Dr Shock MD PhD

Friday, August 31, 2007

Another Drug Company rewrites entry in Wikipedia

Abott Lab removed the sentence "increased risk of cancer" as mentioned for their arthritis drug Adalimumab (brand name Humira) on Wikipedia.

Two minutes later, someone with the username Gscshoyru, whose Wikipedia profile describes him as a “recent changes patroller,” added the information back to the entry.

Jeffrey Light, who runs the one-man nonprofit Patients not Patents used Wikipedia Scanner to see what the drug industry had been up to on Wikipedia. He made a press release on this subject, you can download this press release from the article on HealthBlog from the Wall Street Journal.

Wikipedia Scanner -- the brainchild of Cal Tech computation and neural-systems graduate student Virgil Griffith.
This software offers users a searchable database that ties millions of anonymous Wikipedia edits to organizations where those edits apparently originated, by cross-referencing the edits with data on who owns the associated block of internet IP addresses.

This is the second drug company that was discovered doing this. The other company was AstraZeneca for their drug seroquel. Would like to use WikiScanner on some other drug companies as well, but it takes a lot of time.

Other post on this subject on this blog:
Drug company rewrites entry on Wikipedia

Thursday, August 30, 2007

9 Steps for Treatment-Resistant Depression

50 to 60 % of patients with a depressive disorder fail to respond to their first antidepressant. These rates increase in clinical practice setting to 65 to 85%. Estimates of TRD prevalence varies greatly depending on treatment setting. The lowest TRD prevalence is in primary care and progressevily higher rates occur in outpatient psychiatric settings, inpatients settings and academic tertiairy setting.

Compared to non-TRD, TRD patients have been reported to have significantly higher outpatient medical costs, and to be approximately twice as likely to be hospitalized, either medically or psychiatrically

From: Nemeroff CB. J Clin Psychiatry. 2007;68 Suppl 8:17-25.
Prevalence and management of treatment-resistant depression. Abstract

What is Treatment-Resistant Depression?
An inadequate response to an adequate course of treatment in a patient meeting criteria for major depressive disorder. Treatment is usually antidepresssants. Depression is not bipolar depression. This diagnoses needs a different approach. An adequate course is a course of an adequate dosage of the antidepressant for at least 6 weeks. This has been operationalized in criteria for different stages of TRD:

Stage 1. Failure of an adequate trial of 1 class of antidepressant

Stage 2. Failure of adequate trials of 2 distinctly different classes of antidepressants

Stage 3. Stage 2 plus failure of a third class of antidepressant, including a tricyclic antidepressant

Stage 4. Stage 3 plus failure of an adequate trial of a monoamine oxidase inhibitor

Stage 5. Stage 4 plus failure of an adequate course of electroconvulsive therapy

From: Thase ME, Rush AJ. J Clin Psychiatry. 1997;58 Suppl 13:23-9.When at first you don't succeed: sequential strategies for antidepressant
nonresponders. Abstract

What can they do about Treatment-Resistant Depression?

1. Be sure they diagnosed the depression properly, subtype of depression

2. Exclude somatic illness

3. Exclude comorbid psychiatric illness

4. Evaluate antidepressant treatment for compliance, tolerabillity, duration, and dosage. If necessary optimize by increasing dosage or extending the duration.

5. Switch to an other antidepressant if previous measures failed

6. Augment the antidepressant

7. After cessation of all antidepressants start a monoamine oxidase inhibitor

8. Reconsider diagnoses and use Electroconvuslive therapy

9. Don't forget cognitive therapy, Interpersonal psychotherapy, running therapy, family therapy.

Treatment algorithm for Treatment-Resistant Depressed Inpatients

In a recent study some of these steps were studied in a treatment algorithm with depressed patients admitted to a depression unit.

Step 0: Washout, Diagnostic phase, and placebo run-in (1 week)

Step 1: Antidepressant monotherapy (imipramine or fluvoxamine; 6 weeks)

Step 2: Lithium addition (5 weeks)

Step 3: Nonselective monoamine oxidase inhibitor (MAOI; phenelzine or tranylcypromine; 5 weeks)

Step 4: Electroconvulsive therapy (flexible number of weeks)

Results of a treatment algorithm for treatment-resistant depression

149 patients (50%) were included in the 4-step algorithm. Of the 56 patients who were excluded from
step 1 because of proven refractoriness to antidepressants during the index episode, 54 were enrolled directly into step 3 of the algorithm. Only 4 (7%) of these 54 patients had received lithium addition. Ten patients needed immediate ECT.

