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Spanking increases agressive behavior in young children

15 Apr

Spanking. Corporal punishment. Aversives. There is obviously a major controversy about punishment in the autism community (for example, the Judge Rotenberg Center). But what about spanking in general, for the general population? Is it effective in reducing aggression? According to a new paper in the journal Pediatrics, the answer is a clear no. Not only that, but spanking leads to more aggressive behavior.

This is shown in Mothers’ Spanking of 3-Year-Old Children and Subsequent Risk of Children’s Aggressive Behavior, Catherine A. Taylor et al..

Here is the abstract:

Objective The goal was to examine the association between the use of corporal punishment (CP) against 3-year-old children and subsequent aggressive behavior among those children.

Methods Respondents (N = 2461) participated in the Fragile Families and Child Well-being Study (1998–2005), a population-based, birth cohort study of children born in 20 large US cities. Maternal reports of CP, children’s aggressive behaviors at 3 and 5 years of age, and a host of key demographic features and potential confounding factors, including maternal child physical maltreatment, psychological maltreatment, and neglect, intimate partner aggression victimization, stress, depression, substance use, and consideration of abortion, were assessed.

Results Frequent use of CP (ie, mother’s use of spanking more than twice in the previous month) when the child was 3 years of age was associated with increased risk for higher levels of child aggression when the child was 5 years of age (adjusted odds ratio: 1.49 [95% confidence interval: 1.2–1.8]; P < .0001), even with controlling for the child's level of aggression at age 3 and the aforementioned potential confounding factors and key demographic features.

Conclusions Despite American Academy of Pediatrics recommendations to the contrary, most parents in the United States approve of and have used CP as a form of child discipline. The current findings suggest that even minor forms of CP, such as spanking, increase risk for increased child aggressive behavior. Importantly, these findings cannot be attributed to possible confounding effects of a host of other maternal parenting risk factors.

I decided to not go into detail on the paper. The relevant information for this discussion is there in the abstract: children who are spanked at age 3 are more likely to be more aggressive at age 5. Long term, spanking makes things worse. It doesn’t “teach a child a lesson”.

This isn’t an autism paper, but LeftBrainRightBrain is an autism blog and I’ve been wondering how this might apply to young autistics. Are autistic children (or developmentally disabled children in general) more susceptible to the harmful effects of frequent spanking or aversives? I have to admit, I wonder about the effect of electric shocks on older children and young adults at the Judge Rotenberg Center. Whether it actually makes things worse for some of their students in the long run.

Brian Deer discusses Andrew Wakefield’s “autistic enterocolitis” in the BMJ

15 Apr

Before the General Medical Council reached a verdict on Dr. Wakefield, Brian Deer was promising that he was going to report on the data Dr. Wakefield used for his now retracted Lancet paper. We were told that he would give a first time ever view of a journalist allowed to check the facts on a scientific research paper.

After the GMC verdict was handed down, I watched the Sunday Times for such an article. I waited. Well, the wait is over. And it isn’t in the Times. Mr. Deer reports his findings in the British Medical Journal (BMJ).

Although much of the attention on Dr. Wakefield’s work has centered on the possible MMR connection, the topic of a “new syndrome” called “autistic enterocolitis” was proposed in that paper. In Wakefield’s “autistic enterocolitis” under the microscope, Mr. Deer takes a closer look at that claim. He does what is very rarely done: he obtained original data used for the study and obtains expert opinions on that data.

In his introduction, he notes the “new syndrome” and the MMR angles of the Lancet paper. Citing the press release from the Lancet paper:

“Researchers at the Royal Free Hospital School of Medicine may have discovered a new syndrome in children involving a new inflammatory bowel disease and autism,” the institution announced in a press release in February 1998. “Their paper . . . also suggests that in a number of cases the onset of behavioural symptoms was associated with MMR vaccination.”

Mr. Deer notes that before any patients were investigated, Dr. Wakefield was already proposing in a submission to the Legal Aid Board that such a new syndrome exists and it is linked to regression in children.

“In contrast to the IBD cases, which have a prima face [sic] gastrointestinal pathology, children with enteritis/disintegrative disorder form part of a new syndrome,” said Wakefield and the lawyer in a confidential submission for legal aid funding for the project in June 1996, before any of the 12 children in the paper had been investigated. “Nonetheless, the evidence is undeniably in favour of a specific vaccine induced pathology.”

For emphasis:

The evidence was “undeniably in favour of a specific vaccine induced pathology”.

Before children were investigated.

That on its own is huge. And, from what I can tell, not consistent with the image Dr. Wakefield is portraying in the alternative media.

That said, was there evidence of this “new syndrome”?

But when the children were brought in to the Royal Free for ileocolonoscopy, between July 1996 and February 1997, a snag in Wakefield’s project emerged. The hospital’s pathology service repeatedly judged colonic biopsy samples to be unexceptional, and thought bowel disease was a possibility in only one child.

The Royal Free’s own pathology service thought that the biopsy samples were unexceptional.

How can Mr. Deer make such a claim? He obtained data from the children’s records from their investigations at the Royal Free. Unfortunately, the actual samples are no longer available, but the reports are, and Mr. Deer submitted these to experts to review:

The biopsy slides are no longer available, according to one of the paper’s authors, Professor Amar Dhillon, but the GMC obtained all but one of the hospital pathology reports, and for the missing case I obtained the discharge summary. I passed the summary and reports to specialists for their reaction. They concluded that most of the 11 children reported as having non-specific colitis in the Lancet paper had been reported by the Royal Free as having normal pathology.

One expert reviewer stated:

“In the present reports and patients, overall, it is my impression that 8 of the 11 [for whom pathology reports were available] were normal,” Karel Geboes, a professor in the gastrointestinal pathology unit of the Catholic University of Leuven, Belgium, told me.

How does this compare to what was reported in the Lancet?

