Respectful Insolence

Excellent.

Having had to work on a talk last night, I didn’t have any time to write anything substantive. Horrified at the thought of this blog going silent on a weekday (going silent on the weekend doesn’t concern me much, given that my traffic almost always falls by around 50% regardless of whether I post on the weekend or not, barring any unexpected links from bigger blogs), I thought about doing what PZ did yesterday and recycling one of my more memorable posts from the old blog. Unfortunately, I couldn’t come up with topic as likely to draw as much interest as PZ’s, and I wasn’t sure if anyone would want to read my old stuff anyway, even though I like PZ’s idea of slowly moving the best of the old blog over to this one. Still, I like fresh material whenever possible, even if much of the old stuff is in essence ancient history, never before read by the majority of my present readership. Consequently, I was happy to remember that my one and only guest blogger from the first incarnation of Respectful Insolence had recently written a new piece that I had been asked to post.

Yes, Kristjan Wager is back. Back in August, Kristjan, a frequent commenter on this and other blogs, guest blogged a post discussing attacks by mercury-autism activists on the Danish Institute that did the widely cited studies showing no decrease in autism incidence after the removal of thimerosal. It was well-written and well reasoned (using English as a second language yet), and, even better, provided a viewpoint bout the Danish health system that Americans might not appreciate. The post, which I published while on vacation, provoked 151 comments, some of them quite heated.

When Kristjan asked me if I was interested in another article, this time discussing common attacks by mercury moms on the actual Danish study itself, there’s no way I was going to say no, and today is the perfect opportunity for me to post it.

So, without further ado, here’s Kristjan:

Last august I wrote a guest post for Orac at his old blog, in which I promised a follow-up post. This isn’t that follow-up post. Instead this is a post dealing with yet another common criticism of the Danish study Thimerosal and the Occurrence of Autism: Negative Ecological Evidence From Danish Population-Based Data by Madsen et al. (link to study).

The study looks at the claim that thimerosal is a risk factor for the development of autism by looking at Danish population-based data, to see if the 1992 discontinuation of thimerosal-containing vaccines in Denmark led to a drop in the number of new cases of autism.

Danish studies can be fairly big, as Danish health data is centrally registered and every person born or living in Denmark is uniquely identifiable by a personal code (similar to the US social security number). This study is no exception, and it looked at every psychiatric admission since 1971, and every outpatient contact in psychiatric departments in Denmark since 1995 (see Figure 1).

What the study found, was that there “was no trend toward an increase in the incidence of autism during that period when thimerosal was used in Denmark, up through 1990.” After 1990 there was an increase, even after thimerosal was removed in 1992. This lead the authors to conclude: “Our ecological data do not support a correlation between thimerosal-containing vaccines and the incidence of autism.”

Together with a few other studies, that has reached similar conclusions, the Danish study has been widely referred to in debates about the possibility of a thimerosal-autism link. Since this is the case, it has come under heavy fire from groups like Safe Minds, which in their paper Danish Thimerosal-Autism Study in Pediatrics: Misleading and Uninformative on Autism-Mercury Link (link .pdf) raises their objections to the study, which again are often quoted by other people as data points against the study. I will only be addressing one of these. They write:

Autism counts were first based on hospitalized, inpatient records and then changed in the middle of the study period to add in outpatient records. This new outpatient registry was introduced in 1995. Therefore, their purported increases after 1994 can be explained entirely by the registration of an existing autism population that did not require hospitalization. The authors minimize this discrepancy and do not adjust for it in their chart (Figure 1), yet in a prior study using the same Danish data, outpatients exceeded the inpatients by a ratio of 13.5 times, and represented over 93% of total cases. This huge gap clearly invalidates their inpatient data, the corresponding time period from 1970-94, and any evidence for a rising trend of autism in Denmark. The authors claim that inpatient admissions were rising also, but the „data [were] not shown‰. They did not explain this omission, the only bit of credible data in their possession, since it compared equivalent populations.

First of all, let me start with stating that I agree with SafeMinds on one thing; it would have been better if the figure that only contained inpatient cases after 1994 as well. Changing data-sources like this is sloppy and only leaves the authors open for this sort of criticism. Having said that, Safe Minds does seem to ignore the fact that the study at least disproves that thimerosal is the cause of autism, since if this was the case, no matter how many other data-sources were included, there would still be a drastic drop. Also, Safe Minds ignore the fact that there should be a decrease in the number of 2-4 year olds in 1994 rather than an increase.

Now, that out of the way, I want to address something else SafeMinds either misses or ignore. Even when one ignores the data after 1990, the study still shows a lack of correlation between autism and thimerosal. How is that, you ask? Well, simply put, SafeMinds looks at the wrong end of the figure.

Let’s start with looking at the figure again and ignoring everything after 1990. Unfortunately the figure is not that big, so it’s hard to see the details, but it’s fairly clear that the number of 2-4 year olds increases from 1971 to 1990, while the 5-6 year olds first drops from in the period from 1971 to 1985, and then increases again. The 7-9 year olds are more or less constant from 1971 to 1990.

This would seem consistent with both the thimerosal-autism link and the lack of same. However, as the study makes clear (but doesn’t otherwise focus on), there was a change in the vaccination program in 1970. The changes was both in the number of vaccinations, which went from 4 to 3, and in the amount of thimerosal/ethyl mercury, which went from 400 μg/200 μg to 250 μg/125 μg. In other words, a drop of 25% of the vaccinations and 37,5% of the thimerosal and ethyl mercury. If there is any kind of link between thimerosal and autism, one would expect this change to be reflected in the numbers in figure 1. In other words, we would expect a drop in the 2-4 year age bracket in 1972-1974, in the 5-6 year age bracket in 1975-1976 and the 7-9 year age bracket in 1977-1979. As we can see on the figure this is not the case in either age bracket.

In other words, this shows a lack of any correlation between autism and thimerosal. And unlike the other end of the graph, this is a comparison between equivalent populations.

