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

 

IMG_4511

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.

CSB Virchow stipend

Are you a young researcher? Want to learn epidemiology? In Berlin? By doing a research project on stroke? Then boy, have I got news for you. The Center for stroke research has made funds available for young scientist to visit Berlin and work on a epidemiological project. From the website strokecenter.de

The Center for Stroke research Berlin (CSB) started the CSB – Virchow Stipend to encourage young stroke researchers to broaden or deepen their knowledge of epidemiology in the field of cerebrovascular disease through the execution of an epidemiological project. The stipend is aimed to stimulate (inter)national collaborations and therefore applicants are encouraged to collaborate with a CSB researcher on a joint project that can be executed during the stay in Berlin.

The stipend allows the awardee to travel to Berlin to work at the CSB for up to 3 months. The stipend covers all costs related to this visit with a maximum of € 4000 (€ 1000 for travel and 3 × € 1000 for accommodation).

Enthusiastic? Apply now for the first round (deadline is 12.12) or perhaps wait for the next call! Please find more information here.

New article published – but did I deserve it?

One of these dots is me standing on a platform waiting for my train! Source: GNCnet.nl

This website is to keep track of all things that sound ‘sciency’, and so all the papers that I contributed end up here with a short description. Normally this means that I am one of the authors and I know well ahead of time that an article will be published online or in print. Today, however, I got a little surprise: I got notice that I am a co-author on a paper (pdf) which I knew was coming, but I didn’t know that I was a co-author. And my amazement grew even more the moment that I discovered that I was placed as the last author, a place reserved for senior authorship in most medical journals.

However , there is a catch… I had to share my ‘last authorship’ position with 3186 others, an unprecedented number!

You might have guessed that this is not just a normal paper and that there is something weird going on here. Well weird is not the right word. Unusual is the word I would like to use since this paper is an example of something that I hope will happen more often! Citizen scientists. A citizen scientist is where ordinary people without any background or training can help in a scientific experiment of some sorts by helping just a little to obtain the data after some minimal instruction. This is wonderfully explained by this project, the iSpex project, where I contributed not as an epidemiologist, but as a citizen scientist. If you want to know more, just read what I have written  previously on this blog in the post ‘measuring aerosols with your iPhone’.

So the researcher who initiated the iSpex project have now analysed their data and submitted the results to the journal Geophysical research letters, and as a bonus made all contributing citizen scientist co-author. Cool!

Now lets get back to the question stated in the title… Did I deserve an authorship on this paper? Basically no: none of the 3187 citizen scientist do not fulfil the criteria of authorship that I am used to (i.e. ICMJE), nor fulfil the criteria of the journal itself. I am no exception. However, I do believe that it is quite clear for any reader what the role of these citizen scientist was in this project. So this new form of a authorship, i.e. ‘gift authorship to a group of citizen scientists’ is a cool way to keep the public engaged to science. A job well done!

New publication “Graphical presentation of confounding in directed acyclic graphs”

source: wikimedia.org

A new publication became available, again an ‘educational’. However, this time the topic is new. It is about the application of directed acyclic graphs, a technique widely used in different areas of science. Ranging from computer science, mathematics, psychology, economics and epidemiology, this specific type of graphs has shown to be useful to describe the underlying causal structure of mechanisms of interest. This comes in very handy, since it can help to determine the sources of confounding for a specific epidemiological research question.

But, isn’t that what epidemiologist do all the time? What is new about these graphs, except for the fancy concepts as colliders, edges, and backdoor paths? Well, the idea behind DAGs are not new, there have been diagrams in epidemiology since years, but each epidemiologist has his own specific ways to draw the different relationship between various variables factors. Did you ever got stuck in a discussion about if something is a confounder or not? If you don’t get it resolved by talking, you might want to draw out the your point of view in a diagram, only to see that your colleagues is used to a different way of drawing epidemiological diagrams. DAGs resolve this. There is a clear set on rules that each DAG should comply with and if they do, they provides a clear overview of the sources of confounding and identify the minimal set of variables to account for all confounding present.

So that’s it… DAGs are a nifty method to talk the same idiom while discussing the causal questions you want to resolve. The only thing that you and your colleague now can fight over is the validity of the assumptions made by the DAG you just drew. And that is called good science!

The paper, with first author MMS, appeared in the methodology series of the journal Nephrology Dialysis and Transplantation, can be found here in pdf, and also on my mendeley account.