Eleven of the 12 children were said to have “non-specific colitis”: a clinically significant inflammation of the large bowel. In all 11, it was said to be “chronic,” while in four it was reported as both “acute and chronic.”

In other words, the report in the Lancet is not consistent with how experts interpret the pathology reports.

Mr. Deer further notes:

In fact the [Royal Free’s pathology] service identified findings suggestive of possible inflammatory bowel disease in only one of the 12 children. “The mild patchy generalised increase in inflammatory cells with lymphoid aggregates and follicles is not very specific but could be in keeping with low grade quiescent inflammatory bowel disease,” it reported for child 2. But this inflammation resolved after two months’ enteral feeding with a product now marketed as Modulen. A repeat ileocolonoscopy found no abnormality, and a food intolerance was diagnosed.

Yes, it appears that the pathology service, at Dr. Wakefield’s own hospital, at the time of the investigation, didn’t find evidence of abnormalities reported by Dr. Wakefied’s team.

In the GMC hearing, one of the co-authors on the Lancet paper, Dr. Susan Davies, discussed her concerns about the changes in the findings from normal to abnormal at the time of the investigation.

These changes—from normal to abnormal, or from healthy to diseased—had also raised concern in the mind of at least one of the paper’s authors. In September 2007, Davies, the lead histopathologist for the Wakefield project, was examined at length before the panel. “When you were given a draft of the Lancet paper, did you read it?” she was asked by Sally Smith QC, for the doctors’ regulator.
“Yes,” Davies replied.
“What was your overall view of the terminology used in relation to the histology findings in the Lancet paper, just when you read the paper?”
“I was somewhat concerned with the use of the word colitis.”
“First of all, what did you understand that word to mean?”
“I personally use that terminology, ‘colitis,’ when I see active inflammation, or a pattern of changes which suggest a specific diagnosis, and it was not my impression that the children coming through in the spasmodic way that they had, I [sic] had formulated some distinct pattern warranting that terminology.”

If even a co-author was concerned, and the hospital’s pathology reports don’t support the diagnosis of colitis, the obvious question would be: how did the paper reach it’s conclusions?

The answer appears to be that the results underwent a second review. This second review is discussed in the Lancet paper, but there is no mention of the review changing the interpretation of the data,

Mr. Deer poses an important question:

[H]ow many peer reviewers would have felt comfortable approving the paper if they had known that the hospital pathology service reported biopsy specimens as largely normal, but they were then subjected to an unplanned second look and reinterpreted?

Which we are fortunate enough to have answered. Mr. Deer was able to obtain an answer from one of the peer reviewers:

“I’m surprised the GMC didn’t make more of this,” said David Candy, paediatric gastroenterologist at St Richard’s Hospital, Chichester, who reviewed the paper in 1997. “That’s an example of really naughty doing—to exclude the original pathology findings.”

“Really naughty doing”. Not very clinical but I think it tells the story well.

Is it possible that the hospital’s pathology service missed the condition? Apparently at least one author (Dr. Walker-Smith, a co-defendant with Dr. Wakefield in the GMC hearings) noted this in his GMC testimony:

And how bad was this “colitis,” such that the hospital’s pathology service didn’t spot it as the children came through? Walker-Smith told the GMC panel that he had “concerns” about the service and its ability to detect inflammation.

In his report, Mr. Deer counters with:

Yet inflammatory indices that were not reported in the Lancet paper, including serum C reactive protein concentrations and other blood tests, were almost all within normal ranges for the 12 children.6 And as an alternative explanation for any inflammation that was present, nearly all of the children had constipation with megarectum16 (unreported in the paper), which specialists say can cause cellular changes.

Mr. Deer attempted to speak with Dr. Dillhon, a co-author on the Lancet paper. Dr. Dillhon viewed the slides made from the samples taken from the children, and he graded them with Roman numerals to rank the degree of inflammation. At some point, those Roman numerals were translated into “non-specific colitis”.

So who translated these scores on the grading sheet into findings of “non-specific colitis” in the paper? Dhillon says it wasn’t him. He says he would like to see the slides again, but they are missing from the Royal Free laboratory. “He [Dhillon], Andrew Anthony, and Wakefield all looked at them,” I was told, on Dhillon’s behalf, by a senior member of staff at the Royal Free. “Andy [Wakefield] then synthesised their results into what appeared in the paper.”

But still, according to Mr. Deer, “…how the Roman numerical scores, histopathological gradings for a variety of sites in the colon, became the “colitis” findings might, under such circumstances, be anybody’s guess.”

Mr. Deer posits a possible scenario, based on Dr. Wakefield’s complaint to the press complaints commission:

Wakefield wrote: “When the biopsies were reviewed and scored by experts in bowel pathology—namely, Drs Dhillon and Anthony—these doctors determined that there was mild inflammation in the caecum, ascending colon, and rectum,” he said. “This was correctly reported as non-specific colitis in the Lancet.” In other words, it looks like it was Wakefield who translated the scores.

A companion editorial was published in the BMJ by Prof. Sir Nicholas Wright, warden, of Barts and the London School of Medicine and Dentistry, Queen Mary University of London. He lists in his conflict of interest statement: “He has provided expert opinion in the case of Wakefield v GMC and acted as a character witness for Professor John Walker-Smith.”

His editorial:

Does autistic enterocolitis exist?
Despite the retracted Wakefield study, questions remain

His conclusion:

Is autistic enterocolitis a histopathological entity or even an entity at all? In view of the lack of data and the entrenched position of many of the protagonists and antagonists, any firm conclusion would be inadvisable. The expert review, referenced by Deer, concludes that key areas such as the prevalence and best treatment of gastrointestinal disorders in people with autistic spectrum disorders are incompletely understood, and that evidence based recommendations are not yet available. We should remember, as recent experience in several fields has shown, that although science has its defects, it is a self correcting process. Time is, perhaps, the wisest counsellor of all. In the meantime, this case offers a salutary reminder for researchers and journal editors alike that coauthorship means bearing responsibility for what is written.

