Old Year/New Year Dutch Grand Ground – Grote visite 1.10

Welcome to the OLD YEAR/NEW YEAR edition of the ‘grote visite’ or Dutch Grand Rounds.

The theme of this Grand Round is past (what has been, history), present (hot news) and future (what to expect, wish, foresee).

We ring out the Old Year with two excellent posts of the dedicated bloggers and initiators of the Dutch Grand Round Jan Martens of MedBlog.nl and Dr. Shock of Dr Shock MD PhD

Jan Martens writes about Transcranial Magnetic Stimulation Historical Research. As some of you might know (I didn’t) Jan is conducting a historical research about the use of electricity and magnetism in psychiatry. Here he is focussing on video’s of Transcranial Magnetic Stimulation. He searched Youtube with “transcranial magnetic stimulation” and only found a handful of interesting modern videos, but no old videos of guinea pigs in a magnetic stimulator -which he had hoped for. He would be most obliged if you could help him out with historical videos or other information about TMS.
Dr Shock has already responded to his request, but has found no older video’s. Perhaps youtube is to young for historical video’s, but I can also imagine that researchers are reluctant to show guinea pig experiments to the general public.

Dr Shock MD PhD presents Dr Shock’s popular posts from 2008 and a look ahead for 2009. Dr. Shock wonders whether the popularity of his two most popular posts this year (at least according WordPress Blog Stats), i.e. Sex, Video Games and the Brain and How much Chocolate is Good for your Health? is mainly based on the title and keywords (or the picture? -see his post). He also gives an overview of other top posts and the posts he found the most pleasurable to write. This was a post about empathy in the doctor patient relationship, part of a series about patient doctor relationship and it’s different aspects such as education, self-disclosure to name a few as well the post Why do psychiatrists like detectives?
I share his idea that the most popular posts are not always the posts you enjoyed yourself the most and vice versa. I often wonder why some posts become popular and others don’t.

Dr Shock intends to focus more on the developments of health 2.0 and medical education in the coming year 2009. He made a first step this year to become member of the tweeple community at twitter. A useful community, isn’t it @DrShock?

Dr Shock also asks us which of his posts we enjoyed the most. I think the unanimous answer is: “We like them all, it is the mix”.

Please visit Dr Shock’s blog to read more.

That concludes this edition. Or perhaps it concludes the Dutch Grand Round…….

I took a look at the carnival submission form, but found no new rounds planned, perhaps because a new scheme is still to be made, or perhaps because it will end here and now….

I do hope the Dutch Grand round will be continued, because there are enough good Dutch medical bloggers around. The question is why just few of them actively contribute to this round? Hopefully 2009 will bring a change.

Photo credit: loesenlodewijk Flickr Creative Commons

Grand Round 5.15 at Moneduloides. At the interface of evolution and medicine.

The theme for the old year/new year Grand Round was not an easy one: “At the interface of evolution and medicine“. This theme was chosen to celebrate the coming bicentenary of Darwin’s birth, and the 150th anniversary of the publication of On The Origin of Species.

Moneduloides:

“Coming from the perspective of an individual who conducts medical research in evolutionary genetics, I have found that very few people outside of the world I work have been exposed to all of the ways evolutionary biology interfaces with medicine. My hope is that with this edition of Grand Rounds those who have not yet been exposed to this topic become, at the very least, sufficiently intrigued.”

Although there are less submissions than usual, the subject has been well covered by several bloggers. It has certainly triggered me to learn more about evolutionary biology and the implications on (clinical) medicine.

You can read the elaborate summaries at Moneduloides post here.

Interested in what Moneduloides means: it is derived from Corvus moneduloides, a crow species and the only non-primate animal known to invent new tools by modifying existing ones. Want to get a glimpse of Moneduloides, then read this article (“Evolutionary Biology Offers Glimpse Into Medicine’s Future”) in today’s Medscape Today!

Next Round is at Edwin Leap’s site.

Evolution and Medicine. Cancer and adaptive immune responses as evolutions ‘within’.

I had almost finished my submission for the Grand Round when I took a look at the site of the host, Moneduloides*, to find that this edition had “the interface of evolution and medicine” as a theme.

What should I write about, considering I only had a few hours to write about this difficult theme?

Quite coincidentally (or not, considering the forthcoming bicentenary of Darwin’s birth (1809) and the 150th anniversary of the publication of ‘On the Origin of Species’) the December 2008 Lancet is a Special Issue: Darwin’s Gifts. But it would be to easy to just summarize one or two articles from this Lancet issue…

Evolution and Medicine can be interpreted differently. One can just see it as the evolution of medicine. Enough to write about this theme….

One can also see the theme in the light of consequences of evolution on medicine or illnesses. Indeed there are ample examples of the consequences of men’s evolution on the susceptibility to certain illnesses, e.g. see moneduloides’ blog about the consequence of human bipedalism.

