Silly Sunday #42 Open Access Week around the Globe

23 10 2011

Open Access logo and text

Open Access Week, a global event now entering its 5th year, “is an opportunity for the academic and research community to continue to learn about the potential benefits of Open Access, to share what they’ve learned with colleagues, and to help inspire wider participation in helping to make Open Access (OA) a new norm in scholarship and research”.

It takes place from October 24 to 30 in many places around the globe.

Benjamin Hennig, whose PhD research was built on the work of the Worldmapper project (see earlier post here) created and updated a map of this year’s OA- activities together with SPARC (Scholarly Publishing and Academic Resources Coalition), who are the organisers of the event.
It is a positive trend that India and parts of Africa have many OA-activities next week. (they are relatively large on the map, especially when compared to proportion of scientific papers produced in the world, as shown on Worldmapper).

For further information see the blog post of Benjamin Hennig at his blog: Views of the Worlds.

You can follow Worldmapper at Facebook.





Complementary Medicine & Pharmacists

30 11 2009

I don’t know if the situation is the same in other countries, but in the Netherlands we can only get prescribed medications in pharmacies. Drugstores are only allowed to sell over-the counter (OTC) medicines.

Most Pharmacies have a small shop of 5 square meters (besides a large storage room). What surprises me is that the counter is not only full with non-allergic creams, and the shelves are not only filled with liquorice and plasters, but the counter and shelves predominantly display naturopathic and herbal “medicines”. In this flu-season there are even leaflets how to prevent flu with all kinds of naturopathic medicine. Dr Vogel’s Echinaforce “helps to augment your natural resistance, lowers the risk of flu and shortens the duration or decreases the severity of symptoms once you have the flu” (..”vermindert u de kans op griep en herstelt u sneller als u toch ziek wordt“). Apparently A Vogel.nl (via Biohorma) started a campaign in the Netherlands. At their website there is even an advertisement for an offer by an insurance company -OHRA- because it generously refunds homeopathic medicine. Biohorma also made a You-Tube video.
In contrast, in the US there is a disclaimer at the Echinaforce site:” These statements have not been evaluated by the Food and Drug Administration (FDA). This product is not intended to diagnose, treat, cure or prevent any disease.”

There is no evidence that Echinacea prevents flu (see Cochrane Review and de Volkskrant [Dutch newspaper referring to clinical trials]), although it is not excluded that it helps for the early treatment of colds in adults.

Isn’t such a promotion of ineffective stuff a bad advice considering we have  a real flu-epidemic, and given the inverse relationship between pediatric vaccination and CAM usage (see Respectful Insolence)?

It is quite confusing, however, because Echinacea is advertised as an homeopathic medicine, whereas it seems a herbal medicine (not diluted ad infinitum). To date there is no evidence that homeopathy ‘works’. All 6 published Cochrane systematic reviews with ‘homeopathy’ or ‘homeopathic’ in the title conclude that there is little or no evidence that it works beyond the placebo-effect.

During the recent The House of Commons Science and Technology Committee meeting calling in homeopaths and scientists to discuss evidence for the alternative therapy Prof. Dr Ernst (with experience as a homeopath) said: “I have supplied a list of systematic reviews of homeopathy. There are two dozen. None in that list were positive.” (see this excellent summary of the meeting by Ian Sample). For the entire memorandum of Dr Ernst see here.

Besides that the clinical trials are ineffective, the whole theory is incompatible with the laws of physics and chemistry.

Nevertheless:

  • There is a lot of homeopathic research going on, i.e. funded by the NHS (National Health Sevice) in the UK and the NCCAM (National Center for Complementary and Alternative Medicin, NIH) in the US.
  • In the UK homeopathic medicine is endorsed by the MHRA (Medicines and Healthcare products Regulatory Agency)
  • CAM is booming business (£1.5bn industry in the UK)
  • CAM is covered by insurance companies.
  • CAM is sold and sometimes advocated by pharmacists.

