Monday, March 19, 2007

Paediatric Grand Rounds Wants Your Post, Please

Mock-up cover for Standing Baby magazineYes, it is out with the begging bowl, as I shamelessly rattle the post collection bag and ask you for your contributions to Paediatric Grand Rounds. As you can see from the magazine cover, we are open to conventional and more off-beat topics.

The next edition of PGR will be hosted by Dr. Rob Lamberts at Musings of a Distractible Mind on March 25. Please send your contributions to
rob(dot) lamberts(at) gmail (dot) com
in good time to let the inimitable Dr. Rob do his stuff. Please - there are threats of goats, monkeys and accordions if you don't...

Clark Bartram is looking for more hosts of Paediatric Grand Rounds so please consult the schedule and volunteer your efforts.

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Why Both Misdiagnosis or Inappropriate Allergy and Intolerance Tests Can Harm Children

Allergies
I have been writing a lot about allergy and intolerance tests recently; a number of factors have contributed to this. The House of Lords is currently scrutinising allergy and intolerance in the UK. When I look through the medical histories of the children with whom I work, in 60-80% of them, the parents have usually indicated that there are several allergies and intolerances. I would estimate that there is clinical confirmation of these allergies etc. in fewer than 2% of the children.

It is breathtakingly difficult to obtain a referral to a clinical allergist in the UK. In the whole of the UK, we have the equivalent of 26.5 consultant posts: approximately 5 of those are specialists in paediatric allergy. It is frequently argued that the lack of NHS allergy diagnosis and management pushes people who suspect that they have allergies towards the more dubious fringes of CAM or to testing laboratories that claim clinical validation and "sound science" for their product range of tests.

Both allergies and intolerances can have a dramatic and deletrious impact on quality of life. Allergy can kill. It is difficult to write about less severe forms of allergy because it is not practical to predict whether or not a mild allergy might suddenly become a life-threatening allergy.

A number of children 'grow out of' allergies. Some children have allergies that are multi-systemic and this puts them at particular risk. Allergies are typically managed, not cured. An exception to this is the laborious process of immunotherapy for some allergens which is rarely available on the NHS in the UK and is reserved for those people for whom medical management has failed.

Dr. Glenis Scadding is a consultant allergist with an fine reputation. She has clearly and elegantly stated that IgG tests for the diagnosis of food intolerance are "a waste of money". She has criticised the availability of direct-to-consumer IgE tests because they lead to "mis-diagnosis and mis-allergen avoidance". When she gave testimony to a recent House of Lords SubCommittee meeting she gave an excellent example.

(This recording of the SubCommittee meeting on 15 March 2007 is available from the archive for 28 days: thereafter, an authorised transcript will be available. I have used CM to indicate that the speaker is a member of the House of Lords' SubCommittee. Any punctuation, emphases or mistakes in the transcript are mine.)

Start transcript.

CM: Tell us what you think about self-testing kits and whether they should be-are they sufficiently-regulated?

Dr. Scadding: They should be banned.

[Laughter.]

Dr. Scadding: I'm very sorry...But...For example, I saw a child this morning before coming here and she had...We did skin tests that are well recognised and she had skin tests to house dust mite and also to tree pollens. Two kinds of tree pollen. She has absolutely no symptoms referable to the tree pollen whatsoever. She does not have Spring Hayfever. She has good symptoms related to the house dust mite, so I treated her with house dust mite avoidance and anti-allergy therapy.

If she had got a kit, then she would have felt that she was tree pollen allergic as
well and something had to happen about that. She has sensitisation but not clinical disease. And if you do a test, only about half the people with that positive test will have clinical disease.

So, you can not have self-testing kits: they're going to lead to mis-diagnosis, mis-allergen avoidance. You need both the test and a detailed history taken by somebody who has some experience of allergy history taking and interpretation of tests.

End transcript.

Dr. Scadding regularly sees children who have suffered clinical harm, e.g., unnecessary surgical procedures such as tonsillectomy, adenoid removal, the placement of grommets etc. when the real problem has been undiagnosed, and therefore untreated, allergy. Later in the meeting, Dr. Scadding answers a question about inappropriate treatment.

Transcript starts.

CM: Dr. Scadding, how often do you see patients whose treatment has been inappropriate? I'm not talking about the ones where the allergic allergen has been missed but where they've actually been treated inappropriately for their allergy and have therefore come to clinical harm before they're referred?

Dr. Scadding: At least once a week-and often more than that.

CM: And what are the main causes?

Dr. Scadding: The main causes are that they have been unrecognised or under-treated or treated for something other than allergy.

End transcript.

In addition to clinical harm, children who are mis-diagnosed with allergies or intolerances may follow a very restricted diet that might not provide all of the nutrients that they need and may lead to malnutrition. So, I apologise in advance, but I shall be covering the topic of allergy and allergic diseases in children for some time to come.

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Friday, March 16, 2007

Food Allergy and Intolerance Tests: YorkTest Gives Evidence to the House of Lords

A young boy and his dog in a position of prayer
And please let Shinga hear some decent testimony before she explodes.

Dr. Glenis Scadding is a consultant allergist with an fine reputation. She has clearly and elegantly stated that IgG tests for the diagnosis of food intolerance are "a waste of money". She has criticised the availability of direct-to-consumer IgE tests because they lead to "mis-diagnosis and mis-allergen avoidance".

However, at the same hearing where Dr. Scadding spoke, and earlier in the session, Dr. Hart, a representative of YorkTest, gave evidence at a meeting of the House of Lords, Science and Technology SubCommittee hearings that are investigating allergy and allergic disease in the UK.

In summary, Dr. Hart acknowledged that IgG levels are not necessarily related to either food intolerance or chronic conditions. She also explained that the testing criteria for food intolerance are not as standardised or as high quality as other clinical testing. One might question why it is worthwhile for consumers to spend money on a test that is not agreed to diagnose food intolerance and does not attain the same standard as other clinical tests.
The antibody, the presence of antibodies, and this, I believe is true for IgG and IgE, doesn't necessarily mean disease or no disease.

Unfortunately, in our business, it's not like measuring thyroid function tests, where you've got a beautiful, international reference preparation, all laboratories are controlled, we know exactly what we are measuring, we know the normal ranges. We haven't got the luxury of our higher order standards, the international reference preparations ...so that we, in putting a food down onto the plate, and we have got a wide range of fruits, vegetables and the key foods on the plate. That's what we use.
It can be difficult to understand oral evidence at specialist hearings. However, when the questions are simple it is irritating that an expert's evidence should be so muddled and difficult to follow. I shall comment on Dr. Hart's testimony in follow-up posts. For now, I thought that it might be helpful to post some more of the oral evidence in the House of Lords' investigation in allergy and allergic diseases.

This recording of the SubCommittee meeting on 15 March 2007 is available from the archive for 28 days: thereafter, an authorised transcript will be available. I have used CM to indicate that the speaker is a member of the House of Lords' SubCommittee. Any punctuation, emphases or mistakes in the transcript are mine.

Dr. Gill Hart is the Technical Director of YorkTest Laboratories. Mr. Dillon is the representative for NICE, the National Institute for Clinical Evidence.

Start transcript.

CM: Can you explain to me, as a lay person, how the IgG food allergy tests work given that people who are not allergic to specific foods can still produce an IgG antibody response when they eat those foods?

Dr. Hart: Yes, of course. I think when we consider the antibody response to an antigen challenge we need to really think that the antibody response is only the first part of the whole reaction. The antibody, the presence of antibodies, and this, I believe is true for IgG and IgE, doesn't necessarily mean disease or no disease.

What does make a difference is the complex cascade of events that occurs after that antibody has been raised. And what we find, that the IgG we use as a marker, that a reaction has occurred but that doesn't necessarily mean that the reaction has gone on to provide a cascade of results resulting in disease.

Now, we know that the mechanisms for this are unclear and as a company we have tried to support and collaborate with groups that find out more about these mechanisms. Indeed, we have provided tests to a leading London hospital who have now shown, and this evidence is going to be presented in Digestive Disease Week in Washington in May, that in inflammatory bowel disease, there is a significantly higher IgG titres than in normal groups and it is the first time this has been shown.

In addition, we've also shown, or the group has also shown independently but using our test, that people's reported food sensitivities, i.e., filling in a questionnaire, saying, "What am I sensitive to?", actually correlates very, very well with the IgG levels and this is particularly in ulcerative colitis. Very preliminary research and it's something that we really hope the team, at this London hospital will build on. We have struggled, working with others, to get grants to do this sort of work. But we really want to encourage the understanding of these mechanisms which we know are not yet clear.

CM: Could I ask you how often you find negative results?

