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.

Andrew Zimmerman Finally Speaks

24 Mar

A year ago I tried to talk to Andrew Zimmerman about the Hannah Poling case and was told:

Dr. Zimmerman…….is not able to publicly discuss this patient. As a participant in this case, the family provided consent for Dr. Zimmerman to share information with the court, but we do not have parental consent to discuss the patient publicly – as we are bound by HIPAA privacy regulations, as in any healthcare setting in the U.S.

And in the year that has followed the Polings have not allowed Zimmerman to publicly comment once. Now I’m beginning to understand why.

Sullivan told me that yesterday the Expert Witness reports for the Respondents were made public and that Zimmermans was eyebrow raising to say the least.

Furthermore, there is no evidence of an association between autism andthe alleged reaction to MMR a nd Hg, and it is more likely than not, that there is a genetic basis for autism in this child.”

“Michelle Cedillo’s developmental regression was likely to have been
preprogrammed before birth to emerge, as it does in Rett syndrome, long after birth.”

“Autism, in most cases, begins before birth, and the maternal
“environment” in the womb is likely to be important in the process.”

“there is no scientific basis for a connection between measles, mumps and rubella (MMR) vaccine or mercury (Hg) intoxication and autism.”

“Autism is primarily a genetically determined disorder.” There is a
hypothetical basis, but very limited evidence, for environmental factors
(such as stress or the drug terbutalinel l) that may act together with
an individual’s genetic susceptibility to increase the risk of autism.
There is strong evidence that the origins of autism begin before birth,
based on genetic and anatomical studies as well as chemical findings at birth in children who go on to develop autism. The usual time
period when autism appears and is diagnosed during the 2nd and 3′” years of life reflects the dynamic nature of the child’s developing brain and the appearance of pre-programmed disordered expression of genes and preexisting cellular abnormalities that result in the child’s regression with loss of language and social skills.”

Recall once more that this is the man – along with Jon Poling himself and along with John Shoffner (who also doesn’t think much of Polings beliefs) who co-authored the only piece of science performed on Hannah Poling.

No wonder the Poling’s were so keen to keep Zimmerman quiet.

Thanks to Sullivan for some of this.

Stop the hate speech: r-word dot org

21 Mar

The Special Olympics have started a media campaign, including a website, to help eliminate the “r-word” (retard) from common speech.

I couldn’t say it better than they do on their website:

Most people don’t think of this word as hate speech, but that’s exactly what it feels like to millions of people with intellectual disabilities, their families and friends. This word is just as cruel and offensive as any other slur.

r-word.org

I am very glad to see the Autistic Self Advocacy Network (ASAN) as one of the supporting organizations for this campaign.

In the last couple of years, there have been a few very prominent uses of the “r-word” in the media. I found it very unfortunate that many in the autism community argued, “our kids aren’t retarded” rather than calling it out as the hate-speech it is.

This campaign appears to be getting a lot of publicity due to a misstep by President Obama on the Tonight Show. From the CNN story:

He told Leno that he bowled 129 in the White House bowling alley and said his bowling skills are “like Special Olympics or something.”

Mr. Obama moved quickly to apologize,

The comment during the taping of the show prompted Obama to pick up the phone on Air Force One and call Special Olympics Chairman Timothy Shriver to preemptively apologize for the remark before it hit television screens. He also reportedly invited Special Olympic athletes to Pennsylvania Avenue to hit the lanes and give him tips or shoot some hoops.

The president “expressed his heartfelt and sincere commitment to work with our athletes and make this country a more accepting place for people with special needs,” Lum, the organization’s president, said.

Thank you, Mr. Obama.

I would really like to find a bigger version of the print-ad used for the r-word campaign.  Here is the small version on the CNN website.  It says it pretty darned well.

Autism, HBOT, and the new study by Rossignol et al.

21 Mar

I recently read the BMC Pediatrics article, “Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial”1. I know this paper is attracting a lot of attention in the media, and it is certainly being ballyhooed about the internet. Hell, I’ve even received e-mail spam about this study! But I’m sorry to say, I don’t really share the excitement. In fact, I see what looks like a pretty significant error in the methodology of this study. It’s one of those types of potential errors that stand out like a strobe light or a siren – it’s really tough for me to pretend it’s not there.

Once again, I’m going to ask readers to set aside, for the moment, anything they may know about the role of hemoglobin in oxygen transport and how the minute increases (probably around 3-4%) in total blood oxygen content afforded by this kind of hyperbaric therapy, or simple O2 therapy for that matter, are probably pretty likely to be insignificant.

Both the paper and ClinicalTrials.gov2 list the Center for Autism Research and Education, Phoenix, Arizona, as a study location. This is a problem, because the stated treatment pressure in the study (1.3ATM) seems highly unlikely to actually be achievable in Phoenix with the equipment that was apparently used for this study.

