New paper: Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults

2017-06-16 09_26_46-Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young2017-06-16 09_25_58-Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young

Just a relative risk is not enough to fully understand the implications of your findings. Sure, if you are an expert in a field, the context of that field will help you to assess the RR. But if ou are not, the context of the numerator and denominator is often lost. There are several ways to work towards that. If you have a question that revolves around group discrimination (i.e. questions of diagnosis or prediction) the RR needs to be understood in relation to other predictors or diagnostic variables. That combination is best assessed through the added discriminatory value such as the AUC improvement or even more fancy methods like reclassification tables and net benefit indices. But if you are interested in are interested in a single factor (e.g. in questions of causality or treatment) a number needed to treat (NNT) or the Population Attributable Fraction can be used.

The PAF has been subject of my publications before, for example in these papers where we use the PAF to provide the context for the different OR of markers of hypercoagulability in the RATIO study / in a systematic review. This paper is a more general text, as it is meant to provide in insight for non epidemiologist what epidemiology can bring to the field of law. Here, the PAF is an interesting measure, as it has relation to the etiological fraction – a number that can be very interesting in tort law. Some of my slides from a law symposium that I attended addresses these questions and that particular Dutch case of tort law.

But the PAF is and remains an epidemiological measure and tells us what fraction of the cases in the population can be attributed to the exposure of interest. You can combine the PAF to a single number (given some assumptions which basically boil down to the idea that the combined factors work on an exact multiplicative scale, both statistically as well as biologically). A 2016 Lancet paper, which made huge impact and increased interest in the concept of the PAF, was the INTERSTROKE paper. It showed that up to 90% of all stroke cases can be attributed to only 10 factors, and all of them modifiable.

We had the question whether this was the same for young stroke patients. After all, the longstanding idea is that young stroke is a different disease from old stroke, where traditional CVD risk factors play a less prominent role. The idea is that more exotic causal mechanisms (e.g. hypercoagulability) play a more prominent role in this age group. Boy, where we wrong. In a dataset which combines data from the SIFAP and GEDA studies, we noticed that the bulk of the cases can be attributed to modifiable risk factors (80% to 4 risk factors). There are some elements with the paper (age effect even within the young study population, subtype effects, definition effects) that i wont go into here. For that you need the read the paper -published in stroke- here, or via my mendeley account. The main work of the work was done by AA and UG. Great job!

New paper in RPTH: Statins and the risk of DVT recurrence

coverI am very happy and honored that i can tell you that our paper “Statin use and risk of recurrent venous thrombosis: results from the MEGA follow-up study” is the very first paper in the new ISTH journal “Research and Practices in Thrombosis and Hemostasis“.

This new journal, for which I serve on the editorial board, is the sister journal of the JTH, but has a couple of focus point that are not present in the JTH. Biggest difference is the open access policy of the RPTH. Next to that, there are a couple of things or subjects that the RPTH welcomes, which are perhaps not so common in traditional journals (e.g. career development articles, educationals, nursing and patient perspectives etc).

Our paper is however a very standard paper, in the sense that it is original research publication regarding the role of statins and the risk of thrombosis recurrence. We answer the question whether statins indeed is linked with a lower risk of recurrence based on observational data, opening up the door to confounding by indication. To counteract, we applied a propensity score, and most important of all, we only used so-called “incident users”. Incident vs prevalent users of statins is a theme that has been a topic on this blog before (for example here and here). The bottom line is this: people who are currently using statins are different from people who are prescribed statins – adherence issues, side effects, or low life expectancy could be reasons for discontinuation.  You need to take this difference between these type of statin users into account, or the protective effect of statins, or any other medication for that matter, might be biassed. In the case of statins and DVT recurrence it can be argued that the risk lowering effect of statins is overestimated. In itself that is not a problem in an observational study. But if the results of this observational study is subsequently used in a sample size calculation for a proper trial, that trial will be underpowered and we might have lost our (expensive and potentially only) shot at really knowing whether or not DVT patients benefit from statins.

RPTH will be launched during ISTH 2017 which will be held in Berlin in a couple of weeks.

New paper: A Prothrombotic Score Based on Genetic Polymorphisms of the Hemostatic System Differs in Patients with IS, MI, or PAOD

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frontiersin.org
My first paper in frontiers of cardiovascular medicine, an open access platform focussed on cardiovascular medicine. This is not a regular case-control study, where the prevelance of a risk factor is compared between an unselected patient group and a reference group from the general population. No, this paper takes patients with cardiovascular disease who are referred for thrombophilia testing. when the different diseases (ischemic stroke vs myocardial infarction / PAOD) are then compared in terms of their thrombophilic propensity, it is clear that these two groups are different. The first culprit to think might be that thrombophilia indeed plays a different role in the etiology of these disease, like we demonstrated in a RATIO publication as well as this systematic review, but it might also be that there is just a different referral pattern. in any case, it indicates that the role of thrombophilia – whether it is causal or physician suspected – is different between the different forms of arterial thrombosis.

Advancing prehospital care of stroke patients in Berlin: a new study to see the impact of STEMO on functional outcome

There are strange ambulances driving around in Berlin. They are the so-called STEMO cars, or Stroke Einsatz Mobile, basically driving stroke units. They have the possibility to make a CT scan to rule out bleeds and subsequently start thrombolysis before getting to the hospital. A previous study showed that this descreases time to treatment by ~25 minutes. The question now is whether the patients are indeed better of in terms of functional outcome. For that we are currently running the B_PROUD study of which we recently published the design here.

Virchow’s triad and lessons on the causes of ischemic stroke

I wrote a blog post for BMC, the publisher of Thrombosis Journal in order to celebrate blood clot awareness month. I took my two favorite subjects, i.e. stroke and coagulation, and I added some history and voila!  The BMC version can be found here.

When I look out of my window from my office at the Charité hospital in the middle of Berlin, I see the old pathology building in which Rudolph Virchow used to work. The building is just as monumental as the legacy of this famous pathologist who gave us what is now known as Virchow’s triad for thrombotic diseases.

In ‘Thrombose und Embolie’, published in 1865, he postulated that the consequences of thrombotic disease can be attributed one of three categories: phenomena of interrupted blood flow, phenomena associated with irritation of the vessel wall and its vicinity and phenomena of blood coagulation. This concept has now been modified to describe the causes of thrombosis and has since been a guiding principle for many thrombosis researchers.

The traditional split in interest between arterial thrombosis researchers, who focus primarily on the vessel wall, and venous thrombosis researchers, who focus more on hypercoagulation, might not be justified. Take ischemic stroke for example. Lesions of the vascular wall are definitely a cause of stroke, but perhaps only in the subset of patient who experience a so called large vessel ischemic stroke. It is also well established that a disturbance of blood flow in atrial fibrillation can cause cardioembolic stroke.