Thus all over the world people are buying these ineffective homeopathic medicines while believing they ‘work’, or at least cause no harm. However, while homeopathic medicines may not harm themselves, they may cause harm if they are used in place of proven treatment for any life-threatening illness.” Indeed the WHO has warned people with conditions such as HIV, TB and malaria not to rely on homeopathic treatments (BBC NEWS 20 August 2009

For me it is incomprehensible, that pharmacists who are trained in pharmacology and chemistry (at the University Level), just sell those ineffective costly water-dilutions and advocate them directly or indirectly by putting them on the shelves, providing ample leaflets and brochures and giving positive “advise”. What could be the reason for doing that other than ignorance or MONEY?


Recommended Reading:

Photo Credits

  1. Pharmacists mortar and pestle http://commons.wikimedia.org/wiki/File:PharmacistsMortar.svg
  2. Homeopathic Medicine on the shelves http://www.flickr.com/photos/caseywest/ / CC BY-SA 2.0
    (this photo has nothing to do with the subject)
, but all kind of complementary medicine (CAM).
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Martin Bril: the Author, his Death and his Cancer

23 05 2009

Martin BrilMartin Bril is dead.

No “news“, it happened a month ago: April 22.

Martin Bril was a well known Dutch writer, poet and columnist – and the man who invented “skirt day”.

He loved live -and love- in all it’s simplicity. He needed few words to describe the essence of things or as he would say: “The surface is deep enough”. But you know, it is looking at one drop of water and understanding the ocean.

Other expressions: “Good is better than bad” and “You’ve people that bang the guitar really hard for hours, but I rather hear J.J. Cale. Always finished within 4 minutes, but the music stays with you.”

I liked his stories/columns most of the time, they often made me smile.

It is always sad when somebody dies young (Martin was 49), whether a “celebrity” or not. Especially when he leaves two young children and a wife.

I didn’t expect it and it really hit me. Why? I knew he had had cancer, but I thought it had gone. So did he a few years ago. I found a video-interview with him in 2007, where he said: “soon I will be declared “cured” – but then you will see it will return the other day.” In another interview I read: You never beat cancer”, that’s Lance Armstrong-language. Cancer goes away or it stays. It often stays.

I always thought he had colon cancer, but it was esophageal cancer. That’s the trouble with Dutch:Martin Bril Donkere Dagen

  • esophagus = slokdarm,
  • jejunum, ileum = dunne darm
  • colon = dikke darm.

Notice they all have “darm” in them. Mostly colon cancer is called “darmkanker” (or “dikke darmkanker”), and because esophagus is called slokdarm, slokdarmkanker is mistaken for darmkanker, which is quite another disease with other prospects.

Stupid, journalists keep on using the wrong name. Not that it matters a lot now, but still.

More “incorrect” was the fact that I first saw the announcement of his death in a newsletter from dokterdokter.nl (below). It is an online medical information site for patients. I have been getting their newsletter for years now, because -for one thing or another- I’m unsuccessful in unsubscribing to it. Dokterdokter.nl is typically a website that gives very general information, mostly leading to the advise “to check your doctor first”.

dokterdokter Martin Bril geheel

What struck me (besides the fact that I was taken by his death) was that his death was presented as Medical News, next to an enormous “oral sex” headline and the headline “what happens if you die?”. As if it was a tabloid. The message (he died the day before):

Martin Bril finally succumbed to esophageal cancer at the age of 49. Esophageal cancer has a bad prognosis. Why?
(if you click: )

“Martin Bril, the well known author …, died of esophageal cancer at the age of 49. He was a real hedonist. Cigarettes and alcohol were part of his life. Many years he had fought cancer, but Wednesday April 22 he lost his fight. Few people really completely recover from this illness.”

(….) Generally, the disease has to do with your lifestyle. In Western Countries, smoking and excessive alcohol consumption are the most important causes of esophageal cancer.

And then it continues summarizing the brochure of the Dutch Cancer Society (KWF- kankerbestrijding)

Whereas most medical sites (including the Dutch Cancer Society, from which all the information was taken) just neutrally say that the cause is unknown, but that alcohol and smoking are known risk factors for esophageal cancer, -and even more so in combination- dokterdokter puts a direct link between Martin’s lifestyle and his death, as if it was his own fault. Maybe it was, but at that moment I didn’t want to know. It didn’t matter. I found it disrespectful, tasteless. I’m quite interested in health and medicine and mechanisms, but the reason of his death -at this moment- was less important than his death itself.