As described in the section titled, “Interventions”:

“These procedures included covering control switches, inflating and deflating the chambers to simulate pressure changes, and masking the sounds from the chambers.”

The use of inflatable monoplace hyperbaric chambers, is a clear indication that the actual total pressures (and quite likely results of this study) would have been affected by the ambient air pressures at the times and locations of treatment. In fact, the ambient air pressure is the largest component of the stated treatment pressure in this study (ambient pressure + added treatment pressure = total treatment pressure).

Ambient pressure

Local atmospheric pressure is typically reported as sea-level pressure3 for its utility to aviation, and the meaningful interpretation of weather maps, etc., but the actual station pressure is affected by the elevation. The expected ambient atmospheric pressure, corrected for altitude, (or station pressure) in Phoenix, Arizona4 is 28.69 in Hg (where there is a modest elevation of 1161’ AMSL). Wanting to give this paper the benefit of the doubt, and knowing that “high pressure” weather is typical of the Phoenix climate, I looked at 30-day data5 for actual station pressure in Phoenix at a station of slightly lower altitude than the Center for Autism Research and Education. The 30-day mean station pressure is 28.81 in Hg, so I’ll use that one for calculations, as it will yield results more likely to be in the study’s favor.

Added treatment pressure

The actual operating pressure of the inflatable chambers, as stated by the manufacturer, is 4 PSI. 6,7 This pressure is also indicated on the Center for Autism Research and Education’s website:

“The chambers used at care utilize a pressure of 4 psi.”8

Total treatment pressure

The total treatment pressure can be easily calculated with the following conversions:
in Hg * 0.491 = PSI
PSI + PSIG = Total PSI
Total PSI * .068 = ATA

For Phoenix, Arizona, this gives a calculated total treatment pressure of 1.23 ATA.

28.81 * 0.491 = 14.15 PSI
14.15 PSI + 4 PSIG = 18.15 PSI
18.15 PSI * .068 = 1.23 ATA

Damn, that’s a pretty big difference from the paper’s stated 1.3 ATM – representing an addition of only .23 ATM (instead of .30 ATM) above mean sea-level pressure of 1 ATM.

I’ve corresponded with the lead author of this study in the past, and he stated that he observes gauge pressure of 4.15 PSI. Despite the manufacturer specs, the FDA-cleared medical device premarket notification, and the Center for Autism Research and Education’s website (which all indicate operating pressure of 4 PSI), and wanting to give the benefit of the doubt, I’ll use 4.15 PSI for the next calculation, as it will be more likely to yield results in the study’s favor.

28.81 * 0.491 = 14.15 PSI
14.15 PSI + 4.15 PSIG = 18.30 PSI
18.30 PSI * .068 = 1.24 ATA

It could be argued that treatment pressure for the other study locations were properly rounded up to 1.3 ATM (even though the actual pressures were quite likely to be considerably lower), however, even with all the calculations purposely leaned in favor of a higher number for Phoenix, Arizona, the study’s stated treatment pressure, there, should have properly rounded to 1.2 ATA! This suggests an overstatement of the added treatment pressure for the Phoenix location of 50% (.3 ATM is 150% of .2 ATM). Even if given the benefit of the doubt yet again, and an exception to proper rounding were made for solely for the Phoenix location in this study, the study’s likely overstatement in added treatment pressure for Phoenix is still a full 25%. (.3 ATM is 125% of .24 ATM – 25% more added pressure above 1 ATM was claimed in this paper, than was probably delivered).

I think this is a big enough boo-boo, that the editors of BMC Pediatrics should call for detailed errata. In the interest of scientific accuracy, it would seem prudent for BMC Pediatrics to:

1. Clarify for its readership and the scientific community, that the stated pressure of 1.3 ATM in this study is rounded up, and includes the ambient air pressure, or alternatively, state the estimated pressure in terms of ATA.

2. Clarify for its readership and the scientific community, that the stated pressure of 1.3 ATM in this study is an estimated pressure, since no actual measurements of ambient station pressure for the locations, and dates/times of treatments were reported.

3. Note for its readership and the scientific community, that the stated pressure of 1.3 ATM was not likely to be uniformly achievable across all study locations due to the use of inflatable hyperbaric chambers and changes in elevation (and atmospheric pressure) across study locations, potentially confounding the results of this study.

4. Note for its readership and the scientific community, that estimated pressures in the placebo control group are affected by these same issues that affect the treatment group, potentially confounding the results of this study further.

What do you think?

