Monthly Archives: July 2009

Blog Review: Small Gray Matters

The blog reviewed here is ‘Small Gray Matters‘. The blog has a simple but effective design with a blue title pane and for the articles, black text on a cream background with hypertext links appearing as a pale green (or at least it looked like a pale green). On the right hand pane, articles are indexed in the monthly archives and also in categories. There is also a summary of recent posts, links and an RSS feed. I couldn’t find an About section but reading through the articles, the author works (or has worked) in fMRI research, is most likely American judging from the title and conference attendance, has graduated in the not too distant past, with a background in statistics and experience in several programming languages. The impression I got from reading this blog, is that the author is exceptionally intelligent and is able to bring this intellect to bear on many different domains within the neurosciences, hardly ever deviating from making a serious analysis of the topic to hand and always seeming to have a very deep, highly structured understanding of the subject matter. My guess is that this approach allows for the rapid acquisition of domain expertise and with continued application within the field of interest – fMRI – would all other things assumed, at some point result in the author becoming one of the leading figures in this field. Of course, this is all rather speculative but is the impression I got on reading through the blog. Another interesting feature of the blog is that the posts are very infrequent (indeed with a one year hiatus at one point) but of very high quality.

The first archived article dates back to June 2006 and is a defence of neuroimaging in response to a Seed article. This is followed by a really excellent article on ‘Neurons, blood flow, and their intimate relationship‘ and I would recommend this to people with an interest in fMRI as the author covers some of the reasoning behind the fMRI methodology starting with an analysis of an important paper in Nature by Logothetis. The author goes on to say

The reason most people like fMRI is because it optimizes a bunch of trade-offs in a way that previous methods haven’t been able to do

The author follows this up with another post ‘How Much Should Scientists Worry?’ which contains another great quote

We don’t do experiments thinking we’ve got all the assumptions covered; we do them in spite of the fact that we know we’ll be wrong a good deal of the time. Because that’s the only way science can work

In a 2006 article titled ‘More on fMRI‘, the author makes some comments that preempt the debate that was started with Vul et al’s Voodoo paper (reviewed here) after looking at the problems posed by the size of the datasets produced in fMRI studies

Given that level of complexity, it’s not surprising that people have generally stuck with familiar methods imported from other areas of behavioral research. T-tests on subtractive contrasts aren’t necessarily the most natural way to explore brain activity, but they’re what’s closest to standard analyses of experimental treatments in other fields

In this article ‘trendsetting the fMRI literature‘ the author looks at using PubMed to identify trends in fMRI research  (covering an area of research examined in a study reviewed here). The author is able to add an original slant to this subject as is the case with other topics examined.

I would recommend this blog to those with an interest in neuroscience for insights into important developments in the field.

Podcast

You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

Responses

If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk

Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Book Review: The Woman Who Couldn’t Forget

The audiobook reviewed here is ‘The Woman Who Couldn’t Forget’ by Jill Price with Bart Davis. The narration is clear, with an excellent conveyance of the mood of the piece that takes the listener into Price’s world. Price tells us about a condition named ‘Hyperthymestic Syndrome’ which means that according to the case report below the person ‘spends an abnormally large amount of time thinking about his or her personal past’ and ‘the person has an extraordinary capacity to recall specific events from their personal past’. Price goes on to tell us about her memory and at the beginning says

from 1984 it’s near perfect

before going on to describe how she can recall what she was doing on a particular date as if watching a stored movie with vividly recalled emotions as well. Price is well read and brings a lot of the scientific theory on memory into her work. Price has also developed a habit of keeping a very detailed diary which began shortly after meeting her first boyfriend as she realised that it may be transient and wanted some record of this. However this writing then took on a life of it’s own and she estimates having written during one period the equivalent of 50,000 pages in this journal. Her manner of writing matches that of her memory in that the material selected is both important and not so important. Thus she tells us that there is no selectivity and also in her memories there is no prioritisation. The obvious question to ask here is whether such a voluminous amount of writing might be contributing to her memory. Price argues that it does not as she does not refer to the journal entries again. Indeed further along Price reveals another intriguing point – that she considers the writing as a means to make her memories real

once I write it down I own it…in some indefinable way it makes these memories real….it has to be tangible…something I can handle…to write an event down means it really happened

