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.
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.
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!
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.se, healio.com, medicaldaily.com, medpagetoday.com, medonline.at, drugs.com / healthday.com / webmd.com / usnews.com / doctorslounge.com, medicalxpress.com, medicalnewstoday.com, eurekalert.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
— JAMAInternalMed (@JAMAInternalMed) November 23, 2015
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.
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
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
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.