As a matter of fact, Martin stopped using liquor and cocaine in 1997 after given an ultimatum by his wife (“you have two young kids!”) and after attending a trial of a drug baron (Johan V., de Hakkelaar) (to write about). He also wanted to quit smoking. I don’t know whether he succeeded, but he helped STIVORO (“for a smokeless future”) with their campaign (2002) by writing a beautiful column and making a video about (the difficulty of) quitting smoking. “I stopped smoking, because I didn’t like it anymore. Moreover, my kids didn’t want me to die because of smoking……..”

How much better was the reaction of STIVORO to the death of Martin, saying “we have lost a talented author” and thanking him for his input. Just a short notice and ending with the column Martin had written for them: “Did you ever tried to quit smoking?…I did”.

——————73554771_f75ce49f1a rokjesdag

Bij Nederlanders hoef ik Martin Bril nauwelijks te introduceren. Dat ik hier over hem schrijf heeft vooral te maken met het stukje dat ik in de nieuwsbrief van Dokterdokter.nl las. In feite was het dit bericht, waardoor ik wist dat hij gestorven was. Voor mij een schok. Ik lees de Volkskrant niet meer, dus het was mij ontgaan dat het slecht met hem ging. Het is ook een jonge vent, jonger dan ik, met twee dochters, net als ik. Zo kom het altijd nog een beetje dichterbij. En hij kon mooi schrijven. “De oppervlakte was diep genoeg,” zo zei hij, maar het was bij hem net of je in een druppel de hele oceaan kon zien.

Voor het eerst zag ik trouwens dat hij slokdarmkanker had. De meeste journalisten spraken van darmdanker, waar men in de regel toch dikkedarmkanker mee bedoelt. Slokdarmkanker is een heel andere ziekte, met een heel andere prognose. Vreemd dat het meerendeel van de journalisten het toch steeds over darmkanker heeft

Maar dit terzijde. Ik vond het vreemd, dat het bericht als een “nieuwsaankondiging” stond naast de kop “orale sex” en “hoe voelt het als je dood gaat”. Misschien had Martin er wel om kunnen lachen, maar ik vond het bizar. Het verhaal zelf vond ik ook nogal ongepast.

Wat stond er?

De ziekte slokdarmkanker werd schrijver Martin Bril op zijn 49e fataal. Het is een ziekte met slechte vooruitzichten, mede omdat het vaak laat wordt ontdekt.

“Schrijver Martin Bril, bekend van boeken als De kleine keizer en Arbeidsvitaminen en van zijn columns in de Volkskrant, is op 49-jarige leeftijd aan slokdarmkanker overleden. Hij was een echte levensgenieter, sigaretten en alcohol waren een vast onderdeel van zijn leven. Al vele jaren streed hij tegen kanker, maar woensdag 22 april was zijn strijd gestreden. Maar weinig mensen weten volledig te herstellen van deze ziekte.”De ziekte heeft meestal te maken met de leefstijl van mensen. Roken en overmatig alcoholgebruik zijn in Westerse landen de belangrijkste oorzaken voor het ontstaan van slokdarmkanker.

Andere bronnen -ook de KWF-brochure, waar dit stuk aan ontleend is, schrijven steevast dat de oorzaak niet bekend is, maar dat roken en alcohol (vooral in combinatie) de belangrijke risicofactoren zijn. Mogelijk is zijn leefwijze inderdaad de belangrijkste reden geweest dat hij slokdarmkanker heeft gekregen. Nou en? Is het nodig om dit zo op te schrijven? Een dag na zijn dood? Ik vond het nogal oneerbiedig. Misschien dacht men bij dokterdokter.nl dat het schrikeffect mensen zou weerhouden om veel te roken en te drinken, want “kijk, daar krijg je slokdarmkanker van!!” Behalve dat dokterdokter niet bepaald het juiste publiek (de “zelfkanters” en “hedonisten”) zal bereiken, zal zo’n actie sowieso weinig zoden aan de dijk zetten. Dan was Martin’s bijdrage aan de Stivoro campagne “stoppen met roken” (2002/2003) waarschijnlijk veel effectiever. Hij schreef een column voor ze en werkte mee aan een video.