New publication in NTVG: Mendelian randomisation

Together with HdH and AvHV I wrote an article for the Dutch NTVG on Mendelian Randomisation in the Methodology series, which was published online today. This is not the first time; I wrote in the NTVG before for this up-to-date series (not 1 but 2 papers on crossover design) but I also wrote on Mendelian Randomisation before. In fact that was one of the first ‘ educationals’ I ever wrote. The weird thing is that I never formally applied mendelian randomisation analyses in a paper. I did apply the underlying reasoning in a paper, but no two-stage-least-squares analyses or similar. Does this bother me? Only a bit, but I think this just shows the limited value of formal Mendelian Randomsation studies: you need a lot of power and untestable assumptions which greatly reduces the applicability of this method in practice. however, the underlying reasoning is a good insight in the origin, and effects of confounding (and perhaps even others forms of bias) in epidemiological studies.Thats why I love Mendelian Randomisation; it is just another tool in the epidemiolgists toolbox.

The NTVG paper can be found here on their website (here in pdf) and also on my mendeley account.

Quackery conference kicked out of LUMC

So I got a newsarticle in my RSS reader from the Dutch society against quackery describing the story how a quack conference was banned from the lecture halls from the LUMC. This is an interesting item, because it shows what happens when there are non scientific groups working in an academic environment. With that I mean that the guys from the Boerhaave committee, which is the LUMCs own conference bureau, can be approached by anyone to organise a conference. But a conference ‘organised by the LUMC’, held in the LUMC lecture halls has a different feel to it then just some guys who booked a room in a hotel somewhere. It feels like the content is sanctioned by the LUMC. Academia and academics must be aware of their status and not just lend their name(s) to anyone, even if you can earn an honest buck or two. This important understanding of the role of academia in society will become ever more important with valorisation and industry-academia partnerships.

Now I know that there are safeguards in place to prevent this from happening with the Boerhaave committee and apparently this kind of works, since the guys from the Society for Scientific Exploration (SSE) are no longer welcome in the Halls of the LUMC. Although I did not study the scientific validity of ‘biophotons’ completely, what I have been reading is not pretty.

Full disclaimer: I am a member of Dutch the society against quackery, I am an employee of the LUMC and I have worked with the Boerhaave committee in the organisation of the WEON.

Moving to Berlin!

After about 8 years learning and working in Leiden at the LUMC, it is time for something new. I’ve got a new job as the head of the ‘Clinical Epidemiology and Health Services Research in Stroke’ unit at the Center for Stroke research in Berlin (CSB, http://www.schlaganfallcentrum.de). This a very exciting opportunity for me: working with new colleagues on new projects, learning more about stroke research and strengthen the epidemiological studies that are executed at the CSB. I am looking forward to work with these brilliant and creative minds especially the guys from the CEHRIS team.

With moving to Berlin I will have to leave Leiden, which do regret. Not only because of the great research, but also because of the students and co-workers. Fortunately, I think that this new chapter in my academic life will provide ample opportunity to start new collaborations between Berlin and Leiden.

“BKO”

Today I got a letter stating that I have fulfilled all requirements for my BKO certificate. “BKO” is the Dutch acronym of the University Teaching Qualification certificate. It is the cornerstone of a nationwide effort to ensure that all teachers at the university have a basic understanding of everything related to teaching. Or, as is stated at the website of the Leiden University

Good teaching is of critical importance to the University. Good teaching is a skill in itself and it is one that you must develop and maintain. Only then can the University offer the quality that students deserve. The Dutch universities therefore introduced the University Teaching Qualification (UTQ) in 2008. The UTQ is a mark of quality for lecturers who have thus proven that they have mastered the craft. It is a basis from which they can further develop their skills. Show what you can do!

 

Although it is a bit of a hassle to do all courses and assignments, I believe that ensuring a basic teaching quality for university teachers is in principle a good thing… But is “BKO” enough? Only time will tell.

