New Masterclass: “Papers and Books”

“Navigating numbers” is a series of Masterclass initiated by a team of Charité researchers who think that our students should be able to get more familiar how numbers shape the field of medicine, i.e. both medical practice and medical research. And I get to organize the next in line.

I am very excited to organise the next Masterclass together with J.O. a bright researcher with a focus on health economics. As the full title of the masterclass is “Papers and Books – series 1 – intended effect of treatments”, some health economics knowledge is a must in this journal club style series of meetings.

But what will we exactly do? This Masterclass will focus on reading some papers as well as a book (very surprising), all with a focus on study design and how to do proper research into “intended effect of treatment” . I borrowed this term from one of my former epidemiology teachers, Jan Vandenbroucke, as it helps to denote only a part of the field of medical research with its own idiosyncrasies, yet not limited by study design.

The Masterclass runs for 8 meetings only, and as such not nearly enough to have the students understand all in and outs of proper study design. But that is also not the goal: we want to show the participants how one should go about when the ultimate question is medicine is asked: “should we treat or not?”

If you want to participate, please check out our flyer

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!

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!

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

 

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

2016-10-09-18_05_33-1-s2-0-s0049384816305102-main-pdf
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.

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.