Archive | March, 2009

The vaccine debate has a real cost

31 Mar

Of course, this isn’t news. But usually the cost is characterized in the danger to public health.

What about the cost to people with autism? Here’s a blog post from the Simons Foundation. (as an aside–there is a real autism organization). They are quoting Cathy Lord and Paul Shattuck.

Given the diversity of the panel’s members, the strategic plan was, unsurprisingly enough, hotly debated, and continues to be scrutinized.

Most of the debate centers around the plan’s emphasis on environmental risk factors. Lord says this came at the cost of research on more worthwhile topics, such as how to expand treatment services to low-income families — a project for which she was hoping to be funded.

“It’s gone, just gone. I was pretty astonished to see that that had disappeared,” she says.

The report also doesn’t emphasize studying autism’s course beyond childhood, notes Shattuck. “The amount of money that goes into understanding services and aging and supporting people in their daily lives seems disproportionately small,” he says.

One of the problems with the vaccines-cause-autism groups is that they really don’t advocate for people with autism. They have abandoned entirely people of low income and minorities (except where they can be used for political gain).

It isn’t just that groups like SafeMinds, Generation Rescue and the rest can’t be bothered to spend the time worrying about minorities or adults. It’s the fact that the data those groups use to support the “epidemic” makes ZERO sense when you consider minorities.

Consider this: the “rate” of autism is 0.3 per 1,000 for Hispanics in Wisconsin, but 10.6 for Whites in New Jersey.

Why isn’t Generation Rescue calling for an investigating the Hispanics of Wisconsin? Shouldn’t they want to know what is “protecting” that subgroup from autism?

They don’t care, they don’t want to bring attention to the Hispanics in Wisconsin (or the under represented minorities across the nation), because it blows a big hole in the “epidemic”. Obviously we still aren’t counting all the people with autism in our prevalence estimates. How can we rely on the historical data that shows an “epidemic” if we aren’t doing a good job even now?

We’ve covered this many times in the past. It is one thing when the damage caused is more abstract. But when it become very real, when minorities are being left out in the cold, it is an outrage.

Hours and hours were spent in the IACC meetings wordsmithing the vaccine language. To groups like SafeMinds and people like Lyn Redwood, the Strategic Plan was a political document. It was a statement by the government, and it was critical to get as much “admission” of autism being caused by vaccines as was possible. So what if another generation of minorities gets mislabeled with Intellectual Disability or some other Special Education category when SafeMinds was able to get the IACC to admit that many parents think vaccines cause autism?

This is what happens when psuedo “Vaccine-injury” advocates pretend to be Autism advocates and take seats at the table. Lyn Redwood put her own interests and those of her organizations ahead of the well being of people with autism.

That’s just plain wrong.

Mild hyperbaric therapy for autism – Shh!…don’t say it’s expensive

30 Mar

When I recently wrote about the new HBOT-for-autism study (Rossignol et al. 2009)1, I took issue with unlikely claimed treatment pressures for at least one of the study locations. While a potential methodological weakness, this is probably a fairly small problem in light of potential issues with blinding and interpretation of the results as quantitatively and objectively meaningful with respect to autism. But let’s set those potential issues aside for a moment.

Let’s assume that treatment with slightly enriched air (24% vs. 21% oxygen) in an inflatable hyperbaric chamber pressurized to 4 PSI2,3 above ambient atmospheric pressure, could confer some sort of benefit to an autistic child.

I’m not suggesting assumption that it does confer benefit. I’m asking readers to set aside any knowledge of hemoglobin’s role in oxygen transport, as well as any knowledge of real hyperbaric oxygen therapy (breathing 100% oxygen at greater than 1 ATA)4, and evaluate a simpler proposition. Accept the proposal that some sort of benefit is scientifically possible, but then ask yourself a fairly simple question:

Compared to 24% O2 at 4PSI above ambient atmospheric pressure in an inflatable hyperbaric chamber, equivalent oxygen delivery can be achieved with simple oxygen therapy (an oxygen mask) at a fraction of the cost5 – why is a study of the hyperbaric version of this increased oxygen important?

One possibility: studying what’s already for sale

While some might call it being on the “cutting edge”, others may consider it putting the cart before the horse. No matter how you see it, it’s no secret that some Defeat Autism Now practitioners were already selling this type of hyperbaric oxygen therapy well before this study came out. It should be noted that this study’s authors did disclose this conflict of interest with respect to derivation of revenue in their clinical practices from HBOT.

DAR, LWR, SS, CS, AU, JN, EMM, and EAM treat individuals with hyperbaric treatment in their clinical practices and derive revenue from hyperbaric treatment.

Lisa Jo Rudy over at autism.about.com6 had additional comments about the subject:

Dr. Rossignol is “the” proponent of HBOT, and has been speaking at conferences all over the world in support of the treatment. Clearly, he has a personal and professional stake in seeing that the outcomes of a research study are positive.

The present study was funded by the International Hyperbarics Association, a trade group of private hyperbaric therapy centers. Clearly, they have a similar stake in seeing positive outcomes.

