HealthWatch president Nick Ross will present the award to Dr Smith as recognition
for his work as a champion of medical journalism and of ethics in research and
publishing. He will address the meeting on a controversial subject, Are medical
journals simply an extension of the marketing arm of pharmaceutical companies?
(This topic is currently of key relevance to HealthWatch—see articles
by Michael Allen and Andrew Herxheimer,
and feature by John Garrow, in this issue).
In the last 13 years, as journal editor and chief executive of the BMJ Publishing
Group, Dr Smith has enabled the group’s research reporting to reach ever
wider audiences and directed moves to raise ethical standards for researchers
and authors, such as helping form the Committee on Publication Ethics. The winner
of four awards for journalism and medical writing, Richard Smith has written,
lectured and broadcasted widely to both lay and professional audiences in Britain
and overseas. His advice is sought by government committees, and he is a member
of three Royal College of Physicians working parties.
In July this year Dr. Smith announced his resignation from the BMJ to become
chief executive of the European arm of UnitedHealth Group, the largest healthcare
company in the United States.
HealthWatch’s sixteenth AGM and Open Meeting, which is free and open to
all, will take place on Tuesday, 19th October 2004 at The Medical Society of
London, 11 Chandos Street, Cavendish Square, London W1M 0EB (nearest Underground:
Oxford Circus). Reception is to begin at 6.30pm, followed by the HealthWatch
Annual General Meeting at 7.00pm and award presentations. (Please note: while
all are welcome at the meeting, only members can vote at the Annual General
Meeting.)
As well as the HealthWatch Award, Nick Ross will present the HealthWatch Student
Prize to the winners of this year’s competition assessing the quality
of clinical trial protocols. The meeting will conclude with Dr Richard Smith’s
address; a lively discussion is expected.
As usual, any present who would like to continue to debate the meeting’s
issues with committee members over dinner can join them in a buffet with wine
at 8.45pm at a cost of £27. Bookings for the meal must, however, be made
in advance. Please contact Michael E Allen as soon as possible on 0208 789 7813
to reserve a place at the buffet.
The Prince of Wales had addressed the UK’s leading cancer charities in
his capacity as president of his Foundation for Integrated Health, at a conference
on “Complementary Therapies and Cancer Care” held at The Royal College
of Obstetricians and Gynaecologists in London on 24th June 2004. The meeting
aimed, he said, “to discuss, explore and develop new ways of integrating
complementary therapies into the care of cancer patients”. In calling
for more research into the value of complementary therapies in cancer, Prince
Charles claimed, “I know of one patient who turned to Gerson Therapy having
been told that she was suffering from terminal cancer, and would not survive
another course of chemotherapy. Happily, seven years later she is alive and
well…many patients use and believe in Gerson Therapy, yet more evidence
needs to be available as to who might benefit or what adverse effects there
might be.”
In an open letter to the British Medical Journal titled, “With respect
your Highness, you’ve got it wrong”, Professor Michael Baum begged
the Prince to exercise “extreme caution when advising patients with life
threatening diseases to embrace unproven therapies”. He criticised in
particular the use of anecdotes when discussing cancer, a disease with an unpredictable
natural history. “With advanced breast cancer the median expectation of
life might be 18 months, but many of my patients live for many years longer,
with or without treatment.”
The professor’s outrage was shared by many leading commentators. Another
HealthWatch Awardwinner Polly Toynbee, in an article in the Guardian (30 June),
condemned the Prince’s comments as “dangerous”. The Gerson
Therapy costs $4,900 a week, Toynbee says, adding that “After 60 years
it has failed to get mainstream authentication for its wild claims…the
American Cancer Society warns it may be dangerous.”
British Medical Journal 2004; 329: 118 (10 July)
A website makeover has just been completed, giving the HealthWatch site a new
and more modern look while making information even easier to find. The address
remains the same, at http://www.healthwatch-uk.org
We have also set up a new dedicated e-mail address for the editor of the HealthWatch
Newsletter. From now on, please send your letters and articles to newsletter@healthwatch-uk.org
(The editor aims to acknowledge all correspondence within seven days).
