persisted and worsened. Lignocaine was added with no response. The patient suffered a cardiac arrest, and cardiopulmonary resuscitation was begun. Arterial blood gas analysis performed during the arrest revealed a sudden rise in serum potassium level, to 8.8 mmol/L. Throughout the arrest, rhythms varied, from asystole to broad complex bradycardia to some narrow complexes with an output. Despite cardiopulmonary resuscitation, asystole became permanent and unresponsive. The patient’s pupils became fixed and dilated, and cardiopulmonary resuscitation was ceased. The case was referred to the Coroner who confirmed the cause of death to be acute selenium toxicity. DiscussionThe growth in the use of complementary and alternative medicine in Australia has been well documented.1 Selenium is an essential trace element and an important constituent of the antioxidant glutathione peroxidase.2,3 It is found in many foods, including seafood, grains and eggs,2 and dietary intake is usually 20–300 μg/day.4 An intake below 400 μg/day is considered safe for almost all individuals.5 In Australia, selenium tablets are marketed as a health supplement, while sodium selenite powder is mainly used as a livestock supplement for animals grazing on selenium-deficient soil. Selenium has been discussed in many epidemiological investigations into prevention and treatment of cancer, especially prostate carcinoma.6,7 Excessive doses of selenium result in intoxication, which is characterised by continuous vomiting, garlicky breath, mucosal irritation, abdominal pain, hypersalivation, haemolysis, necrosis of the liver, cerebral and pulmonary oedema, coma and death.3,8 Selenium presents a nutritional conundrum because of its dual status as an essential but highly toxic trace element.9 The exact mechanism of selenium toxicity is as yet unknown.8,10 It has been suggested that the ready substitution of selenium for sulfur in biochemical reactions may inactivate the sulfhydryl enzymes necessary for oxidative reactions in cellular respiration,10 contributing to the acute toxic effect. Cases of selenium poisoning are rare, with Gasmi et al citing only 18 documented cases before 1997, half of them fatal, generally as a result of cardiocirculatory failure and/or pulmonary oedema.11 Although there is no defined point at which selenium becomes toxic, our patient consumed about 10 g of sodium selenite and, 4 hours after ingestion, had a serum level of 68.0 μmol/L (RR, 0.6–2.3 μmol/L), which proved fatal. The ingested quantity of 10 g was about 10 000 times the recommended daily dose of supplemental selenium. It is almost impossible to rapidly reduce a patient’s serum selenium level, as absorbed selenium is mostly contained in erythrocytes or bound to α- or β-globulins. For this reason, haemodialysis is not an established treatment for selenium intoxication, but may reduce serum selenium levels slightly.8 In regard to our patient’s hyperkalaemia, the extracellular potassium level is expected to increase in metabolic acidosis. However, our patient showed a progressively worsening metabolic acidosis with a falling potassium level. The administration of 25 mmoles of potassium over 40 minutes would be expected to raise the serum potassium level, but did not account for the sudden and dramatic rise, from 3.2 mmol/L to 8.8 mmol/L. This sudden hyperkalaemia has not been described in previous cases of selenium toxicity. A brief Internet search revealed 287 000 sites discussing the use of selenium in prevention and treatment of prostate cancer. This provides the public with large amounts of information that is not critically evaluated for validity. After reading Internet information on the possible link between selenium and prevention and treatment of prostate cancer, our patient was able to purchase 200 g of sodium selenite powder without adequate instructions. He selected a dose himself, with catastrophic consequences. This case highlights the risks associated with failure to critically evaluate Internet material and exposes the myth that natural therapies are inherently safe. Internet sites which fail to disclose the potentially fatal effects of advocated treatments are an emerging threat to health. The World Health Organization has devised guidelines to help consumers evaluate medical information on the Internet, which are available online through the Therapeutic Goods Administration.12 Adverse outcomes of complementary and alternative medicines should be better publicised and more stringently reported to the Adverse Drug Reactions Advisory Committee (ADRAC), in tandem with adverse outcomes of conventional medications, to create a database of side effects of all current therapies.

Katharine A See · Peter S Lavercombe FRACP, FJFICM, MBA(Dist) · Jasmine Dillon MB BS, BSci · Riesa Ginsberg FRACEM

Acute generalised exanthematous pustulosis (AGEP) is a clinical reaction pattern that is induced, in over 90% of cases, by systemic drugs (most frequently antibacterial drugs). This is the first reported case of AGEP caused by the herbal remedy Ginkgo biloba. Clinical recordA 45-year-old man developed a symmetrical maculopapular eruption on his limbs. Within 2 days, the rash generalised to involve the face. Disseminated non-follicular small pustules on erythematous skin were predominant (Box 1). The palms, soles and mucous membranes were spared. His body temperature was 38.8°C. The rash had developed 48 hours after starting oral Ginkgo biloba treatment for tinnitus (Ginkgo biloba was the only ingredient listed on the medication). The patient denied previously taking Ginkgo biloba and was not on any other medication. He reported no previous adverse drug reactions and no history of psoriasis. Blood tests returned the following results: C-reactive protein 135 mg/L (reference range [RR], < 12 mg/L); white blood cells 17.2 × 109/L (RR, 4.0–11.0 × 109/L); neutrophils 15.8 × 109/L (RR, 2.0–7.5 × 109/L); and eosinophils 0.79 × 109/L (RR, 0.04–0.40 × 109/L). A skin biopsy showed neutrophil-containing spongiotic pustules in the epidermis and a mixed cellular infiltrate with oedema in the papillary dermis, consistent with acute generalised exanthematous pustulosis (Box 2). The rash cleared within 10 days after withdrawal of Ginkgo biloba. The patient refused a follow-up cutaneous patch test. DiscussionAcute generalised exanthematous pustulosis (AGEP) is considered to be a clinical reaction pattern, induced, in over 90% of cases, by systemic drugs. It is a rare presentation of an adverse drug reaction most frequently triggered by antibacterial drugs. AGEP can be difficult to distinguish from other pustular dermatoses. To my knowledge, this is the first reported case of AGEP caused by the herbal remedy Ginkgo biloba. Ginkgo fruits and seeds have been used in traditional Chinese medicine for millennia, mostly to treat asthma and chilblains. The flavonoids and terpene lactones from the ginkgo leaf, which today is used for medicinal purposes, are associated with diverse pharmacological actions. In clinical practice, ginkgo is mostly used to treat memory impairment,1,2 dementia,3 tinnitus4 and intermittent claudication.5 In some European countries, ginkgo is registered for these indications; in the United States, it is marketed as a dietary supplement. In-vitro and in-vivo studies suggest that ginkgo has antioedemic, antihypoxic, antioxidant, metabolic, antiplatelet, haemorrhagic, microcirculatory and free-radical-scavenging actions.6,7 Reported adverse skin reactions to Ginkgo biloba include contact dermatitis and diffuse morbilliform eruption. The primary allergens from the ginkgo leaf appear to be ginkgolic acids. Ginkgolic acid molecules have similar side-chains to the catechols of the poison ivy group and are suspected of displaying some cross-allergenicity.8 Allergic contact dermatitis to the Rhus antigen present in the ginkgo fruit seeds has been extensively documented.8,9 This raises the question of whether or not ginkgolic acids could evoke a systemic reaction if taken orally. Systemic contact dermatitis can develop from oral challenge after contact sensitisation with other allergens.10 The criteria for diagnosis of AGEP are defined by the EuroSCAR score.11 Features of the condition include acute onset of small, sterile, non-follicular pustules on erythematous skin beginning in intertriginous areas or on the face; systemic signs, with fever over 38°C (in a typical course, an acute rash appears within 1–2 days and resolves by skin desquamation within 4–10 days after discontinuation of the causative agent); and neutrophilia, in the setting of a consistent histological pattern.11 The patient described here had a classic drug-induced AGEP with typical morphology, course and histology and a validation score of 12 points (the range for definite AGEP is 8–12).11 Ginkgo biloba treatment is commonly recommended by non-medical practitioners. With the rise of complementary and alternative medicine, there may be an increase in frequency and type of adverse reactions to this treatment. 1 Disseminated small pustules on erythematous skin 2 Histological section of skin biopsy The section shows neutrophil-containing spongiotic pustules (black arrow) in the epidermis and a mixed cellular infiltrate with oedema (clear arrow) in the papillary dermis (haematoxylin–eosin stain, original magnification &times 100).

