Wednesday, December 26, 2007

My 2008 posts

I am sorry that I haven't been posting for 2 weeks. Here are a few posts that I am thinking of writing about.

- the best research published in 2007.

- my predictions for 2008.

- that small defects can lead to big effects.

- Barry Guitar's book that I am currently reading and the things I disagree with, especially on environment and temperament.

- follow-up on the Zyprexa case study.

- any new research published.

- more focus on the importance on secondary symptoms

- the relevance of the Valsava mechanism

- looking into whether I can reycle some old but relevant posts, because readers rarely read the older posts.

- more on genetics and whether they say something about environmental influences.

- my suspicion on temperament being important in childhood stuttering.

- watching out that the Lidcombe people don't oversell their approach with flawed studies.

- computing the probability that a child who just started stuttering has a younger sibling born at the same time.

- the study that will compare between Lidcombe and demand and capacities therapy approach.

Any other suggestions?

Wednesday, December 19, 2007

A speech and language research blog

I just found this blog on speech and language research, but they are definitely slower in breaking the news than TheStutteringBrain though they are obviously more generalist. See here.

Tuesday, December 18, 2007

The history of stuttering

It is just amazing how creative people are in drawing wrong conclusions, from wikipedia:
For centuries stuttering has featured prominently in society at large. Because of the unusual-sounding speech that is produced, as well as the behaviors and attitudes that accompany a stutter, stuttering has been a subject of scientific interest, curiosity, discrimination, and ridicule. Stuttering was, and essentially still is, a riddle with a long history of interest and speculation into its causes and cures. Stutterers can be traced back centuries to the likes of Demosthenes, who tried to control his disfluency by speaking with pebbles in his mouth. The Talmud interprets Bible passages to indicate Moses was also a stutterer, and that placing a burning coal in his mouth had caused him to be "slow and hesitant of speech" (Exodus 4, v.10)
Galen's humoral theories remained influential in Europe into the Middle Ages and beyond. In this theory, stuttering was attributed to imbalances of the four bodily humors: yellow bile, blood, black bile, and phlegm. Hieronymus Mercurialis, writing in the sixteenth century, proposed methods to redress the imbalance including changes in diet, reduced lovemaking (in men only), and purging. Believing that fear aggravated stuttering, he suggested techniques to overcome this. Humoral manipulation continued to be a dominant treatment for stuttering until the eighteenth century. Partly due to a perceived lack of intelligence because of his stutter, the man who became the Roman Emperor Claudius was initially shunned from the public eye and excluded from public office.
In eighteenth and nineteeth century Europe, surgical interventions for stuttering were recommended, including cutting the tongue with scissors, removing a triangular wedge from the posterior tongue, cutting nerves, and neck and lip muscles. Others recommended shortening the uvula or removing the tonsils. All were abandoned due to the high danger of bleeding to death and their failure to stop stuttering. Less drastically, Jean Marc Gaspard Itard placed a small forked golden plate under the tongue in order to support "weak" muscles.
Italian pathologist Giovanni Morgagni attributed stuttering to deviations in the hyoid bone, a conclusion he came to via autopsy. Blessed Notker of St. Gall (ca. 840–912), called Balbulus (“The Stutterer”) and described by his biographer as being "delicate of body but not of mind, stuttering of tongue but not of intellect, pushing boldly forward in things Divine," was invoked against stammering. Other famous Englishmen who stammered were King George VI and Prime Minister Winston Churchill, who led the UK through World War II. Although George VI went through years of speech therapy for his stammer, Churchill thought that his own very mild stutter added an interesting element to his voice: "Sometimes a slight and not unpleasing stammer or impediment has been of some assistance in securing the attention of the audience…"
For centuries "cures" such as consistently drinking water from a snail shell for the rest of one's life, "hitting a stutterer in the face when the weather is cloudy", strengthening the tongue as a muscle, and various herbal remedies were used. Similarly, in the past people have subscribed to theories about the causes of stuttering which today are considered odd. Proposed causes of stuttering have included tickling an infant too much, eating improperly during breastfeeding, allowing an infant to look in the mirror, cutting a child's hair before the child spoke his or her first words, having too small a tongue, or the "work of the devil."