At the end of the algorithm, 129 (87%) of 149 patients achieved response. Complete remission was achieved by 89 of 149 (60%) patients. Three patients switched into
hypomania during the algorithm: 2 receiving a combination of imipramine and lithium and 1 patient receiving phenelzine. These patients were considered both as responders and remitters. Overall dropout of the algorithm amounted to 24 (16%) of 149 patients. When including patients who entered the algorithm at step 3 (treatment with a nonselective MAOI) the figures are as follows: 165 (81%) of 203 responded during the algorithm and 101 (50%) achieved remission. Overall dropout, including the 54 additional patients, was 30 of 203, i.e., 15%.

These results emphasizes the importance of persisting with stepwise antidepressant treatment in non-responders to the first antidepressant. Important is to note that this trial was done on a depression unit in a academic/tertiary centre.

From: Birkenhäger TK, van den Broek WW, Moleman P, Bruijn JA. J Clin Psychiatry. 2006 Aug;67(8):266-71. Outcome of a 4-step treatment algorithm for depressed inpatients. Abstract

I was inspired by an article from the MayoClinic.com about Treatment-resistant depression

Wednesday, August 29, 2007

Predict treatment response in electroconvulsive therapy

Your genes probably predict response to ECT more accurate then any clinical variable.

Genes, enzymes and neurotransmitters
Genes are located on DNA in the nucleus of the cells in your body. You usually have two genes on each arm of a chromosome ( one from dad and one from mum). If the two genes are identical it's called that they are homozygote, if they are different it is heterozygote. Genes are read by other cell nucleus material (RNA) which starts a sequence to produce proteins. The most important proteins being enzymes. Enzymes are needed for the metabolism of neurotransmitters among others. Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a neuron and another cell in the brain.
Catechol-O-MethylTransferase (COMT) is a major enzyme in the brain for the metabolism of dopamine, a neurotransmitter. A polymorphism in the gene coding for COMT results in substantial effects, with a homozygote allele variant leading to a three to fourfold reduction in enzymatic activity compared to the other homozygote variant.
In general, polymorphism describes multiple possible states for a single property. This single property being a single amino-acid sequence in the allele for COMT. The presence of Met/Met and Met/Val or Val/Met results in a much lower activity of COMT than Val/Val (high activity).

Low Dopamine concentration in Prefrontal Cortex
The high genotype of COMT was associated with better treatment response to ECT than low allele containing genotypes. Since high genotype results in a high activity of COMT and a low dopamine concentration in the prefrontal cortex we can assume that low dopaminergic activity in the prefrontal cortex is associated with a better response to ECT.

This was shown in 119 treatment-refractory depressed patients admitted consecutively for electroconvulsive therapy (ECT). The effect of clinical variables also related to a better response to ECT were studied using univariate analysis of variance. These covariates: higher illness severity, age, age at onset, sex and the number of ECT treatment did not affect the treatment response.

Not all studies with COMT polymorphism and response to antidepressants found an association between this polymorphism and response. COMT also plays a role in the metabolism of norepinephrine, another important neurotransmitter in the brain. Other limitations of this study are a small patient sample and the concomitant use of psychotropic drugs during ECT. ECT itself was properly performed.

Biological variables predicting response
A very nice publication in a new field of research. Important topic predicting response in a patient with biological variables.

Publication:
Catechol-O-methyltransferase(COMT) polymorphisms predict treatment response in electroconvulsivetherapy

The Pharmacogenomics Journal (2007),1–4.

Sami Anttila et al.

Correspondence:

Dr S Anttila,Department of Psychiatry,

Tampere University Hospital,Pitkaniemi

33380,Finland.

Abstract

Tuesday, August 28, 2007

PubMed in a Web2.0 dress, Gopubmed.

Most scientist know PubMed. It is a powerfull search engine for scientific literature. It is a bit dull, not so very geeky. In comes Gopubmed. It has the power of PubMed and then some more. It has some nice graphic as well as usability improvements compared to the original PubMed. The results page is divided into two sections. On the right hand side the latest 1000 PubMed citations that match your search term. But the fun is on the top of the right side:

If you click the “show statistics for these 1000 articles” you get the citations summarized on the basis of a number of variables such as top authors, journals, cities, countries and years. This is pretty nifty if you want to get an idea of who is publishing most in the area, where the publications are coming from and what journals are publishing that kind of content. Some examples of the statistical analyses are shown below. Another cool thing is you can click on names, journal and locations to get those specific citations.

On PsychPlash these add ons are illustrated with graphics from gopubmed.