Three out of five clinicians in Israel report using placebos—inactive
treatment or drugs—on their patients. A survey of hospital doctors, head
nurses and family doctors carried out from the Herzog Hospital and Hadassah
School of Medicine in Jerusalem revealed that almost all—94%—believed
placebos were effective to some degree. Placebos were prescribed for conditions
ranging from anxiety and vertigo to asthma and even angina, says the paper,
published on BMJ
ONline First. While the use of placebo is officially disapproved of, the
authors suggest that judicious use of dummy treatments may actually have a genuine
role in treating patients. They call for an open debate on their effectiveness
and the ethics of their application.
British Medical Journal, 18 September 2004 http://press.psprings.co.uk/bmj/september/placebo.pdf
The Traditional Health Practitioners Bill, which would give formal recognition
to 200,000 traditional healers in South Africa, was approved in the Parliament
of South Africa’s National Assembly in September. South Africa’s
traditional healers are all in private practice, and take on much of the demand
for healthcare that would otherwise fall to the state to provide. But the bill
raised concerns, one being that traditional healers would give patients leave
to take an excessive amount of time off work. The legislation would make it
illegal for anyone not registered as a traditional healer to offer treatment
or a cure for HIV and Aids, though spokespeople pointed out that this is not
to infer that registered Traditional Health Practitioners are able to offer
a cure for Aids. The bill now goes to the National Council of Provinces for
concurrence.
Sapa, 9 September 2004
I can’t think of a better cause than preventing cancer. However, the Cancer
Prevention Research Trust has been admonished by the Advertising Standards Authority
for the claim that “cancer is a preventable disease”. The ASA considered
that the claim was likely to mislead and have sought the Trust’s written
assurance that it will be removed from their advertisements and replaced with
a less categorical claim, such as “you could reduce your risk” or
similar.
They failed to uphold a complaint that the claim was offensive, and indeed it
would have been better if the complainant had said it was hurtful rather than
offensive: it is no joke for a cancer patient to be told they needn’t
have contracted the disease, especially when it isn’t true, which is usually
the case.
The advertisement was in the front section of the 2004 Who’s Who, where
they list people who have died since the previous edition, and it solicits donations.
The CPRT seems an unusual organisation, and the advice on their website is a
little odd (is a pet cat really carcinogenic?) but an Internet search shows
that it funds some perfectly bona-fide postgraduate research.
A HealthWatch member, name withheld
There has been a great deal of interest in Direct to Consumer Advertising (DtCA)
of prescription medicines over the last few years; two years’ back Nick
Ross and I drafted a Position Paper on the subject for the HealthWatch Newsletter
(issue 48, January 2003). In this we pointed
out that DtCA has never been permitted for prescription medicines within the
EU where the physician was learned intermediary—only he or she was thought
to be qualified to make judgements about which medicine was appropriate for
a specific condition and which could be dangerous if misapplied.
We also noted how the relationship between doctor and patient has changed and
that attempts of the former to intermediate may now be met with scepticism and
hostility. We commented upon the value of the patient information leaflet (PIL)
and Summary of Product Characteristics (SPC) which provide detailed information
on the product to the patient and physician and on the many other ways that
information on prescription products can get to the public. The Position Paper
is on the HealthWatch website.
At the time, the European Commission proposed a cautious experiment by permitting
DtCA for a few categories of medicines; processes within the EU are always slow
and this initiative has been further delayed by the European Parliament. Therefore,
no progress has been made to alter the legal position within UK or the wider
EU. Behaviour in each EU member state is different, reflecting local history
and custom; UK is moving through a time of great change due to the need to control
NHS expenditure. Initiatives such as making products previously prescription-only
available through the pharmacy and studies of cost-effectiveness made by the
National Institute for Clinical Excellence (NICE) are symptoms of this struggle.
Meanwhile, the UK pharmaceutical industry has found interesting and effective
ways to circumvent any prohibition on DtCA by their generous support for patient
groups and through initiatives such as the Ask about Medicines week, the next
being due in November this year. Here industry uses a different sort of learned
intermediary, the educated patient, to carry their promotional message. The
way this is done currently is a model of appropriate behaviour: the supportive
role of industry is clearly stated, no specific product promotion is carried
out and contact details of the patient groups are given. But industry gets access
to explain the benefit of their new medicines to patients who have a vested
interest in their early use and who then act as surrogates to take the promotional
initiative that the industry cannot itself make. Involvement of the educated
patient is certainly something of which I approve; they are concerned to get
the best treatment available regardless of cost and thus act as a democratic
counterbalance to NICE, where cost and benefit both must be considered.