Comments

  1. #1 Kristjan Wager
    April 12, 2006

    Suprisingly few comments.

    If I have overlooked something, I would love to know.

  2. #2 Orac
    April 12, 2006

    Yeah, I’m rather surprised myself at the lack of response. It happens sometimes. On occasion I’ve posted stuff that I expected to provoke a lot of commentary and got almost none, and other time I’ve posted quickies that I thought little of and got lots of comments.

    It could be worse; I might have waited to ban Fore Sam, and he could have contributed comments.

  3. #3 María Luján Ferreira
    April 12, 2006

    Hi Orac and Kristjen
    First of all, thank you for the comment. Second, I think that epidemiology only can quantify a risk at a population level, considering all the participants equal in front of the supposed insult. In this sense I do not think that epidemiology of only one potential collaborator can give us answers. I consider autism very complex in nature, multicausal and of individual presentation
    I have some questions about the figure you posted.
    a- Do you have some information about other vaccinations in the period between 4 and 9?
    b-Do you have some information about how children were counted before thimerosal was banned and after? I have read that before only hospitalized children were considered (and this was only 1/5 of the total)
    c-Did the diagnosis criteria changed in the period considered in the figure, such as was a shift from DSMIII to DSMIV?
    d-For me there are several numbers of autistic children. First what is considered autism? Let me please consider from ADHD to autism as a continuum differing in degree or numbers of matches of the DSM criteria.
    Second, there are the real number of ASD children, teens and adults, the diagnosed properly and the reported ones ( by schools, by doctors)
    How were these numbers obtained and what is the difference considered to be present in Denmark between these numbers?
    Do these numbers included only Autism or also differential diagnosis such as Asperger?
    Thank you again for your time.
    María Luján

  4. #4 Kristjan Wager
    April 13, 2006

    As the study clearly explains, the numbers included inpatients only until 1994. Inpatients are, in Denmark, people who are hospitalized or who goes to the hospital daily for treatment.

    From 1995 outpatients, i.e. non-hospitalized people, were included as well.

  5. #5 Kristjan Wager
    April 13, 2006

    And in regards to a), there were no other vaccines containing thimerosal.

  6. #6 María Luján
    April 13, 2006

    Thank you Kristjan,
    I thought that perhaps there were more information, not explicitly included in the study about in/outpatients. Sorry if it sounded too obvious.
    Again, I wonder if the increase is seen from 1995 is related to a broader criteria and counting ONLY. My question was related to other kind of potential stressor for a susceptible child.
    I do think that because our children are born autistic, and in this sense weak in his immune system and other biochemical imbalances, they can not manage vaccines, antibiotics and toxic insult- what we breathe, drink, eat. Vaccines do not produce autism in them for me, only make it more evident and symptomatic, affecting the degree ( or severity) of autism. There are not ( following Michelle Dawson and I consider her an expert) consistency in severity epidemiology of autism in time. We do not know or we can not trust the data. So this is possible, although unproven.

    What is the effect of vaccines ( including Hg, Al, etc) in an autistic child from birth-even if it is noticed or not- even if the oddity is biochemical and the only way to detect is to know what to search at birth-that we do not know today?

    All the vaccines can make damage because vaccination is a medical procedure with risks.
    The wrong question for me is
    Can vaccines-thimerosal-Al-antibiotics -Pb, heavy metals, pollutants etc produce Autism?
    The right one for me is
    What vaccines-thimerosal-Al-Antibiotics, Pb, heavy metals,. Pollutants etc do to an autistic child, susceptible from birth, different in his/her genetics and therefore in the gene expression-proteomics-, gene regulation, protein/enzyme concentration and regulation, receptors function and number in brain, nervous system and immune system from birth? This has not been evaluated, only studied a bit (BDNF, Other GF) so it is unexplored, not discarded.

    In this sense, the educational data and epidemiological studies only are looking at the resulting combination of medical, political and sociological aspects that can contaminate seriously the analysis of data, being them then incomplete to obtain conclussions.
    I imagine autism for a child as composed of A+B+….Z. For each individual the combination can be extremely complicated or less complicated, but it has more or less the A to Z components. When the question is done the wrong way, all the analysis is focused in for example C (thimerosal), or E (MMR) but what about all the others? How are they collaborating? Besides how are collaborating all the other medical (in terms of criteria) and sociological (population) and political ( in terms of availability to services by law) aspects?

    My question a) was related a bit about these ideas. I wonder for example if
    a-new vaccines- without thimerosal- were included since 1995?
    b-has an increase in autoimmune/immune disorders be found in Denmark in the period 1995-2005?
    c-are there in Denmark studies about GI issues or immune issues in autistic children, whatever the criteria was used?

    What do you think?
    Orac, please let me know if you consider too long this post. It is a drawback from me to do long posts (probably because I try to explain to avoid being misunderstood) Thank you for understanding.
    Thank you in advance
    María Luján
    PD: Kristjan , do not worry about your english. It is my second language too and I know that sometimes I am not enough clear. Sorry.

  7. #7 Kristjan Wager
    April 13, 2006

    Maria, you ask quite a lot of relelvant questions, but they are not easily answerable for me, a lay-person.

    Right now, I will focus on your first set of questions:

    c-Did the diagnosis criteria changed in the period considered in the figure, such as was a shift from DSMIII to DSMIV?

    d-For me there are several numbers of autistic children. First what is considered autism? Let me please consider from ADHD to autism as a continuum differing in degree or numbers of matches of the DSM criteria.
    Second, there are the real number of ASD children, teens and adults, the diagnosed properly and the reported ones ( by schools, by doctors)
    How were these numbers obtained and what is the difference considered to be present in Denmark between these numbers?
    Do these numbers included only Autism or also differential diagnosis such as Asperger?