Dr. Hart: Yes, of course. We actually provide a food intolerance indicator test. Bear in mind that the people who come to YorkTest have chronic conditions. They have...Our recent survey data, which we published, showed that over 70% of the people that come to YorkTest have suffered for more than three years with their condition. So, it isn't a normal population that comes to YorkTest. What we find is that between 75 and 80% of those people will have at least one positive scoring to one of our 113 foods.

CM: Perhaps I could ask the other members of the panel...I understand that the IgE antibody tests are an established part of NHS diagnostic routines, is there any evidence to support the use of IgG antibody food tests.

[Silence and confusion.]

CM: Mr Dillon?

Mr Dillon: I'm sorry. I've no information to enable me to answer the question. NICE hasn't looked at that particularly.

...

Dr. Hart: For me, to support the use of IgG tests? Yes, there have been independent clinical trials that have been carried out and published in, this one key one, which is a double-blind placebo controlled trial published in Gut in 2004 by Atkinson which was actually an independent study but used the YorkTest test. There has been a study, recently published, in Nutrition and Food Science. Another in Headache Care.

And indeed the recent study that has been carried out using the YorkTest test commissioned by Allergy UK and independently audited by the University of York, used with 5286 of our consumers has shown that people who rigorously adhere to our diet, 3 out of 4 of those people are showing some benefit to their chronic conditions. The considerable amount of data...and we know ourselves as a company that we don't do a lot of aggressive advertising, we can't do that, and the company's grown rapidly, mainly on word-of-mouth, because people are showing benefit and we see every day that people, there is, as we know, an unmet need and people are suffering and are then seeing benefit by using our service.

CM: Can I just be clear? That with these tests, you're measuring the amount of the molecules of IgG, you're not measuring specific IgG or IgE, are you?

Dr. Hart: We're measuring food-specific IgG in our IgG tests. So we have, so when you talk about...

CM: Sorry, when you say food-specific...what foods? Are you looking at specific...?

Dr. Hart: We are. We have a range of different services but the main one is 113 different foods. You can imagine on a ..The test we use is an ELISA test methodology. So you can imagine that a purified food preparation put onto one of our ELISA plates, is actually a mixture of proteins. Of course, wholemilk would be a mix of different proteins.

Unfortunately, in our business, it's not like measuring thyroid function tests, where you've got a beautiful, international reference preparation, all laboratories are controlled, we know exactly what we are measuring, we know the normal ranges. We haven't got the luxury of our higher order standards, the international reference preparations ...so that we, in putting a food down onto the plate, and we have got a wide range of fruits, vegetables and the key foods on the plate. That's what we use.

CM: I don't particularly want to concentrate on Dr. Hart all the time, I apologise to the others. You mention the report commissioned by Allergy UK, we've got a copy of it here. I wonder if you can tell us, has it been published? Has it been shown in a professional journal yet?

Dr. Hart: It has. It was published at the beginning of February in the Journal of Nutrition and Food Science.

CM: And you talk about chronic medical conditions but it's quite unspecific about these.

Dr. Hart: Yes, that's the interesting area really in terms of the type of people that come to YorkTest with chronic conditions. As you can see from the paper, it clearly outlines the different sort of conditions that people do come with and I think, because I understand that in the medical community, people are used to looking at specific conditions, it's very difficult to sometimes understand the concept that one or two different factors, like removing food from the diet, could actually benefit a range of conditions.

CM: I think that a lot of conditions will get better with a better diet won't they?

Dr. Hart: That's true.

CM: That is a concern.

Dr. Hart: That's true. But what we do find is that specific combinations of foods do actually show more benefit than removing the typical foods that you might imagine would be responsive to allergy. It's those particular combinations that we can identify using our test.

CM: I'm sorry to keep asking you...Do you ever find that there is such a wide range of IgG reactions when you do your test that the person who sent the kit in is almost on a starvation diet?

Dr. Hart: We're very, very aware of this. As you're probably aware we do provide a nutritionist service with our...nutritional consultation with our...service. We do very unusually find, well not very unusually, we do find people with sometimes which have a high level of reactivity; say, greater than 10 differents foods in our test. We treat these with extreme caution and we always talk to that particular customer and talk through about how they may want to prioritise. We'd never advise removing lots of different foods from one's diet-and that's very irresponsible-but we would suggest that they prioritise and maybe take some of the ones with a particularly high titre out from the diet first and see whether that benefits.

In the end, this is an aid to management of diet. It's a little route-map rather than going through the laborious trials of elimination diet which-elimination diet and challenge which-maybe you're never going to find the exact combination of foods that people are intolerant to. This is an aid to management of diet and a route-map through for the consumer to help them.

End transcript.

Related posts:
Food intolerance testing and migraine
Truthiness and referenciness make the case for IgG food intolerance tests
More allergy and intolerance testing nonsense: part 1
More allergy and intolerance testing nonsense: part 2
Quote Mining and Misrepresentation: Poor Ways to Claim Clinical Validation or Sound Science
What is the Significance of IgG Antibodies and Testing?
Why IgG Testing for Food Intolerance Is Not As Simple As ABC or Doh Ray Mi

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Thursday, March 15, 2007

IgG Tests Are A Waste of Money: House of Lords Committee Hears Evidence, Let's Hope That They Listen

Bronze sculpture of a figure with a migraine by Jose SacalI think that IgG tests may accurately measure IgG levels but I do not believe that there is scientific support to confirm the relevance of IgG levels in the diagnosis of food intolerance. I have stated this in several posts over the last few weeks (see list at foot of post).

Today, the House of Lords SubCommittee that is looking into allergy and allergic diseases in the UK heard Dr. Glenis Scadding, Consultant Allergist of the Royal Nose, Throat and Ear Hospital, state this in a far more succinct and elegant fashion. My draft transcript of the full exchange from today's meeting (audio recording: available for 28 days and thereafter in transcript form) follows but the highlights from the redoubtable Dr. Glenis Scadding are:
What I do dispute is that it is worth making any attempt to identify IgG antibodies. We all make IgG antibodies to food....I see no way in which this can be used to guide diet.

I don't think there's any point in spending money on IgG antibody tests. You're better off going to see a dietitian and using an exclusion diet followed by reintroduction. The IgG antibody tests are liable to leave patients on diets that are inadequate and patients often like to think they're improving. They carry on in the teeth of very little improvement and may end up malnourished.

I think [self-testing kits] should be banned.
My draft transcript of the relevant part of today's committee meeting is as follows. I will amend this when a better recording is available or as an authorised transcript is available. I have identified the speakers where practical: CM indicates that a subcommittee member is speaking. Any mistakes or emphases in the transcript are mine.

Start transcript of oral session, 15 March 2007.

At around 1:23 the committee members discuss the YorkTest consumer satisfaction survey paper commissioned by Allergy UK and irritable bowel syndrome. Ms McManus of Allergy UK praises the value of the Hardman and Hart study and its implications for chronic illness.

Dr. Scadding: It's well known that irritable bowel syndrome can respond to dietary exclusion; I have no dispute with that. What I do dispute is that it is worth making any attempt to identify IgG antibodies. We all make IgG antibodies to food. Pam Ewan will tell you that 100% of the population she studies has IgG antibodies to egg and I see no way in which this can be used to guide diet.

In the Gut paper, which is the best paper produced, the sham group did not avoid dairy or wheat which are the two major problems with IBS patients and therefore it's not surprising that at the end of the survey there was a 10% difference. In that paper you needed, the number needed to treat was 9, whereas if you do an exclusion diet the number needed to treat is somewhere between 1 and 2.5.

So, I don't think there's any point in spending money on IgG antibody tests. You're better off going to see a dietitian and using an exclusion diet followed by reintroduction.

The IgG antibody tests are liable to leave patients on diets that are inadequate and patients often like to think they're improving. They carry on in the teeth of very little improvement and may end up malnourished.

CM: These [are] self-testing kits you're referring to.

Dr. Scadding: No. These are the York Laboratories' blood tests.

CM: Tell us what you think about self-testing kits and whether they should be-are they sufficiently-regulated?

Dr. Scadding: They should be banned.

[Laughter.]

Dr. Scadding: I'm very sorry...But...For example, I saw a child this morning before coming here and she had...We did skin tests that are well recognised and she had skin tests to house dust mite and also to tree pollens. Two kinds of tree pollen. She has absolutely no symptoms referable to the tree pollen whatsoever. She does not have Spring Hayfever. She has good symptoms related to the house dust mite, so I treated her with house dust mite avoidance and anti-allergy therapy.

If she had got a kit, then she would have felt that she was tree pollen allergic as
well and something had to happen about that. She has sensitisation but not clinical disease. And if you do a test, only about half the people with that positive test will have clinical disease.