On the left-hand side :
1. Gopubmed annotates the resulting citations with GO and MeSH terms
2. Content Filters are extremely useful in helping you answer specific questions relating to your initial search query
3. The Document Filters are the same as the citation statistics mentioned in the blockquote above
4. The site has an extensive help function.

Try electroconvulsive therapy. The next picture is the top 20 cities and countries with this search term. Is that The Netherlands on place 6?

Monday, August 27, 2007

Taking the Pulse of the Healthcare Blogosphere

Trusted.MD is conducting a new survey about medblogs. If you're a health care blogger do the survey

WHY WE NEED YOUR HELP

We can't continue to get a better understanding of the healthcare blogosphere without your help. We need as many healthcare bloggers (those devoting at least 30% of their blogging time to healthcare) to take the survey so that we can make valid conclusions about the size and shape of this growing part of the global blogging community.

New Meta Search Engine AllPlus

In the recent past I was interested in search engines. You have different kind of search engines, the most famous being Google. Google is a traditional search engine.

A meta-search engine is a search engine that sends user requests to several other search engines and/or databases and returns the results from each one. Meta search enables users to enter search criteria once and access several search engines simultaneously. Since it is hard to catalogue the entire web, the idea is that by searching multiple search engines you are able to search more of the web in less time and do it with only one click. The ease of use and high probability of finding the desired page(s) make metasearch engines popular with those who are willing to weed through the lists of irrelevant 'matches'. Another use is to get at least some results when no result had been obtained with traditional search engines.

Science Roll , A medical student's journey inside genetics and medicine through web 2.0, had an article about a new meta search engine: AllPlus
It delivers results from:

relevant sites/articles
blogs
news
relevant images and videos
cluster tree and graph

Try electroconvulsive therapy

Video on YouTube from a patient during his ECT course

Sunday, August 26, 2007

Women in the medical academic workforce

Only 1 in 10 medical clinical professors are women in the United Kingdom (UK). No female professor was employed in 6 medical schools. The newer medical schools had a better gender balance than some of the more established schools.
For the lower ranks in medical academia these numbers are somewhat higher but still much lower than for men.
In FTEs lecturers in 2005: 36% were women, senior lecturers and readers: 25% were women. In 2005 there were a total of 3365 clinical academics, of whom 21% were women. There was a wide range in the number of professors per speciality; the majority were physicians. The percentage of women professors ranged from 0% (in occupational medicine) to 20% and over (e.g. in radiology, general practice). This gender difference remained relatively constant between 2004 and 2005.

These results were published in Medical Education. This study was needed since data available about gender-specific workforce in clinical academics were limited. These data are reported in order to allow comparison over time.

These data are also supported by a publication in the NEJM in July 2006 about The Gender Gap in Autorship of Academic Medical Literature.

Conclusions Over the past four decades, the proportion of women among both first and senior physician-authors of original research in the United States has significantly increased. Nevertheless, women still compose a minority of the authors of original research and guest editorials in the journals studied.

The United States of America is a favourable exception when it comes to enhancing the careers of women in clinical academics. In Europe conditions are far worse on academic careers for women.

Women and Science in Europe

Source: Women and Science Statistics and Indicators

Women and Science in The Netherlands
In The Netherlands 400 female professors are needed in the coming years in order to answer the European agreements in 2010.

What hinders academic careers for women?
1. Lack of role models and support for female staff
2. Family/carer commitments
3. Lack of network because there aren't many females. Men seem to help each other more to get in key positions
4. High levels of teaching, administrative and pastoral care loads for women. These tasks are not recognised as much as research output
5. Discrimination. Part time work in women is seen as lack of commitment
6. Generational and other issues. A large number of baby boomers in senior positions are not moving on.

For more information and staying up to date see the blog Women in Science.

Women and Science is dedicated to the women in science and engineering, past and present.

Saturday, August 25, 2007

Medical education and films, how can they help?

" If you can't take good care of yourself, how can you take care off your patients?", this is what I tell my residents at least once during their training. 60 to 80 working hours a week is not taking good care of yourself nor your patients.

You can't perform well with this schedule, you can't be patient, you will make mistakes, especially when working long hours at a stretch. Pilots know that and doctors should as well. Tutors should be role models for residents and teach them that they are responsible for their own performance. They should discourage the macho attitude of doctors being able to work long hours, it being part of their job. It is in contempt of their responsibilities and patients entrusted in their care.

Patient-doctor interaction
Another important topic is how a doctor can remain sensitive to the demands of his or her patients. In other words how can a doctor be empathic without loosing his professional distance necessary for good judgment and decision making. Avoiding excessive emotional involvement which can harm his care for the patient, obscure his clinical judgment.