Less well studied, but perhaps not less relevant, is the role of hypercoagulation as a cause of ischemic stroke. It seems that an increased clotting propensity is associated with an increased risk of ischemic stroke, especially in the young in which a third of main causes of the stroke goes undetermined. Perhaps hypercoagulability plays a much more prominent role then we traditionally assume?

But this ‘one case, one cause’ approach takes Virchow’s efforts to classify thrombosis a bit too strictly. Many diseases can be called multi-causal, which means that no single risk factor in itself is sufficient and only a combination of risk factors working in concert cause the disease. This is certainly true for stroke, and translates to the idea that each different stroke subtype might be the result of a different combination of risk factors.

If we combine Virchow’s work with the idea of multi-causality, and the heterogeneity of stroke subtypes, we can reimagine a new version of Virchow’s Triad (figure 1). In this version, the patient groups or even individuals are scored according to the relative contribution of the three classical categories.

From this figure, one can see that some subtypes of ischemic stroke might be more like some forms of venous thrombosis than other forms of stroke, a concept that could bring new ideas for research and perhaps has consequences for stroke treatment and care.

Figure 1. An example of a gradual classification of ischemic stroke and venous thrombosis according to the three elements of Virchow’s triad.

However, recent developments in the field of stroke treatment and care have been focused on the acute treatment of ischemic stroke. Stroke ambulances that can discriminate between hemorrhagic and ischemic stroke -information needed to start thrombolysis in the ambulance-drive the streets of Cleveland, Gothenburg, Edmonton and Berlin. Other major developments are in the field of mechanical thrombectomy, with wonderful results from many studies such as the Dutch MR CLEAN study. Even though these two new approaches save lives and prevent disability in many, they are ‘too late’ in the sense that they are reactive and do not prevent clot formation.

Therefore, in this blood clot awareness month, I hope that stroke and thrombosis researchers join forces and further develop our understanding of the causes of ischemic stroke so that we can Stop The Clot!

Increasing efficiency of preclinical research by group sequential designs: a new paper in PLOS biology

We have another paper published in PLOS Biology. The theme is in the same area as the first paper I published in that journal, which had the wonderful title “where have all the rodents gone”, but this time we did not focus on threats to internal validity, but we explored whether sequential study designs can be useful in preclinical research.

Sequential designs, what are those? It is a family of study designs (perhaps you could call it the “adaptive study size design” family) where one takes a quick peek at the results before the total number of subject is enrolled. But, this peek comes at a cost: it should be taken into account in the statistical analyses, as it has direct consequence for the interpretation of the final result of the experiment. But the bottom line is this: with the information you get half way through can decide to continue with the experiment or to stop because of efficacy or futility reasons. If this sounds familiar to those familiar with interim analyses in clinical trials, it is because it is the sam concept. however, we explored its impact when applied to animal experiments.

Figure from our publication in PLOS Biology describing sequential study designs in or computer simulations

Old wine in new bottles” one might say, and some of the reviewers for this paper published rightfully pointed out that our paper was not novel in terms of showing how sequential designs are more efficient compared to non sequential designs. But there is not where the novelty lies. Up untill now, we have not seen people applying this approach to preclinical research in a formal way. However, our experience is that a lot of preclinical studies are done with some kind of informal sequential aspect. No p<0.05? Just add another mouse/cell culture/synapse/MRI scan to the mix! The problem here is that there is no formal framework in which this is done, leading to cherry picking, p-hacking and other nasty stuff that you can’t grasp from the methods and results section.

Should all preclinical studies from now on half sequential designs? My guess would be NO, and there are two major reasons why. First of all, sequential data analyses have their ideosyncrasies and might not be for everyone. Second, the logistics of sequential study designs are complex, especially if you are affraid to introduce batch effects. We only wanted to show preclinical researchers that the sequential approach has their benefits: the same information with on average less costs. If you translate “costs” into animals the obvious conclusion is: apply sequential designs where you can, and the decrease in animals can “re-invested” in more animals per study to obtain higher power in preclinical research. But I hope that the side effect of this paper (or perhaps its main effect!) will be that the readers just think about their current practices and whether thise involve those ‘informal sequential designs’ that really hurt science.

The paper, this time with aless exotic title, “Increasing efficiency of preclinical research by group sequential designs” can be found on the website of PLOS biology.

Associate editor at BMC Thrombosis Journal

source: https://goo.gl/CS2XtJ
source: https://goo.gl/CS2XtJ

In the week just before Christmas, HtC approached me by asking whether or not I would like to join the editorial board of BMC Thrombosis Journal as an Associate Editor. the aims and scope of the journal, taken from their website:

“Thrombosis Journal  is an open-access journal that publishes original articles on aspects of clinical and basic research, new methodology, case reports and reviews in the areas of thrombosis.Topics of particular interest include the diagnosis of arterial and venous thrombosis, new antithrombotic treatments, new developments in the understanding, diagnosis and treatments of atherosclerotic vessel disease, relations between haemostasis and vascular disease, hypertension, diabetes, immunology and obesity.”

I talked to HtC, someone at BMC, as well as some of my friends and colleagues whether or not this would be a wise thing to do. Here is an overview of the points that came up:

Experience: Thrombosis is the field where I grew up in as a researcher. I know the basics, and have some extensive knowledge on specific parts of the field. But with my move to Germany, I started to focus on stroke, so one might wonder why not use your time to work with a stroke related journal. My answer is that the field of thrombosis is a stroke related field and that my position in both worlds is a good opportunity to learn from both fields. Sure, there will be topics that I have less knowledge off, but here is where an associate editor should rely on expert reviewers and fellow editors.

This new position will also provide me with a bunch of new experiences in itself: for example, sitting on the other side of the table in a peer review process might help me to better understand a rejection of one of my own papers. Bottom line is that I think that I both bring and gain relevant experiences in this new position.

Time: These things cost time. A lot. Especially when you need to learn the skills needed for the job, like me. But learning these skills as an associate editor is an integral part of the science apparatus, and I am sure that the time that I invest will help me develop as a scientist. Also, the time that I need to spend is not necessary the type of time that I currently lack, i.e. writing time. For writing and doing research myself I need decent blocks of time to dive in and focus  — 4+ hours if possible. The time I need to perform my associate editor tasks is more fragmented: find peer reviewers, read their comments and make a final judgement are relative fragmented activities and I am sure that as soon as I get the hang of it I can squeeze those activities within shorter slots of time. Perhaps a nice way to fill those otherwise lost 30 minutes between two meetings?

Open science: Thrombosis journal is part of the Biomed central family. As such, it is an 100% OA journal. It is not that I am an open science fanboy or sceptic, but I am very curious how OA is developing and working with an OA journal will help me to understand what OA can and cannot deliver.

Going over these points, I am convinced that I can contribute to the journal with my experience in the fields of coagulation, stroke and research methodology. Also, I think that the time that it will take to learn the skills needed are an investment that in the end will help me to grow as a researcher. So, I replied HtC with a positive answer. Expect email requesting for a peer review report soon!

New team member!