So, you can not have self-testing kits: they're going to lead to mis-diagnosis, mis-allergen avoidance. You need both the test and a detailed history taken by somebody who has some experience of allergy history taking and interpretation of tests.

CM: But because the number of experts is so few and far between...It's inevitable

Dr. Scadding: Absolutely right...

CM: ...it's inevitable that you are going to be using tests.

Dr. Scadding: People are training-a lot of Primary Care nurses are being trained in doing skin prick tests and interpreting them, in places like the Respiratory Training Centre at The Athaneum in Warwick. And I think that may be a way forward.

CM: [Calling on Dr. Mills]

Dr. Mills: I'd just like to endorse what Glenis had said and I think actually for food allergy it's even worse. And that there are a lot of people who will have apparently been sensitised to foods like wheat but actually don't have any symptoms. And that can be really problematic when people eliminate important food groups from their diet.

CM?: What about the issue of inflammatory bowel disease that we heard about in the last evidence session.

Dr. Mills: What? You mean in terms of the IgG or the...

CM: Yes.

Dr. Mills: It's not particularly my area of expertise. But I think that it's a symptom and that people do benefit from dietary interventions. But the link at a molecular basis between IgG and irritable bowel syndrome is not apparent. And we make these antibodies to our food protein as part of our normal functioning.

CM: Ms McManus? This was a study that, if I'm right, your organisation commissioned. I just wondered if you had anything that you want to add to what's been said.

Ms McManus of Allergy UK: I think the main thing that I've got to say is as we were saying. You know... It's a lack of other places to send these people to. Err, we would give the YorkTest purely because it's the only one that has undergone trials-particularly for IBS and that's what we would say, that we would [be] happy to endorse it for, would be for those kind of symptoms. Eh, but, you know, we wouldn't recommend any other test.

End transcript.

I have to say that I am surprised to hear Ms McManus say that, as Muriel Simmons endorsement of YorkTest tests has been used considerably more liberally than solely in the promotion of IgG tests for IBS. I have said repeatedly that if Allergy UK limit their endorsement of YorkTest food intolerance tests to irritable bowel syndrome then they should state this unequivocally.

Allergy UK might consider whether it is premature at best to discuss the purported value of food intolerance testing in the treatment of chronic illnesses. They have said, repeatedly, that the people who contact them rely upon them for a good quality of advice and place their trust in them. It now seems as if some of the proxy trust that people have been asked to place on the value of IgG tests for food intolerance has been misplaced. Similarly, questions may need to be asked about Allergy UK's collaboration and endorsement of an IgE test (the YorkTest Allergy UK MAST (multi allergy screening test)) that does not mandate the involvement of a suitably qualified professional in the interpretation and implementation of the results.

If Allergy UK is truly recommending YorkTest faute de mieux and for want of anywhere else to make referrals then I have some suggestions:
  • coach the enquirer to advocate for themselves or someone else when approaching a GP
  • if a GP is unable/unwilling to make a referral to an NHS Allergy Clinic, then advise the enquirer to consider a private referral to a Clinical Allergy specialist. Even in London, for the cost of a YorkTest 113 foodSCAN test for intolerances, it is possible to purchase:
    • a consultation and tests at a well-regarded allergy clinic
    • a consultation with a leading consultant and researcher plus several tests
    • a consultation with a leading consultant and researcher, but tests would an additional cost
    • outside London, I would expect people might be able to have a consultation with an expert and comprehensive and relevant testing
  • several consultations with a dietitian (NB, appropriately qualified dietitian, not a nutritionist) who can guide and support the enquirer through an elimination diet.
If an enquirer suspects that they might have a mix of allergies and intolerances and requires both the YorkTest Allergy UK MAST (multi allergy screening test) and the 113 foodSCAN test, then the price comparison with the cost of seeing a relevantly qualified and experienced Clinical Allergy Consultant is even more favourable. Any of these suggestions are more likely to result in a more relevant outcome for the enquirer than an IgG test.

Related posts:
Food intolerance testing and migraine
Truthiness and referenciness make the case for IgG food intolerance tests
More allergy and intolerance testing nonsense: part 1
More allergy and intolerance testing nonsense: part 2
Quote Mining and Misrepresentation: Poor Ways to Claim Clinical Validation or Sound Science
What is the Significance of IgG Antibodies and Testing?
Why IgG Testing for Food Intolerance Is Not As Simple As ABC or Doh Ray Mi

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Tuesday, March 13, 2007

Multiple Chemical Sensitivity and the House of Lords Review

Bottle with skull and crossbones danger labelWhat do you call it when somebody attempts to flatter the intellect of their audience and then bamboozles them to the point that it feels as if they have cast ground glass and fine grit in people's eyes? I felt like this during a recent discussion of multiple chemical sensitivity.

The House of Lords has appointed a committee to investigate allergy and intolerance in the UK. The Committee is investigating some important issues with implications for public health and public policy so I was hopeful that the written submissions and oral hearings would involve robust explorations of the science and associated issues.

One of the topics under investigation is multiple chemical sensitivity. Unsurprisingly, most of the experts and bodies that submitted evidence on this topic concentrated on their own niche of expertise and emphasised their own perspective on various conditions and treatments rather than reviewing those with which they disagreed.

In a recent oral session (uncorrected draft that may be subject to amendment), the committee chairman asked the panel of experts to discuss multiple chemical sensitivity. Not all of the committee members have a scientific background. After some discussion from two experts, the other two experts had an interesting exchange.
Prof. Wessely: [Multiple chemical sensitivity] is an imprecise label. People develop multiple subjective symptoms in response to perceived exposures for which there are no obvious toxicological explanations.

Dr. Monro: I do not agree with that. I believe that there are explanations emerging now. There is a considerable amount of evidence that there are two principal pathways for allergies. Most allergies present at the surfaces of bodies, the whole of the outside surface and the surfaces of mucal membranes. There the gatekeeper cells-I am going to mention something because this is a scientific committee-the dendritic cells, are the gatekeepers of allergies. These are linked with some of the very fine nerve cells which are linked to the autonomic nervous system called C-fibres. C-fibres transmit information extremely fast and the information is passed into the autonomic nervous system and into the central nervous system. There are two principal mechanisms in allergy. One is the local mechanism where reactions can occur peripherally and the second is central mechanisms where the neural system of allergy invoked. We know that the neural system of allergy can be very easily switched on by exposure to chemicals. There are receptor [sites] on these C-fibres which will allow responses to be perceived quite quickly. Hence there is in fact a physiological mechanism to explain a very swift onset of symptoms which can be perceived neurologically as well by individuals and often having an expression through the autonomic nervous system.

Prof. Wessely: I am not an academic or clinical immunologist and I do not have postgraduate qualifications in it, I am not sure that any of us do, but those who do I do not believe would recognise that. The people in academic immunology and allergy in my institution and elsewhere repeatedly give the definition I have just given that this is where symptoms areise which do not have a recognised allergic, immunological or toxicological basis. If they did, life would be easy and we would not be here.
Just to be clear, it is Dr. Monro's response that makes me feel that somebody has cast stuff into my eyes.

I am a little confused by Dr. Monro's answer to Baroness Perry of Southwark's question.
Baroness Perry of Southwark: I would like you to explain to us something about what I think is called the provocation or neutralisation test which is used by environmental allergists; how does it work?
Dr. Munro likened it to low-dose immunotherapy although I doubt that that comparison is wholly appropriate. When asked a question about the quality control of the materials that are used, Dr. Monro comments as follows on the vaccine strength for provocation neutralisation therapy (which seems to be practised at Breakspear Hospital of which she is the director).
The dilutions are parts of that, perhaps one in 25 or one in 125 parts, just as an example, so that when one knows the original strength one can calculate what the strengths of the others are. The point is that immunotherapy has been shown to be beneficial. I can quote from a paper from Nature Reviews Immunology in October last year which says: "It will prevent the onset of new sensitisations to different allergens, reduce the development of asthma in patients with allergic rhinitis caused by inhaled allergens, and it is disease modifying rather than palliative.
I am unable to find that quotation within the paper although there are similar sentences and it is possible that this will be amended in the transcript. The paper does not discuss provocation neutralisation therapy and it seems a little disingenuous to quote it in that context.

However, in general, I can not find any support for the idea that provocation and neutralisation is a form of low-dose allergen-specific immunotherapy. Dr. Adrian Morris has repeatedly given his opinion that provocation neutralisation therapy has no clinical evidence to support it in the role as either a diagnostic technique of treatment modality. Having looked around Entrez Pubmed, it does not seem as if there is any critically reviewed evidence that provocation neutralization works. It is difficult to see more resemblance between them than their form, which is sounding dangerously like cargo cult science.