In order to introduce medical students to this responsibility the book: The case of Dr Sachs and the film La maladie de Sachs is recommended by Josep-Eladi Baños from Barcelona, Spain. He wrote a letter to the editor of one of my favorite journals: Medical Education.
In this book and film a French doctor practising in a rural area has a "disease".

The symptoms of his disease involve excessive worry about his work of caring for other people, to a point where he neglects to care for himself and devotes most of his time to doctoring.

Another suggestion for introducing medical students to their future activities he recommends: A Taste of My Own Medicine: When the Doctor Is the Patient
In this book and the film "The Doctor" based on this book the author describes how it feels to be diagnosed with a severe illness, along with all the feelings of uncertainty and fear.

The book is especially revealing about how a doctor might feel when he is treated as a patient and how he considers the disease from the perspective of a patient

Conclusions

The author of the letter to the editor recommends that it is easier to discuss the films than the literary works, the focus being the doctor-patient relationship.
The two suggested books and films are excellent teaching material for medical students on the topic off patient-doctor relationship.

Other article on this blog about films and medical education.

Friday, August 24, 2007

Gene-environment interaction in Psychiatry

As a clinician I always wondered why some abused patients had more trouble recovering from their psychiatric illness than others. This article about the gene environment interaction in Psychiatry clarifies some of the variations in outcome. This article explains in relatively accessible written prose some of the experiments that have influenced our thinking about gene and environment interactions in relation to psychiatry. It is written by David D. Olds, M.D. Columbia College of Physicians and Surgeons New York.
He teaches clinical psychiatry and psychoanalysis at Columbia University and is an editor of the journal Neuro-Psychoanalysis. He has written often on the relationship between neuroscience and psychotherapy. Wanted to comment on his article. Curious how psychotherapy with sexually and or physically abused patients influences our brains or perhaps even genes. Maybe a topic for a future article on this blog.

Thursday, August 23, 2007

Cognitive side effects of electroconvulsive therapy in adolescents

No severe cognitive side effects of ECT used on adolescents could be demonstrated. ECT in adults causes memory complaints, retrograde and anterograde amnesia. The tests used in trials with adolescents are limited in measuring these side effects. Moreover there are no prospective studies on this subject with adolescents and the studies discussed have a small number of subjects with possible lack of statistical power.

Publications about ECT and side effects in adolescents
So far I was able to find four articles about cognitive side effects of ECT in adolescents. They belonged to two different research groups.
From the department of psychiatry of the university of Michigan there is a study in which 5 of 11 adolescents treated with ECT were tested both before and 1-5 days after the last ECT. The neuropsychological tests revealed a significant decline in attention, concentration and long-term memory search. In another publication by this group they collected retrospective data resulting from clinical care with naturalistic follow up of 16 adolescents treated with ECT for mood disorder. Cognitive tests administered before ECT were compared with results at 7 days following the last treatment as well as another testing at 8 months after the last treatment.

Cognitive side effects 1

Testing directly after ECT and compared to the test before ECT yielded significant impairments of concentration, attention, verbal- and visual delayed recall, and verbal fluency. A complete recovery of these functions was noted at the second post-ECT testing. There were no impairments of motor strength and executive processing, even during the early period post ECT.

These studies had little focus on memory disturbances with ECT in adolescents.
The other group from Paris, France focused on memory function. 20 adolescent patients treated with ECT during the period 1987-1996 were contacted for follow up. For various reasons only 10 could be included. Another 10 subjects comparable for sex, age, date and place of hospitalization and diagnosis were considered as a control group.
All subjects were given a battery of clinical and cognitive evaluations. The most important being the Wechsler Memory Scale and California Verbal Learning test , which assesses anterograde amnesia and verbal learning as well as Squire's Subjective Memory Questionnaire for subjective memory complaints.

Cognitive side effects 2

The ECT group did not differ significantly on all cognitive tests at an average of 3.5 years after the last ECT compared to the matched control group.

Lousy tests
Trouble is that all these tests are of no use for the memory effects of ECT at all. The Wechsler Memory test is like the original Wechsler Memory Scale, and provides only a rough estimate of overall memory functioning. The multidimensional index scores have not been shown effective in describing the nature or the pattern of memory deficits. The California Verbal Learning Test (CVLT) is a popular clinical and research test that claims to measure key constructs in cognitive psychology such as repetition learning, serial position effects, semantic organization, intrusion, and proactive inteference.