Yesterday @carlosrizo (twitter) pointed out a link to “Darwinian Medicine 2.0″. Since this would be of special interest to this web 2.0 audience, I took a look to see if I could ‘use’ this blogpost. However the post appeared to be based on a rather distorted interpretation of natural selection. Darwinian Medicine 1.0. is considered synonymous with eugenics (!), whereas Darwinian Medicine 2.0 is “gentler, interested in finding “evolutionary causes and remedies for diseases.” while leaving out the genocide”. The counterpart blog being intelligentdesign.org. it is easy to position their view.

Although this blog merits no further discussion, it highlights the often wrong interpretations of the natural selection theories. Eugenics is “just” a political interpretation by some of Darwin’s theorie (see Wikipedia). Darwin himself thought it “absurd to talk of one animal being higher than another” and saw evolution as having no goal.

As a biologist I grew up with the following definition of natural selection.

Natural selection is the process by which favorable heritable traits become more common in successive generations of a population of reproducing organisms, and unfavorable heritable traits become less common, due to differential reproduction of genotypes.

In other words natural selection genetic alterations are mostly random and chance (environment, conditions) will determine whether the genotype exhibiting a new phenotype will continue to exist or even will be more likely to survive (natural selection).

Antibiotic resistance
During my biology study we did all kind of mini-evolution experiments. For instance, we treated bacteria that were deficient for a specific amino-acid (AA) with mutagens and plated them on solid agar plates with or without that particular AA. Only bacteria with a mutation making them independent of that AA would survive on AA-less plates.

Although this is not an experiment of nature, a very similar example of natural selection in action is the development of antibiotic resistance in microorganisms (see wikipedia).

Enhancement of antibiotic resistance by natural selection - modified from wikipedia

Natural populations of bacteria contain considerable variation in their genetic material, primarily as the result of mutations. When exposed to antibiotics, most bacteria die quickly, but some (red in Figure) may have mutations that make them less susceptible. If the exposure to antibiotics is short, these individuals will survive the treatment. This selective elimination of maladapted individuals (lighter colors) from a population is natural selection.

Evolutions within
It is not difficult to see how infectious diseases were driven by natural selection (of the organisms causing these diseases). Because all rules that apply to eukaryotic organisms apply to prokaryotic organisms as well. But I would make a point that evolution and natural selection also takes place at a lower level: that of viruses (non-living organisms, see post about sputnik-virus here) and of “individual cells” within an organism. That is to say: the same mechanisms apply.

Clonal selection and B-cell adaptive immune response.
One example of a cellular evolution is the development of the B cell (and T cell) immune repertoire. B and T cells are cells of the adaptive immune response. In contrast to the innate immune response, which is always ready to respond to whatever intruder, the adaptive immune response matures throughout life, is antigen-specific and long-living. The specificity of B cells lies in the variable region of their immunoglobulins or antibodies, Y-like molecules, anchored in the B cells’ plasma membrane. There are endless antibody variants and each B cell (and its progeny) produces antibodies with one particular specificity.
How is this diversity established? In the Pre-B cell phase, when B cells do not produce any immunoglobulins individual gene segments coding for the V, (D) and J regions of the heavy and light chain of the immunoglobulin molecule are randomly assembled to one molecule. The random assembly of 51 V, 27 D and 6 J gene segments provides a minimum of 8.300 different possible combinations for the heavy chain alone, but since the recombination process is not precise and extra nucleotides are inserted the number of possibilities of antibody V region diversity turn out to be greater than that.[2]
(The following excellent animation is recommended: www.blink.biz/immunoanimations/ (be sure to choose Open > Antigen Recognition > Recombination)

When an organism encounters a foreign microorganism or other antigen, only those B cells that recognize the antigen are stimulated to divide and to become plasma cells which produce many antibodies specific for the particular antigen. This process is called clonal selection. It results in a B cell repertoire skewed towards the antigens encountered in life. The advantage is that those B cells are selected that have been proved useful. The next time the same antigen is encountered the response is quicker, stronger and more specific, a process called memory.This is also the principle behind vaccination and boostering.

The principle of clonal B cell selection is very similar to the development of antibiotic resistance, discussed above.

Carcinogenesis: Follicular Lymphoma
However, sometimes clones are selected that erroneously react with ‘self’ which results in ‘autoimmunity‘.

Cancer can also be considered as another faulty ‘evolution’, be it within the organism. Cancer cells are better at surviving and reproducing than other cells, because they have escaped the body’s controls. This allows them to increase their population much faster than other cells.

In an interesting editorial, J Breivik comments on the work of Vineis and Berwick[4,5]:

Vineis and Berwick argue that ‘Carcinogenesis, at least for some types of cancer, can be interpreted as the consequence of selection of mutated cells similar to what, in the theory of evolution, occurs at the population level’. Taking a more conclusive stand, I will ague that carcinogenesis is an evolutionary process within the multicellular organism. Evolution by means of natural selection is a scientific principle that reaches far beyond the origin of the species and is applicable to all systems of inheritance, including somatic development.