A couple of weeks ago I announced that my team was looking for a new post-doc. I received many applications, some even from as far as Italy and Spain. Out of this pile of candidates we were able to find an individual candidate who fulfilled all the requirements we had mind and than some. It is great that she will join the team in December. JH has worked in the field of epidemiology for quite some time and is not only experienced in setting up new projects and provide physicians with methodological input on their clinical research projects, but she also has a great interest in the more methodological side of epidemiology. For example, she is co-author/developer of the program DAGitty which can be used to draw causal diagrams. She is also speaker for the working group methodology of the German Society of Epidemiology (dgEpi). Her background in psychology also means that she brings a lot of knowledge on methods that we as a team do not have so far. In short, a great addition to the team. Welcome JH!

 

 

Berlin Epidemiological Methods Colloquium kicks of with SER event

A small group of epi-nerds (JLR, TK and myself) decided to start a colloquium on epidemiological methods. This colloquium series kicks off with a webcast of an event organised by the Society for Epidemiological Research (SER), but in general we will organize meetings focussed on advanced topics in epidemiological methods. Anyone interested is welcome. Regularly meetings will start in February 2017. All meetings will be held in English.
More information on the first event can be found below or via this link:

“Perspective of relative versus absolute effect measures” via SERdigital

Date: Wednesday, November 16th 2016 Time: 6:00pm – 9:00pm
Location: Seminar Room of the Neurology Clinic, first floor (Alte Nervenklinik)
Bonhoefferweg 3, Charite Universitätsmedizin Berlin- Campus Mitte, 10117 Berlin
(Map: https://www.charite.de/service/lageplan/plan/map/ccm_bonhoefferweg_3)

Description:
Join us for a live, interactive viewing party of a debate between two leading epidemiologists, Dr. Charlie Poole and Dr. Donna Spiegelman, about the merits of relative versus absolute effect measures. Which measure of effect should epidemiologists prioritize? This digital event organized by the Society for Epidemiologic Research will also include three live oral presentations selected from submitted abstracts. There will be open discussion with other viewers from across the globe and opportunities to submit questions to the speakers. And since no movie night is complete without popcorn, we will provide that, too! For more information, see: https://epiresearch.org/ser50/serdigital

If you plan to attend, please register (space limited): https://goo.gl/forms/3Q0OsOxufk4rL9Pu1

 

The paradox of the BMI paradox

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I had the honor to be invited to the PHYSBE research group in Gothenburg, Sweden. I got to talk about the paradox of the BMI paradox. In the announcement abstract I wrote:

“The paradox of the BMI paradox”
Many fields have their own so-called “paradox”, where a risk factor in certain
instances suddenly seems to be protective. A good example is the BMI paradox,
where high BMI in some studies seems to be protective of mortality. I will
argue that these paradoxes can be explained by a form of selection bias. But I
will also discuss that these paradoxes have provided researchers with much
more than just an erroneous conclusion on the causal link between BMI and
mortality.

I first address the problem of BMI as an exposure. Easy stuff. But then we come to index even bias, or collider stratification bias. and how selections do matter in a recurrence research paradox -like PFO & stroke- or a health status research like BMI- and can introduce confounding into the equation.

I see that the confounding might not be enough to explain all that is observed in observational research, so I continued looking for other reasons there are these strong feelings on these paradoxes. Do they exist, or don’t they?I found that the two sides tend to “talk in two worlds”. One side talks about causal research and asks what we can learn from the biological systems that might play a role, whereas others think with their clinical  POV and start to talk about RCTs and the need for weight control programs in patients. But there is huge difference in study design, RQ and interpretation of results between the studies that they cite and interpret. Perhaps part of the paradox can be explained by this misunderstanding.

But the cool thing about the paradox is that through complicated topics, new hypothesis , interesting findings and strong feelings about the existence of paradoxes, I think that the we can all agree: the field of obesity research has won in the end. and with winning i mean that the methods are now better described, better discussed and better applied. New hypothesis are being generated and confirmed or refuted. All in all, the field makes progress not despite, but because the paradox. A paradox that doesn’t even exist. How is that for a paradox?

All in all an interesting day, and i think i made some friends in Gothenburg. Perhaps we can do some cool science together!

Slides can be found here.

predicting DVT with D-dimer in stroke patients: a rebuttal to our letter

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Some weeks ago, I reported on a letter to the editor of Thrombosis Research on the question whether D-Dimer indeed does improve DVT risk prediction in stroke patients.

I was going to write a whole story on how one should not use a personal blog to continue the scientific debate. As you can guess, I ended up writing a full paragraph where I did this anyway. So I deleted that paragraph and I am going to do a thing that requires some action from you. I am just going to leave you with the links to the letters and let you decide whether the issues we bring up, but also the corresponding rebuttal of the authors, help to interpret the results from the the original publication.

ECTH 2016

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ecth2016.org

Last week was the first edition of the European Congress on Thrombosis and Hemostasis in the Hague (NL). The idea of this conference is to provide a platform for european thrombosis researchers and doctors to meet in the dull years between ISTH meetings. There is a strong emphasis on enabling and training the young researchers, as can be from the different activities and organisational aspects. One os these things was the Junior advisory board, of which I was part. We had the task to give advice both solicited and unsolicited, and help organise and shape some of the innovative aspects. For example: we had the so-called fast and furious sessions, where authors of the best abstract were asked to let go of the standard presentation format and share their research TED talk style.

I learned a lot during these sessions, and even got in contact with some groups that have interesting methods and approaches that we might apply in our studies and patient populations. My thoughts: targeting FXII and FXI as well as DNAse treatment are the next big thing. We also had a great selection of speakers for meet-the-experts and how-to sessions. These sessions demanded active participation of all participants which is really a great way to build new collaborations and friendships.

The 5K fun run with 35+ participants was also a great succes.

The wednesday plenary sessions, including the talks on novel and innovative methods of scholarly communications as well as the very well received sessions from Malcolm Macloud on reducing research waste where inspiring to all. Missed it? do not worry, they have shared their slides online!

All in all, the conference was a great success in both numbers (750+ participants) as well as scientific quality. I am looking forward to the next edition, which will be held in Marseille in two years time. Hope to see you all there!

How to set up a research group

A couple of weeks ago I wrote down some thoughts I had while writing a paper for the JTH series on Early Career Researchers. I was asked to write how one sets up a research group, and the four points I described in my previous post can be recognised in the final paper.

But I also added some reading tips in the paper. reading on a particular topic helps me not only to learn what is written in the books, but also to get my mind in a certain mindset. So, when i knew that i was going to take over a research group in Berlin I read a couple of books, both fiction and non fiction. Some where about Berlin (e.g. Cees Nootebooms Berlijn 1989/2009), some were focussed on academic life (e.g. Porterhouse Blue). They help to get my mind in a certain gear to help me prepare of what is going on. In that sense, my bookcase says a lot about myself.