We live in a world where the market rules; there would be little viable applied
pharmaceutical research without a profitable industry. In HealthWatch Newsletter
issue 53 (April 2004) John Garrow reported on the difficulties put in the
way of academic research. Now, one sees how easily governmental intentions on
DtCA can be circumvented. I remain ambivalent; the process is currently honest,
but may not be in the future. Will we always be able to trust the answer?
Michael E Allen
Regulatory Consultant and Honorary Secretary, HealthWatch
A booklet describing Ask about Medicines week can be downloaded from http://www.askaboutmedicines.org
It is arguably the sheer size of this influence—rather than outright malpractice—that
currently results in over-estimation of drug benefit and underestimation of
drug harm, suggests Herxheimer. He calls for measures that might lead to greater
transparency in this field and specifically freedom of information—including
protection for whistle-blowers.
“The industry takes little pro-active interest in adverse effects of drugs;
only legal or commercial concerns move it to do more than the regulators require,”
Herxheimer claims. “The drug regulatory framework encourages this complacency
by relying excessively on pre-marketing clinical trials in defining drug safety
profiles.”
Competition is based far more on innovative marketing methods and public relations
than on the effectiveness and safety of its products. One result is that drug
treatments are uppermost in the minds of doctors and the public, and non-drug
treatments (including non-intervention) are very often not adequately considered.
Another inevitable result is that the pharmaceutical industry must strive to
control information—especially unfavourable information—about its
products and its work.
Current procedures for dealing with adverse effects once a drug is in use—known
as pharmacovigilance—also come under criticism. “Companies rarely
do more research on safety aspects unless they need to defend the product when
a serious adverse effect is alleged or suspected, or to show that it is safer
than a competing product. The design of studies performed in these circumstances
is liable to be much influenced by legal and commercial considerations.”
Herxheimer goes on to highlight a specific danger: drug doses recommended by
manufacturers are often higher than is medically necessary. “About one
in six drugs have had dosage recommendations modified (generally downwards)
at some time after licensing,” he says, calling for companies to be compelled
to submit more detailed evidence on dose-related risks and benefits, and for
publicly-funded research into the mechanisms of adverse effects.
For more information, see http://www.parliament.uk/parliamentary_
committees/health_committee/hc180604_25.cfm
We all agree that medical treatment should be based on sound evidence of efficacy. In his address when receiving the HealthWatch Award in 1996 Professor David Sackett said: “The problem is to distil the message buried in some 600,000 published randomised controls into a form which is accessible to clinicians when they need it.”(1).
The solution to that problem is to fund groups of skilled meta-analysts who
would search out all the published evidence relevant to a particular clinical
condition, combine the results of the trials by arcane mathematics that gives
different weights to the results of individual trials depending on the size
and quality of the trial, and arrive at a single score that shows the best estimate
of the benefit (or harm) of a treatment compared with the outcome of a control
group who did not have the treatment. Old-fashioned reviews were written by
individuals who might have axes to grind (e.g. citing excessively their own
research) but the meta-analysis was to be a distillation of pure truth, derived
from what was, by consensus, the best evidence.
For most of my professional life I have been concerned with the treatment and
prevention of human obesity—a topic that has recently been given high
priority by NHS health authorities. I was therefore eager to read a massive
(A) meta-analysis, published in May 2004, entitled “Systematic review
of the long-term effects and economic consequences of treatments for obesity
and implications for health improvements” (2). The authors’ Introduction
said they would evaluate, for the treatment of adult obesity, “…all
aspects of diet and lifestyle alteration, with or without pharmacotherapy, and
in some cases surgery.” I was therefore amazed, and deeply concerned,
that the “Implications for healthcare” paragraph at the end of the
Executive Summary (the part that healthcare providers would read, and on which
they would base their planned expenditure) began with the sentence “Orlistat,
sibutramine and metformin appear beneficial for the treatment of adults with
obesity.”
The sentence quoted is (to a degree) true: orlistat and sibutramine have been
shown in large randomised trials to cause a statistically significant increase
in the weight loss, compared with controls given placebo, after one year of
treatment. But to give these drugs first place in a summary of effective treatments
verges on the comical. The eight trials of orlistat involved a total of 3,885
obese patients (mostly women) who were, on average, initially more than 30kg
overweight (B). Some were given orlistat and some a similar placebo capsule.