While there may certainly be an aspect of genuine scientific interest in understanding if this type of hyperbaric oxygen therapy is beneficial for autistic kids, I think there may also be a certain degree of assumption that it is. After all, why would a practioner already be selling something if they didn’t “believe” it worked? Given the stated conflicts of interest, it doesn’t seem implausible that the authors might have an interest in seeing a long-term revenue stream that could come from additional, and deeper pockets than those of parents willing to “believe” and pay – despite the lack of really convincing scientific evidence at this point.

Consider the following portions of an interview with Dr. Dan Rossignol7:

We chose 1.3 ATA because a lot of children with autism are currently receiving this dose and we are hoping to prove that it works.

“Hoping to prove that it works.”

Dr. Rossignol’s point does not seem unclear. HBOT is popular, and he is, in his own words, “hoping to prove that it works”. This is a valid reason, I suppose, if he is also open to the possibility that it may not, or that it may be a completely moot point if something on the order of one tenth of the cost can do the same thing. Following Dr. Rossignol’s communication about the hope to “prove that it works”, the interviewer asks:

How is the insurance situation coming along?

Insurance situation? Coming along? Was this situation already a well-known “work in progress” back in 2006 (e.g. had it been decided by some, prior to the science, that “mild” HBOT for autism does work, and that insurance reimbursement is really the goal now? Let’s see if we can get Dr. Rossignol’s take on this.

Well, obviously, HBOT is not approved for autism, but we hope to get there. Interestingly, if you take the ABC scale and look at the lethargy subset score, we saw a 49% improvement in symptoms at 1.5 ATA with a p-value of 0.008. If you look at the New England Journal of Medicine study on risperidone from 2002, there was a 56.9% improvement on the ABC irritability subscale with a p-value < 0.001. So the results we had on these 6 children with 1.5 ATA approached the percentage improvement seen with a drug approved for the use in autism. We just need to be able to reproduce these type of findings in a placebo study.

Hopefully when we finish these studies and show that hyperbaric therapy works, then insurance reimbursement will follow.

I don’t necessarily see a geniune scientific perspective here, but that could just be me. I get more of a vibe (at least from this interview), that the interest may lie more in “finishing” the studies and showing “that hyperbaric therapy works”, rather that actually finding out, with really good quality scientific methodology, whether or not it really does work. I’ll acknowledge that I could be wrong about this. Do you think readers will have noticed that the study result mentioned for comparison, was from 1.5 ATA, and probably totally irrelevant to the 1.3 (or less) studies?

Is it just me, or would it seem naive to wish that a few studies like the recent one, are really going to catalyze insurance reimbursement in the long run? I get the impression that many parents may believe this. Insurance companies work to achieve cost efficiencies. One of the ways they do this is by reimbursing at higher rates for equivalent things at lower costs – hospital stays in contracted facilities, generic drugs as compared to name-brand versions, etc. Why on earth would an insurance company reimburse for a 4-5% increase in blood oxygen content for a couple of hours at a time, in an inflatable hyperbaric chamber (at a few thousand dollars a month), when the identical oxygen increase could be delivered with a simple oxygen mask (for under $200 a month)?

You don’t have to take my word for this comparison of oxygen delivery, you can take Dr. Rossignol’s acknowledgement in that same interview:

Some people have criticized using mild hyperbarics at 1.3 ATA because they state that when compared to this pressure, you can get just as high an oxygen concentration in the blood with oxygen by face mask without a chamber. And this may be true in some cases.

In fact, it’s true in most (if not all) cases. The physics of partial pressures does not discriminate. But there may be more to the story.

Squeeze in some hope

After acknowledging the reality of the partial pressure comparison problem, Dr. Rossignol continues:

However, we must remember we are dealing with 2 separate components with HBOT — the oxygen and the pressure. So it appears that many of the effects of HBOT are from the increased oxygen, but we cannot dismiss the pressure effect. I think we need more studies on this as well.

So “many of the effects” are from the oxygen increase, but we can’t dismiss the pressure effect? What pressure effect? Is there a demonstrated significant clinical effect for autism from a very slight, and very temporary, increase in atmospheric pressure alone?

Although I suppose it is possible, a clinically significant effect for autism at such low pressures doesn’t seem likely at all. If it turns out that I am incorrect, this may be good news for some of the parents of autistic children in several U.S. cities: Albuquerque, NM (5312′ AMSL), Aurora, CO (5471′ AMSL), Colorado Springs, CO (6035′-7200′ AMSL), Denver, CO (5280′ AMSL), Reno, NV (4505′ AMSL), and Salt Lake City, UT (4226′ AMSL), to name a few. Something as simple as a move to a closer to sea-level city might provide increases in atmospheric pressure not a lot unlike those provided by the inflatable hyperbaric chambers. If there were some beneficial effect of slight additional atmospheric pressure for autism, certainly there would have been some observations (anecdotal or media reports) over the years, of families with autistic children who moved from states like Colorado to lower elevation states like California – and noticed. Who knows? Perhaps this is something to yet be uncovered.

So, aside from the fact that an identical oxygen increase can be achieved with simple O2 therapy without a hyperbaric chamber at all (and at a fraction of the cost). And, aside from the point that the minute pressure increase (while certainly possible in a strict scientific sense) isn’t known to be a likely candidate to significantly clinically impact autism, is there anything else about this newest HBOT-for-autism study that may merit some critical thought? Maybe, but it’s really just a side-note (perhaps interesting to some, but not terribly relevant to the science itself).