One example is follicular lymphoma (FL). Follicular lymphoma is characterized by a chromosomal translocation between chromosome 14 and 18, t(14;18), caused by a faulty coupling of the immunoglobulin heavy J chain to the BCL-2 proto-oncogene on chromosome 14 during the normal VDJ-rearrangement process, described above. This mistake leads to a constitutive overexpression of BCL-2, which makes the cell less vulnerable to apoptosis (programmed cell death). Mice bearing a transgene mimicking the BCL-2 translocation have an increased incidence of spontaneous B lymphoid tumors. The lymphomas take many months to develop, however, and the penetrance of disease is low, arguing that BCL-2 overexpression on its own is not highly oncogenic (reviewed in[6]). Indeed our group has shown many years ago that t(14;18) translocations, that were considered specific for follicular lymphoma generally occur in follicular hyperplasias [7] and even in B-cells of healthy individuals [8]. Apparently B cells with the t(14;18) translocation are regularly generated in normal individuals, but only very few cells with the translocation will acquire the additional oncogenic hits necessary to establish the malignant phenotype. Overexpression of BCL-2 only gives the cells a survival advantage. Indeed, according to recent insights [9]:

“Accumulation of genomic alterations and clonal selection account for subsequent progression and transformation. Recently, the role of the immunologic microenvironment of FL in determining clinical behavior and prognosis has been substantiated. Combined genetic and immunologic data may now support a model for the development of FL as a disease of functional B cells in which specific molecular alterations infer intrinsic growth properties of the tumor cells as well as dictate a specific functional cross talk with the immunologic regulatory network resulting in extrinsic growth support.”

The theme of this week inspired me to philosophize about immunity and cancer being examples of evolutionary process. While reading I found that this idea is by no means new; a lot has been written about this concept. For instance in “Understanding Evolution” the writer(s) quite nicely explain the process of evolution within a cell lineage. They first explain that the key elements of the evolutionary process – variation, inheritance, and selective advantage – characterize not just populations of organisms in a particular environment, but also populations of cells within our own bodies.
Furthermore they make the interesting statement that

“cancer – even within one person – isn’t a single entity. It’s a diverse and evolving population of cell lineages. A single tumor, for example, is made up of a variety of cell types, produced as the cells proliferated and incurred different mutations. All of this diversity means that the population of cells could easily include a mutant variety that happens to be resistant to any individual chemotherapy drug we might administer. To make matters even more difficult, treating the patient with that drug creates an environment in which the few resistant cancer cells have a strong selective advantage in comparison to other cells. Over time, those resistant cells will increase in frequency and continue to evolve. It’s not surprising then that a simple cure for cancer has yet to be developed: treating even a single type of cancer is a bit like trying to take aim at a whole set of moving targets all at once”

Thus, this challenge helps explain why research has not yet provided us with a cure, but also points the way toward new solutions that take that evolution into account ….

Sources:

1. Wikipedia (several pages, as indicated)
2. Kimball Biology Pages: [A] AgReceptorDiversity (very good background information in dictionary-format)
3. Evolving Immunity – A Response to Chapter 6 of Darwin’s Black Box. Matt Inlay. [blog] Talkdesign: interesting discussion on whether or not clonal selection system could have evolved in the context of irreducible complexity.
   
4. Cancer the evolution-within, by Dan [blogpost] on Migrations (2007/04/18) referring to:
5. Cancer – evolution within. Breivik, J. Int. J. Epidemiol. (2006) 35, 1161-1162.
6. The Bcl-2 family: roles in cell survival and oncogenesis. Suzanne Cory1, David C S Huang1 and Jerry M Adam. Oncogene (2003) 22, 8590-8607.
7. Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia. Limpens J, de Jong D, van Krieken JH, Price CG, Young BD, van Ommen GJ, Kluin PM. Oncogene. 1991 Dec;6(12):2271-6.(PubMed-link)(
8. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Limpens J, Stad R, Vos C, de Vlaam C, de Jong D, van Ommen GJ, Schuuring E, Kluin PM. Blood. 1995 May 1;85(9):2528-36.(PubMed-link)(Google Scholar)
9. Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic factors. de Jong D. J Clin Oncol. 2005 Sep 10;23(26):6358-63.(PubMed-link)
10. Another perspective on cancer: Evolution within. [blog] Understanding Evolution with a detailed description on natural selection within, and the evolution of cancer cells plus possible solutions.

Figures:

1. Antibiotic Resistance: wikipedia
2. Clonal Selection: http://users.path.ox.ac.uk/~scobbold/tig/clons.gif
3. Recombination: Evolving Immunity – A Response to Chapter 6 of Darwin’s Black Box, adapted from janeway
   

Grand Round 5.14 at ‘Highlight Health’

This week’s Grand Round is up at Highlight Health of Walter Jessen.

Besides of giving an overview of the this week’s medical blogposts Walter has also set up email and RSS subscriptions for a number of credible, rotating health and medicine blog carnivals, including THE Grand Round.
In addition there is an aggregate feed to all eight carnivals.

Grand Rounds Upcoming Schedule can also be consulted at: blogborygmi.blogspot.com.

The New Years Edition of Grand Rounds is being hosted by Moneduloides on December 30th.

Dutch Grand Round. Old Year, New Year Call for Submissions.

The Dutch Grand Round (De Grote Visite) is a rotating blogcarnival of Dutch medical blog posts.