The number one on the list of recommended reads are the standard management best sellers, as I wrote in the text box:

// Management books There are many titles that I can mention here; whether it the best-seller Seven Habits of Highly Effective People or any of the smaller booklets by Ken Blanchard, I am convinced that reading some of these texts can help you in your own development as a group leader. Perhaps you will like some of the techniques and approaches that are proposed and decide to adopt them. Or, like me, you may initially find yourself irritated because you cannot envision the approaches working in the academic setting. If this happens, I encourage you to keep reading because even in these cases, I learned something about how academia works and what my role as a group leader could be through this process of reflection. My absolute top recommendation in this category is Leadership and Self-Deception: a text that initially got on my nerves but in the end taught me a lot.

I really think that is true. You should not only read books that you agree with, or which story you enjoy. Sometimes you can like a book not for its content but the way it makes you question your own preexisting beliefs and habits. But it is true that this sometimes makes it difficult to actually finnish such a book.

Next to books, I am quite into podcasts so I also wrote

// Start up. Not a book, but a podcast from Gimlet media about “what it’s really like to get a business off the ground.” It is mostly about tech start-ups, but the issues that arise when setting up a business are in many ways similar to those you encounter when you are starting up a research group. I especially enjoyed seasons 1 and 3.

I thought about including the sponsored podcast “open for business” from Gimlet Creative, as it touches upon some very relevant aspects of starting something new. But for me the jury is still out on the “sponsored podcast” concept  – it is branded content from amazon, and I am not sure to what extent I like that. For now, i do not like it enough to include it in the least in my JTH-paper.

The paper is not online due to the summer break,but I will provide a link asap.

– update 11.10.2016 – here is a link to the paper. 

 

 

 

 

Does d-dimer really improve DVT prediction in stroke?

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elsevier.com

Good question, and even though thromboprofylaxis is already given according to guidelines in some countries, I can see the added value of a good discriminating prediction rule. Especially finding those patients with low DVT risk might be useful. But using d-dimer is a whole other question. To answer this, a thorough prediction model needs to be set up both with and without the information of d-dimer and only a direct comparison of these two models will provide the information we need.

In our view, that is not what the paper by Balogun et al did. And after critical appraisal of the tables and text, we found some inconsistencies that prohibits the reader from understanding what exactly was done and which results were obtained. In the end, we decided to write a letter to the editor, especially to prevent that other readers to mistakenly take over the conclusion of the authors. This conclusion, being that “D-dimer concentration with in 48 h of acute stroke is independently associated with development of DVT.This observation would require confirmation in a large study.” Our opinion is that the data from this study needs to be analysed properly to justify such an conclusion. One of the key elements in our letter is that the authors never compare the AUC of the model with and without d-dimer. This is needed as that would provide the bulk of the answer whether or not d-dimer should be measured. The only clue we have are the ORs of d-dimer, which range between 3-4, which is not really impressive when it comes to diagnosis and prediction. For more information on this, please check this paper on the misuse of the OR as a measure of interest for diagnosis/prediction by Pepe et al.

A final thing I want to mention is that our letter was the result of a mini-internship of one of the students at the Master programme of the CSB and was drafted in collaboration with our Virchow scholar HGdH from the Netherlands. Great team work!

The letter can be found on the website of Thrombosis Research as well as on my Mendeley profile.

 

Teaching a new module: Critical Thinking in Translational Medicine

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I have the honor to design and teach a new master module in not one, but two master programs at the Charité. This new module has the title “Critical Thinking in Translational Medicine” and will focus on the concept that science is an exercise in uncertainty. But somehow, scientist – especially the young – do not seem to be trained in handling these uncertainties. Overselling of results, scientific fads and the why “most research findings are false” will be on the schedule of this 15 week course starting this October.

But that’s not all. We will also have some topics regarding new innovations and activities in the scientific enterprise: sharing of data, new ways to publish and share your results will be discussed by our students. The goal is that each week we will have some introduction perspective. Of course there will be a some exercise and group discussions. Each week 4 students have the task to summarise the results of the meeting, as well as prepare a pro-contra debate which will be held on two occasions. Perhaps these students even should write some blog entries?

The bottom line is this: science is more than a pipet, understanding confounding or knowing why a regression model does what it does. It is also about the scientific enterprise, which is what it is, and has many shortcomings. Some critical thinking on these topics, together with some good discussion will help our student to form their own thoughts on these issues and hopefully help them to prepare for a wonderful scientific career.

 

 

Starting a research group: some thoughts for a new paper

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It has been 18 months since I started in Berlin to start at the CSB to take over the lead of the clinical epidemiology research group. Recently, the ISTH early career taskforce  have contacted me whether I would be willing to write something about my experiences over the last 18 months as a rookie group leader. The idea is that these experiences, combined with a couple of other papers on similar useful topics for early career researchers, will be published in JTH.

I was a bit reluctant at first, as I believe that how people handle new situations that one encounters as a new group leader is quite dependent on personality and the individual circumstances. But then again, the new situations that i encountered might be more generalizable to other people. So I decided to go ahead and focus more on the description of the new situations I found myself in while trying to keep the personal experiences limited and only for illustrations only.

While writing, I have discerned that there are basically 4 new things about my new situations that I would have loved to realise a bit earlier.

  1. A new research group is never without context; get to know the academic landscape of your research group as this is where you find people for new collaboration etc
  2. You either start a new research group from scratch, or your inherit a research group; be aware that both have very different consequences and require different approaches.
  3. Try to find training and mentoring to help you cope with your new roles that group leaders have; it is not only the role of group leader that you need to get adjusted to. HR manager, accountant, mentor, researcher, project initiator, project manager, consultant are just a couple of roles that I also need to fulfill on a regular basis.
  4. New projects; it is tempting to put all your power, attention time and money behind a project. but sometimes new projects fail. Perhaps start a couple of small side projects as a contingency?

As said, the stuff I describe in the paper might be very specific for my situation and as such not likely to be applicable for everyone. Nonetheless, I hope that reading the paper might help other young researchers to help them prepare for the transition from post-doc to group leader. I will report back when the paper is finished and available online.

 

Thesis can now be downloaded without password

Omslag proefschrift Siegerink

For a long time there was a password needed to access my thesis. There where two reasons: some elements where not yet published in peer-reviewed journal, and some elements where not only to be published on my own website. This is because some journals only allow publication of your own work after some time passed since publication.

A couple of things have changed that have led me to remove the password lock: a lot of time has passed and if that amount of time is not enough I don’t care anymore. That sounds perhaps bad ass, but of course it isn’t – especially since most ideas have been published already. It is a mere results of some slight changes that I went through over the last couple of months regarding publishing and the relationship between authors and journals.Do not be surprised if I will make some remarks to these changes when i provides some more updates on this blog.

 

New office

 

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I just moved to a new office. Bigger, brighter and the possibility to open up a window are the main reasons why I am quite happy with the move. But the best thing is the new view. Now, let’s hope that I still get some work done!

Need directions to my new office? Please visit me!