Who farted in the HBOT chamber? (Shh!…Don’t say it’s expensive)

The original manuscript8 for this study contained what I thought was an appropriately realistic comment from the authors in the conclusion. This comment has value in terms of practical knowledge that readers who are not familiar with hyperbaric oxygen therapy would probably find useful. What follows is the first-draft conclusion of this study with that comment emphasized.

Hyperbaric treatment is a relatively time-intensive treatment and can be costly. However, given the positive findings of this study, and the shortage of proven treatments for individuals with autism, parents who pursue hyperbaric treatment as a treatment for their child with autism can be assured that it is a safe treatment modality at the pressure used in this study (1.3 atm), and that it may improve certain autistic behaviors. Further studies are needed by other investigators to confirm these findings; we are aware of several other planned or ongoing studies of hyperbaric treatment in children with autism.

Again, Lisa Jo Rudy over at autism.about.com notes:

No insurance company will cover the very high cost of HBOT for autism, as it is considered an experimental and unproven therapy.

But the above conclusion is not the conclusion that appeared in the peer-reviewed, edited version. Here it is:

Given the positive findings of this study, and the shortage of proven treatments for individuals with autism, parents who pursue hyperbaric treatment for their child with autism can be assured that it is a safe treatment modality at the pressure used in this study (1.3 atm), and that it may improve certain autistic behaviors. Further studies are needed by other investigators to confirm these findings; we are aware of several other planned or ongoing studies of hyperbaric treatment in children with autism.

Why would the authors remove that valuable bit of practical knowledge about time requirements and high cost? Apparently due to a comment from referee #3 for this paper.

Discretionary Revisions

Page 24 In view of the highly positive findings of this study and the fact that no other trial has demonstrated such benefits under strictly controlled conditions to open the conclusions with negative comments demeans the study. Many other inventions used for ASD children are equally time consuming and hyperbaric treatment need not be expensive.

Authors: “The negative comments were removed from the conclusion.”

Opening the conclusion with negative comments demeans the study? Such comments don’t really touch the content of the study itself, and what the now absent comment did do, was provide some practical perspective – quite likely, very accurate practical perspective. Why would it be suggested by referee #3 that the practical comments demean the study? Perhaps it was meant that the comments demean the use of mild hyperbaric oxygen therapy as an autism treatment (therefore actually demeaning a desired interpretation of this study)? That would seem a real possible concern, since the justification offered, has absolutely nothing to do with the study itself, and doesn’t amount to much more than logical fallacy and simple assertion.

“Many other inventions used for ASD children are equally time consuming…”

This is about as basic an example of the “two wrongs make a right” fallacy as can be presented. Two wrongs don’t make right. Just because other interventions are also time consuming, does not mean a researcher is unjustified, or shouldn’t add the point about practicality that HBOT is relatively time consuming. Further, if the authors are aware of such a potential practical issue, it could be argued that ethics would dictate that it is mentioned. Other treatments presenting similar impracticalities do not automatically relieve any potential ethical responsibility in this regard.

“…hyperbaric treatment need not be expensive.”

Compared to what? Hyperbarics in a gold-plated hyperbaric chamber? If there is no significant effect for autism from the brief, and small increase in added pressure in one of these inflatables, the increased oxygen delivered by providing 24% O2 at 4 PSI above ambient atmospheric pressure, is easily matched (or exceded) with simple O2 therapy. In short, this type of hyperbaric treatment would be the hard way, and the expensive way to achieve the results.

Referee #3 also added the following comment:

The reviewer has a preference for the word treatment rather than ‘therapy’. In view of the proven changes that relate to increased inpsired fractions of oxygen it is suggested that treatment would be preferable.

Authors: “The word “therapy” has been replaced with “treatment” throughout the paper.”

The “T” in the acronym “HBOT” does, in fact, represent the word “therapy” in medical usage. I happen to think the terms “treatment” and “therapy” are fairly interchangeable in the context of drug delivery, but I do wonder if there is any significance to such a preference. Is this a semantics issue that has the potential to impact perceptions of those who make decisions about insurance coverage for autism? But I digress. So what’s up with these comments from referee #3, comments with a little fallacious reasoning, that express possible concern about the perception of a high price tag for mild hyperbaric oxygen therapy, and a commment that communicates a preference for the word “treatment” over “therapy”?

I honestly don’t know. What I can tell you is that referee #3 was Philip James, MD. Dr. James is a professor in the field of hyperbaric medicine and hails from the U.K. He appears to have published quite a bit in the field of hyperbaric medicine as well.

According to the International Hyperbarics Association website:

Dr. James is responsible for founding the Hyperbaric Trust in the United Kingdom which promotes the treatment of cerebral palsy and the brain injured child and was responsible for having the National Health Service pay for this therapy.

Dr. James (Referee #3) appears to have been categorized (with a doctor profile) as a medical advisor to International Hyperbarics Association back in February of 2006 (shortly before this study9 began). Hey wait a minute, there’s that name again – International Hyperbarics Association. Where have I seen that before? Oh yeah, in the study itself:

We are grateful for the work of Shannon Kenitz of the International Hyperbarics Association (IHA) for an unrestricted grant which funded this study, which included use of hyperbaric chambers and funding for all hyperbaric technician salaries during the study. The IHA had no involvement in the study design, collection, analysis, interpretation of data, writing of the manuscript, or in the decision to submit the manuscript for publication.