Robert S Pennisi MPhil, FRACGP, DPD

The placebo effect and health. Combining science and compassionate care. W Grant Thompson. New York: Prometheus Books, 2005 (350 pp). ISBN 1 59102 275 4. The placebo effect, surrounded by myths resistant to time and research, fascinates researchers and clinicians alike. It has been said that the placebo effect is the only action which all medical treatment has in common, and, in some instances, it is the only useful action. Therefore, we all should have a keen interest in it. Understanding the placebo effect is difficult. There are, it seems, more definitions on offer than research groups investigating it — and all are unsatisfactory in one way or another. Difficulties increase when trying to answer some of the many questions that placebos pose. Do we need placebos to generate a placebo effect? What elements constitute a placebo response? Are placebo effects always beneficial? Are some situations more placebo-prone than others? What ethical implication does the use of a placebo have in research or clinical practice? Grant Thompson, a clinician, researcher and science writer, addresses these and other questions with analytical clarity. Well read and up-to-date on recent developments, he makes complex things understandable without oversimplifying them. His book is extensively referenced and helped by a detailed index — a text that can be used for reference as well as for reading. The “story” that Thompson develops before his readers’ eyes is coherent and exciting. There are of course many books on placebo, but this one is among the better ones in its class. It is not aimed at the specialist researcher nor at the uninformed layperson. For the many people who find themselves between these two extremes The placebo effect and health will be useful. Its strength lies in that it is easy to read, even when the subject matter is complex. As the placebo effect is responsible for so much of the success of medical interventions, it seems a good idea to know what it is about. Edzard ErnstDirector, Complementary Medicine Peninsula Medical School, Exeter, UK

Edzard Ernst

Objective: To survey the use, cost, beliefs and quality of life of users of complementary and alternative medicine (CAM).Design: A representative population survey conducted in 2004 with longitudinal comparison to similar 1993 and 2000 surveys.Participants: 3015 South Australian respondents over the age of 15 years (71.7% participation).Results: In 2004, CAMs were used by 52.2% of the population. Greatest use was in women aged 25–34 years, with higher income and education levels. CAM therapists had been visited by 26.5% of the population. In those with children, 29.9% administered CAMs to them and 17.5% of the children had visited CAM therapists. The total extrapolated cost in Australia of CAMs and CAM therapists in 2004 was AUD$1.8 billion, which was a decrease from AUD$2.3 billion in 2000. CAMs were used mostly to maintain general health. The users of CAM had lower quality-of-life scores than non-users. Among CAM users, 49.7% used conventional medicines on the same day and 57.2% did not report the use of CAMs to their doctor. About half of the respondents assumed that CAMs were independently tested by a government agency; of these, 74.8% believed they were tested for quality and safety, 21.8% for what they claimed, and 17.9% for efficacy.Conclusions: Australians continue to use high levels of CAMs and CAM therapists. The public is often unaware that CAMs are not tested by the Therapeutic Goods Administration for efficacy or safety.

Alastair H MacLennan MD, FRCOG, FRANZCOG · Stephen P Myers PhD, BMed, ND · Anne W Taylor BA, MPH

Complementary medicine in clinical practice. David Rakel, Nancy Faass. Massachusetts: Jones and Bartlett, 2006 (xvii + 552 pp). ISBN 0 7637 3065 3. There is mounting evidence to demonstrate increasing consumer use and acceptance of complementary and alternative medicine (CAM). Further, the evidence suggests that health care consumers are not seeking CAM therapies to the exclusion of dominant Western medicine approaches. Rather, they are choosing to integrate various forms of health care to suit their perceived health needs. It is in this context that Rakel and Faass discuss the concept of integrative medicine, providing information about eight major forms of CAM and methods of integrating their use into routine medical practice. Because the landscape of the public seeking health care is changing, conventional medical practice needs to change. The authors not only recognise this but embrace it and propose a new model of integrative medical care. As a chiropractic clinician and an educator, I was interested to learn how the authors defined integrative medicine. Many CAM practitioners can be somewhat defensive and sceptical, fearing that their therapy may be consumed by the dominant Western medicine practice. So it was refreshing and comforting to read that this text advocates a collaborative approach to health care, where CAM therapies are encouraged to work alongside Western medicine to deliver “holistic health care” to the patient. This text also “walks the talk”. It embraces an evidence-based approach to medical practice, using such an approach to argue the case for incorporating complementary therapies and services. The list of contributors is impressive — those that are leaders in their field. The reader can therefore be confident that they are receiving up-to-date, best practice information. I am very comfortable recommending this text. It has an easy reading style. It introduces CAM and integrative medicine in a logical and informative way, provides strategies for integrating them into current medical practice, and then gives succinct information about the eight major systems of CAM from research, educational and practical perspectives. Complementary medicine in clinical practice is suitable not only for the Western medical practitioner but also for their allied health practitioner colleagues. Barbara I Polus Associate Professor of Chiropractic, RMIT University, Melbourne, VIC

