Patientsäkerheten kräver att alla data från kliniska prövningar publiceras

Öppet brev till de svenska Europaparlametariker som sitter i gruppen för Miljö, hälsa och livsmedelssäkerhet.

Kära Carl, Åsa, Christofer, Marit och Marita,
Jag skriver till er eftersom ni är med i Europeiska parlamentets grupp för miljö, hälsa och livsmedel som arbetar med frågan om publicering av data från kliniska prövningar. Jag är läkare och arbetar som ST-läkare i anestesiologi och intensivvård vid Akademiska sjukhuset i Uppsala och driver en forskargrupp som arbetar med högt blodtryck och akut njursvikt vid Uppsala universitet.  

Det är av yttersta vikt att alla kliniska prövningar publiceras, och att alla data från kliniska prövningar finns tillgängliga för metaanalys och jämförande forskning. Som medlemmar i Europeiska parlamentet har ni en unik möjlighet att föra den evidensbaserade medicinen ett stort steg framåt. Idag publiceras inte alla prövningar och bakomliggande data tillhandahålls inte för metaanalys av oberoende forskare.

Detta är oacceptabelt från ett patientsäkerhetsperspektiv eftersom läkare kan föreslå suboptimala eller rent av felaktiga behandlingar om de inte har tillgång till all information. 

Det försämrar europas möjlighet för forskning och utveckling genom att forskare i onödan gör om prövningar som redan gjorts bara för att de aldrig publicerats.

De patienter som ställt sig till förfogande för forskningen har en förväntan att deras uppoffring skall leda medicinen framåt. Genom att tillåta att data från kliniska prövningar undanhålls bryts patienternas förtroende för den kliniska forskningen. 

Publiceringskravet bör gälla alla kliniska prövningar för alla mediciner som säljs, oavsett om dessa är nya prövningar eller tidigare prövningar som aldrig publicerats. Om gamla prövningar tillåts förbli opublicerade kommer fortfarande majoriteten av de mediciner som används idag att ha okompletta data. 

Ni kan hitta mycket mer information på sidan http://alltrials.net. 

Tack för att ni tog er tid att läsa detta och för att ni ställer er på patienternas, medicinens och forskningens sida i denna avgörande fråga för den framtida folkhälsan och medicinska utvecklingen.  

Vänligen, 

Michael

Ni som läser detta kan också skriva till era EU-parlamentariker. Deras e-postadresser hittas på http://www.europarl.europa.eu/committees/en/envi/members.html#menuzone 

Renovating Jigoro Kano

Most judo clubs have a picture of the founder, Kanō Jigorō (28 October 1860 – 4 May 1938), close by the practice area. It is supposed to hang on the front wall. That is, the wall you face when entering the dojo, called the shōmen (front wall), or kamiza (high seat). The latter because before the advent of the picture that was where the head of the dojo would sit, and over-see practice (As in the below illustration by Shuzan Hishida).

In Bergen the picture had gone missing, and in Uppsala it is a framed but dilapidated poster. Anyway, I decided to get a new one, but quickly found out that it is all but impossible. As a photographer, and, if I say so myself, not a bad printer, my next thought was to find a picture online and print it. This is the story renovating a scan of an old Jigoro Kano portrait for printing. Luckily, by Japanese law any photographs taken before 1946 are part of the public domain (or that is what Wikipedia says).

When working with a picture you obviously want to start with the highest possible quality and resolution, and with a bit of work I found this rather good scan at 3543x4375 pixels (click on the picture to go to the original URL).

It is only a j-peg but with that kind of resolution you can do a lot without destroying it. This is good because there was a lot to be done. There are scratches that seem to be from the original photograph, including one prominent on his left eye-brow. There are some blotches on the background, and I do not want the text or the old name-badge. Finally, it is made from an old tinted photograph, and I don't like the tint.

So, I loaded the image into the old editor, i.e. Adobe Photoshop, and cleaned it up. I tried to upload the actual TIFF to Wikimedia-commons, but that didn't work so I have just uploaded the final j-peg. If I find another place to put the layered file I will, and then you can easily adapt it to your needs. It prints quite well up to A3.

Winter-meeting in Oslo

The Norwegian Hypertension Society held its bi-annual scientific meeting in Oslo last week. It was a long time in planning. We set the place and date about two years ago. Sent the first announcement in the spring of 2012 and the call for abstracts in September. Then, at the very deadline, the abstracts and registrations start to trickle in. As with all meetings, we pushed the submission-deadline back a week just to allow people without basic planning skills with pressed schedules to join the meeting and present their data. Then, in as little time as possible, all the abstracts have to be formatted into a program, and session-chairs has to be found and matched so that they have an interest but aren't speaking themselves.