Trying out medication: Week 10

Here is the week 10 update from one reader who is trying out Zyprexa (Olanzapine):
It's been 10 weeks since I started on the Zyprexa and so far I am a fan. I had the blood tests at week 6 and there were no elevated levels, so that was a relief. I increased from 5mg to 10mg at week 6 and the sedation effects kicked in but are now waning again, so thats a relief. I have gained around 10 pounds in weight, however I have been less active over the last 3-4 weeks, so I am sure that if I had been more commited to an exercise plan, the weight gain would have been less (very busy at work)

With regards to the speech - most if not all of the secondaries have gone, no more twiches and facial contortions which is a relief. I find that my anxiety about speaking situations has reduced and as a result I dont worry about rearranging my words in advance. Most of the "well", "actually" and "you knows" have gone to assist with the onset of speech - things seem clearer now. I would say that my speech has improved by 80% and with any remaining blocks, I can 'plow' through them easier with less struggle.

So far, I am a fan, and according to my doctor, the full benefits will not be evident for another few months.

Monday, December 17, 2007

Gene studies more tricky

I was quite enthusiastic about genetic studies, but I now realise that it is a bit more tricky than standard genetics.

There are two ways to look for genetic influences in a disorder. First, twin studies show the strength of the genetic component by comparing the probability of both twins having the disorder for the monozygotic (share the same DNA) and heterozygotic case. Second, you can look at affected families or populations to locate responsible genes in the chromosomes. The key is to associate a trait with the disorder. For example, blue eyes or red hair are good traits.

However, stuttering is more complicated. In stuttering it is not clear what the trait is. Stuttering is not really a trait as such, but symptoms, or I think what geneticists call a state. The real trait could be a dysfunctional motor region or the failure to initiate sounds properly. And, recovered stutterers might also have this trait but they do not stutter because they compensate well. And there might be many different traits leading to the same symptoms. Therefore, overt stuttering is only roughly related to the trait, and the signal strength of any research like twin studies or family trees will be significantly reduced.

Saturday, December 15, 2007

Holger visits TheStutteringBrain

Holger Stenzel is visiting me in Luxembourg over the weekend. He is very interested in stuttering medication and writes a lot about his experiences and on current medication trials and research in forums. He took Olanzapine (Zyprexa) in a self-trial for two and a half year. He said that the duration and strength of block seems to have been reduced but he didn't experience a continuous improvement of his speech. He is currently not taking any medication.

Thursday, December 13, 2007

Should females treat males?

There are many more female than male therapists and most patients are male. As we all know men and women are different, though old-fashioned science-ignorant feminists and post-modernist pseudo-philosophers would argue that gender is a purely social construct. But there can be no doubt that the body is different, the brain is different, and the mind is different. Luckily, nature has given us just about enough overlap in interest and abilities to live more or less happily side by side. :-)
I think few female therapists have the ability to behave outside of their nature, and naturally put more emphasis on areas and behaviours that work for them but that do not work for most men (with some exceptions as usual). Men do not mind talking about psychological and social issues, but we have an internal timer that rings after 15 minutes. We want to move on to something else. We do not need someone to listen to us, but someone that can help us solve our problems. We don't need someone who is constantly telling us Well done, but someone who shows us what we should do and in no uncertain terms tell us when we get off course. We want to do things and not talk about things.

Why are there so many women?

Most of the speech and language therapists are female, and most people who stutter are male. The differences are most apparent in Western Europe, especially the UK. The reasons for the high proportion of female therapists in Europe is of course not sexual discrimination against men, though this fallacious argument applies for all areas where men are in a higher proportion! More women than men are interested and naturally inclined to working with children with speech and language development (and with adults to a lesser degree), though the interest and ability argument of course does not apply for any area where men are in a higher proportion!

The situation is somewhat more balanced in the US. They also call themselves speech and language pathologists, and I believe that they have a more science-based education and not just based on administrating treatments. There is also a markable difference between Western and Eastern European countries, with the Eastern European countries being more science oriented. I see it at conference all the time: they usually don't run away when I talk science or stats! There is still some respect for physicists. :-)

And the proportion of males increases with seniority and focus on research as opposed to treatment.

The European hotbed of femaleness in treatment must surely be the Michael Palin Center in London where I have yet to meet a male therapist; it's just pure estrogen. :-)

Wednesday, December 12, 2007

Botox your stuttering away

I never stop being surprised about the extent to which people are searching for a cure or reduction of their stuttering: walking on all four, not speaking for 3 days, remove a part of the tongue, and so on. Now I have come across articles on botox and stuttering: see here at Judy's page. As always the studies show some promising results, and as always they are deeply flawed.

Tuesday, December 04, 2007

Comedy or not.

YouTube classifies stuttering as comedy, and Leys is battling them. You can sign an online petition against the YouTube classifications here.