In this regards, like two other people with similarly remarkable memories, Price is a ‘big collector‘. This is further remarked on when Price tells us that she has written personal aspects of her life on her wallpaper at home. On moving home, she became tearful when separated from the objects in her home for the first time during the removal process and also on removing the wallpaper from the wall which she later kept. In some senses, the external writing almost seems to have become one aspect of Price’s identity. Price also tells us that at parties for instance, she would be sitting down scribbling away in her journal. She began to realise her difference from other family members and was soon relied upon as the ‘family historian’. She made contact with James McGaugh at Irvine University in California and soon became the subject of a paper (see below) and ongoing research. Price finds herself correcting people and also preventing herself from doing so in some cases. Along the way she looks at what is known about memory so that she can work out how she is different and cites works by Sacks, Borges and Nabakov. Price  looks at the types of bias that usually occur and how these might be trade-offs, the disadvantages of rumination and evolutionary psychology perspectives. She tells us about the development of autobiographical memory during childhood and draws an intriguing connection between being able to tell a good story and developing self-defining memories. This is a very profound point particularly as she has commented on the difficulties she has with prioritising memories and which may tie in with some of the aspects of the neuropsychological profile she has mentioned elsewhere. Perhaps one implication of this might be that during development people may train their memories to work in a particular way, which suits their lifestyle and helps them to build a narrative for defining their future – a mythology. If this does not occur, then the memory may be used in other ways. Price goes onto mention that she had difficulties in understanding social nuances which may again relate to this generic ability to prioritise and structure information in a particular way. She speaks of a ‘memory bump’ with reference to theory, a spike in memory abilities that occurs at around age 10 and the relationship of forgiving and forgetting.

Price combines all of these considerations of her memory with parts of her own lifestyle, with the ups and downs of family life, her parents separation, meeting her husband and the tragic events that follow. Having such recall makes some of these episodes much more difficult and all of this is more evident in the level of detail that is able to give about many of these events. However Price also tells us of the therapeutic benefits of writing a life narrative. At this point, I couldn’t help but think of the parallels with blogging. There are many people writing blogs these days. Many of these are about people’s lives and so to some extent, while 20 years ago Price’s writing would have been atypical perhaps now this is not so unusual. The main difference which might not be too important is that bloggers would tend to be typing whereas Price was writing. Included in the definition of Hyperthymnestic Syndrome is the tendency to focus on the biographical aspects of life and in this sense, this is exactly what some bloggers are doing. If we take this further, if this type of activity can improve autobiographical memory (although this is speculation) then does that mean that bloggers memories will be improving. There is a little more to the story here however. The neuropsychological profile revealed strengths and weaknesses and Price has to some extent become an expert in her own autobiographical experiences both in terms of writing and recall. She has trained herself over a prolonged period to think about what she is experiencing and how she should recall that and make that concrete and tangible. Such is the effort that she might have developed this to the exclusion of other abilities. The authors of the case report draw attention to some features of her development – using the left hand as well as the right – to suggest that any answers to questions may be complex. Could this be translated into dementia research? In some forms of work in the dementia care setting – creating an autobiography can form part of a therapeutic intervention. Could the development of the skill of observing one’s own life and writing it down slow down memory decline or prevent onset of memory difficulties? Could this take place through blogging? This can only be answered through research and it is necessary to see whether focusing on executive skills, working memory or autobiographical memory might play the most beneficial role.

I was curious to see if there had been any developments on the Hyperthymestic Syndrome. A quick look at Wikipedia reveals several more cases including Rick Baron and Brad Williams in addition to a mention of the famous case of Shereshevskii the Russian mnemonist described by Luria and discussed above. The published case report, details of which were discussed by Price, is freely available at the University website here. This contains references to other relevant cases including a case series by MacGuire.

I thought this was an excellent audiobook with good narration and a fascinating account by Price of her remarkable abilities as well as an eloquent account of her own at-times poignant autobiography.

References

Jill Price, Bart Davis. The Woman Who Can’t Forget (Unabridged). Narrator – Celeste Ciulia. Recorded Books. 2008.