They were all on a “slightly hypocaloric” diet (C) for 52 weeks.
After a year of treatment those who had taken orlistat (trade name Xenecal)
had lost 3kg more than controls on placebo. At the end of the year the controls
(who had taken no orlistat) had lost about 6kg from baseline weight. These figures
are average weight changes, but the variation within groups was huge, so some
unfortunate participants, both in the orlistat and control groups, actually
finished the year heavier than they were at the outset of the trial!
All these trials were sponsored by Roche, the makers of Orlistat, and three
of the authors declared a competing interest in Roche. The results were analysed
on an ITT (intention to treat) basis. In general this is good practice: if estimates
of the efficacy of a drug is based only on those who complete the trial this
usually yields too favourable a result, because it is the participants who are
doing badly that are likely to drop out. However, in the orlistat trials some
showed a statistically significant extra weight loss with the drug by ITT analysis,
but not if completers were analysed! The dropout rate in all the trials varied
from 24–42% in control groups, and from 15–36% in the drug groups.
On one trial (3) there were 110 people on orlistat who lost 1.99kg more than
the 108 people on placebo, which was significantly greater than zero by ITT
analysis (P=0.016). However the 59 people who completed on orlistat lost 2.48kg
more than the 61 who completed on placebo, and this failed to reach statistical
significance (P=0.092). When calculating the weight loss of people who dropped
out the last recorded weight was used as the final weight—so if someone
lost 10kg in six months, then dropped out and regained 10kg in the next six
months, this would count as a loss of 10kg. Furthermore, the differences between
groups may have been statistically significant, but could not be considered
clinically important in the face of the level of obesity of the trial participants.
If these drugs were really the most effective available treatment for obesity
the situation would indeed be terrible, but there are much better options. Diet
with behaviour therapy (D), or (for very obese people) surgery (E) is much more
effective. Exercise itself does not cause much weight loss (4), but it probably
prevents weight gain—an important topic not addressed in this meta-analysis.
They chose to analyse only trials starting with obese people (F), not people
who were trying not to become obese, or who have lost weight and want to prevent
weight regain. Perhaps this decision relates to the fact that the drugs they
recommend are only prescribed for people who are already obese. Perhaps it relates
to the criteria that were used to judge the quality of the trials included in
the meta-analysis; if the highest weighting is given to well-designed, modern
drug trials, it would not be surprising if studies made with limited resources
but which are none-the-less honest and relevant get a lower weighting. However,
where obese people need to be managed in the real world, the results obtained
by methods other than drug treatment should not receive such academic disdain.
I believe this is a situation in which a meta-analysis has been commissioned,
using public money, and published under the imprint of HMSO. Readers are therefore
entitled to expect that the conclusions are not only impartially derived from
the available evidence, but are relevant to actual clinical practice and useful
to guide the way generalists manage their obese patients. Unfortunately, for
reasons given above, and others (G) I consider that the presentation of this
report is skewed in a way that will promote the use of drugs of marginal benefit,
so public money is wasted.
John Garrow
Emeritus Professor of Human Nutrition
University of London
References
Explanatory notes
A. The hard copy of the report is a document of 194 pages. The 38 Appendices, on 264 pages, are not available as hard copy but on a CD, and the whole report can be downloaded from http://www.ncchta.org
B. The report does not state the initial weight of participants in the orlistat
trials, but Appendix 8 gives the BMI of drug and control groups, which is approx
37kg/m2. Assuming their mean height is 1.65m this implies weight is approx 100kg.
Since upper limit of desirable weight is a BMI of 25kg/m2, then their weight
would need to fall to 68kg, so they are more than 30kg overweight.
C. The diet with 30% of energy from fat was designed to supply 600 kcal/day
less than energy expenditure for the first 24 weeks, and was reduced by 300
kcal/day from the 24th week. This was described as a “slightly hypocaloric”
diet.
D. The meta-analysis showed that, in the selected trials, a low-calorie diet
with behaviour therapy was associated with a weight loss of 7.93kg greater than
that of controls. For very-low-calorie diets the mean extra weight loss after
12 months was 13.40kg.