In an earlier article the lack of proper memory tests for testing retrograde and anterograde amnesia in adults treated with ECT is mentioned.

Sit up straight?

Dr Shock usually "hangs" in his chair. It feels comfortable. Read in this article in LifeScience why sitting up straight might be a bad advice. Scientifically tested with magnetic resonance imaging (MRI).

Wednesday, August 22, 2007

Electroconvuslive therapy fourt edition by Dr Abrams

I read the first edition of this book while on holiday in France. We were cross-country skiing. Not that the weather was bad or the company boring but this book is very informative and easy to read. Read all the other editions as well. For me it is the most narrative book about ECT with a critical appraisal of all the scientific literature. Obviously written by an experienced and good clinician.
This book is reviewed on Medical Heaven, I couldn't have done a better job.

Ranking english written medblogs

A list of medical blogs based on a algorithm with the number of comments, posts, feed readers, incoming links. You can see the widget about it in my sidebar.
Here is a discussion about rating medical blogs.

Sampling sewage for local drug use

The researchers decline naming certain cities but they revealed one trend: use of methadone and methamphetamine (a prescription opiate withdrawal aid and speed) remained constant over 24 days in these cities, but cocaine consumption routinely spiked on the weekends.
A method of taking a small sample of incoming sewage at a water treatment plant is developed. This method can extract the record of local drug use
Environmental analytical chemist Jennifer Field of Oregon State University and her colleagues, using an automated system to test small samples automatically collected at wastewater treatment plants over a 24-hour period. Solids are centrifuged out and the sewage sample is then chemically separated in various compounds of interest chemically. By measuring the relative mass of the various residual chemicals, the chemists can then identify what specific drugs have been recently used in that community.
The technique might help communities determine where to apply law enforcement or track the success of targeted drug-use prevention efforts.
This article about sampling for local drug use appeared on Scientific American.
I remember an article in a Dutch newspaper mentioning that with a comparable method it has been shown that in Spain the abuse of cocaine is the highest of Europe.

Tuesday, August 21, 2007

Myths and stigma's about ECT

Leon Rosenberg, a former dean of medicine at Yale University, had just attempted suicide by overdose. He was admitted to hospital and prescribed electroconvulsive therapy, or ECT.

This is the start of an excellent article by Michael Evans an associate professor at the University of Toronto and staff physician at Toronto Western Hospital.
This article also discusses some other myths, for instance about depression:

Those on the outside still see it as not really a disease but a weakness. Those on the inside see it as a chronic disease like any other, but with a twist.

Or this one about suicide, one of the complications of depression:

"Heart attack victims are consoled ('Isn't it a pity?'); suicide victims are cursed ('How could he?')."

About ECT:

We discount a therapy that has proven effectiveness because of its image, yet every day embrace unproven therapies that have benefited from a public-relations makeover.

To my opinion the most nuanced view on side-effects of ECT:

Memory loss seems the side effect of most concern to patients. With current ECT, it is usually transient, but any unauthorized withdrawal from the memory bank is a travesty. The medical community has occasionally shown insensitivity to this, but researchers are now attempting to better delineate the cause and effect.

Monday, August 20, 2007

Just watch, he is getting better

Homeopathy or poison for depression or mourning

Homeopathy claims that their pills go with your individual symptoms of depression and personality. Ignatius for instances cures "depression" after a loved one's death. Ignatius is made from the ignatius bean. Ignatius beans were frequently used as a cheap strychnine substitute for Strychnos nux vomica, strychnine. Ignatius beans are used chiefly as a homeopathic remedy, administered in very small doses because of extreme toxicity. Improper dosage-internal consumption of as little as a fraction of an ounce - can result in muscle spasms and painful convulsions and even death by asphyxiation.
Not only are homeopathic "medicines" usually expensive, their efficacy is not scientifically tested.
Recently there has been a debate about depression in the British Medical Journal. Gordon Parker defended the opinion that depression is over diagnosed. At first I didn't want to support his point of view, but calling mourning a depression as is done in this article promoting homeopathy for treating depression makes me uncertain again.

Sunday, August 19, 2007

Top 10 pdf tricks

In medicine as well as in other fields pdf files are widely used. A free reader from adobe is available. But if you need to do other things with the pdf files please go and see this article on lifehacker.com.
It has many suggestions for both Mac and Windows users.
The most important which I use a lot is:
1. merge pdf files
2. edit pdf files
3. save any file as pdf file.

10 Steps for doing better research

All you med students out there or other students. Here is an article on how to prepare a research paper.
On one of my favorite blogs on productivity, getting things done and lifehacks: lifehack.org.