Podcast

You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

Responses

If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk

Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Review: Estimating Future Numbers of Adults with Profound Multiple Learning Disabilities in England

The article reviewed here is a Department of Health document titled ‘Estimating Future Numbers of Adults with Profound Multiple Learning Disabilities in England’ and which is freely available here. This document is based on research undertaken by the Centre for Disability Research and the article is authored by Eric Emerson. The aim of the associated project is defined as being to ‘estimate change in the future numbers of adults with profound multiple learning disabilities in England over the period 2009 to 2026′. The methodology is described clearly and begins with an estimation of children with special educational needs from a 2008 school census involving 6.8 million pupils. The prevalence rate estimates are stratified according to age group and gender and there are some assumptions about age at entry and leaving school in people with profound multiple learning disabilities. A trend towards a decreasing prevalence from age 7 to 15 is noted although the reasons are unclear. This is equivalent to an increase prevalence of 4.8% annually and further supporting evidence is provided. Using data from a Sheffield case registry and adjusting for population demographics, the annual increase in prevalence during this period was calculated at 4.7% which is close to the figure obtained from this analysis and thus provides supporting evidence and reasons for why this might be a cohort effect are given. A demographic analysis of the data was undertaken and a number of findings were consistent with previous research including gender and ethnicity results.

The next stage was to adjust for mortality, a very difficult area given the heterogeneity of conditions leading to profound multiple learning disability, the heterogeneity of comorbid illness, advances in management during the project period and a number of other confounding factors. The estimate was that there would be an ‘average annual percent increase of 1.8%’ during the period 2009 to 2026 although it is also noted that there will be a decline in the number of people reaching adulthood in the general population during this period (with an upturn in the latter period due to increasing birth rates). Thus for a catchment area of 250,000 people they estimated that ‘the number of young people with PMLD becoming adults in any given year will rise from 3 in 2009 to 5 in 2026′ although the difficulties in estimating mortality rates are noted.

This is a useful piece of research which can be further revised as data from other sources becomes available and has implications for planning service delivery.

Podcast

You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

Responses

If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk

Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Review: A Meta-Analysis of Self-Help Therapy for Insomnia

The paper reviewed here is ‘Self-help Therapy for Insomnia: A Meta-Analysis’ by van Straten and Cuijpers. The authors note the use of pharmaceutical approaches to insomnia as well as psychotherapeutic interventions. However they are interested in those approaches that the person with insomnia can use by themselves with some supervision if necessary. For this purpose the authors have selected randomised controlled trials looking at self-help for insomnia in comparison with a control group. They describe the process for selection of papers – they searched through several databases – ‘Pubmed, PsycInfo, Embase and digital dissertations’. Here they inform the reader that papers are selected up to January 2007 although they do not stipulate the start year in each database. They also use a secondary method for identifying papers of searching through the references of identified papers. They excluded papers that had greater than 50% loss to follow-up but otherwise papers under the general heading of ‘self-help’ were included meaning that a patient could use this approach ‘independently’ although they go on to add that they did include papers in which there was time-limited supervision for patients in learning to use these approaches. Since sleep diaries were used, the authors were able to use total sleep time, sleep onset latency, sleep efficiency, wake after sleep-onset and the secondary outcomes of anxiety and depression. The authors explain their analysis methods very clearly – they subtract means scores of the control group from the experimental group and divide by the ‘pooled standard deviations of both groups’ to produce an effect size. What I found interesting here is that there is a specialised computer package for use in meta-analysis – Comprehensive Meta-Analysis which the authors used. There were a variety of approaches used in calculating the effect sizes in the different groups and they used the package to look for any publication bias with a funnel plot followed by  a trim and fill procedure*. They identified 14 randomised studies with varying conditions for the control groups (e.g. waiting list and active treatment). 7 of the studies included participants aged 18 or over although other studies included other age groupings. The impression I got from reading through the results section was that there was great variation amongst studies in a number of areas including inclusion and exclusion criteria, recruitment strategies, support and self-help approaches. With a random effects model they found variation in the effectiveness of interventions on sleep-outcomes whereas with a fixed effects model they found benefits on all sleep outcome measures  with the exception of total sleep duration. There weren’t found to be any significant benefits in the analysis of studies that had follow-up – with the follow-up period of 4 months chosen for the analysis. The authors found that smaller studies more positive results and after using the Trim and Fill method the effect size wasn’t statistically significant. There weren’t any significant findings from an analysis of subgroups in the study. In their discussion, the authors note that they couldn’t identify any significant improvement in depression or anxiety scores. I didn’t see any mention of what the authors thought about the difference in the results obtained using random versus fixed effect models in the discussion however. Initially I couldn’t see any benefit to including such a heterogenous group of studies in the meta-analysis but on further reflection thought it provided a useful starting point to asking more specific questions.