 

 

Cardiovascular events after ischemic stroke in young adults (results from the HYSR study)

2016-05-01 21_39_40-Cardiovascular events after ischemic stroke in young adults

The collaboration with the group in finland has turned into a nice new publication, with the title

“Cardiovascular events after ischemic stroke in young adults”

this work, with data from Finland was primarily done by KA and JP. KA came to Berlin to learn some epidemiology with the aid of the Virchow scholarship, so that is where we came in. It was great to have KA to be part of the team, and even better to have been working on their great data.

Now onto the results of the paper: like in the results of the RATIO follow-up study, the risk of recurrent young stroke remained present for a long-term time after the stroke in this analysis of the Helsinki Young Stroke Registry. But unlike the RATIO paper, this data had more information on their patients, for example the TOAST criteria. this means that we were able to identify that the group with a LAA had a very high risk of recurrence.

The paper can be found on the website of Neurology, or via my mendeley profile.

Pregnancy loss and risk of ischaemic stroke and myocardial infarction

2016-04-08 13_36_29-Posteingang - bob.siegerink@charite.de - Outlook

Together with colleagues I worked on a paper on relationship between pregnancy, its complications and stroke and myocardial infarction in young women, which just appeared online on the BJH website.

The article, which analyses data from the RATIO study, concludes that only if you have multiple pregnancy losses, your risk of stroke is increased (OR 2.4) compared to those who never experienced a pregnancy loss. The work was mainly done by AM, and is a good example of international collaborations where we benefitted from the expertise of all team members.

The article, with the full title “Pregnancy loss and risk of ischaemic stroke and myocardial infarction” can be found via PubMed, or via my personal Mendeley page.

Statins and risk of poststroke hemorrhagic complications

2016-03-28 13_00_38-Statins and risk of poststroke hemorrhagic complicationsEaster brought another publication, this time with the title

“Statins and risk of poststroke hemorrhagic complications”

I am very pleased with this paper as it demonstrates two important aspects of my job. First, I was able to share my thought on comparing current users vs never users. As has been argued before (e.g. by the group of Hérnan) and also articulated in a letter to the editor I wrote with colleagues from Leiden, such a comparison brings forth an inherent survival bias: you are comparing never users (i.e. those without indication) vs current users (those who have the indication, can handle the side-effects of the medication, and stay alive long enough to be enrolled into the study as users). This matter is of course only relevant if you want to test the effect of statins, not if you are interested in the mere predictive value of being a statin user.

The second thing about this paper is the way we were able to use data from the VISTA collaboration, which is a large amount of data pooled from previous stroke studies (RCT and observational). I believe such ways of sharing data brings forward science. Should all data be shared online for all to use? I do am not sure of that, but the easy access model of the VISTA collaboration (which includes data maintenance and harmonization etc) is certainly appealing.

The paper can be found here, and on my mendeley profile.

 

– update 1.5.2016: this paper was topic of a comment in the @greenjournal. See also their website

update 19.5.2016: this project also led to first author JS to be awarded with the young researcher award of the ESOC2016.

 

 

Causal Inference in Law: An Epidemiological Perspective

source:ejrr

Finally, it is here. The article I wrote together with WdH, MZ and RM was published in the European Journal of Risk and Regulation last week. And boy, did it take time! This whole project, an interdisciplinary project where epidemiological thinking was applied to questions of causal inference in tort law, took > 3 years – with only a couple of months writing… the rest was waiting and waiting and waiting and some peer review. but more on this later.

First some content. in the article we discuss the idea of proportional liability that adheres to the epidemiological concept of multi-causality. But the article is more: as this is a journal for non epidemiologist, we also provide a short and condensed overview of study design, bias and other epidemiological concepts such as counterfactual thinking. You might have recognised the theme from my visits to the Leiden Law school for some workshops. The EJRR editorial describes it asas: “(…) discuss the problem of causal inference in law, by providing an epidemiological viewpoint. More specifically, by scrutinizing the concept of the so-called “proportional liability”, which embraces the epidemiological notion of multi-causality, they demonstrate how the former can be made more proportional to a defendant’s relative contribution in the known causal mechanism underlying a particular damage.”

Getting this thing published was tough: the quality of the peer review was low (dare I say zero?),communication was difficult, submission system flawed etc. But most of all the editorial office was slow – first submission was June 2013! This could be a non-medical journal thing, i do not know, but still almost three years. And this all for an invited article that was planned to be part of a special edition on the link between epi and law, which never came. Due several delays (surprise!) of the other articles for this edition, it was decided that our article is not waiting for this special edition anymore. Therefore, our cool little insight into epidemiology now seems to be lost between all those legal and risk regulation articles. A shame if you ask me, but I am glad that we are not waiting any longer!

Although i do love interdisciplinary projects, and I think the result is a nice one, I do not want to go through this process again. No more EJRR for me.

Ow, one more thing… the article is behind a pay wall and i do not have access through my university, nor did the editorial office provide me with a link to a pdf of the final version. So, to be honest, I don’t have the final article myself! Feels weird. I hope EJRR will provide me with a pdf quite soon. In the meantime, anybody with access to this article, please feel free to send me a copy!

Where Have All the Rodents Gone? The Effects of Attrition in Experimental Research on Cancer and Stroke

 

source: journals.plos.org/plosbiology

We published a new article just in PLOS Biology today, with the title:

“Where Have All the Rodents Gone? The Effects of Attrition in Experimental Research on Cancer and Stroke”

This is a wonderful collaboration between three fields: stats, epi and lab researchers. Combined we took a look at what is called attrition in the preclinical labs, that is the loss of data in animal experiments. This could be because the animal died before the needed data could be obtained, or just because a measurement failed. This loss of data can be translated to the concept of loss to follow-up in epidemiological cohort studies, and from this field we know that this could lead to substantial loss of statistical power and perhaps even bias.

But it was unknown to what extent this also was a problem in preclinical research, so we did two things. We looked at how often papers indicated there was attrition (with an alarming number of papers that did not provide the data for us to establish whether there was attrition), and we did some simulation what happens if there is attrition in various scenarios. The results paint a clear picture: the loss of power but also the bias is substantial. The degree of these is of course dependent on the scenario of attrition, but the message of the paper is clear: we should be aware of the problems that come with attrition and that reporting on attrition is the first step in minimising this problem.

A nice thing about this paper is that coincides with the start of a new research section in the PLOS galaxy, being “meta-research”, a collection of papers that all focus on how science works, behaves, and can or even should be improved. I can only welcome this, as more projects on this topic are in our pipeline!

The article can be found on pubmed and my mendeley profile.

Update 6.1.16: WOW what a media attention for this one. Interviews with outlets from UK, US, Germany, Switzerland, Argentina, France, Australia etc, German Radio, the dutch Volkskrant, and a video on focus.de. More via the corresponding altmetrics page . Also interesting is the post by UD, the lead in this project and chief of the CSB,  on his own blog “To infinity, and beyond!”