Martin zei: “Ik stopte met roken omdat ik er geen zin meer in had. Bovendien; mijn kinderen vonden dat ik er niet dood aan moest gaan”. Eerder, na een ultimatum van zijn vrouw en het bijwonen van een zitting tegen de drugsbaron de Hakkelaar, was hij al gestopt met alcohol en coke.

Zo anders was ook de reactie van Stivoro. Niets vingertje wijzen: “zie je wel!”, maar dit:

“Samen met de rest van Nederland treurt STIVORO om het heengaan van een bijzonder mens en groot schrijver: Martin Bril

STIVORO heeft Martin leren kennen toen hij zich enthousiast inzette voor onze ‘Stoppen met roken’ campagne van 2002/2003. Hij was toen bereid zijn persoonlijkheid en zijn schrijftalent voor deze campagne in te zetten.

Wij zijn dankbaar dat we met hem hebben mogen samenwerken. We wensen zijn familie en andere dierbaren heel veel sterkte toe.

Hij schreef voor ons de volgende column:

“Bent u wel eens gestopt met roken?
Ik wel……..”

Photo Credit (CC):





What I learned in 2008 (about Web 2.0)

2 02 2009

Grand Round is a weekly collection of the best writing in the medical blogosphere. The coming Grand Rounds (February 3rd, 2009), hosted by Not Totally Rad has the following theme:

February is the first anniversary of my blog. Therefore, the loose theme for submissions will be anniversary-related: write about something cool or important that you’ve learned in the past year.

Well, I have learned a lot in the past year. The most profound personal experience was the death of my father. I experienced how it is to loose a beloved, but I also learned that death and grieve can affect people so deeply that it changes their behavior. I now understand this behavior (anger, mental confusion) is a manifestation of deep grief, which is transient and natural. Luckily our body and mind appear very resilient.

I will restrict to another thing I’ve learned: Web 2.0.
Just like the “Samurai Radiologist” I started a blog in February 2008. Thus Laika’s MedLibLog also celebrates its first anniversary.

Useful Web 2.0 tools

This blog was started as a tool to communicate thoughts, new found skills and ideas with other (>150) SPOETNIK course members, Spoetnik being a Learning 2.0 project to encourage library staff to experiment and learn about the new and emerging Internet technologies.

During the library 2.0 course I learned the basics of blogging, chatting, RSS, Podcasts, Wiki’s and social bookmarking. Each week another item was addressed. This learning program had a direct and positive impact. For instance, I could inform my clients how to create a RSS-feed for PubMed searches. By taking RSS-feeds/email alerts to interesting blogs, wiki’s and journals I kept better informed.

Hard to imagine (now) that I hardly new anything about web 2.0 one year ago.

Web 2.0 is not just a set of tools.

In the beginning I considered blogging largely as a selfish activity. It also appeared a lonely activity. As long as we discussed a course assignment there always was an interaction with at least a handful of other participants. But as soon as the program came to an end, I started to write more and more about medicine, EBM and medical library related matter, which didn’t appeal to most of the other course members. I wrote about things that interested me, but the writing would be absolutely useless if nobody would read it. Thus, how to get an audience?

There were I few things I had to learn and there were a few people who gave me a push in the right direction .