* Duval and Tweedies trim and fill procedure

Steps To Treatment = 4

Steps To Treatment (STT)

STT = Steps To Treatment. An estimate of the number of steps between the results and translation into treatment. This is an opinion.

References

Annemieke van Straten and Pim Cuijpers. Self-help Therapy for Insomnia: A Meta-Analysis. Sleep Medicine Reviews. 2009. 13. 61-71.

Podcast

You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

Responses

If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk

Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Review: Results of Phase 3 of the CATIE Schizophrenia Trial

The article reviewed here is ‘Results of Phase 3 of the CATIE Schizophrenia Trial’ by Stroup and colleagues. The authors place the CATIE trial in the context of other studies including the CUtlass Study (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and the EuFEST study (European First-Episode Schizophrenia Trial as well as other phases of the CATIE study that had already been reported*. Part of the methodology was described elsewhere but essentially the CATIE is a multi-centre trial with random assignment to Ziprasidone, Risperidone, Quetiapine, Olanzapine and Perphenazine with follow-up for 18 months and then some complicated pathways in which medications can be discontinued before participants are randomised to further treatment arms. In the third phase, the phase being reported here, paticipants could choose from one of 9 treatment pathways

1. Clozapine

2. Olanzapine

3. Perphenazine

4. Quetiapine

5. ‘Antipsychotic monotherapy with Aripiprazole’

6. Risperidone

7. Ziprasidone

8. Long-acting injectable fluphenazine

9. A combination of two of the above

There were many exclusion criteria which need to be considered in interpreting the results. Participants were aged 18-65 with a DSM-IV diagnosis of schizophrenia determined by Structured Clinical Interview. Some of the exclusion criteria were schizoaffective disorder, first-episode of schizophrenia, ‘treatment resistance defined by persistence of severe symptoms despite an adequate trial of one of the proposed treatments or prior treatment with clozapine for treatment resistance’, ‘serious and unstable medical condition’. Looking at these exclusion criteria more closely it seems that the participants should not have a new onset, nor should they still have severe symptoms after a trial of one of the antipsychotics above. So it seems as though the type of participants are those who have passed through the initial stages of the illness and settled on a medication without severe symptoms. I was curious as to why some of the exclusion criteria exist. For instance if a group with ‘serious and unstable medical condition’ is included then they could be analysed separately if it is thought that this group might influence the overall results (although it might be argued that analysing this group separately might require a suitable sample size). By the time the participants have been randomised to the individual arms in the third phase, the numbers in each arm is relatively small ranging from just 4 in the perphenazine group to 41 in the Olanzapine group. The discontinuation rates in the arms range from 33% (Aripiprazole, combination and fluphenazine) to 50% (perphenazine). There was flexible dosing in the third phase and choice of medication was based on previously trialled medication in a way which maintained the blinding within the trial since the data had already been collected. The primary outcome measure was the discontinuation rate which is influenced by a number of important practical factors. A large number of secondary outcome measures were also examined including PANSS scores. There are several tables showing an extensive list of baseline characteristics for the different treatment options above as well as adverse effects associated with medication. The statistics are descriptive as the primary outcome measure was discontinuation rate alone so the remainder of outcome measures are in effect included in a secondary analysis. 39% of the patients discontinued treatment with a mean duration of treatment of 7.7 months. Although this is a secondary analysis there are p-values for the outcome measures by safety and the method used to calculate these values varies according to the outcome measure. Those reaching the highest level of significance were Sialorrhoea (38% in the clozapine group), hesitancy (36% in the Quetiapine group), weight change (10.5 lbs in the Perphenazine group) and Prolactin (24.2ng/mL in the Risperidone group). It’s useful to have some comparative data on the adverse events although with small sample sizes for individual antipsychotics there are difficulties in interpretation as the authors have noted and perhaps a meta-analysis of adverse-events from other trials for individual antipsychotics might be interesting to see.