I’m not sure how the International Hyperbarics Association defines itself exactly – are its listed medical advisors excluded from that definition? That would seem likely.

As of this writing, Dr. Rossignol is listed as a medical advisor at the IHA website. 10
As of this writing, Dr. Neubrander is listed as a medical advisor at the IHA website. 10
As of this writing, Dr. James (referee #3), is categorized as a medical advisor at the IHA website with a physician profile page.11,12

Side notes aside, where to, from here

So all in all, it seems that “mild” HBOT-for-autism researchers may have their work cut out for them. Although probably not very likely, it is possible that a small temporary change in atmospheric pressure could do something for autism, and that should be studied next, then, better replications should follow.

In the long run, it will be difficult to ignore the scientific fact that simple oxygen therapy alone can easily provide identical increases in blood oxygen content, at a fraction of the cost of mild hyperbaric oxygen therapy (as it currently being studied for autism). If HBOT-for-autism proponents think insurance companies should step up to pay for an expensive treatment that provides a 4-5% increase in blood oxygen (without scientifically establishing benefit of the small and temporary pressure increases), they might do well to consider these famous words (most recently from Barack Obama) – “You can put lipstick on a pig. It’s still a pig.”

Notes:

1 Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial

Click to access 1471-2431-9-21.pdf

2 Medical device pre-market notification (FDA-cleared)

Click to access K001409.pdf

3 Manufacturer product sheet

Click to access vitaeris-lowres2007-8.pdf

4 Definition of Hyperbaric Oxygen Therapy
http://www.uhms.org/ResourceLibrary/Indications/tabid/270/Default.aspx

5 Hyperbarics and Hypotheses

Schooling and Statement

6 Hyperbaric Oxygen as a Treatment for Autism: Let the Buyer Beware
http://autism.about.com/b/2009/03/14/hyperbaric-oxygen-as-a-treatment-for-autism-let-the-buyer-beware.htm

7 Interview with Dr. Dan A. Rossignol: Hyperbaric Oxygen Therapy Improves Symptoms in Autistic Children

Click to access Rossignol%20HBOT%20Medical%20Veritas%202.pdf

8 Pre-publication history
http://www.biomedcentral.com/1471-2431/9/21/prepub

9 ClinicalTrials.gov Identifier: NCT00335790
http://clinicaltrials.gov/ct2/show/NCT00335790

10 Medical Advisors
http://www.ihausa.org/

11 Index of /docs
http://www.ihausa.org/docs/

12 International Hyperbarics Association Medical Advisor – Professor Philip B. James, M.D.
http://www.ihausa.org/docs/james.html

Features of autism

29 Mar

I was planning on writing something about this for the 1 year anniversary of when the Department of Justice concession to Hannah Poling was leaked.

Why wait until now? Because it was basically impossible to discuss this last year. Immediately after the leak, the phrase “features of autism” was made into a running joke. The vaccines-cause-autism people all made great fun of how the government coined the phrase, presumably to avoid using the simple word, autism.

Anyone want to go back and look at the document now? Search for the word “features”.

First hit:

Dr. Zimmerman observed that [Hannah Poling] watched the fluorescent lights repeatedly during the examination and would not make eye contact. Id. He diagnosed [Hannah Poling] with “regressive encephalopathy with features consistent with an autistic spectrum disorder, following normal development.”

Note that that’s in quotes: “features consistent with an autistic spectrum disorder”. That’s right, Andrew Zimmerman, Hannah Poling’s own neurologist used the phrase “features of autism” about her, long before the Department of Justice ever did.

This is the same Andrew Zimmerman who submitted an expert report on Hannah Poling. This is the same Andrew Zimmerman who wrote an expert report, for the government side, in the Autism Omnibus Proceeding.

Not the only place “features” is mentioned in the Rule 4(c) report, either:

Second Hit:

[Hannah Poling] was evaluated by Alice Kau and Kelley Duff, on May 16, 2001, at CARDS. Pet. Ex. 25 at 17. The clinicians concluded that [Hannah Poling] was developmentally delayed and demonstrated features of autistic disorder.

So, why is it surprising that the Department of Justice would write:

In sum, DVIC has concluded that the facts of this case meet the statutory criteria for demonstrating that the vaccinations [Hannah Poling] received on July 19, 2000, significantly aggravated an underlying mitochondrial disorder, which predisposed her to deficits in cellular energy metabolism, and manifested as a regressive encephalopathy with features of autism spectrum disorder.

That’s the third place that “features” is used in the concession document. But, hey, it isn’t funny to talk about Hannah Poling’s own specialists describing her as having “features” of an autistic spectrum disorder.

It is very easy to make more out of this than is warranted by the scant information we have available. We don’t know what is in the rest of the documents that were provided as part of the case. What we do know is that the U.S. government did not create the phrase “features of autism” to describe Hannah Poling.

Growing up fast

27 Mar

I wrote a few days ago about autism, murder, crime and morality. The conclusion I reached was that based on the studies I read, criminality was uncommon among autistic people compared to non-autistic controls. Morality was also present in all degrees of autistic severity.

In a disturbing and frightening post at Salon yesterday Ann Bauer told the world about the reality she faces with her autistic son Andrew.