  • Wowter, who gave feedback to my posts right from the start and who encouraged me to continue blogging, posted a list with 17 tips for beginning bloggers (in Dutch) of how to increase visibility and findability of your blog. I became aware that ‘linking’ to others is what is making the web 2.0 world interconnected.
  • Second Dymphie, a Dutch Medical Librarian, encouraged me to start twittering. It took quite a while before I grasped the value of twitter as a networking tool. Twitter is not meant to say “what you do”, but it is a way to share information of any kind. Before you can share it, you first have to find interesting tweeple (people on twitter) and it did take a while before they followed me back (partly because my first tweets weren’t that interesting). Thus I had to learn by trial and error how to become a prolific twitterer.
  • Third I read a very interesting blogpost on “I’m not a geek” of Hutch Carpenter called Becoming a web 2.0 jedi, showing a simple but very accurate chart of the ever deeper levels of involvement one can have with Web 2.0 apps and the Web 2.0 ethos, as Hutch calls them. “Down are the lower levels, those of passive involvement, level 2 is giving up little pieces of yourself, while level 3 is a much bigger sharing experience. Share your own life, share your knowledge, share the stuff you find interesting. A big leap for a lot of us used to being more private. May the force be with you.”
    Seeing his post I realized that my journey had been quite different (figure below, made in September 2008). During the Spoetnik course emphasis was given to the tools themselves not to the ways you should use and share them and contribute to others. We skipped the reading of blogs and wiki’s, the lurking on twitter, but started with chatting, RSS and blogging. Although Web 2.0 tools are the basis, Web 2.0 is more an attitude than the usage of tools, it is about sharing information and thoughts.Or as Dean Giustini says it: It is about people.

The Ecosphere of Twitter and blogs.

I also experienced that all web 2.0 tools are not stand-alone tools, but can reinforce each other. This is for instance true for RSS, bookmarking tools , blogs, but also twitter (a microblogging service). A recent post of Sandnsurf (Mike Cadogan) at Life in the fast Lane uses a brilliant ecosystem metaphore to describe the twitter-blogging relationship. He describes the blogging ecosphere, where twitter decomposes information from journal articles and long blog posts into readily digestible information (nutrients and humus). See Figure from his post below (but read his post here for the whole story). Just like the Jedi chart this diagram illustrate exactly what web 2.0 is about.

Lessons to be learned

I have learned a lot. Am I now a real web 2.0 Jedi?
I’m not sure. In the ecology-model my blog is a young tree, surrounded by many others. But some ecologic dangers are luring.

  • The relative success of my blog results in “an abundance of light which results in a pressure to keep producing enough good quality posts”.
  • I’ve subscribed to so many RSS-feeds I seldomly read them.
  • I have so many twitter-followers (app. 300) that I can’t keep up with all of them as much as I would like to.
  • I read so many things, but haven’t got the time to work them out (or I simply forget).
  • I find it difficult to separate chaff from wheat. Many blogposts and web 2.0 information are not very accurate and superficial. Furthermore people often echo a subject without careful checking or without adding value.

Or in the words of sandnsurf: the death of a blog can ensue due to excessive exposure and Twittaholism. I hope It will not go in that direction, but I have to figure out a way to coop with the overwhelming amount of information and find a balance. That will be part of my (web 2.0) learning process in 2009.

One other thing:

I forgot to mention one very important experience. During my web 2.0 journey I virtually met many interesting, kind and helpful people from all over the world, from US, UK, Eastern Europe to India and Australia. Closer to home I also ‘met’ many very nice Dutch and Belgian people. I never liked the idea of intentional networking, but in web 2.0 the networks arise spontaneously. In a very natural and gradual way I became a member of a large health and library community and that feels good.

You might also want to read:





The Web 2.0-EBM Medicine split. [1] Introduction into a short series.

4 01 2009

Since the three years I’m working as a medical information specialist, I’ve embraced the concept of evidence based medicine or EBM. As a searcher I spend hours if not days to find as much relevant evidence as possible on a particular subject, which others select, appraise and synthesize to a systematic review or an evidence based guideline. I’m convinced that it is important to find the best evidence for any given intervention, diagnosis, prognostic or causal factor.

Why? Because history has shown that despite their expertise and best intentions, doctors don’t always know or feel what’s best for their patients.