Click on the image or visit Flickr for the credit.

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Monday, March 12, 2007

Discouraging News from the Review of Allergy and Intolerance: Homeopathy Means We Need to Rewrite Textbooks

Skit on Prince Charles support for CAM as anti-elitistWhen people want you to consider rewriting "textbooks in physics, pharmacology and chemistry", you hope that they have good evidence behind it and some workable hypotheses with which to replace these erroneous and out-moded doctrines that have maintained a stranglehold in scientific and medical education. Sadly, it doesn't seem as if either the evidence or workable replacement mechanisms of action will be available any time soon so 'we mun dree oor wyrd' and hope for a paradigm shift to happen before error leads us into catastrophe.

The House of Lords has appointed a committee to investigate allergy and intolerance in the UK. The Committee is investigating some important issues with implications for public health and public policy so I was hopeful that the written submissions and oral hearings would involve robust explorations of the science and associated issues.

Unsurprisingly, most of the experts and bodies that submitted evidence concentrated on their own niche of expertise and mentioned technologies, techniques, treatments or dubious techniques with which they disagreed in passing rather than reviewing them. Both The Society of Homeopaths (pdf) and the Faculty of Homeopathy (pdf). offered written evidence.
[T]he Society [of Homeopaths] calls on the Government to send a stronger signal to primary care organisations that homeopathy has an excellent evidence-base in [allergy and allergic diseases] and to give them permission to refer patients to registered homeopaths (RSHom) for treatment.
I was interested to read about the "excellent evidence-base" but the submission only contained references to a handful of studies and did not mention any of the meta-analyses that found no benefit for homeopathy. According to The Society of Homeopaths:
Homeopaths believe the incidence of allergy and allergic diseases is rising owing to a lower immune function in more individuals. This is probably brought about by a variety of factors that could be considered 'triggers', toxins in the environment; diets poor in unrefined foodstuffs and rich in additives; and possibly the over-vaccination of very young children before inherent immunity has developed.
Unfortunately, although it sounds science-y and related to medicine, the document does not expand on what is meant by a "lower immune function", "toxins in the environment", what sort of food additives they are complaining about, or "the over-vaccination of very young children". The complaint about vaccination stands in contrast to Dr. Peter Fisher's claim that 'respectable' homeopaths support vaccination. There are no figures or references to substantiate the claims that:
[i]n addition to being a safe, effective, and cheap method of treatment, homeopathy helps patients and their carers to feel more involved in their progress to health.
Similarly, although The Society refers to financial benefits to using homeopathic treatment and alludes to case-studies and pilot projects, there are no references.

The Faculty of Homeopathy (pdf) written report does explain that homeopaths have 3 different approaches to treating allergies and allergic disease.
In homepathy there are a number of therapeutic strategies for the treatment of allergic disorders. These are commonly termed "local", "constitutional" or "miasmatic" strategies. Local prescribing is a strategy based on the patient's actual allergic symptoms. The advantage of this strategy is that it can be achieved in a standard GP appointment or even through self-prescribing. Constitutional prescribing is based on a more in-depth consultation which takes into consideration the patient's allergic symptoms and, additionally, their unique patterns of coping with any disease. Miasmatic prescribing is based on an elaboration of the patterns of allergic disease which can be seen to run certin whole families. This approach can be particularly appropriate in complex allergic conditions...Isopathy is similar to homeopathy but the main difference is that the treatment is selected solely on the basis of the patient's proven allergies (as shown, for example, by skin testing). It involves giving a patient a substance to which they are allergic in a homeopathic potency, usually orally, for a short course of a few days in order to reduce the allergic response.
The Faculty of Homeopathy refers to the treatment that is available in the Homeopathic Hospitals within the NHS.
Patients often find it easier to accept advice about allergy from the homeopathic hospital, which can steer them away from the more extreme (and expensive) fringes of untested alternative treatments. This can be of particular benefit with food sensitivities and allergies or multiple sensitivities.
However, it seems as if the Royal London Homeopathic Hospital (RLHH) blends a number of techniques and modalities in its approach to allergies and allergic diseases which must make it difficult to attribute success to various interventions.
Classical allergic diseases are managed with avoidance advice, conventional treatment where appropriate, dietary advice, homeopathic medication, Western Herbal Medicine, and also (uniquely in the NHS) with a form of desensitisation treatment called enzyme-potentiated desensitisation (EPD). The clinic is also one of the very few centres able to effectively manage patients with 'food intolerance' in all its manifestations.
Infuriatingly, there are no references or follow-up information for any of these claims about the work of the hospitals. However, the RLHH does declare itself
fortunate to have a dietician who is expert in food allergy and intolerance, a rarity in such services. This enables patients to be treated who have adopted an unnecessarily restricted diet on the basis of spurious 'food allergy tests' available on the high street, gradually broadening such diets, offering authoritative advice, checking nutritional status and advising on supplements.
The Faculty of Homeopathy does provide an overview of their claim for an "evidence base for homeopathy in the treatment and management of allergic conditions" although I can not comment on the literature because I haven't seen it yet.

I have read a number of explorations of homeopathy, including Oliver Wendell Holmes' Homeopathy and Its Kindred Delusions and a further exploration of what the practice of homeopathic dilution of remedies means in reality.
Take a grain of rice. Cut it in half. Cut it in half again. That is the amount of your original solution.

Now, take the distance from where you live to the south pole. Now think about the distance around the earth. Now think about the distance from the earth to the sun. Ok, now think about the distance from the sun to Pluto. Pretty big, huh? Ok, now think about the distance from here to the nearest star. It takes light 4.3 years (light that came from our sun when Bush was re-elected will reach that star 4 months after he leaves office) to reach that star, Proxima Centauri.

Got that? Ok now imagine a cube with each side the length of that distance. I am going to hide that crumb of rice in that cube. Try to find it...
So, I was looking forward to a rigorous examination of some of the claims of homeopathy by some of the committee members during oral evidence 21 February 2007 (unapproved, draft transcript of testimony). The session started off in quite a lively manner when the homeopath, and representative for The Society of Homeopaths, Kate Chatfield said:
In homeopathy, as far as I am aware, we do not have any significant evidence for the treatment of asthma but we do with allergic rhinitis, with hay fever and a lot of clinical evidence...evidence suggests that homeopathy could be of great benefit in eczema as well
Prof. Ernst (Director, Complementary Medicine, Peninsula Medical School) then refers to his book which summarises many complementary therapies and the trials in which they have been evaluated and declares:
For no treatment modality is there good evidence that it is clinically effective in asthma, isotopic eczema or hay fever.
Later, committee member Lord Taverne asked Ms Chatfield to explain the difference between homeopathy and isopathy and asked her to compare them with "conventional treatments in efficacy and cost". Despite the assertions about the comparative costs in the written evidence, Ms Chatfield says that she doesn't have enough information to speak about the comparative costs. Ms Chatfield presents her explanation about homeopathy and isopathy and then, rather charmingly, adds:
I think homeopaths would consider homeopathy more effective than isopathy but I do not think we have any evidence to show that.
She is a lecturer in homeopathy, a research ethics adviser and representative for The Society of Homeopaths but is unable to make a simple declaration on the matter. This is the more remarkable because she later responds to Lord Taverne's enquiry about the meta-analysis of 110 homeopathy trials that reported "no evidence whatsoever that homeopathy performed better than placebos" with the criticism that it was 8 trials, not 110 because the authors excluded most studies on the grounds of insufficient quality:
What they did was single out what they called the high quality homeopathy trials and narrowed them down to ten trials of homeopathy which were not homeopathy when you looked at them. They were isopathy, not homeopathy. It was unbelievable that they could draw that conclusion from eight trials of isopathy.
Although, from her own words, there is no evidence to show that homeopathy is more effective than isopathy. Ms Chatfield's later attempt to clarify the matter does not help me although it may be more meaningful to others:
The major problem with meta-analyses and homeopathy is that they incorporate lots of different kinds of prescribing and it would be prescribing for the whole person, prescribing for the disease, using isopathy, comparing them all, lumping them all in together as if they are one thing when they are not.
I am assuming that Ms Chatfield will have an opportunity to clarify what she mean in follow-up submissions because I am flummoxed at this point. Lord Taverne initiated one of the most entertaining exchanges in the session.
Lord Taverne: In a recent debate in the House of Lords the president of the Royal Society said that if medicines can really work even if only a single molecule is left this would entail some entirely new scientific principle with amazingly broad ramifications and fundamental implications for experiment over the whole of science. Could you explain how the mechanism is supposed to work that achieves these astonishing results?