Barbara I Polus

If experimental conditions are not optimised, correct interpretation of results is difficult Many people throughout the world use complementary and alternative medicine (CAM). In the United States, for example, a survey of 31 044 adults aged 18 years or older indicated that 36% had used some form of CAM in the previous 12 months.1 This widespread use was one reason why, in 1998, the US Congress established the National Center for Complementary and Alternative Medicine (NCCAM) to conduct rigorous research on CAM practices. CAM includes the use of dietary supplements and other natural products; manipulative interventions such as massage; mind–body approaches such as meditation; energy interventions such as acupuncture; and whole medical systems such as traditional Chinese medicine. NCCAM’s mission includes disseminating authoritative information to the public and professional communities concerning which CAM practices are safe and effective and which are not. The use of dietary supplements and natural products is the most widespread CAM practice in the US.1 Thus, one initial approach taken by NCCAM was to sponsor large trials of supplements using doses representative of those commonly used.2 The rationale included the concern that if the common dose is unsafe, it would be important to alert the public. Moreover, these doses were often used in smaller, less well-controlled studies. However, NCCAM found that this is not an optimal research strategy. As NCCAM defines its priorities and strategies for the next few years,3 we recognise that reinvestigation and optimisation of customary procedures, especially dose, is needed if NCCAM is to make informed statements. Is optimisation of CAM interventions needed?It is tempting to accept that the widespread use of CAM signifies that these interventions, as customarily used, are beneficial and safe, and the only research needed is a confirmatory study of customary procedures. Over the past few years, we have recognised these assumptions are often incorrect, largely because of the placebo effect, publication bias, and the inherent complexity of clinical interventions. The placebo effect refers to psychological or physiological changes associated with inert substances or “control” procedures. Placebo effects can be substantial. In an NCCAM-sponsored study on major depression, sertraline (a drug licensed for treatment of depression) was effective in 49% of patients: 25% had full responses and 24% had partial responses. However, placebo was equivalently effective: 43% of patients responded (32% full and 11% partial).4 In a non-NCCAM study, arthroscopic surgery for osteoarthritis of the knee (a procedure used before then on 34 000 patients per year in the US) was no more effective than sham surgery.5 Given the ubiquity and strength of placebo effects, the effectiveness of some CAM practices, as with some other health treatments, may be, at least partially, due to that effect rather than to specific efficacy of the intervention. Publication bias results in negative studies appearing less often in the literature, so that reviews in some journals give an overly positive view of CAM effectiveness. In addition, the literature is unlikely to be conclusive because the manner in which an intervention is commonly used is unlikely to optimise the many factors that together could make an intervention successful. A good example of the difficulty of making correct choices is that of echinacea for the common cold. People could take echinacea for prevention or for treatment of colds; use any of three Echinacea species; take an extract of the roots, or the stems, or the flowers, prepared by any of three procedures; and use any of at least three doses. It is very unlikely that public use has identified the correct clinical indication and the correct echinacea formulation without these parameters being systematically evaluated. In this situation, even well-designed large trials6 may fail to show efficacy. Lack of efficacy of a CAM modality in a given study, coupled with uncertainty about optimal experimental conditions in that study, creates a serious problem in interpretation, and this has practical consequences. If the negative results pertain only to the particular study conditions, more work can be done in the expectation that a positive result will eventually emerge. If conditions are optimal and the results pertain to the intervention generally, the efficacy of the intervention could be more justifiably questioned. Early “negative” results present a particular challenge for CAM, given that some people are very sceptical of the field in general, and will seize upon early results of such trials as demonstrating that a CAM treatment is ineffective entirely. As we became more cognisant of the difficulty in correctly interpreting studies for which conditions were not optimised, we updated NCCAM’s website to address one of these issues: dose optimisation:7 If there are no data to suggest that the proposed dose is likely to give maximum efficacy, or if there are no data to identify the highest tolerated dose that can be tested, the applicant should evaluate a range of dosages to establish the appropriate dose for the study or clearly explain why the optimal dose cannot be established. Use of a suboptimal dose that is safe but ineffective does not serve the larger goals of the CAM community. Any given study can only draw conclusions concerning the dose that was tested. If that dose proves ineffective, the community may conclude incorrectly that all doses of the intervention are ineffective, and patients will be denied possible benefit from the intervention. Dose optimisation: evaluating a range of dosagesAn approach to dose optimisation is suggested by the idealised dose–response curves in the Box. The dose of the intervention rises from a low-dose X to a mid-dose Y to a high-dose Z. “Response” can be considered in terms either of efficacy or of toxicity. In this example, dose X is too low to result in either efficacy or toxicity. Dose Z is so high that toxicity as well as efficacy is seen. Y is an optimal dose, at which high efficacy but only modest toxicity is seen. These curves should hold for any intervention, not just for biologically active agents. Natural product regimens need to be optimised with respect to dose of material in each pill, the number of pills per day, and the number of days of treatment. Mind–body, manipulative, and other CAM interventions also require optimisation of the dose, frequency, and duration. Meditation, for example, is typically taught in group courses of a given length, with patients told to practise a certain number of times per day. There is little literature on the dose–response relationships between the length of training or the frequency of practice and clinical outcomes. Thus, part of NCCAM’s new strategic plan for mind–body research calls for studies to “optimize the timing, components, duration, and level of mind–body interventions to achieve health benefits”.8 For most interventions, NCCAM considers that the dose that is commonly practised in the community is likely to fall between X and Y and have low to modest specific efficacy. With this assumption, placebo-controlled phase I/II clinical trials of that intervention should start with the customary dose, then increase the dose until high efficacy, a plateau of efficacy, or intolerance in terms of toxicity or patient burden is observed. CAM practices often involve complex botanical substances in which the active ingredient is very dilute, or other interventions that can be time-consuming to deliver or practise. For CAM, “intolerance” could be an inability to swallow more product, drink more tea, participate in more classes, or devote more time to certain behaviour such as meditation, rather than the classic systemic toxicity of conventional drugs. If substantial specific efficacy is seen before intolerance, the conclusion will be that an “optimal” dose of the intervention may have been identified, one that is ready for testing in a larger clinical trial. Only if an optimal dose of the intervention is used can definitive decisions about the effectiveness of an intervention be made. Dose–response relationships for beneficial interventions

Jonathan Berman MD, PhD, FAAP · Margaret A Chesney PhD

When a prominent Australian politician, the then Premier of Tasmania, The Honourable Jim Bacon, publicly announced in February 2004 that he had lung cancer, he was inundated with well-wishing communications sent by post, email and other means. They included 157 items of correspondence recommending a wide variety of complementary and alternative medicines (CAMs). The most common CAMs recommended were meditation, Chinese medicine, “glyconutrients”, juices, Laetrile and various diets and dietary supplements. Although proof of benefit exists or promising preliminary laboratory studies have been carried out for a small number of the recommendations, no scientific evaluation has been performed for most of these treatments. Their potential benefits and harms are not known. Several recommendations were for treatments known to be useless, harmful or fraudulent. Bacon’s experience suggests that cancer patients may receive unsolicited advice to adopt one or more forms of CAM. Both patients and practitioners need access to authoritative evidence-based information about the benefits and dangers of CAMs.