First, I would submit that Dr. Wright is not being clear on the subject. It is not whether autistics have a greater prevalence of GI issues, or whether there is a difference in the treatment for autistics. The question is whether there is a specific entity which is unique to autistics: autistic enterocolitis. Further, it is also a primary question whether “autistic enterocolitis” is causal in autism. While one can hide behind the “you can’t prove a negative” shield, the answers at present appear to be no to both questions.

Second, the idea that science is a self correcting process is often times true. In this case, it clearly is not. The science, the Lancet paper, was not corrected through science but through investigative journalism. Without the stories in The Sunday Times, Dr. Wakefield’s “science” would likely still be in the official record of The Lancet. Much more, the Lancet study and the presumed expertise of Dr. Wakefield would have likely been key in litigation in the UK and the US. Without Mr. Deer’s continued scrutiny, the facts behind the research into the Lancet paper, specifically that the pathology reports on those children were not consistent with the findings of the paper, would almost certainly not have come to light.

Returning to Mr. Deer’s article, he concludes:

So what should we make of all this? Now the Lancet paper is retracted, its findings don’t officially exist. And, if Dhillon is right in saying the slides can’t be found, the ultimate proof is missing. All we have are the pathology reports, which independent specialists seem to agree are largely unremarkable. “They wanted this bad,” commented Tom MacDonald, dean of research at Barts and the London School of Medicine and coauthor of Immunology and Diseases of the Gut. “If I was the referee and the routine pathologists reported that 8/11 were within normal limits, or had trivial changes, but this was then revised by other people to 11/12 having non-specific colitis, then I would just tell the editor to reject the paper.”

Clearly the Lancet paper should have been rejected. But this isn’t just a scientific paper that made a bad conclusion. This paper impacted multiple families inside the autism communities to believe that their child’s autism was caused by MMR. This paper led many families in the autism communities to apply poorly researched “therapies” to their disabled children. This paper led many families to stop vaccinating their children, leading to outbreaks of measles in the UK and elsewhere.

It is easy to go through Mr. Deer’s paper in the BMJ point by point in a clinical fashion, noting how the research went awry, showing that “autistic enterocolitis” has what appears to be no founding in science. But how does one express the reaction to so much damage caused by Dr. Wakefield’s investigation?

Of course, a further question I have and I bet I share with Dr. Wakefield’s supporters is this: is Brian Deer finished or is there even more yet to be unearthed in this sad tale of research gone awry?

Blogging about IMFAR

12 Apr

INSAR‘s annual International Meeting For Autism Research (IMFAR) is convening in Philadelphia this May (May 20-22).

Thanks in part to a generous travel grant from the Autism Science Foundation, I’ll have the opportunity to attend – and of course I’ll be blogging about it here at LBRB.

For the most part, I plan to write about research, projects, researchers themselves, or talks that I find interesting and attain sufficient understanding, but I’ll also be sharing a little with LBRB readers, about the overall IMFAR experience upon my return. I’m also looking forward to attending the Autism Science Foundation’s “Science and Sandwiches” where plans for this IMFAR lunchtime edition include presentations “from six ASF-funded pre-doctoral students who will describe their new research projects”.

I’ve always been pleasantly surprised by, and appreciative of scientists in general. I’ve had the opportunity to exchange ideas with many over the last few years while writing articles at both LBRB, and Autism Street, and even had the benefit of informal peer review (for some of the more scientifically involved articles) prior to publishing.

If the opportunity arises to meet and talk with individual researchers, I also hope to write some brief “Meet the Researchers” type pieces for those who might be able to take 10 minutes for a few questions. Hopefully this can bring a certain aspect of personal conversation with some of the scientists who’ll attend this year to readers at LBRB.

As more details about the planned presentations (and even posters) become available, be sure to let me know about any you (dear readers) think look particulary interesting. Simply leave a comment, or drop me a note at:

autism blogger at gmail (remove the spaces, and use the symbol for at).

U.S. Government calls for proposals in autism research

7 Apr

Do you want to know what sort of research the U.S. government is considering funding? Well, here is the announcement This call for grant proposals is based directly on the Interagency Autism Coordinating Committee’s (IACC) Strategic Plan.

Last amongst the list, and likely in terms of funding, is “services”. This is the one are where adults are specifically mentioned.

Here are a few lines pulled out for those who may not want to read the entire call. Emphases are added by me:

Under epidemiology:

Studies of the genetic and environmental epidemiology of autism to determine risk and protective processes in the etiology of autism…

So, yes, environmental causation is being funded. Also under epidemiology:

studies of their developmental course across the life-span

This is good and much needed: an understanding of how autistics develop across the lifespan. This is not, after all, a childhood disorder.

Yes, there is funding for treatments, specifically “Pharmacological/Biological Interventions”. These include the opportunity for the alternative medical community to prove itself:

studies aimed at developing and testing the efficacy and safety of botanical and dietary supplemental CAM agents that specifically target symptom management

Here is a more full version of the announcement:

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage research grant applications to support research designed to elucidate the etiology, epidemiology, diagnosis, treatment, and optimal means of service delivery in relation to autism spectrum disorders (ASD).

In response to the urgent public health significance of Autism Spectrum Disorders (ASD), Congress passed the Combating Autism Act (CAA) of 2006. Through this Act, Congress intends to accelerate the pace, and improve coordination of scientific discovery in ASD research. The Strategic Plan for ASD Research, a requirement of the CAA, was developed with the input of the scientific community, as well as advocates and advocacy organizations, including parents, providers, and individuals with ASD. The plan consists of short and long term research objectives across a range of topics, including those relevant to the heterogeneity of ASD. This FOA is intended to support the broad research goals of the Strategic Plan for ASD Research. (http://iacc.hhs.gov/reports/2009/iacc-strategic-plan-for-autism-spectrum-disorder-research-jan26.shtml),

Research Objectives

Autism Spectrum Disorders share a cluster of impairments in reciprocal social interaction, communication, and the presence of stereotyped behavior, interests, or activities. These complex disorders are usually of lifelong duration and affect multiple aspects of development, learning, and adaptation at home, in school, and in the community, thus representing a pressing public health need. The etiologies of these disorders are not yet understood, but may include a combination of genetic, metabolic, immunologic, or infectious or other environmental influences.