She used to be someone who according to herself:

…thought of his autism as beautiful and mysterious.

And now she feels that:

[I must]…break the silence about autism’s darker side. We cannot solve this problem by hiding it, the way handicapped children themselves used to be tucked away in cellars. In order to help the young men who endure this rage, someone has to be willing to tell the truth.

I agree that people should tell the truth. But the truth is not how one feels at one point in time. The truth is separate from onesself and endures after you are gone.

Why is it so difficult for people to see more than one side of any equation? Autism _is_ a difference. It is also a disability and to some a disorder.

By the same token autistic people can be violent. They can also be joyous. Is the joy a product of their autism? Is the violence? Or could it be that people are different the world over regardless of their neurology?

I think Ann Bauer should definitely talk about her son. But I hope she doesn’t see her son as ‘the truth, the whole truth and nothing but the truth’. Because the truth is also Temple Grandin who doesn’t live in a cage. The truth is also Katie McCarron cruelly murdered by an NT mother. The truth is also Sky Steuernagel, Amanda Baggs, Alex Bain, Conor Doherty, Megan Leitch etc etc.

What I’m saying is that the truth about autism is not one persons agenda but a reality that autistic people experience every day. Most of these people are nice and a minority aren’t. Some commit crime. The same is true of bipolar people, gay people, NT people, chinese people etc etc.

My own autistic child turned 9 in Feb. Xe is in the 99th percentile for her age/height and is also well built too. Xe sometimes headbutts, pinches and hits and we struggle to tackle why this is and how we can help. The local education authority are no help. The best they can offer is one session of speech therapy every 3 months. So we taught ourselves and we improvise a lot too. But xe is still my child and I wouldn’t swap xyr for the world. Xyr autism is part of that. I don’t think xe would be who xe is without being autistic.

So because xe has issues should we expect xyr to be violently out of control as xe grows older? I don’t see why. Might xe occasionaly be violent when we fail to understand xyr? Possibly.

But everyones different. I don’t want people having false negative expections of my child because xe shares a diagnosis with someone who is violent.

Pardo letter on neuroinflamation

26 Mar

Neuroinflamation was a big subject in the Autism Omnibus. This was especially true in the “second theory of causation” hearings, which concentrated on thimerosal containing vaccines as a possible causative factor in autism.

Here’s a page from Dr. Aposhian’s presentation at the Omnibus (click to enlarge), which shows the basic logic flow.

aposhianslide76

Or, to put it simply–thimerosal gets changed to ethyl mercury which deposits mercury ions in the brain, causing neuroinflamation which causes autism.

Yes, there are a lot of of missing steps in order to prove this idea.   But, for now, let’s just think about neuroinflamation.  The term (neuroinflamation), as Dr. Aposhian makes clear in his report and slides, is somewhat new, having been coined in the 1990’s. Dr. Aposhian and others spent a lot of time discussing neuroinflamation, astrocytes and glial cells.

The research on neuroinflamation in regards to autism comes mainly from researchers at Johns Hopkins. In particular, Dr. Aposhian cites (on slide 79 of his presentation) the Vargas paper, pulling a quote:

Vargas et al., Neuroglialactivation and neuroinflammation in the brain of patients with autism. Ann Neurol57, 67-81, 2005,

“Our findings indicate that innate neuroimmunereactions play a pathogenic role in an undefined proportion of autistic patients…”

It is important to note that one of the authors on that paper was Dr. Andrew Zimmerman, whose expert report Kev recently blogged. That’s right, Dr. Zimmerman prepared an expert report for the government. The anchor author on the Vargas paper was Dr. Carlos Pardo.

It turns out that a letter from Dr. Pardo is included in the Omnibus docket as well. Here’s the introduction paragraph from Dr. Pardo’s letter:

As per our conversation last year, I would like to clarify some of the concepts regarding the role of neuroimmune response in the brain of patients with autism and the potential significance of such findings in the pathogenesis and pathobiology of the disorder.

Good–he’s trying to clarify some points of his paper. Just the sort of letter we want to read. It is rather thick on the science. Let me cherry pick one sentence, if I may:

These findings are inconsistent with the hypothesis of a potential toxic effect on astrocytes by neurotoxins or toxic material.

It strikes me that the families with claims in the vaccine court are in a really difficult position. Their lawyers and experts are arguing the thimerosal causation issue largely on the idea of neuroinflamation. The problem being that the key people in neuroinflamation and autism are experts for the other side.

The thimerosal cases depend on neuroinflamation. Does anyone else see this as a really tough battle to fight, given that the few world experts on the subject disagree with the contention that neuroinflamation in autistic brains is due to neurotoxins?

Is there an autism epidemic – the latest science

25 Mar

A new paper from Eric Fombonne is in electronic print at the journal Pediatric Research. It will apparently be published in the paper version of the journal some time after April.

The title is ‘Epidemiology of pervasive developmental disorders’ and as the name suggests, Fombonne looks at all the available quality epidemiology he can find relating to PDD’s.

This article reviews the results of 43 studies published since 1966 that provided estimates for the prevalence of Pervasive Developmental Disorders, including Autistic Disorder, Asperger Disorder, Pervasive Developmental Disorder Not Otherwise Specified, and Childhood Disintegrative Disorder.