 

New article published – Ankle-Brachial Index and Recurrent Stroke Risk: Meta-Analysis


Another publication, this time on the role of the ABI as a predictor for stroke recurrence. This is a meta analysis, which combines data from 11 studies allowing us to see that ABI was moderately associated with recurrent stroke (RR1.7) and vascular events (RR 2.2). Not that much, but it might be just enough to increase some of the risk prediction models available for stroke patients when ABI is incorperated.

This work, the product of the great work of some of the bright students that work at the CSB (JBH and COL), is a good start in our search for a good stroke recurrence risk prediction model. Thiswill be a major topic in our future research in the PROSCIS study which is led by TGL. I am looking forward to the results of that study, as better prediction models are needed in the clinic especially true as more precise data and diagnosis might lead to better subgroup specific risk prediction and treatment.

The article can be found on pubmed and my mendeley profile and should be cited as

Hong J Bin, Leonards CO, Endres M, Siegerink B, Liman TG. Ankle-Brachial Index and Recurrent Stroke Risk. Stroke 2015; : STROKEAHA.115.011321.

The ECTH 2016 in The Hague

My first conference experience (ISTH 2008, Boston) got me hooked on science. All these people doing the same thing, speaking the same language, and looking to show and share their knowledge. This is true when you are involved in the organisation. Organising the international soccer match at the Olympic stadium in Amsterdam linked to the ISTH 2013 to celebrate the 25th anniversary of the NVTH was fun. But lets not forget the exciting challenge of organising the WEON 2014.

And now, the birth of a new conference, the European Congress of Thrombosis and Hemostasis, which will be held in The Hague in Netherlands (28-30 sept 2016). I am very excited for several reasons: First of all, this conference will fill in the gap of the bi-annual ISTH conferences. Second, I have the honor to help out as the chair of the junior advisory board. Third, the Hague! My old home town!

So, we have 10 months to organise some interesting meetings and activities, primary focussed on the young researchers. Time to get started!

First results from the RATIO follow up study

Another article got published today in the JAMA Int Med, this time the results from the first analyses of the RATIO follow-up data. For these data, we linked the RATIO study to the dutch national bureau of statistics (CBS), to obtain 20 years of follow-up on cardiovascular morbidity and mortality. We first submitted a full paper, but later we downsized to a research letter with only 600 words. This means that only the main message (i.e. cardiovascular recurrence is high, persistent over time and disease specific) is left.

It is a “Leiden publication”, where I worked together with AM and FP from Milano. Most of the credit of course goes to AM, who is the first author of this piece. The cool thing about this publication is that the team worked very hard on it for a long time (data linking and analyses where not an easy thing to do, as well as changing from 3000 words to 600 in just a week or so), and that in the end all the hard work paid off. But next to the hard work, it is also nice to see results being picked up by the media. The JAMA Int Med put out an international press release, whereas the LUMC is going to publish its own Dutch version. In the days before the ‘online first’ publication I already answered some emails from writers for medical news sites, some with up to 5.000K views per month. I do not know if you think that’s a lot, but for me it is. The websites that cover this story can be found here (dagensmedisin.sehealio.commedicaldaily.com, medpagetoday.commedonline.atdrugs.com / healthday.com / webmd.com /  usnews.com / doctorslounge.commedicalxpress.commedicalnewstoday.comeurekalert.org and perhaps more to come. Why not just take a look at the Altmetric of this article).

– edit 26.11.2015: a dutch press release from the LUMC can be found here) – edit: oops, medpagetoday.com has a published great report/interview, but used a wrong title…”Repeat MI and Stroke Risks Defined in ‘Younger’ Women on Oral Contraceptives”. not all women were on OC of course.

Of course, @JAMAInternalMed tweeted about it

 

The article, with the full title Recurrence and Mortality in Young Women With Myocardial Infarction or Ischemic Stroke: Long-term Follow-up of the Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) Study can be found via JAMA Internal Medicine or via my personal Mendeley page.

As I reported earlier, this project is supported by a grant from the LUF den Dulk-Moermans foundation, for which we are grateful.

A year in Berlin

teamfoto-ag-siegerink

So, it is just over a year since I started here in Berlin. In this year I had the opportunity to start some great projects. Some of these projects have already resulted in some handsome -upcoming- publications.

For those who wonder, the picture gives a somewhat inflated impression of the size of the team, as we decided to include all people who currently work with us. This includes two of our five students and 2 virchow scholars that are visiting from Amsterdam and Hamburg. I included them all in the picture, as I enjoy my work here in Berlin because of all team members. Now, let’s do some science!

Spectrum of cerebral spinal fluid findings in patients with posterior reversible encephalopathy syndrome

source: http://www.springer.com

This is one of the first projects that I was involved with from start to finish since my start in Berlin to be published, so I’m quite content with it. A cool landmark after a year in Berlin.

Together with TL and LN I supervised a student from the Netherlands (JH). This publication is the result of all the work JH did, together with the great medical knowledge from the rest of the team. About the research: Posterior reversible encephalopathy syndrome, or PRES, is a syndrome that can have stroke like symptoms, but in fact has got nothing to do with it. The syndrome was recognised as a separate entity only a couple of years ago, and this group of patients that we collected from the Charite is one of the largest collections in the world.

It is a syndrome characterised by edema (being either vasogenic or cytotoxic), suggesting there is something wrong with the fluid balance in the brain. A good way to learn more about the fluids in the brain is to take a look at the different things you can measure in the cerebrospinal fluid. The aim of this paper was therefore to see to what extend the edema, but also other patients characteristics, was associated with CSF parameters.

Our main conclusion is indeed the total amount of protein in the CSF is elevated in most PRES patients, and that severe edema grade was associated with more CSF. Remind yourself that this is basically a case series (with some follow up) but CSF is therefore measured during diagnosis and only in a selection of the patients. Selection bias is therefore likely to be affecting our results as well as the possibility of reverse causation. Next to that, research into “syndromes” is always complicated as they are a man-made concept. This problem we also encountered in the RATIO analyses about the antiphospholipid syndrome (Urbanus, Lancet Neurol 2009): a real syndrome diagnosis could not be given, as that requires two blood draws with 3 months time in between which is not possible in this case-control study. But still, there is a whole lot of stuff to learn about the syndromes in our clinical research projects.

I think this is also true for the PRES study: I think that our results show that it is justified to do a prospective and rigorous and standardised analyses of these patients with the dangerous syndrome. More knowledge on the causes and consequences is needed!

The paper can be cited as:

Neeb L, Hoekstra J, Endres M, Siegerink B, Siebert E, Liman TG. Spectrum of cerebral spinal fluid findings in patients with posterior reversible encephalopathy syndrome. J Neurol; 2015; (e-pub) and can be found on pubmed or on my mendeley profile

New article: Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis

source: atherosclerosis-journal.com

Together with several co-authors, with first author AN in the lead, we did a meta analyses on the role of Lp(a) as a risk factor of stroke. Bottomline, Lp(a) seems to be a risk factor for stroke, which was most prominently seen in the young.