Clinical research involving these disorders requires well-integrated, multi-disciplinary, methodologically-rigorous scientific approaches and access to a sufficient number of well-characterized patients with these disorders. Basic research into the pathophysiology of autism and autism spectrum disorders, including research on brain mechanisms and genetics, is of special interest. Also of high priority are clinical and applied investigations that may lead to the development of diagnostic research instruments, treatments, and interventions, including complementary and alternative medicine [CAM] strategies. Specific areas of interest thus include epidemiology, early identification and diagnosis, genetic studies, brain mechanisms, communication skills, cognitive neuroscience, psychosocial (behavioral) interventions, pharmacological and other biological interventions, and support and rehabilitative services across the life-span, including adulthood and the transition to adulthood.

Areas of interest include, but are not limited to, the following:

Epidemiology: Studies of the genetic and environmental epidemiology of autism to determine risk and protective processes in the etiology of autism, including environmental exposures during pregnancy and early childhood; longitudinal studies of high-risk populations; epidemiologic research on interactive genetic and environmental factors or processes that increase or decrease risk for autism; research on the expression of the full range of autism spectrum disorders; studies of their developmental course across the life-span; studies that characterize the range of expression within families; and research on co-occurring features, especially research that characterizes and quantifies risk and protective processes associated with co-occurrence. Also of interest are clinical epidemiologic studies of autism spectrum disorders in clinical settings, including studies of clinical decision-making in personal-encounter care for individuals and families.

Screening, Early Identification, and Diagnosis: Key diagnostic and phenotypic features associated with various stages of development; development of new screening tools for use in a variety of settings; assessment of comorbid features including hyperactivity, attentional or executive dysfunctions, and epilepsy; the creation of new measures to be used in longitudinal studies, and measures that further differentiate the subtypes of autism spectrum disorders; and, developmental factors relevant to reliable and valid diagnosis.

Genetic Studies: Family-based or population-based genetic analyses that aim to 1) Identify specific susceptibility genes using candidate gene/region based approaches, whole exome as well as whole genome sequence approaches; 2) Investigate epigenetic mechanisms and long range control of gene expression; 3) Conduct high-resolution mapping and positional cloning studies; 4) Detect locus heterogeneity; and 5) Analyze the interaction of autism susceptibility genes with environmental exposures and/or genes responsive to environmental insult. An area of particular interest is the effect of genetic factors on therapeutic drug response in individuals with ASD (see Pharmacogenomic Studies, below).

Brain Mechanisms: Studies of brain mechanisms underlying the development, regulation, and modulation of behaviors characterizing autism and autism spectrum disorders, particularly those mechanisms involving communication and social interaction; studies of brain mechanisms and biological factors underlying autistic regression, or the loss of previously acquired skills; studies of brain mechanisms involved in the development of abnormal electroencephalograms and epilepsy and studies to clarify the subtypes of seizures and seizure disorders in autism; studies to define the neurobiological basis of neurological abnormalities and neuropsychiatric symptoms and the exacerbation of these symptoms, including the role of neuroimmune/autoimmune factors and mitochondrial dysfunction; studies that seek to define basic processing deficits using neuropsychological and cognitive neuroscience techniques; studies using animal models to examine brain dysfunction related to autism and autism spectrum disorders, based on either genetic or environmental factors or their interaction; studies using novel reagents and tools to identify molecular, cellular, or developmental mechanisms distinguishing autism spectrum and control subjects.

Shared Neurobiology of Autism with Fragile X, Rett Syndrome, and Related Disorders: Studies of developmental and functional processes, pathways, and brain mechanisms that will lead to an understanding of shared etiology or pathophysiology among these disorders. Analysis of autism-related neurobiological and behavioral phenotypes in related “single gene” disorders. Of particular interest are projects that focus on basic research and/or preclinical testing in model systems to develop and assess the safety and biological activity of novel therapeutic compounds that could be used to treat autism and related disorders. There is also significant interest in analyses that would identify useful and specific clinical endpoints that would register measurable improvements in response to treatment interventions in clinical populations as well as studies that would facilitate future development of clinical trials in these populations.

Cognitive Science: Developmental studies of relevant behaviors during infancy including attention to social and nonsocial stimuli, affective behavior, gaze, vocalization, imitation, initiative, reciprocity, attachment, play, compliance, and self-recognition and their emergence in children with autism and autistic spectrum disorders; research on the delays and deviations in social behavior and cognition during preschool and middle school, including empathy, receptive social cognitive deficits (i.e., difficulties understanding others), and expressive difficulties; studies leading to more sophisticated tests of higher cognitive functioning, especially in social, communicative, reasoning, and problem-solving areas, as well as tests of basic attentional, emotional and cognitive deficits that may underlie these deficits or their precursors; studies of theory of mind, of unconventional verbal behaviors, and of the sensory-motor factors involved in relevant social cognition; and the development, validation, and refinement of interventions designed to address deficits in complex social and cognitive abilities or their developmental precursors; interventions designed to lessen or remediate cognitive deficits.

Communication Skills: Longitudinal, developmental studies of behaviors that are precursors to later communication and their emergence in children with autism and autistic spectrum disorders; sensory, motor, and social-cognitive impairments that impact interaction and communication; predictors of loss of or regression in expressive language abilities; interventions designed to remediate communication and related deficits across the life-span.