Combining all these categories together Fombonne presents a prevalence of 60-70/10,000.

For autistic disorder, Fombonne says:

The correlation between prevalence and year of publication was statistically significant and studies with prevalence
over 7/10,000 were all published since 1987. These findings point towards an increase in prevalence estimates in the last 15-20 years.

For PDD-NOS, Fombonne explains that it is next to impossible to get accurate prevalence rates as:

This group has been much less studied in previous epidemiological studies…

Again, for Aspergers, Fombonne says that AS specific epidemiological studies are sparse but, in something of a surprise:

By contrast, other recent autism surveys have consistently identified smaller numbers of children with AS than those with autism within the same survey. In 9 out of 10 such surveys, the ratio of autism to AS prevalence in each survey was above unity, suggesting that the prevalence of AS was consistently lower than that for autism. How much lower is difficult to establish from existing data, but a ratio of 3 or 4 to 1 would appear an acceptable, albeit conservative, conclusion based on this limited available evidence. This translates into a prevalence proportion for AS which would be ? to ¼ that of autism. We therefore used for subsequent calculations an estimate of 6/10,000 for AS, recognizing the strong limitations of available data on AS.

Lastly, for CDD:

Eight studies provided data on childhood disintegrative disorder (CDD). Prevalence estimates ranged from 0 to 9.2/100,000. The pooled estimate based on eight identified cases and a total surveyed population of 406,660 children, was 2.0/100,000. The upper-bound limit of the associated confidence interval (4.0/100,000) indicates that CDD is a very rare condition, with about 1 case to occur for every 103 cases of autistic disorder.

Fombonne then tackles the question everyone wants an answer to – is there an autism epidemic?

In order to answer this accurately, he explains that there has to be tight control over incidence estimates (the number of new cases occurring in a population over a period of time) and prevalence (the proportion of individuals in a population who suffer from a defined disorder). Failure to control these gives false results. Bearing this in mind, Fombonne goes through the five approaches taken so far to try and determine if theres an autism epidemic or not.

1) Referral Statistics.
Trends in time for referral statistics are not reliable. They fail to control for things such as referral patterns, availability of services, heightened public awareness, decreasing age at diagnosis and changes over time in diagnostic concepts and practices. An example of the issues from referral statistics is:

Strong evidence of “diagnostic switching” was produced in California and in all US states indicating that a relatively high proportion of children previously diagnosed as having mental retardation were now identified as having a PDD diagnosis. Decreased age at diagnosis has also been shown to contribute to the rising numbers of children diagnosed with PDD. In the UK, Jick and Kaye (62) have shown that the incidence of specific developmental disorders (including language disorders) decreased by about the same amount that the incidence of diagnoses of autism increased in boys born from 1990-1997. A more recent UK study has shown that up to 66% of adults previously diagnosed with developmental language disorders would meet diagnostic criteria for a broad definition of PDD.

2) Comparison of cross-sectional epidemiological surveys
If I’m understanding his point here (and please correct me if I’m not) Fombonne is saying that too many epidemiological studies are uniquely designed – not enough attempt to replicate a previous study – and hence:

The most convincing evidence that method factors could account for most of the variability in published prevalence estimates comes from a direct comparison of 8 recent surveys conducted in the UK and the USA. In each country, 4 surveys were conducted around the same year and with similar age groups. As there is no reason to expect huge between-area differences in prevalence, prevalence estimates should therefore be comparable within each country. However, there was a six-fold variation in prevalence for UK surveys, and a fourteen-fold variation in US figures. In each set of studies, high estimates derived from surveys where intensive population-based screening techniques were employed whereas lower prevalence proportions were obtained from studies relying on passive administrative methods for case finding. Since no passage of time was involved, the magnitude of these gradients in prevalence can only be attributed to differences in case identification methods across surveys.

3) Repeat surveys in defined geographical areas
So this is the opposite of the above – these are studies where they are being replicated as closely as is possible. However, the issue here is that there are simply not _enough_ of these studies to form a definite conclusion. However, it may be worth noting that in the two studies Fombonne highlighted as being carried out in exactly the same way in exactly the same place to exactly the same age cohort – but just at two different times one showed no increase in prevalence whilst the other showed no increase at 4 sites and an increase at 2 sites.

4) Successive birth cohorts
This means in very large surveys with a wide age range, if the proportion of people who have autism rises this _could_ be a rise in incidence and therefore a good hint that there is an epidemic. I say _could_ as other possible causes need to be ruled out first.

…two large French surveys [used this method]. The surveys included birth cohorts from 1972 to 1985…, and, pooling the data of both surveys, age-specific prevalence showed no upward trend.

A US survey _did_ show an upward trend but:

…the increase was not specific to autism. These analyses also showed a marked period effect that identified the early 1990s as the period where the prevalence estimates started to go up in all ages and birth cohorts, coinciding closely with the inclusion of PDDs in the federal Individual with Disabilities Educational Act (IDEA) funding and reporting mechanism in the US.

5) Incidence studies
The few incidence studies did show incidence trends rising over short periods of time. As noted in point 4) above, this _could_ be attributed to an autism epidemic. However –

…none of these studies investigations could determine the impact of changes over time in diagnostic criteria, improved awareness and service availability on the upward trend.