Ms Chatfield: I think you know very well that I will not be able to because we
have not discovered that yet. I am of the opinion-and I think a lot of homeopaths are who were initially sceptical when they came in and, for a number of reasons, are convinced by the evidence-that science is not a static thing. It changes all the time and just because we do not have an explanation currently we do have a lot of people proposing different theories about how it may work. Just because we can not explain it now does not mean it does not work. Yes, it will mean that science is revolutionised and I do not see that as a bad thing.

Prof. Ernst: There is a fundamental difference in saying we have not discovered the mechanism yet. 50 years ago, we did not know exactly how Aspirin worked but we always knew that there would be a mechanism there because it is pharmacology. With homeopathy, this is fundamentally different. Science tells us there is no mechanism by which it can work and that is an important difference. If we find the mechanism, then we have to rewrite our textbooks of physics, pharmacology and chemistry.

Prof. Brostoff: I do not think there is a problem with rewriting any textbook if new facts arise...
There are several dispiriting exchanges in the session as it seems that both VEGA testing and kinesiology are being treated with more credulity than their mechanism of action or plausibility would merit. However, the low-point is possibly when Lord Colwyn seems to disregard much of what has been said previously and mis-summarises that and tops it off with a personal anecdote:
I am sure the panel would agree that, despite the criticism, there is no doubt that these techniques-we can go back to kinesiology and Vega testing and also homeopathy-have succeses. I have referred patients to a kinesiologist for 30 years and I do not think he has ever got one wrong.
Exercising the level of diplomacy that is expected when responding to the latest outburst of an embarrassing relative during a fraught family gathering, Prof. Corrigan responded:
I am afraid that is the sort of anecdotal report we have to be very careful of. Such observations mean nothing outside a properly controlled trial. Anybody can convince themselves they have benefited, particularly the person who recommended them, but I am afraid that does not constitute scientific evidence.
Prof. Corrigan's patience is being tried very high during the later exchange on appropriate standards of proof which enable medications to be licensed for use or prescription within the UK. For various reasons, homeopathic and herbal medicines were licensed last year and can be prescribed on the NHS; however, allergen immunotherapy is not licensed.
Prof. Corrigan: I am afraid this is appalling nonsense. We have been campaigning as allergists to get allergen immunotherapy licensed by the MHRA for years. This is a very scientifically validated treatment which is of great benefit to thousands of sufferers with hay fever and still the MHRA turned us down because some patients have reactions to the injections. It is very frustrating that they then condone the use of these untried, uncharacterised and untested concoctions on the basis of no evidence at all. It is completely impossible to understand and very frustrating for the practise of a proper, scientifically conducted allergy.
With an unerring lack of clarity, Ms Chatfield responds:
Of course, I do not think it should be taken in isolation as a form of evidence but it is still a kind of evidence. I think the Chinese would be horrified by what you have just said, that because their medicine has not been scientifically proven it should not be used.
Prof. Ernst supports Prof. Corrigan in his use of the nonsense word:
It is a nonsense and it is very regrettable because it sets a double standard for the first time in medicine regulation...We are freezing our knowledge of potentially beneficial herbal treatments if we do not ask for proof of efficacy.
Later, when asked if there is any advantage to be gained by enforcing regulation of the practitioners of complemetary and alternative therapies, Prof. Ernst expanded upon his opinion that there is little to be gained from it:
if you regulate traditional herbalists and there is no shred of positive evidence for their individualised approach, you regulate in my view nonsense and that will result in nonsense.
Lord Taverne tried to take the temperature of the panel of experts as to whether it would be useful to issue guidance about alternative therapies to the public. Prof. Brostoff responded in a manner that may have sounded more germane, responsive or humorous in the session than it reads in the transcript:
It might be interesting to issue a health warning against going into hospital these days. If you take malpractice, if you take 10 per cent of hospital admissions being due to drug reactions plus MRSA, plus clostridium dificil, that would be more appropriate at the moment and it is also a much larger problem.
Prof. Ernst summarises the matter in a typically robust and clear fashion:
From my perspective, guidance against complementary, alternative therapies is nonsensical. Guidance against unproven or disproven treatments, yes. Many treatments in complementary medicine are unproven or disproven, but not all. Some have very good evidence, not in the area of allergy, I am afraid...It is not about a label, complementary versus mainstream; it is about proof of efficacy and safety.
Given the lack of support for homeopathy and other CAM modalities in the diagnosis and management of allergies and allergic diseases, and the heavy use of the nonsense word by Profs Corrigan and Ernst, I have to assume that the Earl of Selborne was asking a faux naif question:
There are currently five NHS homeopathic hospitals which offer homeopathic and other complementary treatments such as acupuncture. Should we have more on the National Health Service and should the range of treatments alongside conventional treatments be extended to such therapies as Vega testing and kinesiology on the National Health Service?
Prof. Corrigan responds admirably:
I could not condone expansion of homeopathic hospitals or any other alternative therapy to the deteriment of setting up a well accessible, conventional allergy service within the NHS.
I am, again, indebted to Ms Chatfield for some light relief when she has an exchange with Lord Broers.
Lord Broers: I have a simple, technical question about homeopathy and drugs. Is it possible to distinguish between homeopathic drugs after they have been diluted? Is there any means of distinguishing one from the other?

Ms Chatfield: Only by the label.
This exchange went some way to mitigating the depression caused by Prof. Brostoff's contribution to the discussion about whether the "present expenditure on [the] five homeopathic hospitals is justified or can be justified":
If you take general surgery or most surgical operations, probably 90 per cent have not been put to a true double blind clinical study and we are using empirical methods which sometimes work better than others. If homeopathy is satisfactory to the patient and adds something to their quality of life and keeps them away from the NHS, I would support it fully.
It is distressing that a supporter of homeopathy can only produce negative rather than positive evidence to support it but a little odd that he has not noticed that the question was about NHS support for homeopathy.

Neither the written nor oral evidence has made the case for homeopathy in the treatment of allergy or allergic diseases: despite the assertions, there is no evidence that it is cheaper than conventional treatments. I am unconvinced of the need to pulp the current range of textbooks for physics, pharmacology or chemistry, and don't consider it necessary to include footnotes or caveats in current editions.

Flickr artist Tom Morris offers a skit of Prince Charles talking about complementary and alternative medicine.

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Paediatric Grand Rounds 1:24 is Up!

Star - text is Paediatric Grand RoundsDr. Sam Blackman at Blog MD has posted Paediatric Grand Rounds 1:24.

Dr. Blackman has put together an interesting blend of posts from those formally charged with the care of children and those who take care of them all the time. There are many interesting stories with some useful teaching points (how to cope with a child who breath holds), a nice side-trip into medical malapropisms, and the murkier waters of bizarre stories and theories about vaccine injuries...Because this is children, we also have the elegaic, the thoughtful and the stories that threaten to tear out your heart. Go over and read them.

The next edition of PGR will be hosted by Dr. Rob Lambert at Musings of a Distractible Mind on March 25. Clark Bartram is looking for more hosts of Paediatric Grand Rounds so please consult the schedule and volunteer your efforts. Do not be shy about this, Clark Bartram would be delighted to hear from you. Compiling PGR gives you an opportunity to poke around many blogs and eavesdrop on a massive range of issues that affect children's health and wellbeing.

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Saturday, March 10, 2007

Radio 4's Check Up on Food Intolerance and Allergies

Allergies
More and more families in the UK are learning what it is like to live with food allergies and intolerance. Radio 4's Check Up bills itself as "your chance to talk to doctors about the health issues that most concern you and your family". Check Up has just explored food allergies and intolerance with Dr. Pamela Ewan, Consultant Allergist as Addenbrookes Hospital in Cambridge. The topics included anaphylaxis, allergies, food intolerance and oral allergy syndrome.

The programme broadcast on 8 March 2007 was about food intolerance and allergies: the programme runs for less than 30 minutes and will be available to listen to for some time and then available as a transcript.

Dr. Ewan strongly makes the case for better food labelling because, in her experience, just advising people to e.g., "avoid nuts" is not sufficient when such ingredients can be included in the most surprising foods, such as nuts in lemon meringue pie. Dr. Ewan deals robustly with the question of parental guilt concerning whether they caused the allergy by too early exposure to an allergen or providing too clean an environment (parental guilt is not justified).

For one caller, Dr. Ewan explores the presented symptoms further to discuss the phenomenon of oral allergy syndrome (around 11:30). Dr. Ewan explains that some people react to some uncooked fruits but may be entirely comfortable eating the cooked fruit.

Several people who contact the programme disclose that they have an allergy to kiwi fruit; Dr. Ewan confirms that this is becoming more common.