Pharmacological/Biological Interventions: In addition to pharmacological agents that specifically target the core features of autism and autism spectrum disorders: studies of the efficacy and safety of pharmacological and combined treatments for the most common and impairing psychopathology associated with autism (e.g., hyperactivity, impulsivity, aggression, self-injury); studies that relate characteristics of individuals (or diagnostic subtypes) to therapeutic response and treatment outcomes (also see Pharmacogenomic Studies, below); new approaches to treatment that build on advances in neuroscience, genetics, immunology, and other neurobiologic fields; identification and validation of novel treatment targets and molecular screening approaches or biomarkers that assess effects on key biological, neurodevelopmental and/or behavioral endpoints disrupted in ASD; focused interventions that test specific theories or hypotheses regarding possible neuropathogenesis; studies that address the benefits of combined drug and cognitive, behavioral, or psychosocial interventions; studies aimed at developing and testing the efficacy and safety of botanical and dietary supplemental CAM agents that specifically target symptom management; development of innovative methodologies and outcome measures.

Pharmacogenomic Studies: Analysis of SNP and DNA sequence data that 1) Predict therapeutic response or adverse reactions to drugs; 2) correlate drug response profiles with intermediate phenotypes (e.g., brain imaging, neurophysiology, learning and memory, sustained attention); 3) identify biomarkers to resolve clinical heterogeneity and heterogeneity of therapeutic drug response; 4) apply high-throughput approaches to screen for drug candidates metabolized by or inhibitors of polymorphic drug-metabolizing enzymes, e.g., CYP2D6; 5) studies of genetically determined functional changes in nuclear and cell surface receptors to explain the ineffectiveness of therapeutic agents and adverse or paradoxical drug responses; 6) studies of allelic variation occurring in individual transporter genes that are associated with a functional consequence.

Psychosocial Interventions: Studies to develop new treatments (e.g., behavioral, cognitive-behavioral, mind/body and manipulative therapies) and that validate, refine, and compare approaches to the treatment of persons with autism and autism spectrum disorders and their families, as well as studies that analyze and define the critical features of effective intervention; studies that relate characteristics of individuals (or diagnostic subtypes) to treatment outcomes; research on relevant contextual factors including physical and community environments, parent-child and sibling-child relationship factors, and peer-child interactions; studies addressing generalization or the transfer of learning from one setting to another; studies that develop and test interventions for infants and toddlers who are at-risk for autism spectrum disorders; studies that develop and test interventions to outcome in school and community settings throughout the lifespan; development of innovative methodologies and outcome measures.

Services Research: Research on the organization, delivery, coordination, and financing of services for persons with autism spectrum disorders, and their families, within or across service settings; studies aimed at better identifying and addressing changes in service and rehabilitative needs across the life-span, including during transitions from childhood to adolescence, and adolescence to adulthood; interventions to improve the quality and outcomes of treatment and rehabilitation services; studies to develop improved measures of adaptive capabilities for children, adolescents, and adults with autism spectrum disorders; studies of ways to coordinate or integrate services across settings including specialty mental health, general health, and other settings such as educational, vocational, and housing services, in order to maximize receipt of appropriate services; and research on the economic factors effecting the delivery of needed services and treatments including cost-benefit, cost-effectiveness, and cost utility analyses of service interventions.

Listen to parents…except when they say things you don’t want to hear

25 Mar

How many times do we hear, “Listen to the parents” on medical issues involving their autistic kids? Usually this comes from alternative medical groups who don’t have the science to back up the safety and efficacy of their therapies. What happens when a parent disagrees with these groups?

In Lawsuit against alternative medical practitioners Usman and Rossignal we discussed a father who has brought suit against prominent Defeat Autism Now (DAN) doctors Usman and Rossignol, and the laboratory Doctor’s Data.

Orac, at Respectful Insolence, has discussed this case as Suing DAN! practitioners for malpractice: It’s about time, where he uploaded the actual complaint.

In that complaint the father is alleging many things. High amongst them is the question of whether the “challenge” chelation tests are valid, These were used on his child and supposedly showed heavy metal poisoning. In a challenge chelation test, a chelator drug is given to a child before a urine test is taken. Chelators are designed to draw metals out of the body and allow them to be excreted through the urine (and other ways). There are no standardized references for metal contents in challenge testing. The American College of Medical Toxicology has made a very clear statement about challenge chelation testing. Here is their conclusion:

It is, therefore, the position of the American College of Medical Toxicology that post-challenge urinary metal testing has not been scientifically validated, has no demonstrated benefit, and may be harmful when applied in the assessment and treatment of patients in whom there is concern for metal poisoning.

Recall, challenge testing is noted in the lawsuit. From the section of claims against the Doctor’s Data (who are also defendents in the lawsuit):

The non-standardized method of testing that Defendant utilized on or about April 22, 2004, January 27, 2006, January 13, 2007, February 26, 2007, May 26, 2007, August 6, 2007, October 30, 2007, November 13, 2007, January 12, 2008, January 26, 2008, April 26, 2008, October 29, 2008, and March 27, 2009, wherein specimens were collected after the administration of a provoking agent and compared to unprovoked or unchallenged specimens was an improper method of determining whether A.J. had a potentially toxic level of heavy metals in his system

So, challenge chelation testing isn’t scientifically validated, has no benefit, but was used to justify certain therapies on this child. How did the Autism Research Institute respond to this? They blame the parent’s marital situation.

No, really, I’m not making this up. Rather than accept the complaints on their face and give this autism parent respect, they dismiss his multiple complaints as being…well, you read it:

Recent articles by ABC News and the Chicago Tribune on M.D.s who subscribe to the Defeat Autism Now! approach to treatment indicate the spread of misinformation and misunderstanding in recent months. The complaints about Drs. Usman and Rossignol resulted from a custody case– a painful situation for any family, one that can lead to accusations that must be sorted out in a court of law—not the media

Yes, it isn’t because the father is really annoyed that he was told challenge chelation testing is valid, or that his family spent lots of money on testing and on chelation. It couldn’t be that the father has not seen benefit from these therapies. It isn’t any of that. It is a custody battle issue. For the record, the defendants in the case do not include his wife.