Contrary to what people who _want_ there to be an autism epidemic, these are non trivial reasons. It stands to reason that if (for example) Birmingham, UK – the countrys second city, goes from having zero service availability and no means of diagnosis in 1960 to having numerous types of service availability both publicly and privately funded and a _lot_ of means of diagnosis in 2000 there will be a _lot_ more autistic people in Birmingham. A hell of a lot. When we then consider that the diagnosis criteria has widened massively than we go from a hell of a lot more autistic people to a _whole hell_ of a lot. If we _also_ consider that people who used to carry one kind of diagnosis are now being swapped to autism then we go from a whole hell of a lot to a descriptive term beyond my ability. This isn’t even science – its basic common sense. The only issue is – ‘a whole hell of a lot’ is not a very accurate measurement.

Fombonne closes by saying that – based on the available data – we still cannot really say one way or the other if there has been an autism epidemic. Remember when you read the quote below that its _incidence_ that gives us an epidemic.

Current evidence does not strongly support the hypothesis of a secular increase in the incidence of autism but power to
detect time trends is seriously limited in existing datasets. Whilst it is clear that prevalence estimates have gone up over time, this increase most likely represents changes in the concepts, definitions, service availability and awareness of autistic-spectrum disorders in both the lay and professional public. To assess whether or not the incidence has increased, method factors that account for an important proportion of the variability in prevalence must be tightly controlled. The possibility that a true change in the underlying incidence has contributed to higher prevalence figures remains, however, to be adequately tested.

Who is antivaccine?

25 Mar

The group that wants to bring the third world up to modern standards of vaccination or the group that wants to bring the US to current third world standards?

I’ve been trying to avoid responding to Age of Autism blog posts. I have a full time job, I don’t need another one. But, this one struck me as worth a few minutes.

Mr. Olmsted posted the blog piece, “WHO is Anti-Vaccine?” In it, he quotes a newspaper article that stated

“In the first nine months of life, the World Health Organization recommends vaccines for tuberculosis, diphtheria, tetanus, whooping cough, polio and measles.”

Mr. Olmsted then tries to draw a parallel between his own organization (Generation Rescue et al.) and the World Health Organization (WHO). Since both organizations recommend fewer vaccines than in the current US schedule, supposedly his group is mainstream.

Mr. Olmsted chafes at the reputation he has earned (and earn it he did) for not digging very deep into a story. He won his battle star, as it were, by missing out on a big part of the Amish story, the Clinic for Special Children. No doubt the revisionist history, complete with stories by angry Amish, will fill at least a chapter in his upcoming book.

Why bring this up? Because once again, Mr. Olmsted looked only far enough to support his preconceived ideas. The WHO campaign he is discussing is well covered on…well, the cryptically named World Health Organization website.

Page 15 of this presentation, gives a good idea of WHO’s goals: by 2015, introduce new vaccines. They discuss adding HepB, Hib and also:

Japanese Encephalitis
Yellow Fever
Rubella
Pneumo (Conjugate vaccines)
Rotavirus Diarrhoea
Typhoid Fever
HPV
Mening Conjugate A

Here is fact #2 in the WHO 10 facts about immunization. Would Mr. Olmsted and his organization agree?

Immunization currently saves between 2 and 3 million lives per year. It is one of the most successful and cost-effective public health interventions.

Mr. Olmsted: enter “autism” into the search box on the WHO website.

First hit MMR and autism.

Based on the extensive review presented, GACVS concluded that no evidence exists of a causal association between MMR vaccine and autism or autistic disorders.

Another of the top links–a page from the WHO Bulletin. The story? ‘Science vs ‘‘scaremongering’’ over measles-mumps-rubella vaccine’.

How about this link, also on the first page: “No vaccine for the scaremongers”. Here’s a nice quote from that article:

While parents in developing countries have, for example, first-hand experience of measles and welcome vaccination against it, the uptake by parents for the combined measles, mumps and rubella vaccine in many developed countries has yet to recover almost 10 years after a study linking it to autism, even though the original study has long since been discredited and there is overwhelming scientific evidence that refutes the link.

Frankly, I think Mr. Olmsted is squarely in the group the WHO would call “scaremongers”. It is ridiculous in the extreme for him to try to draw a parallel between him and his organizations and WHO.

Again I will ask, who is antivaccine, the group that wants to bring the third world up to modern standards of vaccination or the group that wants to bring the US to current third world standards?

Spiderman saves autistic boy

25 Mar

Gotta love a story like this.

I don’t like copying entire news stories, but by the time I cut and paste chunks of this one, I will have most of it anyway:

BANGKOK (AFP) – A Thai fireman turned superhero when he dressed up as comic-book character Spider-Man to coax a frightened eight-year-old from a balcony, police said Tuesday.

Teachers at a special needs school in Bangkok alerted authorities on Monday when an autistic pupil, scared of attending his first day at school, sat out on the third-floor ledge and refused to come inside, a police sergeant told AFP.

Despite teachers’ efforts to beckon the boy inside, he refused to budge until his mother mentioned her son’s love of superheroes, prompting fireman Sonchai Yoosabai to take a novel approach to the problem.

The rescuer dashed back to his fire station and made a quick change into a Spider-Man costume before returning to the boy, he said.