    Maria, if you read the study, you’ll find some of the answers to your questions. Madsen et al wrote:

    Psychiatric inpatient treatment in Denmark has been reported to the Danish Psychiatric Central Research Register since 1969, and since 1995 outpatient activities were registered as well, providing the opportunity to examine long-term trends of the occurrence of autism in a total national population. In Denmark, inpatients refer both to children who stay at the hospital overnight and to children who come to the hospital on a daily basis for evaluation and treatment. The proportion of outpatient to inpatient activities was about 4 to 6 times as many outpatients as inpatients with variations across time and age bands. We obtained information on all children who from the second birthday up to, but not including the 10th birthday were diagnosed with autism in the period from January 1, 1971 to December 31, 2000 in the Danish
    Psychiatric Central Research Register during which period the register is assumed to be complete. The diagnosis of autism in children <2 years of age was considered uncertain. All individuals in Denmark are assigned a unique personal identification number which is used in all national registers. Admissions to psychiatric hospitals in Denmark are coded using this CPR-number, which eliminates the risk of double-counting of cases. The date of onset was defined as the first day of the first admission leading to a diagnosis of psychosis proto-infantilis (International Classification of Diseases, Eighth Revision [ICD-8]: 299.00) or psychosis infantilis posterior (ICD-8: 299.01) or from 1994 onward, infantile autism (International Classification of Diseases, 10th Revision [ICD-10]: F84.0) or atypical autism (ICD-10: F84.1).

    Readering schools reporting cases of autism. I know that that happens in the US, but in Denmark schools don’t diagnose children, they teach them. Like doctors don’t teach children, they diagnose them.
    The Danish health care system is pretty throughout in registrering everything, but also at making sure that there are not the kind of data-polution we have seen in the US. There is no difference between the diagnosed autists and the reported autists – the reported autists are the diagnosed ones.

  8. #8 Kristjan Wager
    April 13, 2006

    “Readering” should be “Regarding”. Sorry, have a hang-over today.

  9. #9 Sue M.
    April 13, 2006

    Ok, a few things. I tried to bring this up on Kev’s blog but he just called me a dummy and ran off. So, I will bring it up here.

    1) It seems to me that nothing can be fairly extrapolated from these Danish studies. They are based on flawed epidemiology. Why would you attempt to make something out of nothing? If “we” were to do this, “you” would be screaming about it. We have the removal of thimerosal in 1992, the diagnostic code change in 1993 and then the inpatient/outpatient “issue” (to put in mildly) in 1995. Nothing can be made of the Danish studies in the 1990′s. Even Kristjan seems to acknowledge this issue when he/she (sorry) writes this:

    “First of all, let me start with stating that I agree with SafeMinds on one thing; it would have been better if the figure that only contained inpatient cases after 1994 as well. Changing data-sources like this is sloppy and only leaves the authors open for this sort of criticism”.

    2) Then Kristjan writes this:

    “Also, Safe Minds ignore the fact that there should be a decrease in the number of 2-4 year olds in 1994 rather than an increase”.

    Kristjan, I am sure that you know that there was a diagnostic code change for autism in 1993, didn’t you? So, in order for you to make a claim about the numbers of children in 1994 you would have to prove to me that the number in 1994 was not impacted by the diagnostic change in 1993. Can you do that? I didn’t think so.

    3) Then, it seems to me that Kristjan is trying to extrapolate information from the autism rates in the 1970′s! He/she writes:

    “In other words, we would expect a drop in the 2-4 year age bracket in 1972-1974, in the 5-6 year age bracket in 1975-1976 and the 7-9 year age bracket in 1977-1979. As we can see on the figure this is not the case in either age bracket”.

    Wait a minute here. You guys have been trying to convince me for months that doctors didn’t know the difference between a mentally retarded child and a hand flapping, spinning non-verbal child back in the 1970′s. Remember all the diagnostic-shifting talk that you always do. Jonathan tried to tell me on Kev’s blog that children back then would have been diagnosed with something different other than autism. Jonathan wrote:

    “They would have dx’ed the obvious one’s with Communication, LD, or emotional/behavioral disorders. Possibly with specific neuroses”.

    So now, I’m supposed to trust the autism numbers in the 1970′s to make something out of the Danish studies. Are you kidding me? Rotten. Rotten. Rotten.

  10. #10 Kristjan Wager
    April 13, 2006

    You are not supposed to trust the numbers from the seventies, but you can’t ignore the fact that even if there were some problems with the diagnoses and numbers back then, there would still be some kind of drop if there is a correlation ebtween thimerosal and autism. It’s actually pretty simple, if you reduce the amount that causes something with a third, it should affect the numbers downwards – not necessarily with a third, but at least a little.

    If I had wanted to pick some years for the different age groups to show this hadn’t happened, I couldn’t have done it better than the years based upon the 1970 change.

  11. #11 Sue M.
    April 13, 2006

    Kristjan,

    Simple question. Do you want to be able to use the 1970′s autism numbers to extrapolate anything about the thimerosal/autism theory or not? I would love to use them as well. I am not “allowed” to because doctors were not intelligent enough back then to recognize the differences between MR and autism. If I can’t use them, you can’t either. Forget about the fact that you can’t (to the best of my knowledge) tell me the exact date of when all doctors “dropped” the 4th vaccine. Did some doctors do it right away? Did others finish up the stock that they had of the vaccine sitting around? Did some parents say, hey you know what, I want my kid to have that vaccine. Now, how about my question in regards to the 1993 diagnostic code change. Any comment?

  12. #12 Kristjan Wager
    April 13, 2006

    Sue, we don’t have to be able to say the exact date, and for your information, it was a national change, not dependent on the doctors, since they don’t have any stock. They get it as they need it.

    And what you can’t use the seventies numbers for is to compare them with todays numbers. You can, without any problems, use them for comparing with other seventies numbers. That’s the big difference in how I use the numbers, and how you try to use the numbers.

  13. #13 Kristjan Wager
    April 13, 2006

    Also the change from 4 to 3 vaccines were not only a change in numbers, but also in the schedule, which you of course know, since you must have read the article that you have criticized so much.