ARI defends their approach in rather vague terms:

The Defeat Autism Now! approach to autism invites the medical community to be more responsive, inquisitive, and knowledgeable about treating these disorders.

The approach is not in itself a source of controversy, since many treatment interventions are commonly prescribed by traditional health professionals.

My view differs from the ARI statement. It would seem to this observer that the approach is the source of controversy. From their own website:

The best diagnostic test for toxic metal overload is the chelation challenge test. The chelation drug is administered, followed by a timed urine test to help assess the body’s burden of toxic elements.

This is in direct contradiction to the statement from the American College of Toxicologists. The ARI approach (including challenge testing) is a key point of the lawsuit. I am not able to reconcile this with the idea that the “approach itself a source of controversy”.

The great problem is rather that chronic, unaddressed illness plagues many, if not most, of the children and adults on the autism spectrum. These conditions, thoroughly documented in the scientific literature, often involve the gastrointestinal system and/or the immune system, but the medical establishment has been professionally insensible to what is a desperate situation in the expanding autism population.

Odd. If anyone outside of the alternative medical community ever makes a statement that the is driven by “desperation”, they are sure to get jumped on.

The focus of the Defeat Autism Now! approach is twofold: to provide patients with allergen-free nutritional support, to uphold and to repair the immune system as needed, and, if appropriate, to reduce the body burden of environmental toxins; to provide clinicians in-depth medical and scientific information, with Continuing Medical Education credits.

There is the mention of what is a main crux of the lawsuit, “body burden of environmental toxins”. That’s it. No mention of challenge testing. They mention that the approach includes reducing “the body burden of environmental toxins”, but doesn’t address the key question: when is this approach “appropriate”. How is that decided? The challenge testing approach has not, to my knowledge, ever been defended in court. This case is

The ARI press release doesn’t discuss the real questions here. Brushing this off as a custody issue is not doing anyone any good and is rather insulting to the parent bringing this suit forward and his child.

Clinical trial on Clinical and Immunological Investigations of Subtypes of Autism

24 Mar

The National Institutes of Health (NIH) have recently updated their webpage of featured clinical trials for autism. Many of the clinical trial recently discussed here at LeftBrainRightBrain are on that list. One that is on the featured list that I caught my eye is Clinical and Immunological Investigations of Subtypes of Autism. It is an old trial (started in 2006), but I thought it worth bringing up again.

The description is quoted below:

The purpose of this study is to learn more about autism and its subtypes. Autism is a developmental disorder in which children have problems with communication and social skills and display restricted interests and repetitive behaviors.

This study has several goals. One aim is to look at types of autism that are known, such as the regressive subtype, (where skills are lost). We will explore whether there is a unique change in immune functioning related to this subtype. Another aim is to serve as one of the sites that will pilot a larger natural history study, entitled Autism Phenome Project. The goal is to further understand autism by identifying other subtypes.

We will look at several types of medical issues that may be related to autism, including immunologic problems. Children will be followed over the course of several years. We aim to capture medical problems that may be related to autism as they develop, and study outcomes in areas such as behavior and language, in order to explore known and new subtypes of autism.

Normally developing children (aged 1) with autism (age 1, and developmental delays other than autism (age 1), may be eligible for this study.

Depending on each child’s study group and age, participants may undergo the following tests and procedures:

Baseline Visit

* Medical and developmental history, physical examination, psychological, cognitive and medical tests to assess symptoms of autism or other developmental disorders, photographs of the child’s face, collection of hair, urine and baby teeth samples. If available, hair samples from the baby’s first haircut and from the biological mother’s hair are also collected.
* Overnight electroencephalogram (EEG): A special cap with electrodes is placed on the child’s head to measure brain waves (brain electrical activity) while the child sleeps in the hospital overnight. Healthy volunteers do not undergo this procedure.
* Magnetic resonance imaging (MRI) scan: The child stays in the scanner, lying still for 10 to 15 minutes at a time. Since it may be difficult for the child to lie still, the test may be scheduled for a time when the child is likely to be sleepy, or the child may be sedated.
* Lumbar puncture (for children in the autism). This test and the MRI may be done under sedation.

Follow-Up Visits

Follow-up visits are scheduled at different intervals, depending on study group, age and aspect of the study the child is enrolled in. The visits include a short interview session with the child’s caregiver and assessment of the child’s development and behavior. Some of the assessment measures used during the baseline examination are repeated, including symptoms ratings, behavioral tests and a blood test. For some children, the final visit will include repeats of the medical procedures.

The section that jumps out to my eye: We will explore whether there is a unique change in immune functioning related to this subtype. Another aim is to serve as one of the sites that will pilot a larger natural history study, entitled Autism Phenome Project. The goal is to further understand autism by identifying other subtypes.

Yes, the NIH is looking at whether regression and immune functioning might be linked. As noted above, this study has been ongoing for some time: the trial was first listed in 2006. But, hey, I figure if I forgot about this one and found it interesting, others might be interested in this as well.

Clinical trial of Donepezil for improving REM sleep in autistic children

23 Mar

A recent lecture I heard discussed how as many as 25% of autistic children get little or no REM (rapid eye movement) sleep. REM sleep is an important sleep phase and it is thought this could contribute to cognition and behavior problems in these children.

Anecdotally (and probably confirmed by studies is my guess) many autistic children have sleep problems. Children are reported to sleep fewer hours, have problems getting to sleep and wake up in the middle of the night. This new result, to me at least, is the first I’ve heard of reduction or lack in REM sleep.

In response to this finding, a clinical trial is underway to study the use of Donepezil (Aricept) with autistic children.