An example. For many years corticosteroids had been used to lower intracranial pressure after serious head injury, because steroids reduce the inflammation that causes the brain to swell. However, in the 1990’s, meta-analyses and evidence-based guidelines called the effectiveness of steroids into question. Because of the lack of sufficiently large trials, a large RCT (CRASH) was started. Contrary to all expectations, there was actually an excess of 159 deaths in the steroid group. The overall absolute risk of death in the corticosteroid group was shown to be increased with 2%. This means that the administration of corticosteroids had caused more than 10,000 deaths before the 1990’s.[1,2,3]

Another example. The first Cochrane Systematic Review, shows the results of a systematic review of RCTs of a short, inexpensive course of a corticosteroid given to women about to give birth too early. The diagram below, which is nowadays well known as the logo of the Cochrane Collaboration, clearly shows that antenatal corticosteroids reduce the odds of the babies dying from the complications of immaturity by 30 to 50 per cent (diamond left under). Strikingly, the first of these RCTs showing a positive effect of corticosteroids, was already reported in 1972. By 1991, seven more trials had been reported, and the picture had become still stronger. Because no systematic review of these trials had been published until 1989, most obstetricians had not realized that the treatment was so effective. As a result, 10.000s of premature babies have probably suffered and died unnecessarily. This is just one of many examples of the human costs resulting from failure to perform systematic, up-to-date reviews of RCTs of health care.[4,5]

The Cochrane logo explained

Less than I year ago I entered the web 2.0-, and (indirectly) medicine 2.0 world, via a library 2.0 course. I loved the tools and I appreciated the approach. Web 2.0 is ‘all about sharing‘ or as Dean Giustini says it: ‘all about people. It is very fast and simple. It is easy to keep abreast of new information and to meet new interesting people with good ideas and a lot of knowledge.

An example. Bertalan Mesko in a comment on his blog ScienceRoll:

I know exactly that most of these web 2.0 tools have been around for quite a long time. Most of these things are not new and regarding the software, there aren’t any differences in most of the cases. But!
These tools and services will help us how to change medicine. In my opinion, the most essential problem of medicine nowadays is the sharing of information. Some months ago, I wrote about a blogger who fights Pompe disease, a rare genetic disorder and he told me about the diagnostic delay. I try to help physicians how they can find information easier and faster. For example: I gave tips how to search for genetic diseases.

Other examples are good functioning and dedicated patient web 2.0 sites, like PatientsLikeMe.

In the medical literature, blogs and slideshare, differences between medicine 2.0 and 1.0 are already described in detail (for instance see the excellent review of Dean Giustini in the BMJ), as well as the differences between medicine 1.0 and EBM (e.g. see the review of David Sackett et al in BMJ).

However, the longer I’m involved in web 2.0, the more I feel it conflicts with my job as EBM-librarian. The approach is so much different, other tools are used and other views shared. More and more I find ideas and opinions expressed on blogs that do EBM no justice and that seem to arise out of ignorance and/or prejudice. On the other hand EBM and traditional medicine often are not aware of web 2.0 sources or mistrust them. In science, blogs and wiki’s seldom count, because they express personal views, echo pre-existing data and are superficial.

split-1231

I’m feeling like I’m in a split, with one leg in EBM and the other in web 2.0. In my view each has got his merits, and these approaches should not oppose each other but should mingle. EBM getting a lower threshold and becoming more digestible and practical, and medicine 2.0 becoming less superficial and more underpinned.

It is my goal to take an upright position, standing on both legs, integrating EBM, medicine 2.0 (as well as medicine 1.0).

As a first step I will discuss some discrepancies between the two views as I encounter it in blogs, in the form of a mini-series: “The Web 2.0-EBM Medicine split”.

Before I do so I will give a short list of what I consider characteristic for each type of medicine, EBM-, Web 1.0 (usual)- and Web 2.0- medicine. Not based on any evidence, only on experience and intuition. I’ve just written down what came to my mind. I would be very interested in your thoughts on this.