Anyway, we got some 17 free communications, varying from experimental physiology to international research politics, but with a heavy focus on epidemiology and clinical research. There were a couple of talks on the recently very hot topic of renal sympathetic denervation for treatment-resistant hypertension (more on that in another post), some interesting sub-group analyses from the LIFE and SCAST studies, and follow-ups on the now 40-year-old Oslo-Ischemia-Study. More of the program at the society home-page.

In addition, we had two invited lectures on statistics in clinical research. The first on how to develop and validate prognostic models by Ingar Holme, and the second on over-adjustment bias in multiple regression models held by Knut Liestøl. It was a useful repetition of the uses and pitfalls of these two very similar kinds of models that require very different study-designs and give very different information in the end. A common problem is that one tries to get etiological information from prognostic research, i.e. treating a risk-factor as a cause for the chosen end-point even though the observational design makes that impossible. The converse is equally common, i.e. trying to infer prognostic information from etiological studies, such as clinical trials, where the highly selected population makes general conclusions very suspect.

All told, it was a very successful meeting, well worth the time both for planning it, and attending.

Blood-to-piss-body-parts

The recent popularity of the up-goer five editor (check out the #upgoerfive hash on Twitter) pin-points an important point in writing: It's bloody hard to express a coherent thought in science without any specialised words. And I don't mean jargon or strange abbreviations but words like function, vessel, pressure, kidney and medicine (This point is made much better by the Center for plain language).

However, trying makes for a good bit of fun. The original fun was had by the brilliant Randall Munroe at xkcd.com when he reproduced a technical drawing of the Saturn V rocket with explanations that only included the 1000 most commonly used words. This excluded the use of "saturn" "V" and "rocket", so it was called the Up-goer five. Now, Theo Sanderson has created an editor that tells you when you have used a word that is not among the 1000 most used words. Here is my attempt to explain kidney function and the effect of hypertension induced injury on blood vessel and kidney function.

My job is to understand how the body parts that make piss work, and why they get hurt by the force that the heart makes when it forces the blood around in the body. In the body there are two blood-to-piss-body-parts. They work by making piss out of blood using many small blood-cell-catch-things so that the blood cells stay in the body. Then the blood-to-piss-body-parts take up most of the water again so that the piss becomes strong, and the body can save water. The blood-cell-catch-things use the force-of-the-heart to push water out of the blood. 

However, the smallest of the blood-roads and the blood-cell-catch-things are not strong, and can be hurt by the force-of-the-heart. In the long run this hurts the blood-to-piss-body-parts, and make them stop working. Before they stop working they work less well for a long time. During this time they are easier to hurt in other ways. One important way is when the force-of-the-heart becomes too low, often because of lost blood, and the blood-to-piss-body-parts get too little blood. Too little blood, and too low force-of-the-heart makes it hard to push water out of the blood to make piss. You then get too much piss in your blood which makes you sick. 

At the same time, air is carried by the red blood cells in the blood and used for doing work in the body. Too little blood to the blood-to-piss-body-parts gives them too little air, which they need in order to take back water from the piss. When the force-of-the-heart is low they need to take back even more water than usual to keep more water in the blood and keep the force-of-the-heart normal. This makes the blood-to-piss-body-parts use more air even though less comes to them. Since the cells that make up the blood-to-piss-body-parts need air to live, too little air hurts them and some of them die.

In a blood-to-piss-body-part that has been hurt by too high force-of-the-heart a sick with too low force-of-the-heart hurts more than in a well blood-to-piss-body-part. This means that for each earlier hurt the next hurt will hurt more and lead to blood-to-piss-body-parts that do not work at all faster and faster.

Too high force-of-the-heart hurts the blood-to-piss-body-parts by hurting the blood-roads first. This hurt changes how much blood passes the blood-cell-catch-things, and how much water is taken back to the body from the piss. Doctors can keep the blood-to-piss-body-parts from getting hurt by giving doctor-stuff that makes them work less hard and by keeping the force-of-the-heart normal. When the blood-roads have been hurt a lot it is hard to save the blood-to-piss-body-parts. Is important to keep the force-of-the-blood normal as much as possible.

If you want to read some other examples go to Ten Hundred Words of Science. Lots of fun for everyone.