  14. #14 BronzeDog
    April 13, 2006

    I’m reminded of people who complain that things used to cost a nickel, but don’t bother mentioning the average annual incomes of the time.

  15. #15 María Luján Ferreira
    April 13, 2006

    Hi Kristjan
    Yes, I have read the manuscript, but again many times what is included is a short report, being reality more complex, especially in Denmark, with different diagnosis criteria and different culture for me. I found this
    psychosis infantilis posterior, etc strange because in my country this is not even known.
    For example
    or from 1994 onward, infantile autism (International Classification of Diseases, 10th Revision [ICD-10]: F84.0) or atypical autism (ICD-10: F84.1).
    so I suppose that ADHD were not considered. Is there a different diagnosis for ADHD? I suppose then that Asperger was included in the diagnosis of atypical autism.
    I knew about DSM but not about ICD therefore was my question in terms of the differences between them, from ICD-8 to ICD-10, being the ICD-10 much more wide so part of the increase can be assigned of,as the authors tell. I was wondering in a parallel to DSM.
    Thank you for your answer
    Ma Luján

  16. #16 Kristjan Wager
    April 13, 2006

    As far as I understand it, ADHD is more a US thing, so it makes sense that ADHD is not considered. Aspergers is included in those numbers somehow, but I don’t know under which grouping to be honest.

    ICD-10 is fairly comparable to the classifications in DSM-IV (169-173) according to Madsen’s ph.d. thesis which is based upon this study (to a lesser degree) and the much bigger MMR-Autism study he also participated in.

  17. #17 Sue M.
    April 13, 2006

    Kristjan wrote:

    “Also the change from 4 to 3 vaccines were not only a change in numbers, but also in the schedule, which you of course know, since you must have read the article that you have criticized so much”.

    - Of course I have read the article a few times. I will admit, however, when the results are so completely bogus it is difficult to take anything from it. Back to your point. Yes, the schedule did change. The number of vaccines changed and the amount of thimerosal changed. Of course the timing of the given vaccines also changed. According to the study from 1961-1970: they had DTP in 4 doses at the ages of 5,6,7 and 15 months old. From 1970-1992: They had the DTP in 3 doses at 5 weeks, 9 weeks and 10 months. Yikes, so in 1970 the infants were given the shots much earlier than previous to 1970 (oh no). Previous to 1970 children’s brains were being allowed to develop relatively free of neurotoxic assaults via vaccinations up until 5 months of age. After 1970, they were only allowed 5 weeks of neurotoxic free assaults. Shame, shame. How can you be sure that the non-drop of numbers in the 1972-1974 group had to do with the decrease in thimerosal given vs. the younger age that the babies were given their shots. I’m quite sure that you can’t. Again, just another point to show you that this study has too many variables. Why are you trying to defend it?

  18. #18 Sue M.
    April 13, 2006

    Bronzedog wrote:

    “I’m reminded of people who complain that things used to cost a nickel, but don’t bother mentioning the average annual incomes of the time”.

    - The problem is… the value of a nickel has flucuated over the years (everyone knows that). The neurotoxic effects of thimerosal have not.

  19. #19 María Luján Ferreira
    April 13, 2006

    Hi Kristjan
    As it happens to me with this study, it happens with any epidemiological study I have read. For example
    In the same analysis, one thing is what it is diagnosed and reported and other thing the REAL number of children with ASD. So it seems to me that 35-40 years ago, the number of diagnosis was too low and therefore the numbers reported were low and now , because of the changes in the diagnostic criteria, the access to hospitals and in/out patients on treatment have increased.
    What if 25-30 years ago the true numbers were higher than reported because of a different society, different treatment, different attentionm from parents to ASD?What if now the numbers are not so high as reported, but different than before ?
    What about the relative contribution of changes of politics of distribution of services in doctors and doctors training and different access to diagnosis?
    How can we analyze a situation resulting theoretically of few known problems and a long list of possible but unproven collaborators and obtain DEFINITIVE conclussions favoring or against ANYTHING?
    What is the impact in these numbers , even of the considered as the basis for epidemiology of
    1-non-diagnosed children. Do you think that the real number of ASD children can be much different from the diagnosed one today or not?
    2-Population movement and increase of global populations of different genetic pool in these years,
    About
    3-Changes in the vaccination schedule, introduction of new variants of the same vaccine or a new one?
    What about compensatory effects, such as the mentioned because of the change in schedule?
    Have Denmark any kind of report of vaccines adverse reactions?.
    The problem with the analysis of this is that it has been not proven. In my opinion there are a lot of clues, but they need systematization and further research for genetically susceptible individuals. Therefore how are we going to analyze something that is theoretical in nature for published science and it has been ruled out by it? The analysis is of only numbers of autistic children. There are no data about clinical studies on the children. There are no data about the impact of DTP ( or other vaccines) in autistic children. Without this information I think that this kind of ideas, even when I personally think that are important to consider and in personal experience were important, can not be mentioned as a contributor for sure because there are no studies about in autism in general. This is why I mentioned my answer before
    What vaccines-thimerosal-Al-Antibiotics, Pb, heavy metals,. Pollutants etc do to an autistic child, susceptible from birth, different in his/her genetics and therefore in the gene expression-proteomics-, gene regulation, protein/enzyme concentration and regulation, receptors function and number in brain, nervous system and immune system from birth?
    Until this question being addresed and answered properly, we only have numbers to analyze and known facts to correlate ( if any correlation is / is not possible).
    It is a circular problem for me. Epidemiological studies are not detecting this as a problem so new epidemiological studies based on the published ones are not detecting them either. Because these are not detected as a problem there are not epidemiological data studied to see if a real problem exists. Always I think that the data presented in several papers are right- considering like in this case all other situations around- the problem is for me the question to answer and the conclussions drawn. It is the problem of the 1000 pieces puzzle trying to be studied to obtain the picture with 10, for me.
    I do think that from one country to another, there must be changes because of the different genetic pool, different environmental insult, different management of the antibiotics, different medical approach to childhood infections, different food quality, air quality, water quality.
    How can all these issues , without considering the mother implication in the child health ( environmental insult during pregnancy), only since birth, affect the epidemiological data?