Presently Dutch Grand Round 1.9 is up at Health Management RX of Jen McGabe Gorman

Laika’s MedLibLog will be Hosting the next Dutch Grand Rounds (1.10) on December 30th!

Since December 30th is on the edge of the old and new year, I would like this edition to focus on the past (what has been, history) and the present (hot news) and the future (what to expect, wish, foresee).

I will not restrict myself to inclusion of Dutch posts on medical, health and fitness: any post on Dutch health care, Dutch medicine 2.0 or Dutch scientific/clinical papers will be considered for inclusion as well. Whether it is about van Leeuwenhoek or the Dutch EHR. So, writers from abroad I hope you do feel inspired!

Do not feel constrained by this theme, however. Each article is reviewed on its own merit.

Submissions are due by Sunday, December 28st at 12.00 am (Dutch time). (06.00 pm EST).

You can submit your articles through Blog Carnival or by email at (laika dot spoetnik at gmail dot com – without spaces; well check the figure).

I look forward to your submissions! Have a nice Christmas!!!

—————-

De Grote Visite is een twee-wekelijkse ronde langs de medische blogs van Nederlandse bodem of ze nu in het Nederlands of het Engels geschreven zijn.

Terwijl de huidige grote visite (enigzins verlaat) te lezen is op Health Management RX van Jen McGabe Gorman, kondig ik alvast aan, dat

Laika’s MedLibLog gastvrouwe is van de volgende Grote visite (1.10). Deze staat gepland op 30 December!

Omdat 30 december op het scheidingsvlak staat van het oude en het nieuwe jaar, leek me dit een prima moment voor een voor en een achteruitblik:

Wat was belangwekkend (op medisch/gezondheidsgebied) in het verleden (mag ver voor 2008, maar ook recent), of wat zijn de verwachtingen, vooruizichten, wensen voor de toekomst?

Niet alleen Nederlanders mogen meedoen, het mag ook gaan OVER nederlanders/nederlandse gezondheidszorg, ontdekkingen, publicaties.

Ik zal me niet streng aan het thema houden. Elk ingediend stuk wordt op zijn eigen merites beoordeeld.

Indiening voor Zondag a.s. 28 December om 12.00 am. (06.00 pm EST).

U kunt uw artikelen via het Blog Carnival indienen of via email: laika punt spoetnik at gmail punt com – zonder spaties (zie figuur).

Ik kijk uit naar uw bijdragen. Een fijne Kerst alvast, allemaal!!

Nomination Best Medical Blogs at MedGadget

It is time for the 2008 Medical Weblog Awards!

Since 5 years Medgadget, an independent on-line journal covering the latest medical gadgets and technologies, organizes a competition “to showcase the best blogs from the medical blogosphere, and to highlight the exciting and useful role medical blogs play in medicine and in society.”

The categories for this year’s awards are:

• Best Medical Weblog
• Best New Medical Weblog (established in 2008)
• Best Literary Medical Weblog
• Best Clinical Sciences Weblog
• Best Health Policies/Ethics Weblog
• Best Medical Technologies/Informatics Weblog
• Best Patient’s Weblog

Nominations will be accepted until Wednesday, December 31, 2008. You can put your nominations (1 in each category) in the comments section on the Medgadget site.
An update of the current nominees is given here. For further information see here.

The OpenECGproject: an admirable Web 2.0 initiative

Web 2.0 is often considered to be a hype for techies, a buzz word. It certainly is not accepted as a reliable and useful tool in the official medical community, at least not the academic world where I work.

But Web 2.0 is more than just web 2.0 tools for geeks, it refers to changes in the ways software developers and end-users use the internet. “Web 2.0 is a trend in the use of World Wide Web technology that aims to facilitate creativity, information sharing, and, most notably, collaboration among users. i.e. by developing web-based communities such as social-networking sites, wikis and blogs.

A very nice example of a new medical use of web 2.0 is the openEGCproject, recently founded by the Kroatian Emergency Physician and IT-geek Ivor Kovic, I recently “met” on twitter.
It is mainly in the form of a wiki, and I fully agree with Giskin of Medical Humanities that this collaborative open-source wikis is very well designed and easy to navigate and not as cluncky as many other wiki’s which are out on the net.

The mission and goals of the openEGCproject are:

“To develop an open source, low cost, and clinically functional electrocardiography solution.
The ultimate goal is to produce a 12-lead PC-based ECG with interpretive software, but the first step is develop a 3-lead PC-based ECG, including both hardware and non-interpretive software. Additional goals include design versions for handheld devices and development of a wireless ECG device.

The main aim of the project is to enable doctors who have poor access to and/or can’t afford expensive commercially available medical equipment, i.e. doctors in developing countries, rural areas, outreach centers (Australia) to develop their own safe, low cost and clinically useful ECGs. It also serves an educational purpose.

The electrocardiogram (ECG) is a vital clinical tool doctors use to assess numerous and sometimes life threatening heart conditions, like myocardial infarction. It is important to have readily access to such a vital diagnostic tool.

The solution is open, which means “free”. It success depends on the contribution of volunteers.