Ray M Lowenthal MD, FRCP, FRACP

There has been a breakdown of the social constraints that limit the Absurd Twenty years ago, the late Petr Skrabanek, physiologist at Trinity College, Dublin, noted the rising interest in sectarian medical schemes (“complementary and alternative medicine”; CAM), and lamented the lack of a clear “demarcation of the Absurd” in medicine.1 He acknowledged that human irrationality, rather than being unusual, is an integral part of being human: “Even the greatest thinkers, Descartes, Berkeley, [and] Newton could not resist the overpowering pull of their own wishful thinking . . . ”.1 This principle, that irrationality is a normal human characteristic, is more functional than the stance that humans are exclusively rational. The Absurd has gained a degree of agency and respect in some quarters of society through the CAM movement. Many complementary practices long known to result from magical thinking and observational errors are regularly trumpeted to be effective —based on new studies. The Absurd has been aided and legitimised through economic, social, and political currents. The internal pull of the Absurd has coalesced with external currents, forming a critical mass for the CAM wave to be propagated through the social system. Observations on human isolation reveal how fragile is one’s hold on rationality. In isolation (intensive care, etc), we can perceive internally generated stimuli and interpret them as emanating from external sources. These anomalies can be controlled simply through human contact and familiar surroundings. We propose that, in a similar way, irrationality in clinical decisions and research is normally modified, neutralised, or controlled by feedback from surrounding colleagues. However, when irrational beliefs are shared with a surrounding community of sympathetic thinkers, errors become institutionalised. Thus are generated medical sects and cults that propagate the Absurd. What has pushed institutions into the Absurd?The guardians that usually keep the institution of medicine from reeling off into irrationality are social contracts built into medical science and ethical behaviour. The academic community guards the contractual borders of science, while laws and regulations encode our ethical system. For the Absurd to have advanced, there must have been some breakdown of these social guardians. Postmodernism has promoted breakdown and reorientation of structured forms of thought. One of its guises is language distortion — the redefinition and use of words to fit personal views. For example, alternative and complementary have been substituted for quackery, dubious and implausible. Another is the invention of integrative medicine — designed to leapfrog methods into practice without need for proof.2 In a recent commentary, one author redefined standard scientific indicators of efficacy as various biases.3 Postmodernism creates an atmosphere in which absurd claims are accepted more readily because they have simply been renamed. In the postmodern catechism, facts and science are artefacts of social constructions, and modern medicine expresses political hegemony over other, subjugated forms of healing,4 such as naturopathy and homoeopathy. Postmodern CAM also tolerates contradiction without need for resolution through reason and experiment, resulting in a medical pluralism. Various “schools” and philosophies of healing — each inconsistent with the others, such as chiropractic, homoeopathy, orthomolecular medicine, and traditional Chinese medicine — create a scientific multiculturalism. Implausible proposals and claims become tolerable and comfortable, and the CAM advocate’s burden of proof is shifted to disproof by the science community, which that community accepts without major objection. These are constructions designed for propagation of the Absurd. Medical teaching and practices reshape themselves in this atmosphere. Of 175 US medical school CAM courses, only four were found to teach critical analysis of absurd claims.5 Public institutions follow. The US National Library of Medicine’s MEDLINE abstracts some 30–70 journals largely devoted to CAM advocacy, and none devoted to CAM critique. The National Institutes of Health’s website refers only to advocates, such as chiropractic and acupuncture guilds. They exclude well known critical and objective web pages such as those found on Quackwatch (www.quackwatch.org). The new sociolegal order also shows breakdown of classical ethics. CAM followers declare it to be ethical to perform clinical trials on scientifically implausible treatments — merely because the treatments are popular.6 In the United States, legislatures pass Access to Medical Treatment Acts allowing previously unethical practices such as chelation therapy. In 2002, the Federation of State Medical Boards set new physician behavioural guidelines that allow physicians to refer to, and work with, unscientific practitioners.7 Outlier pseudomedical occupations such as acupuncture and naturopathy have gained licensure in several US states. As the borders of science and ethics broaden to accommodate these notions, the Absurd occupies its expanded social space. Evidence-based medicine (EBM), relying on results of randomised trials, should be a bulwark against the Absurd. However, the heterogeneity of clinical trial methods and designs, differing population bases, and varying endpoints often result in heterogeneity of outcomes. This has precluded systematic reviews of CAM methods from defining a line of inefficacy.8 EBM also does not include plausibility or consistency with basic science in its methods and reviews, leaving each to physician and patient interpretation. Moreover, there are no solid criteria for evaluating the quality of trials and reviews, especially for detecting erroneous, manipulated, and faked data.9 Thus, most CAM systems remain in an indeterminate limbo state, awaiting enough negative clinical trials to return consensus opinion to the state of decades prior. Can we demarcate the Absurd in science and medicine?Skrabanek recalled Bevan’s warning, also attributed to Galileo: “The aim of science is not to open a door to infinite wisdom, but to set a limit to infinite error”.1 If EBM fails to resolve the indeterminacy of dubious and absurd claims, routes can be found to re-establish borders, and limit error and infinite repetition of borderline results. The most promising in our opinion is to adopt Goodman’s suggestion for using a Bayes factor to express statistical results of reports on anomalous methods.10 Goodman suggested assigning to each P value several values for the prior probability of the null hypothesis being true, and calculating the posterior probability for each value using Bayes’ theorem. The results give the reader the choice of several levels of efficacy depending on the estimated degree of initial plausibility of the tested claim. A Bayesian guardian at the gate to determine which methods are plausible enough to be worthy of further study would at once help to clarify inconsistent trial results and create a saving in clinical trials expense. It would certainly have met with Petr Skrabanek’s approval.

Wallace Sampson MD · Kimball Atwood IV MD

The essential guide to herbal safety. Simon Mills, Kerry Bone. Missouri: Elsevier Churchill Livingstone, 2005 (xvi + 684 pp). ISBN 0 443 07171 3. With the dramatic growth in the use of herbal medicines, consumers and practitioners alike need to access reliable information on the safety and efficacy of herbal medicine. The essential guide to herbal safety is extremely topical and fills a considerable gap in the literature. This is an outstanding reference text on herbal safety that deals not only with a range of critical issues (safety monitoring of herbal medicines, herb–drug interactions, quality control), but also provides a series of exemplary monographs on herb safety. The text brings together contributions by acknowledged experts in the field. The safety monographs contain useful information on the current regulatory status of each herb in selected jurisdictions. The LD50 data for various extracts of the herb serve to highlight the relative risk represented by different extract forms (water, ethanol, etc) and the role of individual phytochemical constituents. Categories descriptive of known toxicity in pregnancy and lactation are provided for each herb. I would have liked the authors to provide similar toxicological categories or grades for general consumers, however this would have required substantial input by clinical toxicologists. Overall, the text is extremely well researched, integrating various data sources. It is an excellent book to have in hand and will undoubtedly become an important resource. At just over $100, The essential guide to herbal safety represents outstanding value. Alan BensoussanDirector, Centre for Complementary Medicine Research University of Western Sydney, NSW