The main finding for me seemed to be the discontinuation rate of 39% as this was the primary outcome measure.  There were some trends towards choosing second generation antipsychotics although that might well result from the study design in which the majority of choices are second generation antipsychotics. The PANSS score changes from baseline at 3 and 6 months seem to all be significant at the 5% level apart from 2 antipsychotics at each of 3 and 6 months which is difficult to interpret given that this is a secondary analysis.

* There are also Conflict of Interest Declarations at the end of the article.

References

Stroup TS, Lieberman JA, McEvoy JP, Davis SM, Swartz MS, Keefe RS, Miller AL,Rosenheck RA, Hsiao JK; CATIE Investigators.Schizophr Res. 2009 Jan;107(1):1-12. Results of phase 3 of the CATIE schizophrenia trial.

Podcast

You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

Responses

If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk

Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

News Round-Up: July 2009 4th Edition

News in Brief

There have been a lot of studies looking at the possible benefits of the ACE inhibitors in reducing the risk of dementia but a new study gives a twist to the story. This is a prospective study involving people without dementia at baseline and the researchers selected 1074 participants from the cohort. They found that taking a centrally-acting ACE-inhibitor was associated with a 65% decrease in cognitive decline (using a modified version of the Mini-Mental State Examination) and that taking a peripherally-acting ACE-inhibitor was associated with a 73% increased risk of dementia compared to those taking other antihypertensive medication. This study occurs in the context of other studies suggesting a benefit of the ACE-inhibitors in dementia on various outcome measures. However it is important to note that the participants in this study were being treated with antihypertensives and were thus a selective group. This may be an important finding and the investigation of the actions of the centrally-acting ACE-inhibitors may well give  some important insights into dementia. It will be very interesting to follow the necessary subsequent research in this area. Researchers at the University of California have identified an association between PTSD and increased risk of subsequent dementia using information from a database on 181,093 veterans over the age of 55-years although this association did not occur after controlling for depression, substance misuse and traumatic brain injury. An engineered protein that can be extracted from goat’s milk has and which interacts with the Beta-Amyloid protein has been suggested as a potential prophylactic agent for people who carry a variant of the Butylcholinesterase inhibitor gene.  Several studies were presented at the 2009 International Conference on Alzhiemer’s Disease which this year was in Vienna. Thus evidence was presented that strictly adhering to a diet for hypertension – the Dietary Approaches to Stop Hypertension (DASH) Diet was associated with improved cognitive functioning compared to those who didn’t adhere as consistently. There were 3,831 participants over the age of 65 who were followed up over 11 years. Adherence to the diet was represented by an ‘adherence score’ and associations with cognition were also found for fruit and vegetables as well as low fat dairy products. In another of the studies, a prospective study of 3075 people aged 70-79 there was a significant association between sedentary lifestyle and lower cognitive scores (modified MMSE) as well as between declining scores and declining physical activity. Another of the studies, this time in post-menopausal women showed a benefit on cognition for moderate exercise but a detrimental effect for chronic strenuous exercise although the study included a small number of participants (90) and it would be interesting to see further replication studies.

A recent committee found evidence of an association between Agent Orange exposure in Vietnam war veterans and risk of developing Parkinson’s Disease based on an an analysis of  16 studies looking at the effects of the herbicides. The authors conclude however that other types of study are needed to examine this association in more detail. A new Xenon delivery system has been developed which may have benefits in protecting against hypoxia-induced brain injury in humans. A single-blinded study (n=78) looked at improving attention (4 types described) in people who had developed a stroke by using Attention Process Training. Although they did find an improvement in attention with this training, at 6-months. A research team at the University of Vermont have been analysing text strings in blogs to estimate how ‘happy’ people are by looking at sentences with the words ‘I feel..’ in them. They were able to use 10 million sentences (from this site) and amongst their many findings they noted that people increasingly used the word ‘proud’ at the time of President Obama’s election, that Michael Jackson’s death was associated with a big drop in the valence scores (valence scores were calculated by rating each type of emotional word to estimate) and that teenagers were more likely to use the word ‘sad’ in the sentence.

Podcast

You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast).

Responses

If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk

Disclaimer

The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.