Speech impediment - Locale in R under OSX

My R-installation developed a language problem ("L" is a statistical ploglamming language). The startup message, all errors and system messages started appearing in German. I do speak German but it was still quite annoying. This ended with a work-around that I published previously in a post about R-startup scripts. I have finally figured out what causes the error. My Language & Text settings for language were as follows:

1. British English 
2. Swedish
3. Norwegian
4. Danish
5. German 
6. French 

The problem lies in using the British English locale. I use it because I hate when all programs always correct my excellent spelling from Proper English™ to American. R does not have a locale for British English, nor for Swedish, Norwegian or Danish. So, to R, the locale priority list actually looks like this:

1.  
2. 
   
3. 
   
4. 
   
5. German 
6. French

So, understandably it goes for what it knows. The solution is to extend the list and put a standard English locale high up:

1. British English
2. English 
3. Swedish
4. Norwegian
5. Danish
6. German 
7. French 

Tai-otoshi - free judo illustrations

Click the image to reach the illustration-library at Flickr, or you may cut and paste this URL: http://www.flickr.com/photos/hultstrom/sets/72157632298341948/
Image is free to use under the Creative commons - attribution - share-alike license.

At our judo club in Uppsala we have been looking over the graduation hand-outs that have been used for years. They are just lists of techniques with some illustrations. The illustrations are a mix of horrid old photocopies, illustrations stolen from different books, and some hastily drawn stick figures. There are two problems with this. First, they are mostly bad, and secondly they are either copyrighted or of uncertain copyright status. In an effort to fix this we went looking for creative commons or other freely available judo illustrations on the internets.

There are photographs for some techniques on wikimedia commons that are not terrible, there are even some illustrations, although mostly not so good. At judoinfo everything is copyrighted, and frankly the quality is not always what you would hope for. In the end we were not able to find more than a handful of usable images, which explains the quality of our present hand-outs as well as the quality online in general.

Since I clearly haven't got enough shit to do, we decided to create a set of illustrations and release them into the wild for the judo community to use and spread. All those books are great, and we all have them, but the children don't and they never will. So, here are (or will be) a collection of free to use illustrations of judo techniques. They are provided under the Creative commons - non-commercial, attribution, share-alike - license, which means that they are free to use for non-commercial purposes as long as they are properly attributed, and any derivative works are also shared freely under the same license.

Original tai-otoshi photograph. Copyright Michael Hultström 2012.

First out is Tai-otoshi, or body-drop. Mostly because that was one I had a good photograph of to use as template. Don't expect this to go quickly, but give us a year or two and there should be fair number of images to use. Quality-wise I will be aiming for proper vectorised line-art in the end, but that is even more work and will take even more time.

Edit: I have been convinced that the non-commercial license is too restrictive as it potentially limits uses I would like to allow. Thus, the illustrations are now re-licensed as attribution, share-alike.

Avoid boring people

Anna-Maria De Mars has some good advice for judo players that is equally applicable to science. What she is saying is, in short: Work harder than the competition, and work with people who are better than you are. Actually, the latter of these was originally advice for scientists from James D. Watson. He wrote a whole book on the subject:

Avoid boring people: Lessons from a life in science. 

Being a sucker for books I bought it immediately. So, thank you Anna-Maria for pointing it out to me (albeit indirectly). The best thing about it is the double-meaning title. Behind this is an autobiography, which is interesting in many ways, but today's subject is the Remembered Lessons at the end of each chapter. There is some very important survival advice there, like:

"Avoid fighting bigger boys or dogs."

 And some advice that will be good for your development no matter what you do:

"Seek out bright as opposed to popular friends." This is really what Anna-Maria was quoting although from a different article as: "Never be the smartest person in the room," which sounds better but not as good as the book-title.

Then, there is some advice for young scientists like:

"Choose a young thesis adviser" that I obviously think all bright young prospects should do now, but which I did not follow myself and do not think I should have.

Or, the more cumbersome:

"Extend yourself intellectually through courses that initially frighten you," which is really good advice, and, like for Watson himself, mostly means study more mathematics and statistics.

and

"Keep your intellectual curiosity much broader than your thesis objective." This is also one of my own goals, and a recurring suggestion for my students. To some degree it comes naturally to medical students, since they have to be able to handle a variety of patients. However, they (MDs) often have to be induced to read more widely from theoretical literature, while students with basic science degrees have to be motivated to read some clinical medicine as well (and everyone has to be forced and whipped to study more mathematics and statistics). 

The autobiographical part is also interesting. James Watson describes how he was very focused on forwarding his career, and not spending time on things (courses, projects, etc) that would not be of direct use for his research or advancement in science. Anyway, that was it for now. I am going to follow his advice to:

"Work on Sundays."