With Medgadget, an independent on-line journal covering the latest medical gadgets and technologies, I would like to call on anyone to visit the site, http://www.open-ecg-project.org, promote it and recommend it to others, and if possible contribute to its content.

You can also stay up to date with the newest advancements, by subscribing to the openEGCproject blog or to follow the openEGCproject on Twitter.
In addition you can subscribe to their YouTube channel.

You can get Medgadgets for your blog or website here:

——-

Het openEGCproject is een initiatief van de Kroatische intensivist Ivor Kovic. Met anderen heeft hij een open wiki gemaakt met het doel om artsen die geen toegang hebben tot commercieel beschikbare ECG-programma’s toch in staat te stellen een ECG te maken. Het gaat dan vooral om artsen in de ontwikkelingslanden, die werken in afgelegen gebieden en/of die niet over voldoende financiele middelen beschikken. Het is een open source project, hetgeen wil zeggen dat het vrij beschikbaar is voor idereen èn dat iedereen eraan mee kan werken. Het uiteindelijk succes hangt daarmee ook af van de inbreng.

Het open-ecg-project is een wiki, die u hier kunt bezoeken. Het is erg overzichtelijk en goed van opzet. Indien U wilt kunt u er ook een inhoudelijke bijdrage aan leveren. U kunt ook op de hoogte blijven door een feed te nemen op het blog van het openEGCproject of door het openEGCproject op Twitter te volgen. Het openEGCproject heeft ook een eigen YouTube kanaal, waarin o.a. een video is over het openEGCproject (niet al te beste kwaliteit).

Hier kunt u codes voor Medgadgets voor op uw blog of website vinden, zoals:

Grand Round 5.13 at ‘A Chronic Dose’

This week’s Grand Round is up at A Chronic Dose.

Since the end of 2008 is in sight, Laurie Edwards theme was “the best of 2008″.
Laurie:

So, please send along what you think is your “best” post of the year…and why. Whether it’s your funniest post, the one that was the hardest to write or stirred up the most dialogue, or touched on a topic that really matters to you, etc, I want to see it.

I found it difficult to choose which one was ‘best’. There really is not ONE particular best post, it is the mix. So I submitted 3 posts and let Laurie decide. Want to see what she selected and get an overview of the best medical blogpost over 2008, then visit Laurie’s grand round here.

Highlight Health will host next week’s edition.

Grand Rounds Archive & Upcoming Schedule can be consulted at: blogborygmi.blogspot.com.

Furthermore a RSS-feed has been made to the Grand Round by Marshall Kirkpatrick.

Here’s the feed: http://feeds.feedburner.com/GrandRoundsFeed, but you can also to subscribe by email (see form here)-

Yet Another Negative Trial with Vitamins in Prostate Cancer: Vitamins C and E.

Within a week after the large SELECT (Selenium and Vitamin E Cancer Prevention) Trial was halted due to disappointing results (see previous posts: [1] and [2]), the negative results of yet another large vitamin trial were announced [7].
Again, no benefits were found from either vitamin C or E when it came to preventing prostate ànd other cancers.
Both trials are now prepublished in JAMA. The full text articles and the accompanying editorial are freely available [3, 4, 5].

In The Physicians’ Health Study II Randomized Controlled Trial (PHS II), researchers tested the impact of regular vitamin E and C supplements on cancer rates among 14,641 male physicians over 50: 7641 men from the PHS I study and 7000 new physicians.

The man were randomly assigned to receive vitamin E, vitamin C, or a placebo. Besides vitamin C or E, beta carotene and/or multivitamins were also tested, but beta carotene was terminated on schedule in 2003 and the multivitamin component is continuing at the recommendation of the data and safety monitoring committee.

Similar to the SELECT trial this RCT had a factorial (2×2) design with respect to the vitamins E and C [1]: randomization yielded 4 nearly equal-sized groups receiving:

• 400-IU synthetic {alpha}-tocopherol (vitamin E), every other day and placebo (similar to the SELECT trial)
• 500-mg synthetic ascorbic acid (vitamin C), daily and placebo
• both active agents
• both placebos.

Over 8 years, taking vitamin E had no impact at all on rates of either prostate cancer (the primary outcome for vitamin E), or cancer in general. Vitamin C had no significant effect on total cancer (primary outcome for vitamin C) and prostate cancer. Neither was there an effect of vitamin E and/or C on other site-specific cancers.

How can the negative results be explained in the light of the positive results of earlier trials?