    -I wonder if an epidemiological study considering for a numerical factor environmental insult, posnatal, beyond genetics for example
    a-Number of antibiotics treatments during the first 3 years /number of bacterian infections the first 3 years
    b-Adverse reactions to vaccines
    c-Dermathological issues, reactions
    d-Streptococal infections
    e-Herpes infections
    f-Childhood disease-if any- even in vaccinated children
    g-allergies to different foods
    cannot give more clues. The point here would be the immune component in autism, for example.
    The highest the reaction, the highest the number. Considering the overall population, I would see if a correlation between ASD and higher numberical factors can be obtained. The problem I see is the need of protected private medical information to do this kind of study.
    Also I have not knowledge in epidemiology therefore it is only an idea.

    I found no study with these questions
    because the focus is to say Autism is not Thimerosal poisoning.

    What do you think?

    Thank you in advance
    María Luján

  20. #20 Kristjan Wager
    April 13, 2006

    Why are you trying to defend it?

    Because I am pro-science. It’s the same reason I argue for evolutionary theory, a HIV-AIDS connection, and many other things on the internet.

  21. #21 BronzeDog
    April 13, 2006

    I hate shifts into discussion of motives. Usually obfuscates the actual issues. Often on purpose.

    The problem is… the value of a nickel has flucuated over the years (everyone knows that). The neurotoxic effects of thimerosal have not.

    The ways we measure and define autism have fluctuated.

  22. #22 Sue M.
    April 13, 2006

    Kristjan wrote:

    “Because I am pro-science”.

    - So, you are still hanging on to this as “science” capable of telling us anything about the autism/thimerosal debate? Scary (and embarrassing).

  23. #23 Sue M.
    April 13, 2006

    BronzeDog wrote:

    “The ways we measure and define autism have fluctuated”.

    - Ok. That was also a beautiful nickel analogy. Now, do you wish to comment on the validity of the Danish studies?

  24. #24 Observer
    April 13, 2006

    Couple of things I was wondering, and I apologize if you have addressed these already but I couldn’t bring myself to wade through all the Sue M. posts.

    On the inpatient vs. outpatient thing: The study says “many patients with autism in former years have been treated as outpatients,” but the curves in Fig. 1 don’t kink upward in 1995, when outpatient diagnoses were added (actually the diagnoses among 7-9-year-olds go down), which seems to suggest that there were few/no autistics in the outpatient caseload, and in the comments on your last guest post, you noted that you thought autism was usually tested for in hospitals under the Danish system, which would fit with that idea. Have you learned any more about that?

    In any case, I am not clear on why the mercury=autism crusaders make so much noise about the addition of the outpatients, because the upward trend in autism counts started five years before that happened. Is there something to their argument I’m not appreciating?

    Thanks.

  25. #25 Sue M.
    April 13, 2006

    Observer wrote:

    “Is there something to their argument I’m not appreciating”?

    - Well, of course there is. Observer may not read my response, so can one of you pass the information on to him/her. Let’s see here, you want to talk about the increase in autism cases starting 5 years before the 1995 inpatient/outpatient fiasco, right. So that would be 1990, right (yes, I’m brilliant). Ok, so let’s look at 1990. Here we have it. The MMR was introduced in Denmark in 1987. Isn’t that convenient. So approximately 3 years after the introduction of the MMR the rates of autism start to go up. Wow, imagine that. Shocking. Of course, maybe aliens also came down and implanted the autism gene into the children of Denmark around that time, or possibly the kids starting eating more ice cream right around then. I can’t account for that. Any more questions? Gosh, this blog post is deadly quiet. Anyone here? Any comments? Come on people. When you have the truth on your side… the pieces all come together.

  26. #26 hollywoodjaded
    April 13, 2006

    Observer and Kristjan:

    “[...] in the comments on your last guest post, you noted that you thought autism was usually tested for in hospitals under the Danish system, which would fit with that idea.”

    This was my understanding as well. Thanks for bringing it up, as I had been wondering about that issue in terms of this recent blogpost. My impression was that it was not at all uncommon for a Danish child to be tested for ASD in a hospital setting, whereas in the US this is certainly not regular procedure by any means. So … I have been wondering about this too.

  27. #27 Kristjan Wager
    April 14, 2006

    I think that autists are quite often initially diagnosed in hospitals in Denmark (certainly they are not diagnosed by family doctors), and then send for futher testing with the psychiatric departments.
    However, when we are talking in- and outpatients relating to this post, we are talking in- and outpatients in the Danish psychiatric hospitals, which is only a subgroup of Danish hospitals, so the cases where hospitals sends them on to the departments, would count as outpatients.

    I’m sorry I didn’t make that clear.

    Regarding the fairly small increase when outpatients were added, there is this from the article:

    The proportion of outpatient to inpatient activities was about 4 to 6 times as many outpatients as inpatients with variations across time and age bands.

    So, this might be an artifact caused by unusual high numbers of inpatients in the proceding few years.

  28. #28 Observer
    April 14, 2006

    Kristjan, thanks for the additional information. I’m still not quite getting it, though. Do you mean that there were unusually high numbers of inpatients in the years preceding 1995? Also, how does the quote shed light on the finding of no jump in 1995?

    I wonder if Madsen himself has ever commented on this. I don’t think there were any followups in Pediatrics. Parker’s review article of all the epidemiological studies remarks that the 1995 addition would have inflated the count for that year, but negates the possibility that this voids the conclusion by observing that the rate of increase continued unabated after that year.

    I think I do understand your clarification about psychiatric hospital admissions versus regular hospital admissions, with autism diagnoses being more likely to take place in the latter.

    This whole tempest is a little silly considering that if thimerosal were the cause of autism, there wouldn’t be *any* autism among native Dane children today.