The results are not the only reason why I am so enthusiastic by this article. It is also about the epidemiological problem that AN encountered and we ended up discussing over coffee. The problem: the different studies use different categorisations (tertiles, quartiles, quintiles). How to use these data and pool them in a way to get a valid and precise answer to the research question? In the end we ended up using the technique proposed used by D Danesh et al. JAMA. 1998;279(18):1477-1482 that uses the normal distribution and the distances in SD. A neat technique, even though it assumes a couple of things about the uniformity of the effect over the range of the exposure. An IPD would be better, as we would be free to investigate the dose relationship and we would be able to keep adjustment for confounding uniform, but hey… this is cool in itself!

The article can be found on pubmed and on my mendeley profile.

Fellow of the European Stroke Organisation

 www.eso-sss-2012.med.unideb.hu

I just got word that I am elected as fellow of the European Stroke Organisation. Well, elected sounds more cool then it really is… I applied myself by sending in an application letter, resume, some form to show my experience in stroke research and two letters of recommendation of two active fellows and that’s that. So what does this mean? Basically, the fellows of the ESO are those who want to put some of their time to good use in name of the ESO, such as being active in one fo the committees. I chose to get active in teaching epidemiology (teaching courses during the ESOC conferences, or in the winter/summer schools, perhaps in the to be founded ESO scientific journal), but how is as of this moment not completely clear yet. Nonetheless, I am glad that I can work with and through this organisation to improve the epidemiological knowledge in the field of stroke.

New articles published: hypercoagulability and the risk of ischaemic stroke and myocardial infarction

Ischaemic stroke + myocardial infarction = arterial thrombosis. Are these two diseases just two sides of the side coin? Well, most if the research I did in the last couple of years tell a different story: most times,hypercoagulability has a stronger impact on the risk of ischaemic stroke at least when compared to myocardial infarction. And when in some cases this was not the case, at least it as clear that the impact was differential. But these papers I published were all single data dots, so we needed to provide an overview of all these data points to get the whole picture. And we did so by publishing two papers, one in the JTH and one in PLOS ONE.

The first paper is a general discussion of the results from the RATIO study, basically an adaptation from my discussion chapter of my thesis (yes it took some time to get to the point of publication, but that’s a whole different story), with a more in-depth discussion to what extent we can draw conclusions from these data. We tried to fill in the caveats (limited number of markers, only young women, only case-control, basically single study) of the first study with our second publication. Here we did the same trick, but in a systematic review.This way, our results have more external validity, while we ensured the internal validity by only including studies that studied both diseases and thus ruling out large biases due to differences in study design. I love these two publications!

You can find these publications through their PMID 26178535 and 26178535, or via my mendeley account.

PS the JTH paper has PAFs in them. Cool!

 

ISTH 2015 Toronto

The ISTH is a bi-annual conference on thrombosis and haemostasis, and this year it convenes in Toronto. We started yesterday with the SSCs which were interesting, but  I am mainly looking forward to some of the sessions in the normal program. As is in line with the announcement 2 years ago, the organising committee strived to include more fields of medicine into the program, one being stroke. There even a couple of stroke themed sessions. Good!

Another topic that has my interest is the link between inflammation and coagulation. This link, perhaps through the intrinsic coagulation proteins, or perhaps through extracellular nucleic acids is quite interesting, as it might provide insight into the link between these two major biological systems that interact in the acute phase of stroke. Next to the SSC meeting this morning and yesterday, there are some plenaries and symposia on this topic; Tuesday seems to be the day for this!

I contributed to three papers that will be presented here, being:

ADAMTS13 AND THE RISK OF MYOCARDIAL INFARCTION: AN INDIVIDUAL PATIENT DATA META-ANALYSIS Alberto Maino*, Bob Siegerink, Luca Lotta, James Crawley, Saskia le Cessie, Frank Leebeek, David Lane, Gordon Lowe, Flora Peyvandi, Frits Rosendaal (Italy)

RECURRENCE AND MORTALITY IN YOUNG WOMEN WITH MYOCARDIAL INFARCTION OR ISCHEMIC STROKE: 19-YEAR FOLLOW-UP OF THE RISK OF ARTERIAL THROMBOSIS IN RELATION TO ORAL CONTRACEPTIVES (RATIO) STUDY. Alberto Maino*, Bob Siegerink, Ale Algra, Flora Peyvandi, Frits Rosendaal (Italy)

STATIN USE AND RISK OF RECURRENT VENOUS THROMBOSIS: RESULTS FROM THE MEGA FOLLOW-UP STUDY Willem Lijfering*, Sigrid Braekkan, Camilla Caram-Deeelder, Bob Siegerink, Astrid van Hylckama Vlieg, Saskia le Cessie, Frits Rosendaal, Suzanne Cannegieter (The Netherlands)

As a last thing: It was a last decision to join this conference, but I am happy I did. the scientific program helps, but more importantly, the Barenaked Ladies are going to perform at the conference party!

Ps one thing that is also quite interesting, but i only saw one oral communication on this, is the authophagy of clots… how cool is that! Keep the blood flowing in the microvasculature!

New article published: the relationship between ADAMTS13 and MI

2015-06-16 14_26_12-Plasma ADAMTS13 levels and the risk of myocardial infarction_ an individual pati

this article is a collaboration with a lot of guys. initiated from the Milan group, we ended up with a quite diverse group of researchers to answers this question because of the methods that we used: the individual patient data meta-analysis. The best thing about this approach: you can pool the data from different studies, even while you can adjusted for potential sources of confounding in a similar manner (given that the data are available, that is). On themselves, these studies showed some mixed results. But in the end, we were able to use the combined data to show that there was an increase MI risk but only for those with very low levels of ADAMTS13. So, here you see the power of IPD meta-analysis!

The credits for this work go primarily to AM who did a great job of getting all PI’s on board, analysing the data and writing a god manuscript. The final version is not online, but you find the pre-publication on pubmed

 

 

Changing stroke incidence and prevalence

changing stroke population

Lower changing incidences of disease over time do not necessarily mean that the number of patients in care also goes down, as the prevalence of the disease is a function of incidence and mortality. “Death Cures”. Combine this notion with the fact that both the incidence and mortality rates of the different stroke subtypes change different over time, and you will see that the group of patients that suffer from stroke will be quite different from the current one.

I made this picture to accompany a small text on declining stroke incidences which I have written for the newsletter of the Kompetenznetz Schlaganfall. which can be found in this pdf.

New article published – Conducting your own research: a revised recipe for a clinical research training project

2015-06-07 15_38_24-Mendeley Desktop
source: https://www.ntvg.nl/artikelen/zelf-onderzoek-doen

A quick update on a new article that was published on friday in the NTVG. This article with the title

“Conducting your own research: a revised recipe for a clinical research training project”

– gives a couple of suggestions for young clinicians/researchers on how they should organise their epidemiological research projects. This paper was written to commemorate the retirement of prof JvdB, who wrote the original article back in 1989. I am quite grew quite fond of this article, as it combines insights from 25 years back as well as quite recent insights (e.g. STROBE and cie Schuyt and resulted in a article that will help young research to rethink how they plan and execute their own research project.