• The conditions may differ from the positive trials:
  • The earlier positive trials had less methodological rigor. These were either observational studies or prostate cancer was not their primary outcome (and may therefore be due to chance). (See previous post The best study design for dummies).
  • Clinical data suggest that the positive effect of vitamin E observed in earlier trials was limited to smokers and/or people with low basal levels of vitamin E, whereas animal models suggest that vitamin E is efficacious against high fat-promoted prostate cancer growth (20), but lacks chemopreventive effects (i.e. see [1,4] and references in [5], a preclinical study we published in 2006).
    Indeed, there were very low levels of smoking in the PHS II study and the effect of the vitamins was mainly assessed on induction not on progression of prostate cancer.
  • Eight times higher vitamin E doses (400IE) have been used than in the ATCB study showing a benefit for vitamin E in decreasing prostate cancer risk! [1,4]
• Other forms of vitamin E and selenium have been proposed to be more effective.
• As Gann noted in the JAMA-editorial, the men in both recent studies were highly motivated and had good access to care. In SELECT, the majority of men were tested for PSA each year. Probably because of this intense surveillance, the mean PSA at diagnosis was low and prostate cancers were detected in an early, curable stage. Strikingly, there was only 1 death from prostate cancer in SELECT, whereas appr. 75-100 deaths were expected. There also were indications of a deficit in advanced prostate cancer in PHS II, although a much smaller one.
  In other words (Gann):
  “how can an agent be shown to prevent serious, clinically significant prostate cancers when PSA testing may be rapidly removing those cancers from the population at risk before they progress?”
• Similarly, in the SELECT trial there was no constraint on the use of other multivitamins and both studies put no restriction on the diet. Indeed the group of physicians who participated in the PHS II trial were healthier overall and ate a more nutritious diet. Therefore Dr Shao wondered
  “Do we really have a placebo group – people with zero exposure? None of these physicians had zero vitamin C and E” [7]. In the Netherlands we were not even able to perform a small phase II trial with certain nutrients for the simple reason that most people already took them.

What can we learn from these negative trials (the SELECT trial and this PHS II-trial)?

• Previous positive results were probably due to chance. In the future a better preselection of compounds and doses in Phase 2 trials should determine which few interventions make it through the pipeline (Gann, Schroder).
• Many other trials disprove the health benefits of high dose vitamins and some single vitamins may even increase risks for specific cancers, heart disease or mortality [9]. In addition vitamin C has recently been shown to interfere with cancer treatment [10].
• The trials make it highly unlikely that vitamins prevent the development of prostate cancer (or other cancers) when given as a single nutrient intervention. Instead, as Dr Sasso puts it “At the end of the day this serves as a reminder that we should get back to basics: keeping your body weight in check, being physically active, not smoking and following a good diet.”
• Single vitamins or high dose vitamins/antioxidants should not be advised to prevent prostate cancer (or any other cancer). Still it is very difficult to convince people not taking supplements.
• Another issue is that all kind of pharmaceutical companies keep on pushing the sales of these “natural products”, selectively referring to positive results only. It is about time to regulate this.

Sources & other reading (click on grey)

1. Huge disappointment: Selenium and Vitamin E fail to Prevent Prostate Cancer.(post on this blog about the SELECT trial)
2. Podcasts: Cochrane Library and MedlinePlus: (post on this blog)
   
3. Vitamins E and C in the Prevention of Prostate and Total Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial. J. Michael Gaziano et al JAMA. 2008;0(2008):2008862-11.[free full text]
   
4. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial. Scott M. Lippman, Eric A. Klein et al (SELECT)JAMA. 2008;0(2008):2008864-13 [free full text].
   
5. Randomized Trials of Antioxidant Supplementation for Cancer Prevention: First Bias, Now Chance-Next, Cause. Peter H. Gann JAMA. 2008;0(2008):2008863-2 [free full text].
   
6. Combined lycopene and vitamin E treatment suppresses the growth of PC-346C human prostate cancer cells in nude mice. Limpens J, Schröder FH, et al. J Nutr. 2006 May;136(5):1287-93 [free full text].
   
   News
   
7. The New York Times (2008/11/19) Study: Vitamins E and C Fail to Prevent Cancer in Men.
8. BBC news: (2008/12/10) Vitamins ‘do not cut cancer risk’.
9. The New York Times (2008/11/20) News keeps getting worse for vitamins.
10. The New York Times (2008/10/01) Vitamin C may interfere with cancer treatment.

Podcasts: Cochrane Library and MedlinePlus

I added two podcasts to the Google-speadsheet wiki: Best Medical podcasts, made by Ves Dimov (see my previous post here): Cochrane reviews and Medline Plus.

Ves Dimov has described his top 5 podcasts in another post [1]. For other medical podcasts see [2,3,4].

A podcast is nothing more than a digital audio or video file, just like any other song or MP3 file on your computer. They can be listened to, saved and shared on the internet. Although podcasts were initially meant for i-pods (hence podcast), you can also subscribe to podcasts by other Podcast-readers, Web browsers or RSS-Readers.

I would like to shortly review the two podcasts.

1. Cochrane Reviews (Click here for Feed)

The Cochrane Library, published by John Wiley for The Cochrane Collaboration, is updated and expanded every three months.
The Cochrane podcasts are freely available audio summaries of:

• highlights of each quarterly issue. This is just a summary of main topics. Example below (with bad handling of the microphone):

• a selection of systematic reviews from The Cochrane Library. I found the ones below very interesting and may blog about them later.
  It is often said that Cochrane Reviews are difficult to understand and that even physicians find them hard to read. The podcasts I’ve heard are very informative and understandable for doctors, journalists, librarians and patients. The essentials of the conclusions are very clear. I think it would be a good thing if all Cochrane Reviews were podcasted this way.