The difference between intolerance and allergy is really in two ways. First of all the mechanism, the way the reaction comes about. And in allergy, what happens is the patient makes a harmful allergic antibody so it's an antibody-mediated reaction. In intolerance this allergic antibody is not involved so the mechanism is a different one...We can test for food allergy. Food intolerance is much more difficult because the mechanism sometimes is known and may be testable but in the majority of cases is not understood and can not be tested so the only way you can diagnose that intolerance is by removing and reintroducing the food and looking at the effect on the symptoms.

The other difference between intolerance and allergy is in the symptoms they tend to produce and food allergy has very distinct symptoms. We heard some of them from earlier callers - the severe reactions in the mouth, throat, airway, rashes, sometimes collapse. So, they are very typical, quick onset, potentially severe reactions. Food intolerance is a more grumbling, slow thing. Not usually so severe. [It] tends to cause tummy problems, bloating, diarrhoea, nausea. [Approx 14:30-15:50.]
Dr. Ewan goes on to describe the problems in dealing with allergies on the NHS because of the small number of specialists that we have in the UK despite the scale of the problem.

We put a lot of emphasis on a detailed history backed up by tests. Tests alone are not terribly helpful but with the history, they're good. So, making a proper diagnosis, because you don't want to be avoiding foods that...you don't have to...But thereafter you can put in place quite a good system to avoid further reaction. [17:50-18:10.]
Dr. Ewan emphasised the importance of a written self-management plan and appropriate drugs, according to the degree of severity and risk. She said that the evidence is that these self-treatment plans are very successful at preventing exacerbations and complications.

Dr. Ewan stresses the importance of a careful supplementation of, e.g., calcium, if dairy products are eliminated from the diet. She emphasises the importance seeking specialist advice because patients need to know what needs to be avoided and what need not, particularly for children.

Dr. Ewan is one of the experts who talks of an epidemic of allergy in the UK. She laid proper emphasis on the need for thorough evaluation of allergies and the role of education in allergen avoidance. However, as she said several times, achieving this may be remarkably difficult in the UK because of the lack of appropriate specialists.

Flickr credits: 1. Allergies be damned, 2. Springtime allergy party pack

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Friday, March 09, 2007

Allergy and Intolerance Under Scrutiny by House of Lords

Question mark and reminders
The House of Lords has a Science and Technology Committee that is one of the main investigative committees in the UK. The Committee is a major forum of independent expertise and its broad remit is “to consider science and technology”. The S & T Committee investigates a range of topics including those with public policy implications and assessing health and research priorities. Committee recommendations are largely directed at Government, though they may also have implications for industry, the professions and consumers and the general public.

Presently, Sub Committee 1 is investigating allergy and allergic diseases and their associated range of policy issues. However, because allergy service provision was recently examined by the House of Commons Health Committee and the Department of Health, it is not the primary focus of this enquiry.

The Committee has specified some interesting questions. The questions are designed to:
  • define the problem
  • explore treatment and management strategies and areas for research
  • investigate the impact of government policies (e.g., housing provision or food labelling legislation)
  • consider patient and consumer issues.
I have a particular interest in this last area because the Committee is inviting evidence on:
  • What can be done to better educate the public and to improve the quality of information that is available to patients and undiagnosed sufferers?
  • Are current regulatory arrangements, for example, those governing private clinics offering diagnostic and therapeutic services and the sale of over the counter allergy tests, satisfactory?
I'm particularly interested in this because a lot of the coverage of allergy and intolerance is such sloppy journalism that it adds to the confusion of people who are looking for accurate and helpful information. Nutritionists who should know much better refer to food allergy and intolerance as if they are synonymous: e.g., see the transcript of a web chat on food allergies by Patrick Holford.

I don't think that most consumers are aware of the lack of evidence to support the claims that some over-the-counter DIY diagnosis tests are clinically-validated or have sound science to support them. I know when I've discussed these tests with some people, they assume that approval by, e.g., Medical Devices, MHRA, means that the test is validated. However, that approval may just cover the use of an approved sterile lancet or appropriate cleaning swab, e.g., some of the individual elements of a kit: it does not verify that the test is effective.

The Committee collected written evidence last year (scroll down the page)and is currently listening to oral evidence. The written evidence is of uneven quality and I shall discuss some of it in the future. Some of the oral evidence will be available for a limited time on Parliament Live TV and I look forward to listening to it.

The Committee shall release its recommendations in the form of a report in June.

Flickr credits for the images. 1. question, 2. Questions?

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Thursday, March 08, 2007

Why So Much Medical Research Is Rot

Graffiti to the side of a tunnel reads: Are you happy? I'm not. Change.
Anybody who spends any time reading through Sandy Szwarc's Junk Food Science is accustomed to robust examination of the claims made about observational studies and vigorous challenges to received wisdom on the topics of obesity, healthy eating and demographic timebombs. Hardened by reading Sandy, I scarcely raised an eyebrow when I read an article in The Economist: Signs of the Times, Why So Much Medical Research Is Rot.

Dr. Peter Austin examined hospital admission records and discovered that astrological birthsigns are associated with particular conditions. E.g., people born under Leo are 15% more likely to be admitted to hospital with gastric bleeding than other birthsigns; similarly for Sagittarians who are 38% more likely to be admitted for a broken arm.

Dr. Austin does not endorse the above findings nor claim that they are meaningful. He used the findings to illustrate the inadequacy of commonly used statistical analyses that "run the risk of identifying relationships when, in fact, there are none". Austin's analysis demonstrates why so many health claims look important at first blush but can not be substantiated in later studies.
The confusion arises because each result is tested separately to see how likely, in statistical terms, it was to have happened by chance. If that likelihood is below a certain threshold, typically 5%, then the convention is that an effect is “real”. And that is fine if only one hypothesis is being tested. But if, say, 20 are being tested at the same time, then on average one of them will be accepted as provisionally true, even though it is not.
Dr. Austin performed a data dredge. He ran the data against 24 hypotheses, two for each astrological sign. He was on the lookout for any instance where a birthsign “caused” a greater risk of a particular condition. When the hypotheses were asssessed individually, then it seemed as if the findings about Leos' intestines and Sagittarians' arms were less than 5% likely and therefore not likely to have occurred by chance. p <0.05 has attained (undeserved) magical status as proof of statistical significance: Sifting the evidence{---}what's wrong with significance tests? is a more elaborate exploration of this.

Dr. Austin emphasises that when he amended his statistical analysis to reflect that he was testing 24 hypotheses rather than 1, the the boundary of significance dropped and none of the astrological associations remained. This is more than an entertainingly cautionary tale about the misuse of statistics (and, I wish that my lecturers and tutors had been so creative). All too frequently in medical research, investigators trawl data for risk factors for diseases but neglect to modify their analyses when they test multiple hypotheses.

Unfortunately, many researchers looking for risk factors for diseases are not aware that they need to modify their statistics when they test multiple hypotheses. Dr. John Ioannidis argues that because researchers fail to adapt their statistical analysis appropriately it is not unusual to discover that striking findings from observational health studies cannot be reproduced by other researchers (the usual way to confirm a scientific finding). Dr. Ioannidis discussed this issue (amongst others) in Why Most Published Research Findings Are False. Ioannidis had famously explored the clash between observational studies and trials in Contradicted and Initially Stronger Effects in Highly Cited Clinical Research (Orac has a good discussion of this paper and dealing with conflicting evidence). In one example, Ioannidis had followed-up the progress of 6 frequently cited observational studies, and discovered that the conclusions from 5 of them were not only unreplicated but later refuted.

Just in case medical statistics was beginning to recover from its grogginess, Ioannidis presented his new work that examines systematic bias in research. According to The Economist, Ioannidis revealed that:
the results of observational studies are likely to be completely correct only 20% of the time. If such a study tests many hypotheses, the likelihood its conclusions are correct may drop as low as one in 1,000—and studies that appear to find larger effects are likely, in fact, simply to have more bias.
This does not mean that we should throw up our hands and declare a plague on all your houses. Ioannidis' earlier work highlights that well-designed, controlled trials refuted the findings from widely-publicised and cited observational studies. However, it does mean that journalists who offer themselves as the people who can mediate between scientists and the public in promoting the understanding of science (particularly medical matters) should have a more thorough understanding of statistics and be more robust in their enquiries. Otherwise, the public understanding of the value of science will continue to erode.

For more information about the image used in the illustration, click on it or visit the detail on Flickr.