    Also, while Madsen’s is a fine study, I think epidemiologists would be more inclined to find the Hviid retrospective cohort study a useful topic of discussion, since that is generally thought to be a more reliable study design. But the mercury people don’t have a sound bite snipe for that one, so they harp on Madsen. (Incidentally, has anyone else noticed that they tend to talk about “the Danish study” as if they don’t know that there have been two of them? I think that, in fact, they do not. And of course they never make mention of Andrews and Heron from the UK, because they can’t refute those either.)

  29. #29 María Luján Ferreira
    April 14, 2006

    Hi Observer
    There are near 12 reviews claiming there is no evidence of a vaccine-autism link. Besides,beyond the Madsen, Hviid, Miller and Taylor I can also mention Stehr Green (2003), Destefano (2004),Williams (2004), Smeeth (2004), Heron (2004), Barbaresi (2005)Honda Rutter (2005) and Seagroatt (2005). You can find comments in the D.Thrower review of 2006 (pages 334 to 354).
    Neither of them presented the problem giving a answer to the questions I presented the table before. If you are interestedin an e.mail discussion about, because we are going off topic, please let me know. If not, sorry if I disturbed you and thank you in advance.
    María Luján

  30. #30 Kristjan Wager
    April 14, 2006

    Madsen alone have made two studies, one looking at a MMR-autism link, and this one. Both were part of his ph.d. thesis, together with an evaluation of the other MMR-autism studies already done by other people in Finland (3 studies, all based upon the same data), Sweden (1 study), the UK (4 studies, 2 based upon the same data) and the US (1 study). At the time of the thesis there were four other studies of a MMR-autism link, which I presume all are done by now.

    The Wakefield study was not included in the evaluation as it was not of a high enough quality. So far that’s the only study that has supported a MMR-autism link. No studies, except perhaps the Geiers’ rather problematic study, have supported a thimerosal-autism link.

    I wonder if Madsen himself has ever commented on this. I don’t think there were any followups in Pediatrics. Parker’s review article of all the epidemiological studies remarks that the 1995 addition would have inflated the count for that year, but negates the possibility that this voids the conclusion by observing that the rate of increase continued unabated after that year.

    I have actually tried contacting Madsen, but he hasn’t responded, so if the email address I found is current, it would seem that he is not really interested in getting involved in this issue. Madsen’s main focus was a MMR-autism link all along, which might explain the lack of follow-up.

    He does seem doubtful if the increase is due to more cases, or if it is due to more awareness of autism.

  31. #31 Kristjan Wager
    April 14, 2006

    And I should perhaps stresas that the biggest problem I have with the criticism of the study, is the idea that if the study is found to have problems it somehow makes a thimerosal-autism link plausible. This is simply not the case, as it goes against all data, all knowledge about the nature of autism, all knowledge about the nature of mercury poisoning, and against the understanding of how the human body works.

    All of those things have to be addressed as well, before a thimerosal-autism link is plausible.

  32. #32 Kristjan Wager
    April 14, 2006

    And here I should probably clearify that I don’t deny that there might be some problems with thimerosal causing an aggrevation in autism or some other weird reaction, but thimerosal as a cause of autism is extremely inplausible.

  33. #33 María Luján Ferreira
    April 14, 2006

    Hi Kristjan
    You say
    “causing an aggrevation in autism or some other weird reaction, but thimerosal as a cause of autism is extremely inplausible”
    I agree with you in the sense of CAUSE, I think that Hg poisoning is possible because of autism ( as combination of individual genetics plus individual gene expression plus epigenetics)
    Please let me know if you are interested on more information to discuss here. I have researched about the possibility and would be glad to discuss with you some ideas based on published research, even off line , by e-.mail, if you are interested on. If you are not , sorry if I disturbed you.
    Thank you in advance
    MAría Luján

  34. #34 Kristjan Wager
    April 14, 2006

    Maria, by all means feel free to share with us – just be aware that we might not respond to all your points.

    Preempting just a bit, there is a good commentary in Pediatrics about the differences between autism and mercury poisoning by Karin B. Nelson and Margaret L. Bauman: Thimerosal and Autism?. One of the points the commentary makes is:

    In the first half of the 20th century, mercury was a constituent of medications administered to treat worm infestations and teething pain. Use of these compounds was associated with illness in young children, affecting chiefly those 8 months old to 2 years old. These infants showed photophobia, anorexia, skin eruption, and bright pink color of hands and feet, which peeled and were painful.44 This condition, called “pink disease” or acrodynia, was relatively common, and the cause of 103 deaths in England and Wales in 1947.45 Survivors were not described to have behavioral disorders suggestive of autism.

    The commentary also mentions other similar cases. If thimerosal leads to more aggrevated conditions of autism (and thus more diagnosed cases), it would seem plausible that other sources of mercury would so as well. Yet, it doesn’t appear to be the case, even though ethylmercury is less problematic than methylmercury (source: Answers to Questions on the Toxicity of Ethylmercury .pdf).

  35. #35 Sue M.
    April 14, 2006

    Observer wrote:

    “Incidentally, has anyone else noticed that they tend to talk about “the Danish study” as if they don’t know that there have been two of them”?

    - Actually almost everyone I know who follows this issue knows that there is more than 1 study. In fact, most of them also know that there are more than 2… You may want to check that out.

  36. #36 Sue M.
    April 14, 2006

    Kristjan wrote:

    “And I should perhaps stresas that the biggest problem I have with the criticism of the study, is the idea that if the study is found to have problems it somehow makes a thimerosal-autism link plausible”.

    - I would like to stress that the biggest problem that I have with the studies is that the CDC continues to link to them and to cite them as evidence of no-link. This is misleading (at a minimum) and/or criminal. It is not so much the studies that are of concern to me (I’m sure that there are thousands of bogus studies out there), it is the way these studies are being used and abused by the powers to be. To use these studies as a reason to stop looking into thimerosal/autism connection is disturbing behaviour.