The clinical trial description is:

Detailed Description:

Autism spectrum disorders are defined by aberrant development of communication and socialization in the presence of restrictive and/or repetitive behaviors. Recent epidemiologic studies have documented an increase in the number of children identified with autism spectrum disorder over the past decade and according to some, the current numbers indicate a prevalence of 1 per 150 (CDC, MMWR 2007, Feb 9th release). Despite the pressing need to identify causal factors, etiology remains elusive. Furthermore, the heterogeneity of presentation complicates attempts to locate autism’s home in the brain.

Polysomnography is a reliable non-invasive tool that can be used to study the basic pathophysiological mechanisms of autism and other developmental and neuropsychiatric disabilities. Our preliminary data in young children with autism supports a growing body of literature demonstrating that sleep architecture is abnormal in this disorder. Previous studies in children with autism have identified various abnormalities in REM sleep including the following: immature organization, decreased quantity, abnormal twitches, undifferentiated sleep and REM sleep behavior disorder characterized by the absence of the muscle atonia that is normal in REM sleep and resulting in an acting out of dreams phenomenon (Tanguay et al ,.1976, Elia et al., 2000, Diomedi et al. 1999, and Thirumalai et al., 2002).

Our cohort spent an abnormally short time in the REM sleep stage of sleep compared to total sleep time (hereafter referred to as SPT REM% for REM sleep as a percent of sleep period time), and had a prolonged latency to REM sleep. The function of REM sleep and its relationship to cognition and overall neurological health is unknown and a subject of ongoing research. We know from animal studies that REM sleep increases after intensive learning sessions. These laboratory findings formed the basis for the hypothesis that this sleep stage is important for cognitive processes and that REM sleep may be useful as an indicator of brain plasticity. Current studies continue to add support for this idea. REM sleep has most recently been implicated in the process of human memory consolidation and several studies suggest that it is crucial to normal cognitive function and in the processing of emotion in memory systems. Acetylcholine (Ach) is one of the major neurotransmitters necessary for normal sleep transitions and abnormalities in Ach have been implicated in REM deficient sleep in other populations, most notably Alzheimer’s disease.

This proposal is for a 6 to 20 week, single arm, open-label study to evaluate the ability of donepezil hydrochloride to enhance REM sleep in children with autism spectrum disorder found to have a low SPT REM% (defined as below 2 standard deviations of observed normative data for age). All patients will come through the screening protocol 06-M-0065. Those who meet a research diagnosis of autism spectrum disorder and are ages 2 to 11 (through the tenth year) will be evaluated for inclusion/exclusion criteria for the study.

The primary outcome measure of this protocol is to increase the SPT REM% in children with autism such that their REM/non-REM ratios begin to approach normative values. Donepezil enhanced REM sleep has been achieved in young healthy adults, in elderly, healthy adults and in elderly, demented adults with Alzeheimer’s disease. Furthermore, the studies in Alzheimer disease by Mizuno et al showed a positive correlation between improved cognition and increased SPT REM %. If REM sleep is necessary for normal cognition, and its deficiency or absence can be remedied by pharmacologic intervention, then it may follow that improvement of REM sleep correlates with improved short and long term cognition in children with autism. Donepezil enhanced REM sleep has not been documented in children. Polysomnography provides a non-invasive tool to assess the effects of enhancing cholinergic tone on the abnormal sleep architecture we have documented in our pediatric, autistic population.

My guess is that some are thinking, “why look at this drug when many already use melatonin to help autistic children sleep”. After all, Aricept is an Alzheimer’s drug, with little study in children.

OK, I admit I did. So I did a quick search and found that melatonin has not been found to increase REM sleep.

Aside from my reservations about giving an Alzheimer’s drug to 2 year olds, this is the type of clinical trial I like to see. A clear question is presented that is supported by data. A clear outcome (increased REM sleep) is measurable. Secondary outcomes, improved cognition and behavior, are also measurable and defined.

Trine Tsouderos and Patricia Callahan honored by the Association of Health Care Journalists for autism series

23 Mar

The Chicago Tribune has run a series of articles lately on alternative medicine and autism. The stories include OSR#1: Industrial chemical or autism treatment? (about a chelation chemical invented for mining operations, now labeled as a supplement and sold for “oxidative stress relief”), the self explanatory titled Autism treatment: Science hijacked to support alternative therapies, Autism’s risky experiments Some doctors claim they can successfully treat children, but the alternative therapies lack scientific proof and Autism treatment: Success stories more persuasive to some than hard data One dad, a doctor, says he was “fooled”

This is part of a series that won the Chicago Tribune one of two awards. Writers Patricia Callahan and Trine Tsuderos were honored.

“This powerful series combines first rate medical writing and rigorous investigative reporting to expose doctors who perform what the authors rightly call “uncontrolled experiments on vulnerable children” with autism,” commented the judges. “Writing with the authority that comes from total command of the material, Tsouderos and Callahan bring new clarity to a notoriously murky subject-autism treatments. They document a horrifying brand of bad science perpetrated by bad doctors on desperate families, but they do it without a hint of hyperbole or sensationalism. Their straightforward, professional tone lets the facts tell the story. The result is an important-and devastating-piece.”

With a tip of the hat to Autism News Beat for his story, Tribune investigation takes first place

addendum:

here is the text of the announcement about the Tribune team:

Chicago Tribune reporters examine Lupron – a testosterone inhibitor used to treat precocious puberty and to chemically castrate sex offenders – and its reputed ability to be a “miracle medicine” for a disease with few mainstream medical answers: autism. In looking into Lupron, the Tribune found a world of alternative treatments for autism with fervent supporters who made big claims they said were backed by science. But when reporters evaluated the treatments, painstakingly analyzing each claim, each paper, each therapy through a lengthy dialogue with scores of medical experts, parents and doctors, they found the therapies were risky and unproven and the science backing them was junk. The Tribune provided readers and parents with hard evidence and some difficult truths, concluding that thousands of children with autism are being subjected to mass uncontrolled experimentation every day.