Monday, December 03, 2007

Pagoclone outlicensing negotiations

One reader, Ora from New York, called Indevus directly and asked them! Here is what he wrote to me about his re-collection of the phone call. I want to make clear that I was not part of this phone call and cannot verify any statements:
Current plan is to partner the drug with a larger firm which specializes in central nervous system drugs. Pagoclone is a legacy drug for Indevus. It went through tests for generalized anxiety disorder. They discovered in the process that it helped stutterers who participated in the trials, and that the benefit subsided after treatment was stopped. They’ve gotten some good info from the Phase II open label extension (since mid-2006).
In the meantime, Indevus' corporate focus has changed. They’ve acquired another company this year. Their corporate focus has shifted toward urology and endocrinology, and pagoclone no longer fits. Although they are still positive on pagoclone, they’ve had to make a corporate decision whether to proceed with it themselves, or devote their attention to drugs within their core focus. They decided to outlicense pagoclone to another company.
The outlicensing talks are “in late-stage discussions”, and they hope to agree with partner by end-of-year. They are in “end stage negotiations”. Timing is uncertain to a degree, but they’re hopeful that they’ll ink the agreement by end-of-year. Might extend into first quarter 2008. They recommend keeping an eye out for Indevus press releases regarding the outlicensing deal, and then closely follow the plans of the new company, including contacting their corporate communications department.
One encouraging fact is that the safety data is very good. This data has come not only from the 132 participants in the stuttering study, but also from the previous studies for anxiety and premature ejaculation, so altogether they have safety data for (I think) about 1600 people.
They have had “end of phase II meeting” with FDA. FDA has asked them to do pediatric studies or incorporate into their trial design; if not, the drug would undoubtedly be prescribed by doctors for off-label use. In the US, any FDA-approved drug can be prescribed by a doctor for any condition, not just the approved diagnoses. So the FDA wants them to design their tests to include children so they have some real data instead of guesses and extrapolations.
I asked what the Phase III study would look like. It would depend on the new company. The design of the trial would depend on discussions with the FDA, and would be adjusted as necessary “to get this through”. The FDA has already been giving them a lot of feedback.
There is nothing really new. It is important to watch their actions on the outlicensing as opposed to their words. We cannot judge the state of such negotiations and need to wait until a public announcement by both companies.

Does fever reduce stuttering?

I have just read a fascinating article: see here.
Fever can temporarily unlock autism's grip on children, a finding that could shed light on the roots of the condition and perhaps provide clues for treatment, researchers reported on Monday.
It appears that fever restores nerve cell communications in regions of the autistic brain, restoring a child's ability to interact and socialize during the fever, the study said...He said the fever effect was believed found only in children, whose brains are more "plastic" than those of adults.
Before doing the same experiment with children who stutter, let's look for anecdotal evidence. I don't really know whether I am more fluent when I have fever. I have never really paid attention as a kid, so I cannot exclude the possibility. Does anyone of you observe such an effect?

Saturday, December 01, 2007

A more sophisticated look at Pagoclone

bwapplegate posted a more sophisticated and more optimistic analysis of the current state of Pagoclone than I did in my last post, here! He seems to be an analyst. Here is his analysis:
Indevus (IDEV) typically does outlicensing deals on compounds they are developing. They've outlicensed several of the ones in their pipeline, including Sanctura and Sanctura XR, which are their flagship medications.
Outlicensing essentially entails up front payments to cover the costs of the Phase III trial in return for the ability to sell the drug once it is approved. Thus, IDEV is looking for a big pharma to come in and offer XXX million for the rights to the medication. They'd give milestone payments - to initiate PIII trials, at the completion of enrollment, at the submissison of the NDA to the FDA, and on approval. After that, IDEV would typically get a royalty payment based on sales of IDEV.
This situation is interesting because:
-IDEV has a colorful past, in which it was tested as a med for GAD and panic disorder but failed. Most people think that the success of pagoclone will not be for stuttering, but for off label use for anxiety.
-Trial design and cost issues. Stuttering trials are somewhat difficult to pull off. There are hazy outcome indicators, difficulties in standardizing patient accrual, and other trial issues. the Phase II trial took something like 15 months to enroll 120 subjects over 15 sites. That's not exactly a high enrollment rate.
-The FDA wants the medication tested on children as part of the approval process. this complicates the trial design, and further complicates the trial and significantly adds to the cost.
I do think that they ultimately will partner with someone in the next quarter to 6 months and that the trial will proceed after that. My sense that IDEV is trying to get a sweetheart deal.