Adverse events of formoterol (and salmeterol) in asthma

St John’s wort for major depression

Cochrane Podcasts of issue 4 2008: you can listen or subscibe to and/or download/embed the podcasts

2. MedlinePlus (click here for feed)

The MedlinePlus podcasts is a weekly series of highlights of health news and accompanying information from MedlinePlus.The update is generally given by Donald A.B. Lindberg, M.D., Director of the National Library of Medicine.
It is very clearly indicated how you can listen or subscribe to these podcasts. There is also a transcript.

The last audio is about the negative results of the huge Vitamine E-Selenium (SELECT) Prostate Cancer, I described almost a month ago in this post.
It is rather long (with disclaimers and links like “go to double u double u double u …dot com etcetera”), but understandable and about interesting topics.

More Reading, viewing or listening (click on grey):

1. MD Ves Dimov has described his top 5 podcasts, including JAMA Audio Commentary and NEJM This Week podcast at his blog. He also gives a short description how you can subscribe to the podcasts/videocasts.
2. Very good and complete medical podcasts-directory at learnoutloud.com. Not only podcast-series, but also individual podcasts, such as class lessons of statistics (which are difficult to follow without seeing figures) or psychology.
   
3. Dean Giustini: [pdf] “Podcasting” howto + select list of medical podcasts http://weblogs.elearning.ubc.ca/googlescholar/CHLA_ABSC_podcasting.pdf
4. See also:Dean Giustini, UBC Health and Library Wiki: Podcasts and Videocasts (very comprehensive!)
5. And if you want to know more why podcasts are useful than view this short commoncraft you-tube video.

——-

Een podcast is gewoon en digitaal audio of video bestand, net als elk ander MP3 bestand op je computer. Je kunt ze beluisteren, downloaden en delen. Hoewel podcasts oorspronkelijk voor i-pods bedoeld waren (vandaar podcast), kun je je ook op podcasts abonneren via andere Podcast-readers, Web browsers of RSS-Readers.

Hier bespreek ik twee podcasts die ik aan de Google-speadsheet wiki Best Medical podcasts heb toegevoegd (zie eerder bericht): Cochrane reviews en Medline Plus.

Ves Dimov heeft zijn top 5 podcasts op zijn blog beschreven [1]. Voor andere medische podcasts, zie [2,3].

1. Cochrane Reviews (Klik hier voor feed)

The Cochrane podcasts zijn gratis audio samenvattingen van:

• De belangrijkste onderwerpen van elke 3-maandelijkse update van de Cochrane Library.

• Een aantal geselecteerde systematische reviews uit de Cochrane Library. Ik vond onderstaande reviews erg interessant en zou willen dat er vergelijkbare podcasts gemaakt werden voor elk Cochrane review. De meeste mensen vinden Cochrane Reviews erg moeilijk te lezen, maar de podcasts zijn zeer begrijpelijk (ook voor patienten) en brengen goed de essentie van de studies over.
  
  Bijwerkingen van formoterol (en salmeterol) bij asthma asthma
  St Janskruid bij ernstige depressie

2. MedlinePlus (klik hier voor feed)

Medline Plus podcasts zijn een wekelijkse serie van hoogtepunten uit het gezondheidsnieuws van de MedlinePlus. De update wordt meestal verzorgd door Donald A.B. Lindberg, M.D., baas van de National Library of Medicine.
Het wordt duidelijk aangegeven hoe je de podcasts kunt beluisteren en hoe je een abonnement (feed) kunt nemen. Er is ook een transcript. Dit heb je er wel een beetje bij nodig. De tekst is verder duidelijk, maar erg droog en lang (incl disclaimers en links. “go to double u double u double u …dot com etcetera”).

Hier is een audio van de laatste week over de negatieve resultaten van de grootschalige Vitamine E-Selenium (SELECT) prostaat kanker trial, Idie ik een maand geleden reeds op dit blog beschreef.

Meer lezen: zie links in engelstalig gedeelte.

Google spreadsheet as a wiki.

Google has developed so many new applications in short time, it is difficult to keep abreast of the latest developments.

One useful application is Google Docs. which is a free, Web-based word processor, spreadsheet, presentation, and form application offered by Google. It allows users to create and edit documents online while collaborating in real-time with other users.

During the Spoetnik Library 2.0 course we used Google Docs to write documents together, which we published on our blogs.

You can also choose to keep documents private. The advantage compared to MS Office is that you can access your docs anywhere from the web. All you need is to log into your Google account.

Ves Dimov of the Clinical Cases and Images – Blog draw my attention to an option in Google Spreadsheets (try-out here) , whereby you can allow people to edit the item as if it were a wiki.

This option was described at the Google Operating System Blog, with unofficial news and tips about Google) as follows:

“Google Spreadsheets added an option in the sharing dialog that allows anyone to view or edit the spreadsheet just by knowing the URL. Until now, you had to send an invitation URL that contained a secret code and the people you invited had to login using a Google account. If you click on the Share tab and enable “Let people edit without signing in*“, your spreadsheet becomes a wiki that can be edited by anyone.”

Not only has Ves described this possibility in a blogpost, he also set up a spreadsheet that lists “The best medical podcasts”.** Anybody can edit the list, see the original spreadsheet here and you are all invited to do so..