  37. #37 Sue M.
    April 14, 2006

    Krisjan wrote:

    “Yet, it doesn’t appear to be the case, even though ethylmercury is less problematic than methylmercury (source: Answers to Questions on the Toxicity of Ethylmercury .pdf)”.

    - The Burbacher study seems to question this idea that ethyl is “safer” (wink, wink) than methyl. It needs more study.

  38. #38 Orac
    April 14, 2006

    I would like to stress that the biggest problem that I have with the studies is that the CDC continues to link to them and to cite them as evidence of no-link. This is misleading (at a minimum) and/or criminal. It is not so much the studies that are of concern to me (I’m sure that there are thousands of bogus studies out there), it is the way these studies are being used and abused by the powers to be. To use these studies as a reason to stop looking into thimerosal/autism connection is disturbing behaviour.

    No, it’s not “disturbing,” “misleading, “criminal,” or “abuse” to cite these studies as evidence of no link; it’s simple practicality. The proposal of a link between thimerosal and autism is implausible scientifically, and these represent large epidemiological studies that fail to find a link in human populations. Yes, the studies have their flaws, but, taken in their totality and combined with other epidemiologic studies and all that we do know about the cause of autism, they represent strong evidence that there is no link between mercury and autism. True, the studies cannot with 100% certainty completely rule out a link in a certain small subset of autistic children, but no epidemiologic study can. Only a very large double-blind randomized study could do that, and such a study will never be done for obvious reasons. It’s impossible ever to prove completely that there is no link; all science can do is to say that, within a certain level of probability there is no link. There will always be a tiny amount of doubt, because science doesn’t work in black and white, but shades of gray. There comes a point when doing more studies is beating a dead horse and wasting resources (particularly since we agreed, mainly as a concession to the hysteria and to prevent vaccination rates from falling further, to remove thimerosal from vaccines anyway). We’re already at or damned close to the “beating a dead horse” point with thimerosal-autism studies.

    In the meantime, money and attention that could go to research that might actually illuminate the causes of autism and factors that predispose or exacerbate it is being diverted to countering the hysteria of the mercury militia.

  39. #39 Sue M.
    April 14, 2006

    Orac wrote:

    “No, it’s not “disturbing,” “misleading, “criminal,” or “abuse” to cite these studies as evidence of no link; it’s simple practicality”.

    - Yes, it is all of those things and more. I notice that you don’t have any actual commentary on the information that Kristjan posted on. Why is that? I would question anyone (especially so-called surgeons/scientists) who would call further research into this matter “beating a dead horse”.

  40. #40 María Luján Ferreira
    April 14, 2006

    Hi Orac
    You say
    The proposal of a link between thimerosal and autism is implausible scientifically, and these represent large epidemiological studies that fail to find a link in human populations.

    Considering the terms of CAUSE, I would agree; considering that thimerosal can cause Hg poisoning in susceptible children since birth-such as autistic children- I would say that it has not been studied. In this sense, there are almost no studies about.
    I can understand what you point out at human population level ; however, at an individual case things can be totally different.Epidemiological studies in this sense will give no answers because for me the question is ill-formulated.
    María Luján

  41. #41 María Luján Ferreira
    April 14, 2006

    Hi Kristjan
    I have included several ideas in a comment that is being moderated. BTW, sorry Orac because it is long. M. Luján

  42. #42 Prometheus
    April 15, 2006

    When I first saw the autism prevalence curve on the Madsen et al study, my immediate thought was, “Damn, that looks exactly like the prevalence curves from the US and the UK.”

    The bitter irony here is that if Madsen et al had published just the prevalence graph, it would have been trumpeted by Sue M and others of that sort as “more proof of an autism epidemic”. This would have been an interesting experiment but, unfortunately, they didn’t think of it.

    Sue M acts as though the Madsen et al study is the only data refuting the thimerosal-autism connection. Sad to say, but the data refuting that hypothesis grows every month. And like many people refusing to face an unpleasant truth, Sue M claims that the data is flawed, biased, corrupt, or part of a massive conspiracy. How pathetic.

    Now, epidemiology is a blunt instrument, to be sure. However, it is sharp enough to tell that:

    [1] Autism diagnoses in the US continue to rise despite thimerosal exposure dropping significantly.

    [2] Autism diagnoses in the UK rose dramatically despite the fact that thimerosal exposure in the UK was static for decades.

    [3] Autism diagnoses in Denmark are continuing to rise – even though thimerosal was taken out of vaccines in 1992. This can’t be explained away by invoking the arguments that Sue M copied from SafeMinds, DAN! and Generation Rescue. THe numbers from 2000 to the present look pretty much like those in the US and UK – without the problem of inpatients vs outpatients.

    At some point, the data will be so overwhelming that even the media and politicians will realize that they have been duped by the mercury-autism groups. Unfortunately, this will probably have devastating effects on research funding for autism.

    That’s the most probable outcome of this little exercise in pseudoscience, Sue.

    Prometheus

  43. #43 María Luján
    April 15, 2006

    Hi Prometheus
    You say

    [1] Autism diagnoses in the US continue to rise despite thimerosal exposure dropping significantly.

    [2] Autism diagnoses in the UK rose dramatically despite the fact that thimerosal exposure in the UK was static for decades.

    [3] Autism diagnoses in Denmark are continuing to rise – even though thimerosal was taken out of vaccines in 1992. This can’t be explained away by invoking the arguments that Sue M copied from SafeMinds, DAN! and Generation Rescue. THe numbers from 2000 to the present look pretty much like those in the US and UK – without the problem of inpatients vs outpatients.

    I agree with you in terms of that these are epidemiological facts, whatever they can be analyzed. BUT under another view, when thimerosal/vaccines/environmental poisoning can be a contributor to worsening ASD, shifting milder cases to more severe, these are not answers. The problem I have is how epidemiology is considered to give absolute answers including the denying of this alternative view ALSO, that has not been considered/studied/analyzed enough, that autistic children because of their genetic/proteomics and due to epigenetics can be more easily poisoned by xenobiotics.
    You say
    the data will be so overwhelming that even the media and politicians will realize that they have been duped by the mercury-autism groups.