Judges comments: This powerful series combines first rate medical writing and rigorous investigative reporting to expose doctors who perform what the authors rightly call “uncontrolled experiments on vulnerable children” with autism. Writing with the authority that comes from total command of the material, Tsouderos and Callahan bring new clarity to a notoriously murky subject-autism treatments. They document a horrifying brand of bad science perpetrated by bad doctors on desperate families, but they do it without a hint of hyperbole or sensationalism. Their straightforward, professional tone lets the facts tell the story. The result is an important-and devastating-piece.

For their piece Dubious Medicine

Does The NIH Want To Study Jenny McCarthy’s Son?

22 Mar

Why would the National Institutes Of Health want to study Jenny McCarthy’s son?

Similarly, there are a large number of anecdotal reports of children with autism who, following intensive biomedical intervention (e.g., gluten/casein free diets, vitamin supplements, chelation), are indistinguishable from their typically developing peers.

Jenny McCarthy seems to have pretty much claimed she cured her son’s autism.

Yeah, I know, she’s apparently claimed a lot of stupid things though:

You know, I could in two months turn Evan completely autistic again. I could do it completely through diet. And maybe getting some vaccine boosters.

I really can’t keep up with Jenny McCarthy’s anti-vaccination and autism nonsense.

If you’re one of those types who’s attracted to McCarthy’s silliness like many are to a car accident, but are smart enough to just keep driving and later try to catch a thumbnail report of what much of the nonsense seems to be about, I recommend reading Kev’s recent piece in response to an article of hers in the Huffington Post.

An Open Letter To Jenny McCarthy

In that Huffington Post article, she wrote the following:

Parents of recovered children, and I’ve met hundreds, all share the same experience of doubters and deniers telling us our child must have never even had autism or that the recovery was simply nature’s course. We all know better, and frankly we’re too busy helping other parents to really care.

Uh huh.

And remember when Jenny McCarthy wrote this a couple of years ago at a CNN blog?

Evan is now 5 years old and what might surprise a lot of you is that we’ve never been contacted by a single member of the CDC, the American Academy of Pediatrics, or any other health authority to evaluate and understand how Evan recovered from autism. When Evan meets doctors and neurologists, to this day they tell us he was misdiagnosed — that he never had autism to begin with. It’s as if they are wired to believe that children can’t recover from autism.

So where’s the cavalry? Where are all the doctors beating down our door to take a closer look at Evan? We think we know why they haven’t arrived. Most of the parents we’ve met who have recovered their child from autism as we did (and we have met many) blame vaccines for their child’s autism.

Source (and emphasis mine)

Autism research was being funded and conducted by U.S. “health authorities” long before Jenny McCarthy entered and re-entered the public eye (rebranded from IndigoMoms.com to Generation Rescue back sometime between 2006 and 2008), of course. But I suppose it’s quite possible they weren’t interested in stories like Jenny’s. That’s apparently a thing of the past (and so should be McCarthy’s claim that they aren’t interested).

While it might not meet McCarthy’s apparent expectation of a personal contact, indeed the NIH is interested in the subject.

Identification of Characteristics Associated With Symptom Remission in Autism

Additional detail here.

This study has apparently been listed since June, and it’s still recruiting!

LBRB blogger, Sullivan, noted this not too long ago:

NIH to study recovered autistics

He had an interesting observation too:

This is a study that should be done, in my opinion. I will note that this study has supposedly been one of the key pieces being sought by multiple parent groups. I will further note that I have not seen any of them mention this study. Quite the opposite, in fact. I see comments occasionally on blogs about how their frustration that such a study is not being performed. Perhaps I missed it, but I am curious why their leadership doesn’t make a big deal out of this.

To repeat, a component of this study (which is also looking at other possible reasons for remission) is looking for Jenny McCarthy:

Similarly, there are a large number of anecdotal reports of children with autism who, following intensive biomedical intervention (e.g., gluten/casein free diets, vitamin supplements, chelation), are indistinguishable from their typically developing peers.

The Sponsor and Researcher for this study? The NIH.
(Note to Jenny: that’s a “Health Authority: United States: Federal Government”)

They’re looking for Jenny. They want to hear her/Evan’s story (they’ll want substantiating detail too, but that won’t be a problem).

I wonder how many of the “Rescue Angels” or other AoA followers have signed up to participate? Did Jenny McCarthy get the word out to her people? I’m sure she did, right? Like Sullivan, did I miss it too? I could have.

If you don’t think she might have, and if you know Jenny McCarthy (cause lord knows, I don’t), please make sure she gets this info:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Shocking news from Danish autism epidemiolgists!

18 Mar

Danish epidemiolgists have looked at criminal behavior in autistics, and the results are nothing short of startling:

In their paper, Pervasive developmental disorders and criminal behaviour: A case control study, authors S.E. Mouridsen, B. Rich, T. Isager, and N.J. Nedergaard, show:

The prevalence and pattern of criminal behaviour in a population of 313 former child psychiatric in-patients with pervasive developmental disorders were studied. The patients were divided into three subgroups and compared with 933 matched controls from the general population. Age at follow-up was between 25 years and 59 years. An account of convictions in the nationwide Danish Register of Criminality was used as a measure of criminal behaviour. Among 113 cases with childhood autism,.9% had been convicted. In atypical autism (n = 86) and Asperger’s syndrome (n = 114) the percentages were 8.1% and 18.4%, respectively. The corresponding rate of convictions in the comparison groups was 18.9%, 14.7%, and 19.6% respectively. Particular attention is given to arson in Asperger’s syndrome (p =.0009). © 2008 Sage Publications.

Yes, autsitics are as much as 20 times less likely to be convicted of crimes as their “typical” counterparts (0.9% compared to 18.9%).

I ran across this abstract and, given the current hype over Danish epidemiologists I couldn’t resist presenting it in this sensational mode. Besides, the title may draw some readers from the contingent bent on portraying child autistics as a looming threat to the well being of society.

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