E. Surgery is not considered systematically in this report. In the Swedish Obese
Subjects trial (Torgerson JS, Sjostrom L. Int J Obes 2001; 25 (suppl 1): 52–54)
typically the weight loss (expressed as a percentage of the initial body weight)
was 33+10% after gastric bypass, 23+10% after vertical banded gastroplasty,
and 21+12% after gastric banding.
F. The study inclusion criteria were that: the trials should be RCT (randomised
controlled trials); a full study report should be available; the follow-up should
be at least 12 months; participants aged over 18 years; and the initial BMI
> 28kg/m2. Appendix 10 lists over 200 RCTs on the treatment of obesity that
were excluded because they failed to meet these selection criteria.
G. The inclusion criteria (mentioned in note F above) greatly favoured drug
trials, and disadvantaged trials of diet, exercise or surgery. In the drug trials
the drug and control groups were on a slightly hypocaloric diet and placebo
for a run-in period—usually 4 weeks. The participants who were compliant
(i.e. who took > 75% of the placebo capsules) were then stratified and randomised
to receive either drug or placebo for the rest of the trial. The weight change
was then measured over 52 weeks following randomisation. Thus, if those randomised
to placebo lost 3kg during the run-in, and another 4kg while on placebo as controls,
this was counted as only a 4kg weight loss, whereas they had lost 7kg in all
on diet alone.
There are some diet vs control (no treatment) studies accepted for analysis,
and these showed efficacy of diet in reducing weight and disease risk factors
that are somewhat better than the drugs (see note D above). However these receive
no endorsement in the executive summary. Indeed the text tends to be rather
dismissive: for example on page 123 a paragraph on “Dietary interventions”
refers to “one small study” of VLCD which produced a weight loss
of 13.40kg compared with untreated controls (95% CI. –18.43 to –8.37kg).
It was indeed a small study (published in BMJ) with only 19 subjects in treatment
and control groups. However with such massive weight loss you do not need a
large study to achieve statistical significance.
Most doctors and scientists reading this brief fiction would say that the news
editor had made a bad decision. The paper’s medical correspondent might
agree. And if you rate worthy-but-unexciting above chancy-but-intriguing, the
news editor is indeed wrong. But decisions about what gets into the media are
influenced by much more than the objective importance of the facts themselves.
This can be a problem for any trialist who’d like his or her findings more widely disseminated. The difficulty is that the media are about real life—sometimes, admittedly, in a rather overblown form!—whereas randomised controlled trials are not. Real life is about opinion, emotion, prejudice, instinct, fashion, style and scores of other honourable or disreputable forms of human outlook and behaviour. Imagine the average newspaper stripped of all such attributes. Even a textbook on philosophy would make a more gripping read.
This is not, of course, to disparage the austerity and the intellectual clarity of clinical trials; but it does mean that their ethos is not one that sits particularly comfortably within the norms of journalism. It follows that even the most scientifically literate journalists may have difficulty selling stories about trials to their editors. Journalism thrives on black and white, not carefully modulated shades of grey. Like the fictitious MRC trial at the beginning of this piece, their results don’t have to be dramatic to be important. But if they’re not dramatic they’re less likely to be reported. And before we get too judgmental about this, we should ask ourselves why we select the paper we buy and the programmes we tune into. Can the news editor really be blamed for choosing the crocodile tear story instead of the MRC one? If his decision was indeed the wrong one, why aren’t more newspapers stuffed full of material of the kind he chose to reject?
And then there’s the source of the new drug: crocodile tears. Irresistible. Once again, before sneering at such base triviality, think of the practicalities of producing a newspaper or a broadcast news magazine that has to entertain as well as inform. Ask people which of two stories they’d be more likely to read: “Scientists today announced the results of a study on drugs derived from a rare tropical mollusc”; or “Scientists today announced the results of a study on drugs derived by entirely conventional methods from a lot of other chemicals with very long names”. It may be exceedingly foolish of us humans to find triviality so seductive. But though the media might play to this regrettable tendency, it was not the Sun or the BBC that invented this predilection.