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Tuesday, March 06, 2007

Food Intolerance Testing and Migraine

Bronze sculpture of a figure with a migraine by Jose SacalI have seen some extravagant claims about the value of food intolerance testing in reducing migraines, e.g., An appetite for migraine?. Barbara Lantin sums up the findings of a (then) recently released study by Rees, Watson, Lipscombe, Speight, Cousins, Hardman and Dowson:
In the first study of its kind, 61 people with moderate to severe migraines were given a food intolerance test. Only one patient had no intolerances at all and the average participant had 5.3. Of those who eliminated the named foods from their diets, 80 per cent reported some improvement in their migraines and more than a third reported significant relief. More than 60 per cent of patients who reintroduced the suspect foods into their diets reported the return of their migraine symptoms.
That is one interpretation of the poster that was presented at a conference: A Prospective Audit of Food Intolerance Among Migraine Patients in Primary Care Clinical Practice (pdf). However, Lantin has omitted the fact that only 39 of the original 61 people completed the 2 month study. The claim that "80 per cent reported some improvement in their migraines" is a little puzzling unless Lantin has had access to an analysis of a sub-group because the authors report the finding that:
After two months, 38.2% of patients reported considerable benefit (scoring 4 or 5), while 32.4% reported little or no benefit (scoring 0 or 1). [Emphasis added.]
There is no attempt to explore the difficulty that people may have had in following an IgG-guided elimination diet and whether this is a possible explanation for the discrepancy between the 61 people who were audited for the study and the 39 who completed the 2 months. The authors report that 56% of the migraineurs "changed their diets 'a lot'" and 33% "made a ‘reasonable attempt’ to change their diet". There is no exploration of "a lot" or "reasonable attempt": the reader does not know whether the former successfully excluded all of the foodstuffs that had returned high IgG levels or not.

Rees and colleagues report that:
[o]ver 60% of patients who reintroduced the suspect foods back into their diets reported the return of their migraine symptoms.
However, it is not too surprising that 60% of patients who believe that IgG levels are indicative of food intolerance would experience a return of symptoms if they knowingly ate a 'suspect' food. The percentage of those who report a return of symptoms is inline with the findings of some nocebo studies: if study participants believe that an intervention or substance can harm them, then some of them will report that effect, even in the presence of an inert substance or stimulus. E.g., a study into the psychologic induction of pain found that:
[m]ore than two-thirds of an unselected sample of 34 college students reported mild headaches when told that a (nonexistent) electric current was passing through their heads.
For the migraine study, the authors conclude that:
[t]his investigation demonstrated that food intolerances mediated via IgG may play a part in the development of migraine attacks and that changing the diet to eradicate specific foods is a potentially effective treatment for migraine. Further large controlled clinical studies are warranted in this area.
However, although these findings are interesting, they do not indicate that food intolerances are mediated by IgG. The authors do not comment on the possible influence of the placebo or Hawthorne effect on their results.

Lantin acknowledges that IgG testing may have "no significant role to play" and writes that:
Food intolerance is only one possible cause of migraine and, even when it is implicated, may not be the only factor. Stress, exercise, travel and the menstrual cycle can also play a part.
However, she quotes one of the study's authors, Dr. Andrew Dowson, as saying:
[t]he fact that something is not at the forefront of medical science now does not mean it isn't important - it may just mean we haven't noticed it yet...

This was a pilot study and we need some more definitive research. For example, a placebo-controlled trial that follows up people over the longer term. But it is an interesting piece of work, with encouraging results, and I see no reason why people with migraine should not take a test.
There is still no published body of evidence to support IgG testing in the diagnosis of food intolerance: relevant professional organisations say IgG tests can not be recommended for that purpose. It was a very short study with a small number of participants. The reported results are within limits for what is known about both the placebo and nocebo effect. I would suggest that there is a potential for harm if people with migraine are encouraged to take a test that has no scientific support: should this intervention fail, then it can lower the bond of trust between the patient and healthcare worker and, through the nocebo effect, may have an adverse impact on the experience of future medical interventions.

As I've outlined in other posts, there may be a range of consequences for children who follow a restricted diet, particularly ones that eliminate foods that are a significant supply of calories or nutrients or are so restrictive that they cause significant social difficulties.

Related posts:
Truthiness and referenciness make the case for IgG food intolerance tests
More allergy and intolerance testing nonsense: part 1
More allergy and intolerance testing nonsense: part 2
Quote Mining and Misrepresentation: Poor Ways to Claim Clinical Validation or Sound Science
What is the Significance of IgG Antibodies and Testing?
Why IgG Testing for Food Intolerance Is Not As Simple As ABC or Doh Ray Mi

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Monday, March 05, 2007

Views on Allergy UK's Stolen Lives Report and Statistics

Sign text reads: Peanuts and peanut dust everywhereAllergy UK launched their Stolen Lives report during Food Allergy and Intolerance Week in the UK. I have concerns about the value of that report and the uncritical way that its claims were reproduced in the UK media.

So, it has been comforting to learn that there have been some rather more robust appraisals. Steve Carper says that:
[t]he kerfluffle started by Allergy UK's moronic poll alleging to prove that one-third of the total British population has food intolerances and allergies continues to roil nicely.
He highlights Dr. Miriam Stoppard's article in The Mirror:
WE'RE asked to believe that nearly half of us are intolerant of one food or another.

I've never heard such rubbish. And this particular rubbish is masquerading as "science" in a survey published a couple of days ago by Allergy UK, a medical charity.

The report feeds into the current fashion for food intolerance. And it's dangerous because someone suspecting they have an intolerance will feel free to go on an exclusion diet, omitting important, nutritious foods without prior diagnosis and without supervision.

As you might suspect there's a commercial agenda.

There are a number of commercially available tests for food intolerance that their manufacturers claim will make the diagnosis for you. They're suspect, unreliable and scientifically unproven. The commonest intolerance - lactose (milk) - is due to a shortage of the enzyme lactase, needed to absorb lactose.

...

Let's keep a sense of proportion here. With food intolerance you can usually get away with simply cutting down on the offending food.
It's good to see that Dr. Stoppard presenting such a straightforward view. Several TV and media doctors quote Allergy UK's statistics as if they were from a validated epidemiological study, rather than an opinion poll. Some of those same TV and media doctors have voiced some support for IgG testing in the diagnosis of food intolerance but a number of them also have connections with YorkTest and similar commercial laboratories.

It would be useful if some of the media doctors were a little more forthcoming of their criticisms of the value of food intolerance tests. It is disappointing that some of the more critical investigations have been left up to The Mirror. E.g., FAD OF THE LAND, Food Allergy Craze Can Damage Your Health and Pocket.
new research shows we could be wasting our money and actually damaging our health by self-diagnosing allergies that simply don't exist...

Catherine Collins, chief dietician at St George's Hospital in south London, has experienced an alarming increase in young people demanding treatment for allergies when there is nothing wrong with them...

ANOTHER major risk of diagnosing a food allergy yourself is that you could overlook a genuine illness.

Catherine says: "Often people will just cut out certain foods rather than visit their doctor.

"But if they had gone to their GP they might have discovered that the bloating was caused by a serious bowel condition."
Patrick Holford recently suggested that the objection to IgG testing for the diagnosis of food intolerance is a reflection that:
some health professionals just haven’t kept up to date. Perhaps it’s because a ‘home test’ takes the power away from the professional and puts it in your hands.
I would suggest that it's because there is negligible published evidence of sufficient quality to support the role of IgG testing in food intolerance and because concerned professionals have genuine reservations about their potential for harm.

Related posts: Asthma and Food Allergies: Fashion or the New Form of Spiritual Re-Awakening?
Some Sticky Numbers and Comparisons for Food Allergy and Intolerance

For more information about the image used in the illustration, click on it or visit the detail on Flickr.

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Sunday, March 04, 2007

Paediatric Grand Rounds Wants Your Post, Please

Mock-up cover for Standing Baby magazineYes, it is out with the begging bowl, as I shamelessly rattle the post collection bag and ask you for your contributions to Paediatric Grand Rounds. As you can see from the magazine cover, we are open to conventional and more off-beat topics.

The next edition of PGR will be hosted by Dr. Sam Blackman at Blog MD on March 11. Please send your contributions to
samuel (dot) blackman (at) gmail (dot) com
by Friday March 9th.

Clark Bartram is looking for more hosts of Paediatric Grand Rounds so please consult the schedule and volunteer your efforts.

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Saturday, March 03, 2007

Truthiness and Referenciness Make the Case for IgG Food Intolerance Tests

A young boy and his dog in a position of prayer
And please let Shinga read some decent research papers before she explodes*.