Alan Bensoussan

It may be difficult for patients to distinguish current concepts of immune function from other, non-conventional explanations of illness Each year, as many as 50%–70% of adults and children with allergic disease consult alternative practitioners.1-3 Some will undergo unproven diagnostic “allergy testing” as used by some alternative (and some conventionally trained) medical practitioners. The potential for adverse outcomes from using unproven diagnostic techniques is not only insidious but also potentially more serious than the more commonly debated issues surrounding costs,1 or the risks and benefits of alternative therapies such as naturopathy, chiropractic, acupuncture, homoeopathy or so-called “allergy elimination therapy”.4,5 Particular concerns arise when “positive test results” are followed by advice to restrict diet, a practice that our combined clinical experience tells us occurs not infrequently, regardless of the presenting problem — even in cases of asthma, allergic rhinitis or recurrent infection in which food allergy is not considered to play a pathogenic role. Such advice may unnecessarily delay more appropriate therapy and sometimes impair nutrition and growth.6 It is not difficult to understand why patients with allergic disease seek help where they can find it. Most people affected by allergic disease are young adults, or parents of young children with eczema, food allergy or allergic respiratory disease — groups that may find concepts of chronicity, and palliation rather than cure, unattractive. Parents of young children may be attracted to non-invasive (“no needles”) allergy testing. Furthermore, the field of allergy and immunology is a non-organ-based specialty, making it difficult for some patients to distinguish current concepts of immune function (or dysfunction) from other, non-conventional explanations of illness. Blurring the meaning of “allergy” to refer to any perceived response to an environmental agent, and use of the term “impaired immunity” interchangeably with “fatigue” (in the media as well as among some alternative practitioners), is conducive to blending concepts of immunology, neurology and spirituality to explain the pathogenesis of disease by some non-conventional philosophies.7 Factors that may contribute to the uptake of unproven diagnostic and therapeutic techniques include congruence with patients’ own philosophies about the pathogenesis of some disorders, a desire for autonomy, long waiting lists for specialty allergy services (and the lack of any publicly-funded clinics in some states, such as Tasmania and Queensland), advice from friends and family, internet-derived information (and misinformation) and uncritical media attention.1-3 Some of the non-conventional “allergy” tests in current use arose in the early 20th century, when allergy practice was essentially empirical.8 At that time, without mechanistic explanations or reliable tests to confirm an immune origin, disorders with a similar phenotype (eg, allergic and non-allergic urticaria) and some non-specific symptoms (eg, migraines, fatigue) were attributed to allergy, if skin tests were positive, or to “allergic toxaemia”, if results were negative.9 Cytotoxic food testing (“Bryans’ test”, and the ALCAT variant — whereby a patient’s leucocyte morphology is assessed after incubation with food extracts) was one, now considered unconventional, technique to arise from a search for more “reliable” tests to explain these phenomena.9 This test continues to be used today, despite evidence that results are not reproducible, are different when duplicate samples are analysed blindly, do not correlate with those from conventional testing, and “diagnose” food hypersensitivity in people with conditions in which food allergy is not considered to play a pathogenic role.10 In the meantime, modern allergy practice relies on understanding the biological mechanisms underlying allergic disorders and the correlation of symptoms with standardised tests to detect allergen-specific IgE.11 Reliable allergy testing increases diagnostic accuracy and facilitates the identification of avoidable inhaled or ingested triggers.12 Advances in scientific understanding have also facilitated the development of medications to block specific inflammatory pathways and novel approaches to immunotherapy.11 By contrast, many non-conventional diagnostic techniques are used without published evidence of clinical utility, and those subjected to formal evaluation have produced uniformly negative results. For example, in a blinded study, iridology practitioners were unable to distinguish healthy from diseased individuals and gave different diagnoses using iris photographs from the same patients taken minutes apart.13 Furthermore, the theoretical basis for iridology — that disease is reflected in iris patterns — is undermined by the use of iris patterns as biometric identification markers because they are considered to be unchanging and unique to individuals, differing even between genetically identical twins. Kinesiology (muscle testing) has been shown, in controlled studies, to be no more accurate than guessing.14 Vega (electrodiagnostic) testing, whereby skin electrical resistance is measured with food extracts present in the same circuit, was unable to distinguish between healthy and allergic individuals, or between control and allergen extracts, and yielded results that did not correlate with conventional test results.15 Rigorous study of other non-conventional methods such as IgG food antibody testing, food immune complexes and sublingual provocation/neutralisation have provided similarly negative results. (These and other techniques are reviewed in more detail at <http://www.allergy.org.au/pospapers/unorthodox.htm>.) In light of the evidence, how can we, as doctors, best serve our patients? First, we need to understand our patients’ belief systems and understand conventional and non-conventional approaches to diagnosis and treatment of allergies. Second, when assessing polysymptomatic patients with normal clinical and laboratory findings, we need to resist the temptation to label medically unexplained illness as “allergic disease”, and should question an allergy diagnosis made by the patient or based on unproven diagnostic techniques. By doing so, we may be able to help our patients to direct their efforts into more productive areas, and minimise unnecessary expenditure resulting from the use of unproven diagnostic techniques. We may also then be able to reconcile concepts of patient autonomy with the medical principle of primum non nocere (first, do no harm) and reduce the possibility that patients may inadvertently harm themselves or their children by pursuing unproven diagnostic techniques.

Raymond J Mullins PhD, FRACP FRCPA · Robert J Heddle PhD, FRACP, FRCPA · Pete Smith PhD, FRACP, FRCPA

Graham R Wicks Medical Hypnotherapist, Department of Psychological Medicine, Women’s and Children’s Hospital, North Adelaide; 9 Collins Street, Collinswood, SA 5081. grwicksATbigpond.net.au To the Editor: I was interested to read the article about managing nocturnal enuresis in children,1 but was surprised and disappointed that there was no mention of the place of medical hypnotherapy. Hypnotherapy can be particularly valuable in the treatment of monosymptomatic nocturnal enuresis in children aged from 7 or 8 years upwards, and has the advantage of being completely non-invasive with no side effects. It focuses on empowering the children to take control of their own bodily functions.2 Hypnotherapy is also of value in the management of nocturnal enuresis associated with day-time symptoms, such as urgency with or without incontinence, and can also be used to enhance the efficacy of treatments like enuresis alarm systems. While there are few well documented comparative studies3 on the benefits of hypnosis versus other treatments for nocturnal enuresis, there are numerous anecdotal reports and studies involving a series of patients being successfully treated with hypnotherapy. Hypnosis should only be used by properly trained doctors or psychologists who have access to the full range of medical investigations. Hypnosis is of course not a panacea, but is an excellent first-choice treatment for monosymptomatic nocturnal enuresis, the commonest type seen by general practitioners. If, after three or four treatment sessions, hypnosis is not effective, other approaches can be employed. A quick search of the internet using the terms “enuresis and hypnotherapy” will reveal over 700 sites with information on the subject, and there are several highly respected professional journals that publish clinical and research papers and articles on the use of hypnosis in medicine and psychology. All of these are published by reputable professional societies whose membership is limited to registered health professionals. The Australian Society of Hypnosis (http:// www.ozhypnosis.com.au) conducts ongoing training courses in all states of Australia for graduates in medicine, psychology and dentistry. Hypnotherapy is now becoming more and more accepted worldwide as a valuable and legitimate tool that can be used, in conjunction with the more traditional approaches, in a wide variety of medical and psychological problems. It is a great pity that many clinicians are either not aware of its value or are still loathe to accept it because of negative connotations associated with its use for entertainment purposes and in the hands of non-professional therapists.

Graham R Wicks

Patrina H Y Caldwell,* Denise Edgar,† Elisabeth Hodson,‡ Jonathan C Craig§ * Staff Specialist and Lecturer, † Head, Department of Nephrology, § Associate Professor and Head of Clinical Research, NHMRC Centre of Clinical Research Excellence in Renal Medicine, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, Sydney, NSW 2145; ‡ Clinical Nurse Consultant, The Continence Foundation of Australia in NSW, Sydney, NSW. PatrinacATchw.edu.au In reply: Thank you for your interesting comments regarding hypnotherapy in the treatment of nocturnal enuresis in children. There are a number of therapies, such as hypnotherapy, electrotherapy and acupuncture, which show great promise for the management of nocturnal enuresis. We only included in our article1 treatments that were supported by evidence from well documented comparative studies. Using comprehensive search strategies, we have not found comparative studies for these complementary therapies. We would be very interested to be directed to studies that have formally evaluated other interventions. There is a huge need for randomised controlled trials comparing alternative treatment strategies with conventional therapy in this area.

Patrina H Y Caldwell · Denise Edgar · Elisabeth Hodson · Jonathan C Craig

Marc M Cohen Professor of Complementary Medicine, School of Health Sciences, RMIT University, PO Box 71, Bundoora, VIC 3083; and President, Australasian Integrative Medicine Association. marc.cohenATrmit.edu.au To the Editor: I read Constable’s article1 on age-related macular degeneration with interest, but was surprised at its somewhat guarded advice on nutritional supplementation and the fact that it gave only passing reference to uncontrolled studies of the carotenoids lutein and zeaxanthin and failed to mention a number of controlled studies that have recently shed light on the potential for these nutrients to influence the progression of age-related macular degeneration (ARMD). Lutein and its isomer, zeaxanthin, are deposited in the macula, where they make up the macular pigments and act as a blue-light filter to protect the underlying tissues from phototoxic damage, as well as providing antioxidant activity. Lutein was not available in supplement form at the time of conducting the Age-Related Eye Disease Study (AREDS).2 However, the more recent Lutein Antioxidant Supplementation Trial (LAST), a double-masked, placebo-controlled, randomised trial of lutein and antioxidant supplementation in people with ARMD, demonstrated that taking 10 mg lutein daily, with or without additional nutrients, improved visual function.3 Interestingly, lutein supplementation was also found to improve vision in a small, randomised, placebo-controlled study of people with cataracts. It was suggested that these improvements were due to improved macular function and increased macular pigment density.4 Furthermore, a recent study showed that lutein supplementation results in increased macular pigment density in both normal and ARMD patients.5 Lutein occurs naturally in foods such as eggs, spinach, romaine (cos) lettuce, broccoli, zucchini, corn, peas and Brussels sprouts. Although lutein is readily absorbed from foods and dietary supplements, surveys indicate that average lutein intake may be below levels that are associated with disease prevention.6 Toxicology studies have established that lutein is generally safe, with potential for use as a supplement in foods and beverages.6 While advice on smoking cessation and increasing fruit and vegetable intake is useful for a wide range of conditions, including ARMD, Constable’s statement that “antioxidant supplements should be recommended if a fresh diet is impractical and if retinal signs of progression are present”1 appears overly cautious. In light of recent findings on the potential benefits of antioxidants such as lutein, and the low cost and minimal risks associated with supplementation compared with the potentially devastating consequences of blindness from ARMD, it may be prudent to make more general recommendations on nutritional supplements, rather than waiting until signs of retinal progression are evident.