EBM – medicine

  • centered round the best evidence
  • methodology-dependent
  • objective, transparent
  • thorough
  • difficult (to make, but for many also to find and also to understand)
  • time-consuming
  • published in peer reviewed papers (except for guidelines)
  • searching: PubMed and other bibliographic databases (to produce) and guideline databases, TRIP, and PubMed (Clinical Queries) or specific sources, i.e. specialist guidelines (to find).
  • Mostly Web 1.0 (with some web 2.0 tools, like podcasts, RSS and e-learning)

Web 1.0 – traditional medicine*

  • centered round clinical knowledge, expertise and intuition
  • opinion-based
  • authority based, i.e.strong beliefs in opinion leaders, expert opinion or ‘authority opinion’ (i.e. head of departments, professor) and own authority versus patient.
  • subjective
  • fast
  • act! (motto)
  • searching: browsing ( a specific list, site or Journals), quick search, mostly via Google**, in pharmacopeia, or protocols and UpToDate seldom in Pubmed (dependent on discipline)
  • Web 1.0: mail, patient-records, quick search via Google and Pubmed

Web 2.0 medicine

  • people-centered and patient-centered (although mostly not in individual blogs of doctors)
  • heavily based on technology (easy to use and free internet software)
  • social-based: based on sharing knowledge and expertise
  • (in theory) personalized
  • subjective, nondirected.
  • often:superficial
  • fast
  • generally not peer reviewed, i.e. published on blogs and wiki’s
  • searching: mostly via free internet sources and search engines, e.g. wikipedia, emedicine, respectively Google**, health metasearch engines, like Mednar and Health Sciences Online. PubMed mainly via third-party-tools like GoPubMed, HubMed and PubReminer. (e.g. see recent listings of top bedside health search engines on Sandnsurf’s blog ‘Life in the Fast Lane’
  • heavily dependent on web 2.0 tools both for ‘publishing’, ‘finding information’ and ‘communication’

*very general. of course dependent on discipline.
** this is not merely my impression, e.g. see: this blogpost on the “Clinical Cases and Images blog” of Ves Dimov, referring to four separate interviews of Dean Giustini with Physician bloggers.

Other references

[1] Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Edwards P et al. Lancet. 2005 Jun 4-10;365(9475):1957-9.
[2] A CRASH landing in severe head injury. Sauerland S, Maegele M. Lancet. 2004 Oct 9-15;364(9442):1291-2. Comment on: Lancet. 2004 Oct 9-15;364(9442):1321-8.
[3] Corticosteroids for acute traumatic brain injury.Alderson P, Roberts IG. Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD000196.
[4] http://www.cochrane.org/logo/
[5] Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.Roberts D, Dalziel SR.Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004454
[6] How Web 2.0 is changing medicine. Giustini D. BMJ. 2006 Dec 23;333(7582):1283-4.
[7] Evidence based medicine: what it is and what it isn’t. Sackett DL et al. BMJ. 1996 Jan 13;312(7023):71-2.






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

29 12 2008

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).

natural-selection-90

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)

vdj-recombination-2

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.

clonal-selection-users-path

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






Laika’s Little Party

21 09 2008

It’s time for some reflections on this blog and for a little party. Why?

So for now I will start with the party (with some wine), the reflections will follow when I’m sober.

This week I received an unexpected email from RNCentral (“the place to learn about nursing online”), anouncing that this blog had made it to the “Top 50 Health 2.0 Blogs list ( see here).

The top 50 health 2.0 list is not based on a kind of “objective” ranking like the Healthcare 100 or MedBlogEN lists, which are a measure of how many people link to your site, find your site by searching or have subscribed to your blogposts: thus an indirect measure of “how popular you are“. In such a list I would not make the top-100.
The RNCental site gives a “subjective” top 50 list of blogs, that appear valuable to the authors. The list is introduced with a very nice definition of health 2.0 blogs, that I can subscribe to:

Health 2.0 embraces the idea of bringing health care into the community of physicians, patients, and those in the health care industry together with technology and the Internet to provide the best possible health care environment. What better way for the various parts of this community to share their thoughts and communicate ideas than through their blogs? From corporate blogs to blogs that are a part of social networks to individual blogs touching on technology or health care policy, these blogs will help bring you into the community, provide information and resources, and may perhaps help you find your voice as well.

I’m thrilled that I’m (literally) placed next to David Rothman in the “Health and Technology”-section. Although, to be honest, I see myself as a true beginner in this web 2.0 world and I learn a lot of established web 2.0 experts like David Rothman, KraftyLibrarian, Berci of Science Roll, MD Anderson on Emerging Technologies Librarian, Dean Giustini (UBC Academic Search), Sachet62 on Twitter, symtym from symtym.com, David Bradley from Sciencebase and Dutch colleagues like Wowter (with a dutch and an english blog), Dymphie (Dee’tjes) and many many more. On my blog I try to integrate what I learn elsewhere (articles, posts, twitter messages) with my own knowledge and interest.