Prof. Ernst has frequently and elegantly rebutted the claim that CAM treatments and therapies are not amenable to standard forms of scientific investigation. However, hand in hand with the claims that CAM is not suited to scrutiny, it seems that there is a certain truthiness and referenciness that predominates in the claims of scientific support for some of these treatments.
Dr Ben Goldacre, used this word to suggest a supposed scholarly reference that wasn't a real one: "The scholarliness of her work is a thing to behold: she produces lengthy documents that have an air of 'referenciness' ... but when you follow the numbers, and check the references, it's shocking how often they aren't what she claimed them to be." ...Stephen Colbert's "truthiness"...describes things that a person claims to know, without regard to evidence, logic, intellectual examination, or actual facts.
Truthiness and referenciness are rife in the claims made for the role of IgG testing in the diagnosis of food intolerance. These claims are in stark contrast to the position statements of various relevant professional organisations.

Some might argue that it is putting the umption before the ass to make any claims about IgG levels and food intolerance until such time as researchers, clinical allergists and immunologists agree whether IgG levels are protective or indicative of a harmful response.

Lately there has been some YorkTest excitement about the value of IgG-guided elimination diets in the amelioration of various symptoms and chronic conditions: 10 Years of NHS treatment and still we're ill says study. They are so pleased with the results of this paper that an enthusiast who works for them may even have founded an e-petition, calling for the provision of intolerance tests on the NHS.

I must re-iterate that I readily admit that what I know about IgG testing for food intolerances could be written on a postcard, leaving plenty of room for the address and a stamp. Nonetheless, I have profound reservations about the value of the Hardman and Hart paper that is the basis for YorkTest's Testing Times report and I doubt that it is a useful contribution to the literature that assesses IgG testing for food intolerance.

Kenny Tranquille is a Nutritional Therapist. According to his profile, he
completed his extensive training at London’s Institute for Optimum Nutrition (ION) and since graduating, has established a strong following and helped hundreds of individuals to feel fantastic and regain their health. BUPA & Ernst & Young are among some [of] the leading companies that have invited Kenny to run workshops and seminars. He is frequent lecturer at the Institute for Optimum Nutrition and a student tutor.
Kenny Tranquille trumpets the report in Testing Times - The Facts.
The UK's largest ever study into Food Intolerance was published this week and makes interesting reading - it contains all the reasons why you would go down the Food Intolerance route to get yourself better...over 3 out of 4 get better...90% recommend out [sic] service to others...over 6 out of 10 feel the benefit within three weeks.
I don't know what Kenny Tranquille lectures in at the Institute for Optimum Nutrition but I trust that it is neither critical thinking nor the interpretation of research.

The Testing Times report is the basis for the Hardman and Hart paper. It is an audit of a customer satisfaction survey. It depends entirely upon self-report. It adds nothing to the literature on the alleged relationship between IgG levels and food intolerance.

The study finds that people who:
  • have a range of symptoms or conditions
  • believe that they have food problems
  • believe that they have food intolerances
  • believe that the measurement of IgG levels is an acceptable proxy for food intolerance
  • believe that a food elimination diet guided by IgG levels will mitigate their symptoms
  • were not asked to provide verification for the nature or duration of their symptoms
  • were not asked to describe the treatments that they had previously tried or were currently following
  • were not asked if they had previously experimented with elimination diets or allergen avoidance
  • paid for the 113 foodSCAN test
  • implemented some form of the dietary advice (not otherwise specified) to follow an elimination diet for a few weeks
  • responded to the survey (conducted over an unspecified period of time and with considerable confusion over which version of the questionnaire they received)
reported a subjective improvement in their assessment of their symptoms. Despite the attacks being made on the NHS, it is not clearly stated that every one of these participants had consulted a GP or other healthcare worker about these symptoms or conditions.

The study is an audit of anecdotes. I would hope that most people would be able to see that this study is a lengthy way of saying, "Because I said so" - by the respondents, and, as such, resembles truthiness rather than clinical rigour. Even the authors do not attempt to place this study within the context of the clinical literature in their discussion of their findings although I do feel that they considerably over-claim the value of their findings.

I feel like I'm trapped in the scene where Father Ted is trying to explain perspective to Dougal by using toy cows as props and pointing to cows in a far-away field:
Father Ted: Now concentrate this time, Dougal. These
[he points to some plastic cows on the table]
Father Ted: are very small; those
[pointing at some cows out of the window]
Father Ted: are far away...
Sound science...wishful thinking. Verifiable evidence...anecdote. Customer satisfaction survey...significant contribution to the scientific literature.

*I am grateful to Chrysalis Angel for permission to use this image.

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Thursday, March 01, 2007

More Allergy and Intolerance Testing Nonsense: Part 2

Pirate Mosaic
Allergy Magazine has recently published a feature on DIY Diagnosis. There is a reasonable introductory summary about the difficulties of gaining access to allergy diagnosis and management on the NHS. There is the usual sloppiness about referring to allergies and intolerance as if they are synonymous. The author uncritically reproduces a number of claims that are frequently repeated but I have yet to see substantiated:
[h]aving an allergy is now one of the most common health complaints in the UK, affecting an estimated 23 million people and four out of ten school children. Up to 40 per cent of the population are sensitive to the three most common allergens: dust mites, pollen and pets. Millions more are intolerant to certain foods, most commonly wheat and dairy.
There is the usual pop quiz where the reader is told that if they have 3 or more of a 16-item list of symptoms then they might have an allergy or food intolerance. The symptoms are the usual suspects: irritable bowel syndrome; constipation; bloating; migraines; anxiety; sinusitis; joint pains; fatigue; low immunity; itchy skin, rashes and eczema; acne or dry skin; itching, swollen lips and face; coughing or wheezing; shortness of breath; dry, itchy throat; diarrhoea or vomiting. Dr. Hadler writes about the medicalization of misery and would probably like a hands-up by anyone who hasn't experienced several of those symptoms over the last year.

The writer does make a handwave towards acknowledging that
[t]here is no clinically proven test for food intolerance yet, but the IgG blood test is the only test with scientific evidence to back up its reliability. [Emphasis added.]
She quotes advice from experts on what to look for in a test.
Liz Tucker, allergy nutrition expert and wellbeing consultant says, ‘Research any test well before you jump in. Some tests are very accurate and have scientific evidence to prove it. But others have no records of accuracy and no evidence to prove it works. Always go for a clinically validated test.’
Liz Tucker is one of the YorkTest-styled experts who endorses YorkTest's range. According to the writer of DIY Diagnosis,
Alex Gazzola, author of Living with Food Intolerance...agrees: ‘Don’t take advice from unqualified people offering unvalidated tests on the high street. I would avoid any test that has not been validated scientifically.’
Gazzola's book is available from YorkTest and endorsed by Allergy UK's Muriel Simmons. At some point, it would be very helpful if somebody other than this self-referential pool of experts were to claim that these tests are clinically or scientifically validated and provide a summary of the research to prove it.

I did have high hopes that I might see some evidence for scientific and clinical validation for allergy and intolerance testing when I read:
Imutest is a clinically proven IgE allergy test, just like those used in hospital laboratories. In a study of 200 patients referred to an NHS allergy clinic for allergy tests, Imutest correctly identified allergies present with an accuracy of 98% in comparison to the gold standard laboratory test method.
I tried to consult Imutest's website but it seems that they have recently gone into receivership. I searched Entrez PubMed and could not find a reference to Imutest. I contacted the journalist but it seems as if this claim was made in the material that was sent to her by Imutest and she no longer has the background research that she did for the piece. That's unfortunate: I don't have much disagreement with a well-conducted IgE test but I would have liked to have seen the reference. At the risk of sounding like a broken record, I don't think that a test result is sufficient as a stand-alone diagnosis; a good diagnosis also depends upon a good clinical history that is interpreted by a clinician with relevant qualifications.

DIY Diagnosis refers to several YorkTest products: the YorkTest Food Intolerance Indicator, the YorkTest 42 Foodscan, the YorkTest 113 Foodscan and the Yorktest Multi-Allergy Screening Test. She writes the following about the reliability of the YorkTest tests:
All tests are highly accurate in diagnosis between 95 -97%. For the Foodscan range, 70% of those tested who followed the advice given reported an improvement in their symptoms.
I have looked high and low for an authoritative source for these claims about the YorkTest tests. I can't find them. I have seen these claims so often that I have to assume that there is reputable and substantial scientific literature to back them up but I have to declare that I have so far been completely unsuccessful in finding that research.

The journalist indicates that she discriminates between reliable, authenticated tests and those of a more dubious provenance. She mentions the BEST (Bio Energetic Stress Test) system and makes this comment about its reliability:
[c]urrently there is no clinical evidence to support this method of testing.
I would say that the current position of relevant professional bodies is that there is no clinical evidence to support the use of IgG testing in the diagnosis of food intolerance (more on the lack of support for IgG testing).

1. ARR!, 2. Yo ho ho, 3. Rogue Orange, 4. My New Pirate Hat

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