Honours Class ‘academic entrepeneurship’

Yesterday I was part of the Honours Class ‘academic entrepeneurship’, organised by the Leiden University in the ‘Living Lab’ | center for innovation. Together with 15 students we discussed how a scientist should be aware of the contect he is working in. From their website

 

Als wetenschapper communiceer je met veel uiteenlopende groepen: mede-wetenschappers, maar ook ‘het brede publiek’: je wilt hen informeren over jouw onderzoeksresultaten, en het is belangrijk dat je duidelijk maakt waarom jouw onderzoek belangrijk is. Verschillende vaardigheden zijn dan van belang: schrijven, presenteren, omgaan met ‘de media’ etc. Met sommige van deze vaardigheden zul je kennis maken in een (gast)college, met andere, zoals schrijven, ga je zelf aan de slag.

Om onderzoek te doen, is geld nodig en de hedendaagse wetenschapper moet daarom ook  ‘academisch ondernemerschap’ ontwikkelen: subsidies aanvragen en budgetteren zijn daarbij belangrijk.

My contribution was that the surrounding of a scientist also influences his actions and choices. We discussed the concept of scientific integrity and how integer behaviour might (or might not) be dependent on the context. In the end the students have to think how they can or might even should be aware of the threats to their scientific independence they might encounter while doing their research… I am curious what their answers are going to be!

preconference workshop ‘crash course peer review’ cancelled

I worked together with some partners on a new workshop for young epidemiologist. The title says it all: WEON preconference workshop ‘crash course peer review’.

Unfortunately, we had to cancel the workshop because the number of participants was to low to justify the effort of not only myself, but especially all the other teachers. I think it is a pity that we had to cancel, but by cancelling we still have a fresh start whenever we want to try again in a different format.

Whilst preparing this workshop I noticed that peer review, or a better term would be refereeing, is not popular. It is seen as a task that task up to much time, with too much political consequences and little reward etc. New initiatives like Pubmed commons and other post publication peer review systems are regarded by some as answers to some of these problems. But what is the future of refereeing, when young epidemiologist are not intrinsically motivated to contribute time and effort to the publication process? Only time will tell.

For those who are still interested in this crash course, please contact me via email.

 

Research in the media

Research in the media. It is however not my own research, but these two newspaper articles are related to my research.The first article (pdf) is on the role of helmets for scooters. This is linked to the publication on the risks related to motorised two-wheel vehicle crashes. (cick here for the pubmed entry)
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The second article from the same edition of the NRC is related to the topic of my thesis. It is about the role of FXII in thrombosis, based on a publication by Thomas Renne et al in Science translational medicine. Antibodies against FXII downregulate the pathological thrombogenenis during extracorporeal circulation. These antibodies might be used in the prevention of clots during heart-lung surgery, but might also be applied in the prevention of thrombosis, both arterial and venous. Click here (pdf) for the NRC newspaper article, and here for the original research by Renne et al.

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New article: the intrinsic coagulation proteins and the risk of arterial thrombosis

I got good news today! A manuscript on the role of the intrinsic coagulation factors in the causal mechanisms leading to myocardial infarction and ischaemic stroke has been accepted for publication by the JTH. It took sometime, but in the end I’m very glad that this paper was published in the JTH because its readership is both clinical as well as biomedical: just the place where I feel most at home.

The basic message? These factors do contribute to ischaemic risk, but not to the risk of myocardial infarction. This is mostly the case for coagulation factor XI, which is a nice finding, because it could be a new target for anti-thrombotic therapies.

The article is now in print and will be made available soon. In the mean time, you can refer to my thesis, in which this research was also described.

Retraction Watch – blog on retractions of scientific articles

I’ve been a fond reader of retraction watch for over a year now. It is quite interesting to read the reports of how science corrects their own mistakes. Sometimes it is just plain old fraud, such as the case of Stapel, but also other Dutch researchers. But sometimes the stories behind the retractions show that there are also ‘legitimate mistakes’ that lead to such a retraction, for example this retraction from Genes and Development in which “it’s quite clear there isn’t even a whiff of misconduct or fraud”. Please check out the Retraction Watch blog or read an interview with one of its founders  which appeared in the de Volkskrant.