“I told him Spider-Man is here to rescue you, no monsters are going to attack you and I told him to walk slowly towards me as running could be dangerous,” Somchai told local television.

The young boy immediately stood up and walked into his rescuer’s arms, police said.

Somchai said he keeps the Spider-Man costume and an outfit of Japanese television character Ultraman at the station in order to liven up school fire drills.

Besides being cute and cool, this is a great story. The fireman responded to the unique needs of the kid in question.

Oldstone letter in the Omnibus docket

25 Mar

When I found that the Autism Omnibus Proceeding expert reports were public, the first one that caught my eye was by Andrew Zimmerman. Obviously, it caught Kev’s attention too 🙂

But, I have only a brief time available today, so I will start with this letter by Dr. Michael Oldstone. It is brief enough that I have copied the body in its entirety below.

To summarize, Rick Rollens asked Dr. Oldstone to consider collaborating with Dr. O’Leary and Dr. Wakefield on the Autism/MMR question. It was a good move on Mr. Rollens’ part, as Dr. Odlstone is one of the preeminent researchers in viral pathogenesis. Has been for decades.

Before agreeing to collaborate, Dr. Oldstone wanted to check on the quality of the results coming out of the O’Leary laboratory. Dr. Oldstone sent tissue samples to Dr. O’Leary’s laboratory, some with measles virus, some without. Dr. O’Leary tested them–and got the wrong answer 20% of the time. Dr. Oldstone sent another batch of samples, some duplicates from the first batch. Not only did Dr. O’Leary’s laboratory get 20% wrong again but, in Dr. Oldstone’s words:

Most troublesome, some samples, when tested twice under different code numbers ‘switched’ from positive to negative or from negative to positive. On this basis of inaccuracies of their PCR test, I declined from further working with either Drs. Wakefield or O’Leary.

This goes directly towards the question of the quality of the data coming from Dr. O’Leary’s laboratory. This is a big question. The Hornig study came out last year, an attempt to replicate Dr. Wakefield’s research. In one of the strangest moves I have ever seen by a researcher, Dr. Wakefield claimed that this study actually supported his research by demonstrating that Dr. O’Leary’s lab is capable of making accurate PCR measurements. Dr. Wakefield neglected the obvious point–being accurate today doesn’t mean one was accurate yesterday. He also neglected the suggestion (made by Dr. O’Leary himself at the press conference for the Hornig study) that Dr. Wakefield’s samples could have been contaminated.

Well, here is a good example that Dr. O’Leary’s laboratory was not making accurate measurements. This was iin the “early 2000’s”. Note that the Uhlman paper (Dr. Wakefield’s team’s paper supposedly finding measles virus in gut tissue) came out in 2002–the same time period.

Below is the letter, dated Oct. 12, 2007, from Dr. Oldstone to Dr. Brian Ward.

Dear Dr. Ward:

I recently became aware that my work in the field of viral persistence is being quoted in support of the hypothesis that the measles virus component of the measles-mumps-rubella (MMR) vaccine is supposedly associated with the development of autistic spectrum disorder (ASD).

Measles virus has been a focus of my laboratory for many years so this autismlmeasles link has been of interest to me. Further, I should state up front that I see at present no evidence whatsoever for such a link.

In the early 2000s I was asked by Rick Rollens to consider a collaborative grant between my laboratory and that of Drs. Wakefield and O’Leary. Prior to making a decision, I decided to assess the performance of Dr. O’Leary’s PCR-based assays targeting measles virus. My laboratory generated samples from tissue culture cells infected with MV as well as tissue samples from our transgenic mouse model of MV infection (including gut and brain tissues), which were coded and sent to the O’Leary laboratory. Samples had varying titers of measles virus as well as appropriate negative control and measles virus positive samples. The arrangement was informal in that the samples were only sent to Dr. O’Leary for testing. After receiving Dr. O’Leary’s results, the code was broken and I discovered that approximately 20% of the samples were incorrect as to the
presence or absence of measles virus. I reviewed the results with Dr. O’Leary as well as his protocols for preparing his assay, which I found to be sound and decided that perhaps there may have been some unknown error and a second set of samples should be sent. This second set was again coded anew and contained both new samples and several original samples. The results of the second round were no better with again approximately 20% of the samples misidentified by Dr. O’Leary’s laboratory. Most troublesome, some samples, when tested twice under different code numbers ‘switched’ from positive to negative or from negative to positive. On this basis of inaccuracies of their PCR test, I declined from further working with either Drs. Wakefield or O’Leary.

Sincerely,
Michael B.A. Oldstone, M.D.
Head, Viral-lmmunobiology Laboratory

Omnibus Expert Reports

24 Mar

As noted in Kev’s recent post, the expert reports from the respondent (government side) have been made public.

The above link is a pdf file. The boxes in the pdf file are live links. I.e. click in the boxes and you will get the expert report.

I am very glad they did this. The best autism experts were pulled in to the Omnibus, and it is great to have the chance to refer to what they wrote. Many of the experts didn’t testify, so this is where you and I can see what they had to say.

I’ve read through some. They are good references. They also support very well what the Special Masters stated in their decisions: this wasn’t a close call. The petitioners just didn’t have good evidence, and the evidence against them was very good.

I’ll definitely be blogging a number of these. They are well worth discussing.

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