Marc M Cohen

Ian J Constable Director, Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western Australia, 2 Verdun Street, Nedlands, WA 6009. ijcATcyllene.uwa.edu.au In reply: While the published literature on dietary supplementation with the antioxidants lutein and zeaxanthin is highly encouraging, it does not yet pass the requisite standards for public endorsement provided by large-scale, independent, evidence-based medical trials. The controlled (“LAST”) trial of lutein1 cited by Cohen consisted of just 91 patients divided into three subgroups including the placebo group, who were followed for only 1 year. The measurement of visual improvement on a Snellen chart would not be accepted as “gold standard” evidence by major granting agencies and regulatory affairs bodies, who demand the higher discrimination of a logarithmic visual acuity chart. Moreover, the data were not derived from multicentre trials and independently assessed. It is instructive to compare the methodology of the LAST trial with that of the ARED Study,2 which involved 11 centres, 3640 patients and an average follow-up of 6.3 years. For these reasons, although I mentioned lutein in an encouraging fashion, I did not endorse it to the same extent as vitamin C, vitamin E and zinc supplements. The other reasons for giving limited recommendation of antioxidant supplements at this stage relate to the fact that it is not yet clear to what extent supplements would be beneficial over and above a diet targeted to provide these antioxidants in plentiful supply. It may yet be shown that a nutritious diet — with emphasis on brightly coloured and leafy vegetables, fresh fruits, nuts and fish, coupled with reduced processed vegetable oils (except olive oil) — can, alone, provide substantial protection. While the supplements are generally deemed to be safe, they are not without occasional serious side-effects and have not been followed long term. Richer, one of the authors of the lutein study, 1 acknowledges commercial relationships with the supplement suppliers, and states that the study requires greater numbers and long-term follow-up to be confirmed. Cohen cited a second article3 that refers to a 2-year study of cataract, in which a mere 17 patients were allocated to three subgroups including the placebo group. It is not usual practice to quote conclusions from such a small, and therefore potentially unreliable, trial design. Cohen is right to point to lutein and possibly zeaxanthin supplements as an encouraging possibility for preventing blindness from macular degeneration, and I hope the evident enthusiasm and rapid marketing of lutein proves justified in the long run by forthcoming major trials.

Ian J Constable

Edzard Ernst Director, Department of Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter, Devon EX2 4NT, UK. Edzard. ErnstATpms.ac.uk To the Editor: The article by Myers and Cheras1 is a good attempt to evaluate the safety of complementary therapies. However, I have one problem with it, which may be significant. The authors rightly state at the outset that “the critical issue in assessing any therapy is its risk to benefit”. At the end of their article they consider the “wider public safety issues” and point out that the risks of complementary and alternative medicine (CAM) are minimal compared with those of conventional therapies. I think this is not quite logical. Comparing risks of therapies does not make sense, because the “critical issue” is the risk–benefit profile. Comparing the risks and benefits of, for instance, acupuncture for severe pain versus opioids for the same type of pain would, I think, favour the latter over the former, even though the risks of acupuncture are minimal compared with those of opioids. In other words, comparing absolute risks of treatments is tempting, but meaningless.

Edzard Ernst

Stephen P Myers,* Phillip A Cheras† * Director, Australian Centre for Complementary Medicine Education and Research, Southern Cross University, PO Box 157, Lismore, NSW 2480; † Deputy Director, Australian Centre for Complementary Medicine Education and Research, University of Queensland, QLD. smyersATscu.edu.au In reply: We stand by our statement that “the critical issue in assessing any therapy is its risk to benefit”. 1 Ernst appears to miss the point made in the subsequent two sentences — that this assessment is available for conventional medicine, but not yet for complementary and alternative medicine (CAM) therapies and products. In the absence of such data, society must be able to make an assessment of health practices and medicines based on their overall risk. Ernst himself has made significant contributions to this literature, and in fact three of his articles2-4 were cited in our review. The second criterion of the Australian Health Ministers’ Advisory Council Criteria for Assessing the Need for Statutory Regulation of Unregulated Health Occupations asks the question: Do the activities of the occupation pose a significant risk of harm to the health and safety of the public? Answering this question for the currently unregulated CAM professions involves consideration of the “wider public safety issues”. This forms part of the determination about the appropriateness of occupational regulation. The two comments juxtaposed by Ernst to make his point are not mutually exclusive. While awaiting the risk–benefit analysis, society will need to make decisions about the absolute risks.

Stephen P Myers · Phillip A Cheras

To the Editor: Colonic irrigation is the introduction of a large volume of fluid into the colon via the rectum. This volume may be up to 50 litres, run in and out by means of a rectal tube, in an effort to empty the bowel. This treatment is often administered by a practitioner of complementary or alternative medicine, without medical advice. The fluid may be driven by gravitational or mechanical force.1 Recognised risks from colonic irrigation are electrolyte imbalance, bowel perforation and communicable diseases such as amoebiasis.2 Colonic irrigation is different from a standard enema given to relieve constipation or to treat a primary bowel disease. An enema involves a small amount of fluid and is usually authorised by a medical practitioner and administered by a trained nurse, attendant or is self-administered. Perforation of the rectum has rarely been reported.3 We document three cases of perforation of the rectum from colonic irrigation, treated by different surgeons at different institutions (Box). All have required surgical intervention. Each patient underwent colonic irrigation to relieve chronic constipation, to “cleanse” or “clear out stale faeces”. None had primary colonic or rectal pathology. None of the three patients were warned about the complication of perforation. Importantly, one patient initially denied the use of colonic irrigation, even with direct enquiry (Case 1), presumably because of embarrassment. This has the potential to delay the diagnosis or lead to inappropriate treatment. Perforation may occur in the rectum by direct injury from the irrigation device (Case 1), or after the irrigation has commenced (Cases 2 and 3), and may be caused by the generation of a high pressure within the lumen of the bowel. Rectal perforation from colonic irrigation may be diagnosed from the history, plain abdominal x-rays or a computed tomography scan with or without meglumine diatrizoate enema. A high degree of suspicion by the attending physician will prompt the diagnosis. Intensive medical therapy with appropriate antibiotics and surgery is necessary. Plain abdominal x-ray did not show an abnormality at 12 hours in the one case where x-ray was taken. We feel that colonic irrigation is of dubious benefit, especially when delivered to remove so-called “toxic waste” when bowel function is satisfactory. There is potential for serious harm. The apparent failure of the operators to warn patients about a risk of any serious complication, the failure to diagnose the possible perforation at the time of injury, and the failure to provide any subsequent follow-up, which might have led to an earlier diagnosis of any complication, probably indicates suboptimal practice. Cases 2 and 3 occurred at the same clinic within a few weeks of each other, suggesting a possible systems failure of the irrigation device. Primary healthcare practitioners need to be aware of the dangers of this treatment. Colonic irrigation should be urgently and formally assessed from an evidence-based, risk–benefit perspective. Case descriptions for three women who had rectal perforation after undergoing colonic irrigation Case Age (years) Timing of symptoms Clinical features Investigations Management 1 59 Pain immediately on insertion of enema tube. No irrigation. Attended emergency department 24 hours after the tube insertion. Lower abdominal and deep pelvic pain. Sepsis. Abdominal computed tomography scan showing perirectal oedema and extrarectal gas. Intravenous antibiotics and transrectal drainage of perirectal abscess. 2 51 Pain started during irrigation. Attended emergency department 4 days after irrigation. Lower abdominal pain. Sepsis. Abdominal computed tomography scan showing gas and fluid in the perirectal fat and retroperitoneum. Intravenous antibiotics and initial transrectal drainage of perirectal abscess. Recurrent abscess formation required laparotomy and rectal resection with stoma formation. 3 56 Pain started during irrigation. Attended emergency department the same day, but was discharged. Re-presented 7 days later. Lower abdominal and deep pelvic pain. Constipation and urine retention leading to urinary infection. Sepsis. Abdominal computed tomography scan showing pelvic abscess posterior to the rectum. Emergency laparotomy, sigmoid loop colostomy and drainage of abscess. Residual abscess drained transrectally 2 weeks after initial surgery.