On being a scientist – second meeting planned

After our first pilot of our workshop ‘on being a scientist’ it is time for the second installment. The date has been set (feb 19th), and the location remains unchanged. Slight changes to the programme though! Afterall, whats the use of a pilot if you don’t learn from it. The main program remains the same, as you can see below:

  • Introduction
  • A short history of scientific misconduct, the case of the Netherlands
  • From Fishy to fraud – a discussion about the grey area
  • PhD candidates: a special case?
  • Closing remarks

Hope to see you there!

credit and accountability: new authorship rules by ICMJE

The international consortium of medical journal editors (ICMJE) have issued a new version of their recommadations.The most important change is the addition of a fourth aspect to the list of authorship criteria. According to their motivation , this addition was inspired by cases of scientific misconduct investigation in which authors denied responsibility (e.g. “I didn’t participate in that part of the study or in writing that part of the paper; ask someone else”). According to the ICMJE, authorship requires:

1 | Substantial contributions to: the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND

2 | Drafting the work or revising it critically for important intellectual content; AND

3 |Final approval of the version to be published; AND

4 | Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved

To my opinion, this addition is a good way to help researchers think about their role in the writing process: am I involved enough to justify an authorship?

However, denying responsibility of a case of scientific misconduct is in my book not the same as being responsible of the misconduct. This addition could lead to the situation where such a denial equals scientific misconduct. Isn’t that a bit to harsh? Also, the fourth criterion reflects your actions in a situation in the future, not the work that has already been done as is the case is criteria 1-3.  It is possible to compare your actions of the past to the criteria, but this is more problematic for the future. For example, a researcher might be willing, but unable to help in an investigation (e.g. change of lab). This might lead to several problems in the future, especially for young scientist who often change research groups. To make this fourth criterion work, the idea of the fourth criterion should lie in the willingness to help, the act of helping itself.

New publication: LTTE in the American Journal of Epidemiology

12.coverAt the department of Clinical Epidemiology of the LUMC we have a continuous course/journal in which we read epi-literature and books in a nice little group. The group, called Capita Selecta, has a nice website which can be found here. sometime ago we’ve read an article that proposed to include dormant Mendelian Randomisation studies in RCT, to figure out the causal pathways of a treatment for chronic diseases. This could be most helpful when there is a discrepancy between the expected effect and the observed effect. During the discussion of this article we did not agree with the authors for several reasons. We, AGCB/IP/myself, decided to write a LTTE with these points. The journal was nice enough to publish our concerns, together with a response by the authors of the original article. The PDF can be found via the links below which will take you to the website of the American Journal of Epidemiology. The PDF of our LTTE can also be found at my mendeley profile.

original article
letter to the editor
response by the author

The pharmaceutical industry, both good AND bad

As said, I spoke at the “Gezondheidszorg in Vogelvlucht” symposium, organised by the Leidse Co-raad for all students doing their clinical rotations on the topic of the role of the pharmaceutical industry in medicine.

Previously I told you that I wondered what kind of presentation it would be. During the preparation the story became clear to me… there is no way to choose between good or bad… they are both. How come? There are some serious problems in the way medicine is organised how it comes to new decisions on treatments. Missing data from trials indeed hamper the way doctors can decide what treatment to give and which not. So, I did talk about the book Bad Pharma and our Bad Pharma Symposium. But this was not all. Science has taken a beating lately, for example in the Economist article from October. And while preparing this talk I learned that Science and pharmaceutcal companies can learn a lot from each other. 

During the presentation I used two books: Bad Pharma, which can be bought everywhere, or borrowed from the Walaeus Library of the LUMC, and Arrowsmith, a great coming of age novel by Sinclair Lewis, about a young scientist doctor who is struggling with the questions young doctors/scientist all encounter. I will write a longer post on that novel somewhat later, but in the mean time you can download the free e-book here

A pdf from my lecture can be downloaded here: Big Pharma co raad symposium  2013 (pdf)

Bad Pharma 2013 – a great succes

bad pharma skype

300 students reading one book, summarising it contents and discussing three propositions in order to grasp the essence of the book. This might sound a bit boring perhaps…But what if it Goldacres book Bad Pharma, you only have to read 30 pages and still get the content of the complete book, and get to Skype with the author? Great fun!

And we weren’t the only who had fun: Ben Goldacre addressed 300 students, all with critical questions, and apparently he enjoyed the whole debate:

We also invited AV, a spokesperson of NEFARMA an organisation who represents most pharmaceutical companies in the Netherlands. With him we discussed whether the AllTrials campaign was a waste of time and money. Also, BB  a reporter from the Mare, who has knowledge on conflict of interest of professors joined in on the discussion whether professors should declare their COI before each lecture. All in all, it was a great day in which some of the students were shocked by the message of Ben Goldacre, whereas other students were not impressed and doubted whether there view is too one-sided… The debate still continues!