    About the alternative view I give above, I hope not.
    For me, the problem is not being considered globally by the analysis of “you” or “them”.

    Unfortunately, this will probably have devastating effects on research funding for autism.

    I hope not. Looking at the published science available recently, it seems it will not the case.

    Sincerely
    María Luján

  44. #44 Prometheus
    April 15, 2006

    Maria,

    You ask about the possibility that thimerosal might shift less severe autism cases to more severe. Well, that hasn’t been demonstrated – nor has its corrollary, that thimerosal doesn’t shift autism toward more severe outcomes.

    However, from several studies of autism then and now, we know that the current population of “autism” contains a much higher percentage of “milder” cases. This is not proof positive that the “thimerosal makes autism worse” hypothesis is wrong, but it sure points that way.

    By the way – it still is up to the people proposing the hypothesis to provide supporting data (actually, to test the hypothesis, but let’s start small). It’s not my job to prove it wrong – although I have reluctantly shouldered that burden on innumerable occasions.

    How about providing some supporting data to back up the suppositions and postulates? Otherwise, I can’t tell if you’re just making this up or if you have some data that points you in that direction.

    If we are to propose hypotheses about autism without any data to support them (ala Geier and Geier), then I propose that autism is caused by proximity to high-speed Internet access. Prove me wrong (just kidding).

    (For the record – I don’t suspect that autism has anything to do with the speed of Internet access, just in case someone out there didn’t recognize humor).

    Prometheus

  45. #45 María Luján Ferreira
    April 15, 2006

    Hi Prometheus
    You say
    You ask about the possibility that thimerosal might shift less severe autism cases to more severe. Well, that hasn’t been demonstrated – nor has its corrollary, that thimerosal doesn’t shift autism toward more severe outcomes.

    This is my point exactly. The possibility is not being studies or discussed and far less demonstrated.

    However, from several studies of autism then and now, we know that the current population of “autism” contains a much higher percentage of “milder” cases. This is not proof positive that the “thimerosal makes autism worse” hypothesis is wrong, but it sure points that way.

    Please Prometheus look at what I wrote

    when thimerosal/vaccines/environmental poisoning can be a contributor to worsening ASD, shifting milder cases to more severe, these are not answers.
    I am talking about the combination of insults, not of thimerosal only , but in combination with other environmental sources of Heavy metal AND vaccines AND other sources of environmental poisoning in susceptible individuals. What if what yesterday was speech delay now is worse?
    You say
    By the way – it still is up to the people proposing the hypothesis to provide supporting data (actually, to test the hypothesis, but let’s start small). It’s not my job to prove it wrong – although I have reluctantly shouldered that burden on innumerable occasions.
    Fair enough. I understand your point. My background is in Chemistry, therefore I have researched a lot about biochemistry and toxicological aspects.Also I am a mom of an ASD child and therefore for me is especially important. However, I do think that are researchers in the field who are enough prepared to conduct such tests with enough scientific care and training. I have always thought that in this kind of medical conditions, it is clear that doctors/researchers in medicine must have the leadership and parents are the supportive team. For me is a team work between researchers with open mind and attention and parents involved at their level of possibilities, including what they saw in their children.
    The situation is such today that it seems a divorce between parents and researchers/doctors, a painful situation that I hope can be revearsed.

    How about providing some supporting data to back up the suppositions and postulates? Otherwise, I can’t tell if you’re just making this up or if you have some data that points you in that direction.

    Fair enough again. I have supporting data in terms of personal research in different fields to support the suppositions and postulates ( I have used pubmed mainly and personal reading and toxicology sources-books and journals). It is long to read- sorry, remember that this is my fault but I think is important to backup enough.
    Do you want me to post here or can I send by e-mail to you the .doc I have prepared? The problem is that spam protection cuts the posts. If you allow me, I can send to you the reviews I have prepared considering our personal experience and research ( do not worry, they are not so long!)
    I have personal experience with my son that make me think the way I think. Remember I live 10000 km away USA.but I never discussed his results publicly because I understand is anecdotic for science. Please let me know if you as a doctor is interested about (I am not looking for advice, sorry, only commenting because your background)
    Thank you for your answer

  46. #46 Kristjan Wager
    April 21, 2006

    Before I wrote this post I mailed Madsen about the graph, but when he didn’t reply, I went ahead and wrote it. Then in the beginning of this week, there was a newsstory that the mail accounts belonging to the Danish association of Doctors hadn’t worked the last couple of weeks. Since I mailed him through such an account, I realized that he probably hadn’t received the mail, and wondered if I should resend it.

    However, before I got around to that, I got a reply from him, so the mails were not lost, just delayed.

    I asked him if it was possible to get the corrected numbers, and he said that while he didn’t have them, he would try to see if one of the others still had, and then get them to me.

    He also explained to me, that according to his memory, the reason why there was only the one graph, and not a graph with corrected data as well, was because the magazine only allowed one graph.

    Watch this space for any developments.

  47. #47 Kaethe
    May 8, 2006

    Excellent job, Kristjan.

    Maria, you say:

    am talking about the combination of insults, not of thimerosal only , but in combination with other environmental sources of Heavy metal AND vaccines AND other sources of environmental poisoning in susceptible individuals. What if what yesterday was speech delay now is worse?

    Even if I accept your premise, unsupported by any data, that the genetic predisposition to autism includes an increased susceptibility to “environmental poisoning”, I still have to ask “so?” Why do you believe that autism has anything to do with immunity?

    Sue, not all avenues of research are worthwhile. Since there is no demonstrable link between thimerosal and autism, since autism is demonstrably not mercury poisoning, then devoting time and resources to learning more about mercury poisoning would be of no use whatsoever to people diagnosed with autism.

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    January 13, 2008

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