The resultant is a rather diverse mixture of subjects in the field of (medical) librarianship, medicine, health (including consumers), evidence based medicine and web 2.0 tools.

Although such a broad mixture might not be appealing to everyone, it is appreciated by some, as is apparent from a recent blog-review in the Library + Information Gazette, 22 August 2008: p5 (UK). The Gazette is only available in print edition and I wouldn’t have known about it if Anne Welsh of “First Person Narrative” had not mentioned it at her blog (see post: “mainstreaming blogs as information sources”). Anne:

“This review is the first in a series “Blog Spotlight” authored by Danielle Worster (the Health Informaticist). It’s aim is to help separating the wheat from the chaff when it comes to blogs in LIS and health informatics.

Any blog that claims to be about information, research, Web 2.0 or health informatics is considered. Each blog discussed is described in terms of its audience, currency, informativeness, authoritativeness / credibility, readability and design, with a brief overview and summary. It’s a nice format, and starts well in this issue with UBC Academic Search , ResearchBuzz and Laika’s MedLibLog.”

With Anne I find it regretful that the gazette is not available online. I surely would like to follow this series.

Luckily I found Keith Nockels (Browsing) willing to make a scan of the Gazette’s review and send it to me.

The Gazette review sketched my blog with very flattering sentences (“colourful, engaging and relevant”, “easy to read and digest”) as well as apt descriptions, which made me grin: “while it does stray to discuss….. Although she writes copious amounts, it is as easy to skim as to read it all…. crammed full of visuals.”

And about Dean’s UBC Academic Blog:

“Very informative: has an uncanny ability to pick up on crucial issue”. …. the blogger’s energy comes through in his shorter sentences….. essential reading.” All true! Dean’s blog is a must in the librarian web 2.0 world!

Apart from these official listings and reviews I got some comments or links that were also heartwarming.

For instance Keith Nockels (a UK Librarian with a nice blog (“Browsing”), apparently familiar with at least a few Dutch words) refers so nicely in his blogpost “More about changes to Ovid”:

“I have since found a posting on Laikas MedLibLog about this, and Laika has obviously looked at this properly! So, I can now report that you (….)
Laikas posting is here (in English and ook in Nederlands) and is gratefully acknowledged. She talks about other things besides, so please read her posting for more!”

And Dr. Shock announcement of the dutch grand round number 1:

Laika Spoetnik presents The Best Study Design… For Dummies (in English).
She writes in English and Dutch so you have no excuse for not reading this excellent post. She clearly explains Randomized Controlled Trials (RCT’s) and the levels of evidence. She uses an example which is easy to follow: Does beta carotene prevent lung cancer.

At Medliblog (the official website of the BMI, Dutch Biomedical Information) Annie (writing about Evidence Based Dietetics refers to the same post, saying:

….handige bijlages met een checklist voor het lezen van wetenschappelijke artikelen en een statistische begrippenlijst, dat laatste blijft toch altijd wel moeilijke stof voor dummies of alfa’s.
Voor die categorie heeft Laika een zeer begrijpelijke blog (zowel Engels- als Nederlandstalig) geschreven, waarvoor mijn dank. Zo’n presentatie zou ik ook wel willen bijwonen.

meaning:

For that category (dummies or alpha people not understanding checklists and studytypes) Laika has written a very comprehensible blogpost (in English and Dutch), for which I would like to thank her. I would have loved to attend such a presentation. (I gave to historians about “how doctors search”).

These comments strengthen me to continue blogging. This is why I blog: that (some) people like to read what I write and learn from some of the posts.

Well that is probably enough shameless self-glorification for now. I do realize that beginners get mild critiques, but as you get more well known the expectations will grow along and the critiques as well.

Next time, at request of Wowter, I will reflect more on the 5W’s of this blog: why, when, who, what, where?








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