Doug V Handley · Nick A Rieger · David J Rodda

To the Editor: The complementary and alternative medicine (CAM) series raised awareness and provided balanced and thoughtful debate. The article by Kerridge and McPhee in that series1 is no exception, but we would like to question their conclusion that “not only is it unclear whether a true integration of conventional and unconventional medicines is possible, but, more importantly, whether it is even desirable”. For a variety of reasons we believe that it is both possible and desirable. There are increasing examples of situations in which medical practitioners can integrate ethical, evidence-based CAM into practice. Apart from the well-known and validated examples, such as Hypericum perforatum (St John’s wort) for depression, ginger for nausea in pregnancy, and Gingko biloba for intermittent claudication, there are other, less well known, but increasingly investigated, examples of CAM for common conditions. With quality information and a little training, these can be readily incorporated into medical practice. To illustrate, Hippocrates was known to use the herb Vitex agnus-castus (chasteberry) for treating symptoms of premenstrual syndrome. Today we have a randomised controlled trial (RCT) to support its use.2 There are RCTs to support the use of Serenoa repens (saw palmetto) for symptomatic relief of benign prostatic hypertrophy,3 and good evidence is accumulating for the use of glucosamine for osteoarthritis4 and mindfulness meditation for preventing relapse in recurrent depression.5 With systematic reviews on these CAMs doctors should be informed about them. However, the resources for promoting them are minimal compared with those used to promote pharmaceuticals. Considering side-effect profiles and patient autonomy, why shouldn’t trained medical practitioners offer effective CAM remedies as first-line therapy instead of a pharmaceutical? To say these therapies should only belong to the realm of CAM practitioners would be to deprive the medical practitioner and patient of a wider choice of treatments. Communication, holism, balance and individualised care are the hallmarks of quality general practice and do not just belong to CAM therapists. If orthodox medical practice is to remain current, evidence-based and relevant, general practitioners have no option but to integrate safe, validated and ethical forms of CAM into their practice. If they are not adequately trained in the relevant discipline they may wish to refer to an appropriately qualified CAM practitioner, although statistics indicate that GPs prefer to refer to GPs already trained in CAM.6

Vicki Kotsirilos · John R McPhee

To the Editor: Although Kerridge and McPhee stress the need to find an evidence base (if there is any) for CAM, they nevertheless claim “medical practitioners and students no longer have any choice but to gain some knowledge about CAM and the interface between conventional and complementary medicine.”1 I suppose that archaeologists, geologists, palaeontologists and biologists now need to gain some knowledge about the interface between Darwinism and Creation Science. And our astronomers need some knowledge about the interface between astronomy and astrology. Science, including effective medical care, is not advanced by pandering to unscientific consumerism about unproven theories, especially if it manages to get the law on its side. Galileo was persecuted for “his heretical view” that the earth revolved around the sun. Have we learnt nothing from his experience?

In reply: We agree with Kotsirilos and Hassed that there are many examples of successful integration of “proven” CAM into conventional medical practice. Our question, however, is whether it is possible to integrate CAM where its theoretical maxims and practices are incommensurate with allopathic medicine (eg, homoeopathy) and whether “integrative medicine” will ulti-mately fragment and diminish CAM, further isolate “non-evidence-based” CAM practi-tioners and make less visible those views of health and disease that are not consistent with modern medicine.1 It is misleading for Arnold to imply that there may be no evidence base for complementary and alternative medicines (CAMs). We suggest that medical practitioners should ask themselves not whether an “evidence base” exists, but what the existing evidence shows. The picture that emerges from a review of the literature is one of variable clinical efficacy. Thus, there is no evidence to support the use of chiropractic for childhood asthma,2 but there is good evidence that phytomedicines may reduce crises in sickle-cell disease,3 that cranberry juice may reduce the frequency of symptomatic urinary tract infections in women,4 and that horse chestnut seed extract is an efficacious treatment for chronic venous insufficiency.5 There is also clinically important evidence about harmful interactions, for example that St John’s Wort, garlic and ginseng may lower blood levels of warfarin.6 Medical practitioners should be critical and sceptical of all untested claims of therapeutic benefit. We suggest they acquaint themselves with evidence about risks and benefits of CAMs, particularly in their own area of practice. This is not pandering to anything. It is evidence-based practice. By the same token, use of CAM may reflect evidence-based decision-making by doctors and patients. It is simply divisive to dismiss it as “unscientific consumerism about unproven theories”, and it is foolish in any case to dismiss the latter. Medicine and science must compete with non-scientific perspectives in the public sphere, for the contest of ideas is never over in human history. Ideological positions are black and white. Science prefers shades of grey. We have indeed learnt much from Galileo’s experience.

Objectives: To review the evidence for the effectiveness of complementary and self-help treatments for anxiety disorders.Data sources: Systematic literature search using PubMed, PsycLit, and the Cochrane Library.Data synthesis: 108 treatments were identified and grouped under the categories of medicines and homoeopathic remedies, physical treatments, lifestyle, and dietary changes. We give a description of the 34 treatments (for which evidence was found in the literature searched), the rationale behind the treatments, a review of studies on effectiveness, and the level of evidence for the effectiveness studies.Conclusions: The treatments with the best evidence of effectiveness are kava (for generalised anxiety), exercise (for generalised anxiety), relaxation training (for generalised anxiety, panic disorder, dental phobia and test anxiety) and bibliotherapy (for specific phobias). There is more limited evidence to support the effectiveness of acupuncture, music, autogenic training and meditation for generalised anxiety; for inositol in the treatment of panic disorder and obsessive-compulsive disorder; and for alcohol avoidance by people with alcohol-use disorders to reduce a range of anxiety disorders.

Anthony F Jorm PhD, DSc · Helen Christensen PhD · Kathleen M Griffiths PhD · Ruth A Parslow PhD · Bryan Rodgers PhD · Kelly A Blewitt BAppPsych

Research funding for CAM is inadequate, resulting in too few good quality studies to support its use. Widespread use of CAM, as well as its media promotion, make this a vital public health issue, and the Australian government has a social and ethical obligation to respond by developing a research infrastructure (as has been done by the United Kingdom and United States governments). We propose a funding model that neither draws directly from the CAM industry nor from current health research budgets, yet would strengthen Australia’s international role in CAM research. Establishing and applying focused research methods in CAM is imperative for strengthening its evidence base and creating fresh options for safe and effective patient care.