Some stories, of course, do rely solely on facts that have virtually no inherent interest beyond their importance. But much of what appears in the media—including some of the best of it—is inspired by the personal and the specific as against the impersonal and the general. Unfortunately, the very essence of a clinical trial is to discount the exceptional. Its findings reflect the group response, but not necessarily that of any one individual. To the scientist, individual experience by itself proves little or nothing; yet personal experience is the essence of much journalism. Hence the demand from journalists for illustrative cases: people who have individually benefited. And that mollusc story raises all sorts of interesting angles (Why a mollusc? How ever did they find out? Might other molluscs have equally interesting properties?) that the MRC report does not.
Accommodations can of course be reached, and trialists with sufficient nous will be sure to have identified representative subjects willing to recount their individual experiences to those hacks who need them. But other conflicts are more difficult. The probabilistic rather than definite nature of many trial conclusions, for example. And there’s also the burden of trying to get others to see why such elaborate methods need to be devised to answer the simple question, does it work? Anyone who doubts that these things can be explained to a lay audience should take a look at the James Lind Library’s web site and its excellent explanatory essays. The logic of the randomised controlled trial—the “fair test”—is spelt out in all its magnificence. The reader learns why researchers make such a fuss about doing them according to the book. But even without references and most of the examples, between them the essays come out at well over 6,000 words.
Space and time are the two commodities in shortest supply in the media. Half a column in a broadsheet might give a journalist reporting a trial the space to say who had been compared with whom, or what with what. But even if space was available, outlining the finer points of research methodology is not part of what the media see as their role. And as for a 25 second report on a news bulletin, it may have time to do little more than quote a single finding and its possible impact.
To cap it all, some journalists writing or broadcasting about medicine—and most of those making the final decisions about what gets used and what doesn’t—are generalists who may share the fears and confusion of the wider public. Take part in a trial and swallow something that might harm me? I think not. Randomised? I want my doctor to choose the treatment that’s best for me, and not by tossing a coin. Take my chance and maybe end up swallowing a dummy pill when I might have taking a real one? No thanks, I want to be treated, not experimented on.
Some trials do get reported. From time to time there are articles and programmes that even explain why they’re important and how they work. Of course, we may see a radical change in the nature of journalism—or even in the human mind. Short of these things, there’s more chance of hearing Prayer for the Day on Beijing Radio than witnessing all the media coverage that enthusiastic trialists might like to see.
Dr Geoff Watts
Journalist and broadcaster
Dear David Bender,
I am surprised your site considers hair analysis unscientific. Hair samples have been sent to poor quality laboratories in the USA which do not do repeated routine sample control tests.
However I have been comparing the results from Biolab of mineral analysis blood
(serum white and red cells), sweat and hair in my patients since the 1980s.
The British Medical Journal in 1989 published the results of our trial of dyslexic
children which showed zinc deficiency in sweat compared with controls (1). The
hair zinc levels did not always correspond to the sweat zinc level for the obvious
internationally accepted reason that in zinc deficiency hair growth slows and
very high or normal hair zinc levels can be found. However, the results matched
for lower chromium and higher copper and toxic metals in dyslexics in both sweat
and hair.
The effect of progesterones and oestrogens in lowering zinc and raising copper levels (higher copper/zinc ratio) is clear in simultaneous sweat, hair and serum tests in my first paper in the Journal of Enviromental Medicine (2) which contains the proceedings of a Symposium on the effects of exogenous hormones.
While I would prefer not to use hair analysis alone, it is clearly useful for toxic metals but hair analysis can mislead for the two commonest deficiencies, zinc and magnesium, if blood and/or sweat tests are not also done.
Nutritional Medicine is a most basic foundation for all Medicine and should be an important part of medical education. Nutritional analysis for people is at least as important as an annual MOT for cars.
Ellen Grant
Dear Dr Grant
One major problem with hair zinc analysis is that many shampoos may contain zinc, which is adsorbed onto the hair when it is washed. Joyce Treuherz read a paper at a Nutrition Society meeting some years ago, and showed a bimodal distribution of hair zinc—although it does not appear in the published paper (3) she admitted in discussion that this was almost certainly due to use of shampoos that did or did not contain zinc. At that time, some shampoos contained high levels of zinc, although this may no longer be the case.
A further problem is that sweat contains a large amount of zinc; this may or may not affect hair analysis, but it certainly affects toe-nail zinc analysis (another method that has been tested for assessment of zinc status). Some years ago I got involved with a podiatry student's research project and we measured zinc in different regions of the toe-nail, including the part that is normally under the skin. We found a considerable gradient of zinc concentration, increasing with the age of the section of nail, and a gradient across the nail corresponding to the direction that (I am told) sweat travels around the foot (4).