1 BMC Pediatrics 2009, 9:21doi:10.1186/1471-2431-9-21
http://www.biomedcentral.com/1471-2431/9/21/abstract

2 http://clinicaltrials.gov/ct2/show/NCT00335790

3Federal Meteorological Handbook No. 1 – Table 11-2
http://www.nws.noaa.gov/oso/oso1/oso12/fmh1/fmh1ch11.htm

4 LAT/LON 33.5º N 118.08º W

5 http://www.wrh.noaa.gov/mesowest/getobext.php?wfo=psr&sid=KPHX&num=720

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

Click to access K001409.pdf

7 Manufacturer product sheet

Click to access vitaeris-lowres2007-8.pdf

8 http://www.center4autism.org/therapyHBOT.asp

Study: Adults with Autism…

19 Mar

…can live fulfilling lives. Or, so say researchers in Utah, according to a recent news story. (study abstract here)

The news story is basically an echo of one that came out last Fall. Kev blogged it then.

I thought it worth blogging again, though. Not because of the good-outcomes nature (although that is a good thing to hear). But, as one of the researchers put it:

Adults with autism haven’t received the attention from researchers that children have…

It is beyond good to see research on adults with autism. It is vital. Even if you are in the “most people with autism are children” camp, learning from today’s adults just plain makes sense.

The adults studied were part of a joint UCLA/University of Utah study in the 1980’s. In this followup, the researchers interviewed people who had IQ’s > 70 in the 1989 study. As Kev noted in his blog post, these are not people with PDD-NOS or Asperger’s, they met DSM-III criteria for autism.

The authors found about half of the study subjects had “very good” or “good” or “fair” outcomes:

By these measures, the researchers found that 24 percent of the participants had a very good social outcome; 24 percent had a good outcome; 34 percent had a fair outcome; and 17 percent were rated in the poor social outcome category. No one’s social outcome fell into the very poor category.

Some of the details include:

About half of the 41 study participants were employed in full- or part-time competitive jobs. Six were living independently, including three who owned homes. Three were married with children, and one person also was newly engaged to be married. Eleven of the participants have driver licenses and the same number had a higher IQ than when assessed 20 years earlier.

IQ was not the main predictor of good outcomes. Instead, independent living skills were key.

The most important factor in whether study participants had a better living outcome was their degree of independence in daily activities—being able to take care of themselves, hold employment, live on their own or at least semi-independently, and take part in meaningful social relationships, according to Farley. Although IQ significantly influences social outcome, daily independence plays an even greater role in determining how well people with autism function, the researchers said.

To me, this seems to be somewhat circular reasoning: if the people are more independent, they have better outcomes. I need to read the actual study and see how they measure outcomes.

It is worth noting that “can live fulfilling lives” is not the same as “will live fulfilling lives”. A large fraction of the adults had “poor” outcomes. Also, we would all like to see fewer people even with “fair” outcomes.

About half the participants could not live or work independently, and the majority lived with their parents, although many of them had a high level of independence in their daily activities. Social isolation is a serious problem as well—44 percent of the group has never dated. In addition, 60 percent of the study participants, even some of those who had achieved independent living and working, were prone to anxiety and mood disorders and worried about a social stigma attached to autism. The IQ of eight participants declined since they first were evaluated 20 years ago.

One question I would have about the study is whether there is any bias in the selection of the study subjects. Out of 241 subjects in the original 1989 study, only 41 were reported on in this recent study. How they were selected for the followup could make a big difference.

Also, I will add that some will characterize this as “Look, another post saying we don’t need to offer any treatment for people with autism”. All I can say is, those of you saying that either have major reading comprehension problems or you have an agenda.

The big question in my mind is to find out what differentiated those who had good outcomes. One suggestion made by recent news sources–the support system of the Latter Day Saints (Mormon) religion/culture which predominates in Utah. According to one story:

And the LDS Church community may play a role in their success, researchers suggest.

“We wouldn’t be surprised if a lot of what contributed to those folks’ better outcomes is the unique social structures in Utah,” said Megan Farley, research associate at the Utah Autism Research Program and lead author of the study, published online Wednesday in Autism Research journal.

“While kids are still made fun of here and they face stigma … there’s this really strong network of multi generational support that are able to foster these kids’ development,” she said.

My first reaction was to brush this off as self-congratulatory. But, they aren’t saying it is the religion. Instead, it is the social structure.

Perhaps the most intriguing statement in the above news story was given a very short comment:

All but six of the adults in the study were still considered autistic.

Wow. 6 out of 41 no longer have autism diagnoses? I really need to get this paper and see if they have PDD-NOS or AS diagnoses. But, consider a 15% “recovery” rate. Begs a lot of questions. As Kev noted in his blog post, it seems unlikely that any of these individuals received biomedical interventions. For that matter, few if any may have received ABA.

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