There are 5 key suggestions that form the backbone of this article i.e. limit the research question, conduct a pilot study, write the article before you collect the data, streamline the research process and be accountable. As the article is in Dutch only at this moment, I will work on an English version. First drafts of this ms, each discussing each of the 5 recommendations might appear on this website. And how about a German version?

Anyway, it has to be mentioned that if it not was for JvdB, this article would have never come to light. Not only because he wrote the original, but mostly because he is one of the most inspiring teachers of epidemiology.

Conference season 2015: ESOC in Glasgow

source: eso-stroke.org

Conference season just had its first kick off with the new ESOC, the new conference by the European Stroke Organisation. The organisation of the was well done, and most sessions were quite interesting. Not only the big plenary sessions (i will talk about them later, but also the smaller sessions where nice. Particularly, it was nice to see some sessions on patient and caregiver centers research. This theme fits well with our “Schalganfall Betroffene hilfen forschen” project, where people affected by stroke (both patients and their caregiver, help us in identifying the need, value and possible ROI of some of our research plans.

The most striking things, as most of the times in conferences on with a strong clinical focus, were presented in the plenary sessions. The bottom line: endovascular treatment where doctors go in and try to pull out the blood clot, seem to be quite effective. This really could revolutionize the acute treatment for stroke patients. Think about the possibilities when we combine this concept with our STEMO?

I was involved in 3 posters that were presented at the ESOC. Their topics: cancer prevalence among stroke patients, coagulation FVIII as a risk factor for ischaemic stroke in young women, and the a history of pregnancy loss as a proxy of high stroke risk. These topics are being converted to articles and the moment we have them published I will get into the details of them. The CERHIS team from the CSB also had another 3 posters, showing our results of evaluation of the user group, the service point and an evaluation of how standardised education of stroke sticks with a lay public.

Next to these posters of work almost finished, I had a lot of conversation about work to be done. All these things to investigate, and so little time! Back to work!

Next meeting to attend: ISTH in Toronto!

Journal Club 2015

http://goo.gl/w4k8uC

A new semester, time for new cool stuff. I am starting a Epi Journal Club for medical students. Here is the recruitment text.

Do you want to learn how to read medical literature?

What is a Kaplan Meier Curve? What is the difference between a case-control study and a case-cohort study? How do you get rid of confounding? What is confounding anyway! Or just in short, what distinguishes a good paper from a bad paper? Do you want to know? Here is a start:

Bob Siegerink is a clinical epidemiologist from the Centrum für Schlaganfallforschung Berlin (CSB) and he is starting a journal club for medical students (5th semester and up) where participants will be discussing both good and bad papers from both ancient and recent history. Although there is no previous experience needed, students have to be highly motivated as this is a fun, but hardcore, crash course in clinical epidemiology. All discussion will be held in English.

I have no clue on how many student will react: the deadline is soon, but this text will end up in the inbox of a lot of students. And as the level of science education in their curricula is limited compared to the Dutch curricula, they might not be triggered by this topic. Or they will… Who knows? I will use some of my previous teaching material, but I guess I need to adapt the content based on the number of participants and their level or knowledge, so everything is possible. I will keep you posted!

– update 18-4-2015: 11 participants… not bad for a first time! we start in 10 days. For the programme, click here

ILS conference in Leiden the Netherlands

source leidenuniv.edu

I am back in the Netherlands this week. I’ve got some meetings planned, catching up with former colleagues, meeting some new people interested in working together on new projects I am starting up in Berlin, and of course I am meeting some friends along the way. But there is one more reason for me to go to the Netherlands this week: I was invited to the Interaction between legal systems conference. This international conference is organized by the Law faculty in Leiden and is focused on how different legal  systems interact, but also how legal systems interact with other fields of research and areas of expertise (e.g. psychology, statistics and epidemiology). More information on the conference can be found here.

But what am I doing there? I am going to talk about my interdisciplinary project on how civil law, and especially liability cases, relate to causal inference in epidemiology. This project, together with ILS conference organiser PWdH, is one of my pet projects in which we compare the concepts behind causal inference in both clinical epidemiology as well as legal systems. Both systems rely on the condicio sine qua non principle, where the idea is that the consequence of a cause would not have happened if the cause would not have been present. This idea is of course known as the counter factual theory in epidemiology, and is related to the potential outcomes approach. But this is only the start, as there are several problems and challenges that come up: although epidemiology has recognized the idea of multi causality for some time (think component causes), legal systems have only been working with  this  only for a couple of years and with some hesitance. A way to use this in liability claims is to use proportional liability, where the claim should be proportional to the number of factors the defendant is responsible for.  Sounds cool, but how to get to a fair division? How to interpret evidence? And can we use population measures like the population attributable fraction to substantiate a ruling on individual level?

I am invited to talk about this project, bust mostly and to tell the story of interdisciplinary research. It goes without saying that working on something so far from your own comfort zone brings along a lot of challenges and problems. For example since you can only oversee the quality and relevance of part of the project, you have might have the feeling that what you are working on is kind of useless (really, is this interesting?). But on the other hand, the questions that came up during this project also provided me with some insight into the concepts of epidemiology. Explaining why the things in your field are as they are will confront you will inconsistencies in your field and in your own thinking. I noticed that this project learned me a lot about the things I thought I understood, and that is for me the true added value of interdisciplinary research.

 – update jan 26: I uploaded a pdf version of the presentation, which can be found here (pdf)
– update march 17:I visited Leiden again, now on the invitation of the dept of criminal law to talk about the concept of multi causality. We decided that we might need to braoden this into a dutch publication, with e viewpoint from both tort law and criminal law. Interesting!

The professor as an entrepeneur

picture: onderzoeksredactie.nl

Today, I’ve read a long read from the onderzoekdsredactie, which is a Dutch initiative for high quality research journalism. In this article they present their results from their research into the conflicts of interest of profs in the Netherlands. They were very thorough: they published a summary in article from, but also made sure that all methodological choices, the questionnaire they used, the results etc are all available for further scrutiny of the reader. It is a shame though that the complete dataset is not available for further analyses (what characteristics make that some prof do not disclose their COI?)

The results are, although unpleasant to realise, not new. At least not to me. I can imagine that for most people the idea of prof with COI is indeed a rarity, but working in academia I’ve seen numbers of cases to know that this is not the case. The article that I’ve read was thorough in their analyses: it is not only because profs just want to get rich, but this concept of the prof as an entrepreneur is even supported by the Dutch government. Recent changes in the funding structure of research makes that ‘valorisation’, spinn-offs and collaboration with industry partners are promoted. this is all to further enlarge the ‘societal impact’ of science. These changes mightinded enforce such a thing, but I think that the academic freedom that researchers have should never be the victim.