David Bender
Dear Dr Bender,
Zinc deficiency is one of the most important diagnoses in clinical medicine. The function of hundreds of enzymes are impeded when zinc is deficient. It is a great pity that the diagnosis of zinc deficiency has been hindered by lack of availability of the most reliable tests and confusion over the results of hair analyses.
In children serum zinc is often within the normal reference range even when zinc is very low in a passive sweat sample which has been collected for one hour from the skin of the back. Zinc deficiency can be confirmed from analysis of white blood cell concentrations. A sweat test can be repeated hourly or daily and repletion of severe deficiency can take up to 14 days, or longer if gut absorption is also impaired. (Although other labs have started to provide the sweat test it is very time consuming compared with WBC zinc so it is the latter that tends to be used instead by other good labs.)
If levels of zinc were very high in a hair sample, a source of contamination would be sought. At one time an anti-dandruff shampoo had this effect, although not in any of my research subjects or patients. Newly grown hair from the nape of the neck is collected as older longer hair gives different results.
Our studies in 1981 (5) and 1989 (1) found significantly higher concentrations
of copper and cadmium in hair, and also in sweat in 1989, in dyslexic children
compared with matched controls. Sweat zinc was severely deficient in the dyslexic
children, being 66% lower than that for control children. Zinc deficiency allows
accumulation of toxic metals which may be important causes of the increase in
autism, asthma, dyslexia and hyperactivity in the past few decades (6,7).
Ellen Grant
References
Published by Routledge, London, June 2004. 218 pages with index. Hardback ISBN
0415321786 price £45.00; Paperback ISBN 0415321794 price £14.99
She would have done well to have directed Mr Humphrys to Dr Michael Fitzpatrick’s book. He proceeds logically through the MMR story and identifies all the ironies, such as vested interests ruling out any orthodox view but not counting for the motives of private clinics, and the way MMR activists pour scorn on medical science unless it supports their beliefs. No rational person could read it and still hold any notion that MMR causes autism, although there’s a problem with his sub-title. The book is indeed what parents need to know but the story has moved beyond the rational, and some of the evidence is quite complicated.
The book is a tour de force. Extensively researched (there are 18 pages of references) and impeccably argued, Fitzpatrick mostly eschews scorn, a scorn that I cannot help feeling for some of the major players. The book is up to date. While it was in the last stages of preparation, various retractions and statements appeared in the Lancet after researcher Andrew Wakefield was discovered to have had a conflict of interest. These are dealt with, entirely appropriately, as a postscript to the preface—a preface in which, for those who do not know, Fitzpatrick tells the story of his own son, who developed autism after being inoculated with MMR. But ‘after’ does not mean ‘because of’—probably the most important reason for the public misunderstanding of science.
Fitzpatrick is critical of Tony Blair’s refusal to say whether his son Leo received MMR, a crucial point in the story. It seemed to me clear, as it was to the middle classes at the time, that Leo had not been inoculated. Fitzpatrick cites the media research showing the astonishing proportion of the population who recall this incident.
Anyone who followed the frenzied e-letters in the BMJ that were prompted by the reviews of the television play Hear the Silence will realise that this book will have no effect whatever on those who believe (the word is apposite) that MMR causes autism. One e-correspondent described Fitzpatrick as evil. A common rejectionist position is that the question can be answered only by studying autistic children, in other words that epidemiology cannot answer it. Fitzpatrick will not persuade them. Another common position is to blame orthodox medicine for autism, because neither cause nor cure is known. Fitzpatrick has sympathy for them, but no solace other than to counsel constructive acceptance rather than destructive blame.
I have only one disagreement with Fitzpatrick. Although single vaccines are a poor substitute for MMR (another irony is that the single vaccines so sought after are less tested than MMR), I think that the situation would have been defused if the government had made them available. It would also have eased the government’s two-faced posture of encouraging patient choice on the one hand while denying it for MMR. But I could be wrong, and there’s no telling. We are where we are, and Fitzpatrick’s last chapter shows just how far we have to go to get back to where we were.
Neville Goodman
Consultant Anaesthetist, Southmeads Hospital, Bristol