Alan Bensoussan PhD, MSc · George T Lewith DM, FRCP

CAM research is leading to changes in the vitamin cabinet and the clinic Many Americans use one or more health promotion, illness prevention or healing practices that are considered as complementary and alternative medicine (CAM).1 In recognition of this, the United States Congress legislated in 1991 to establish the Office of Alternative Medicine to “investigate and evaluate promising unconventional medical practices”. In 1998, Congress expanded this mandate by enacting legislation that created the National Center for Complementary and Alternative Medicine (NCCAM), endowing it with the resources and authority to fund research, train researchers, and disseminate information to the public and healthcare professionals. A number of factors contributed to the creation of NCCAM. First was the popularity of unproven medical practices, with users of one or more CAM modalities tending to be women, people with higher education, those with an interest in the role of the mind in health, or those with some chronic illness.2 Second was an increasing recognition of the importance of traditional healing practices among an ethnically diverse American population. Third, in 1994, the US Congress passed legislation that permitted wide access to dietary supplements without confirmation of their composition, safety or efficacy, and a concomitant loosening of legal restraints on alternative practices such as chiropractic medicine and acupuncture. Setting priorities — science firstGiven the diversity of CAM approaches and questions about their safety and efficacy, setting research priorities for NCCAM is a significant challenge. The US$117.7 million allocated to NCCAM in 2004, while generous by most standards, permits only a limited sampling of possible CAM approaches. To develop its approach, NCCAM sought input from diverse communities of stakeholders. The resulting first strategic plan stressed investment in basic and clinical research, training, dissemination of findings, and integration of safe and effective practices.3 NCCAM made a commitment to aspire to the same rigorous standards that characterise National Institutes of Health (NIH) research in general, while its research priorities would focus on the most promising scientific opportunities. As NCCAM celebrates its fifth anniversary, it is possible to list its not inconsiderable achievements to date (see Box 1), and to reflect on some of the lessons learned for current and future directions. Investing in research centresTo create a sustainable research infrastructure, NCCAM funded a first generation of research centres spanning a range of health disorders and disciplines. Based on formal reviews, a second generation of more focused centres is being developed. Some of these are involved in elucidating mechanisms of action of CAM therapies. Others promote collaborations between CAM and conventional institutions. Still others represent new initiatives to forge scientific partnerships between investigators at US and foreign institutions. Botanical trials — overcoming obstaclesWhen NCCAM was created, it was assumed that existing literature on herbal supplements would be sufficient to justify and design major studies of their safety and efficacy. It quickly became apparent that many botanical preparations are not standardised, and may be contaminated with heavy metals or drugs,4 precluding the conduct of meaningful and ethical studies. As a result, NCCAM is now working with academic and industrial partners to identify more optimal research-grade materials, and requires evidence of product quality for all its sponsored research. These approaches raise the quality of the studies, but consume time and resources. Phase III clinical trials — balancing pressure for progressThe results of NCCAM’s very first large clinical trial dictated a more deliberate and phased approach for future studies, even when high quality products are available. The three-arm randomised controlled trial failed to show that Hypericum perforatum (St John’s wort) ameliorates major depression.5 Advocates for the product faulted the study for having addressed too serious a form of depression. While the target population, the product, its dose, and endpoints had been thoroughly discussed, it was ultimately clear that more preliminary research and consensus development was needed to determine the optimal design of other large trials. Such efforts are being made now in trials of Ginkgo biloba for cognitive decline in the elderly, and glucosamine for osteoarthritis. Each of these, and other ongoing trials (Box 2), are being conducted with input from relevant communities of patients, practitioners and scientists, and cofunded by other NIH institutes. Brain–mind–body medicine — an emerging scienceThe capacity of the brain and mind to affect health is a CAM domain that is receiving more attention at NCCAM. Surveys indicate that about one in five adults use at least one mind–body therapy.6 Functional neuroimaging provides powerful new tools to identify changes in brain structures involved in generating emotional responses, interaction of distress and pain, and response to treatment. With this and other new laboratory and ambulatory methods, NCCAM is funding investigators to identify pathways of influence, and to test interventions, such as meditation in preventing illness, slowing disease progression and promoting well-being. Planning for the futureLessons learned at NCCAM forecast a future with a greater emphasis on preclinical and early-phase clinical studies that are designed to elucidate mechanisms, identify optimal dosing and schedules, and select appropriate target populations and control conditions before launching clinical trials. Clinical studies at all levels are increasingly being conducted as collaborative efforts between funded investigators and NCCAM staff, who provide technical guidance, from sophisticated design and statistical consultation, to advice on recruitment and retention. Research on natural products is being conducted within a framework in which NCCAM either provides well-characterised and standardised clinical trial materials for investigators to use, or tests products being used by investigators to assure characterisation and standardisation. Finally, NCCAM is taking full advantage of new technologies, from genomics to brain imaging, and applying them to new areas, such as the capacity of the mind to affect health, in its multidisciplinary research. While NCCAM first built a domestic scientific constituency, it seeks to engender and strengthen relationships with other countries that have both established research in conventional medicine, and a tradition that is rich in indigenous practices. We invite scientific leaders in these countries to join the global CAM research effort. 1 Activities of the National Center for Complementary and Alternative Medicine in its first 5 years It built a centre responsive to its mission and integrated into the other institutes at the United States National Institutes of Health It funded over 780 projects at 123 institutions, resulting in over 700 scientific publications It awarded more than 100 individual doctoral and postdoctoral training and career awards It enrolled nearly 40 000 participants in clinical protocols It received over 1.5 million visitors to the website <www.nccam.nih.gov> each year who search for information about CAM, clinical trials, and research opportunities It developed a database known as “CAM on PubMED” that lists nearly 400 000 articles on CAM-related subjects published in 45 languages from 70 countries It informed public policy, patient choice, and clinical practice through outreach activities, including public town meetings, public media, and scientific and professional conferences 2 Status of National Center for Complementary and Alternative Medicine Phase III Clinical Trials Complementary and alternative medicine modality Target disease Sample size Status National Institutes of Health Partner Acupuncture Osteoarthritis 570 Trial complete; analysis underway NIAMS Glucosamine/chondroitin Osteoarthritis 1 588 Enrolment complete; ongoing NIAMS Ginkgo biloba Dementia 3 073 Enrolment complete; ongoing NINDS, NIA, NIMH Shark cartilage Lung cancer 756 Patients enrolling; ongoing NCI Vitamin E Prostate cancer 32 400 Enrolment complete; ongoing NCI St John’s wort Minor depression 300 Patients enrolling; ongoing NIMH, ODS EDTA chelation therapy Coronary artery disease 2 372 Patients enrolling; ongoing NHLBI Saw palmetto Benign prostatic hyperplasia 2 860 Final protocol under development NIDDK, ODS NIAMS = National Institute of Arthritis and Musculoskeletal and Skin Diseases; NINDS = National Institute of Neurological Disorders and Stroke; NIA = National Institute on Aging; NIMH = National Institute of Mental Health; NCI = National Cancer Institute; ODS = Office of Dietary Supplements; NHLBI = National Heart, Lung, and Blood Institute; NIDDK = National Institute of Diabetes and Digestive and Kidney Diseases.

Margaret A Chesney PhD · Stephen E Straus MD