According to Ves (and Google) you can easily embed the Medical Podcast spreadsheet by just copying this HTML code in your own website. Alas, WordPress.com blogs appear to be a notable exception (again Grrr!).

Thus, to see how the spreadsheet evolves you have to go to the URL, Ves’s blogpost here or embed the spreadsheet yourselves.

To give you an impression I will show a figure of the (provisional) embedded spreadsheet instead:

* original text: Anyone can edit this document WITHOUT LOGGING IN

** a closer look at the date revealed that the blogpost already stems from May 2008.

————

Google Spreadsheets (try-out hier) is een, gratis, Excel-achtig bestand binnen Google Docs waar je online vanaf elke PC met internetaansluiting aan kunt werken, – zonder gebruik te hoeven maken van usb-sticks of e-mail- (zie Spoetnik-cursus, week 8). Je kunt alleen of samen aan een document werken.

Door Ves Dimov van het Clinical Cases and Images – Blog werd ik geattendeerd op een optie binnen Google Spreadsheets, waardoor mensen niet ingelogd hoeven te zijn om mee te werken aan je spreadsheet. De spreadsheet functioneert dan als een soort wiki.

Deze mogelijkheid werd reeds in mei dit jaar beschreven op het Google Operating System Blog. Wanneer je een Google spreadsheet hebt aangemaakt, kun je in het dialoogvenster aangeven dat je de spreadsheet wilt delen (“share tab“) en dat mensen het kunnen bewerken zonder in te loggen (“Let people edit without signing in*). De URL, (gemarkeerd bij 4 in bovenstaand figuur) kun je naar andere mensen sturen die het vervolgens kunnen bewerken. Belangrijk is om de spreadsheet daarna op te slaan en af te sluiten.

Ves heeft gelijk de daad bij het woord gevoegd en een lijst van beste medische podcasts toegevoegd, die eenieder kan bewerken. De oorspronkelijke spreadsheet vind je door hier te klikken.

Mij lukte het niet om deze spreadsheet te embedden in WordPress. Dus om de lijst van beste medische podcasts “real time” te kunnen zien kun je naar Ves’s blogpost gaan, de URL bekijken en/of deze zelf embedden.

Internet Cool Tools for Physicians [book]

The well known medical librarian-geek David Rothman of Davidrothman.net contributed to a (probably) very cool book:

Internet Cool Tools for Physicians
Rethlefsen, Melissa L., Rothman, David L., Mojon, Daniel S.

Bibliographic information: 2009, XIV, 154 p. 79 illus., Softcover
ISBN: 978-3-540-76381-9

It can be obtained from amazon.com or from Springer Publishing. It costs appr. $30.

I immediately wanted to order it, but even in the US it is not available for another month….

Sources:

• Twitter: search.twitter.com: tweets of @berci, @allergynotes and @laikas
  
• Davidrothman.net: “The Book” (blogpost)
• Springer.com: more info on the content.
  

Twitterview with Berci of Scienceroll

If you are a reader of this blog you probably know that Twitter is a popular social networking and “micro-blogging” service that allows you to send updates of maximal 140 characters, also called tweets.

New to my vocabulary is Twitterview. This is an interview held via Twitter. Questions and answers are therefore constricted to 140 characters.

Today at 12:00 EST @Berci (Bertalan Meskó) was twitterviewed by @diariomedico of Diariomedico, a Spanish Medical Site.

Bertalan is a Hungarian medical student, writer of the blog Scienceroll, founder of Webicina, tutor in and connaisseur of web 2.0 tools. He also hosts several blog carnivals. And he uses Twitter as one of the web 2.0 tools to keep informed.

You can still read the short questions and answers in the characteristic 140 character-long format here: http://tinyurl.com/6dd4fs, which is a twittersearch for (@diariomedico OR #DM1) since:2008-12-10 until:2008-12-10.
Alternatively, you can perform a search yourselves at Twittersearch and take a feed to the query, i.e. to follow upcoming twitterviews of @diariomedico.

A short note of Berci on his interview is posted at his own blog (here)

A selection of (mainly) answers appears below.

Temporary Wrong OVID EMBASE Source Field.

This post is only of interest to those who regularly search the EMBASE database from OVIDSP and load the records into Reference Manager or other reference management software, like Procite.

My colleague, Arnold, noticed that off half November the EMBASE records wouldn’t load properly into Reference Manager. This was due to the inclusion of the Publisher in the Source field.

New:
Source European Journal of Surgical Oncology. W.B. Saunders Ltd. 34(12)(pp 1285-1288), 2008. Date of Publication: December 2008.

Old:
Source European Journal of Surgical Oncology. 33(4)(pp 524-527), 2007. Date of Publication: May 2007.

Unfortunately it was not possible to make a new, completely working EMBASE-import filter.

Meanwhile our library has contacted OVID and they have restored the problem quite smoothly. The problem was apparently caused by the EMBASE reload of November 17th.

If you have loaded EMBASE records during the last 3 weeks it might be worthwhile to reload them in your reference manager software. Old EMBASE-filters should do the thing.