Cantabrians, this is your life

There is little more precious than our health and that of those we love. “Research saves lives” is  Canterbury Medical Research Foundation’s (CMRF) proudly held motto. The CMRF has been supporting the people of Canterbury for 55 years thanks to the generosity of Cantabrians. In that time they have funded more than $22 million in grants.  Yesterday I attended the launch of their new logo and branding.  The logo depicts a medical cross and the four avenues of Christchurch.  This new logo is intended to signal CMRF’s intention to be fresh and more external facing with a broader appeal to the Canterbury donating community and a bigger emphasis on  partnerships with other funding organisations to leverage money to best effect.  My own fellowship, jointly funded by the CMRF, the Emergency Care Foundation, and the Canterbury District Health Board is an example of that.  CMRF are also expanding the breadth of research they will fund and are now working to expand their influence in the translational, population health and health education spaces. Their vision is to be giving $2 million in grants per annum within 5 years.  What a great boost that will be to Canterbury. A key partner largely funded through CMRF is the NZ Brain Research Institute - their logo has also changed to mirror that of CMRF.

CMRF_launch

Acute Kidney Injury Following Cardiac Surgery: A Well-studied Cohort of AKI

Originally posted on AJKD Blog:

Dr. John Pickering Dr. John Pickering

Acute kidney injury (AKI) following cardiothoracic surgery has been well reported in the nephrology literature with numerous studies published in the last decade, although the definition of AKI was variable in many of these studies.  In a recent article published in AJKD, Pickering et al perform a systematic review and meta-analysis of the literature to assess the different definitions of AKI in these studies.  Dr. John Pickering (JP), the first and corresponding author of the study, discusses this topic with Dr. Kenar Jhaveri (eAJKD), eAJKD Editor.

eAJKD:Can you explain why your team felt this topic was important to study?

JP: There is a long history of studies evaluating AKI after cardiopulmonary bypass surgery, but the information is heterogeneous and cannot be easily used to understand the extent of the problem.  We thought it was important to quantify the association and its consistency across several global…

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beyond reasonable doubt: a significant improvement

For the second time in a week I have removed the word “significant” from a draft manuscript written by a colleague of mine in clinical medicine. In a significantly p’d I wrote about the myth of significance – that is about the ubiquitous use of the term “significant” in the medical literature to mean a specific probability  incorrectly rejecting the hypothesis that two things (eg two treatments) are the same (you may need to read that twice).  What I pointed out was the “significant” does not mean “meaningful.”   Here I want to propose an alternative.  But first, I need to discuss two major problems with the term.

Where common is not specific

In my experience the common usage of “significant” to mean important is the normal interpretation of the word in the science literature even by many medically trained people and sometimes the authors of articles themselves.

The tyranny of p<0.05

When the maths wiz Ronald Fisher talked about significance (in an agricultural journal not a medical one!) he used 0ne in 20 (p<0.05) as an acceptable error rate in agricultural field trials so that trials did not have to be repeated many times.  That p<0.05 has taken on almost magical proportions (‘scuse the pun) in the medical literature is scary and shameful.  I don’t want to delve into all that now.  If you want to, a starting point maybe the Nature article here.

My proposal

I propose that in all scientific literature that authors replace the term “significant” with the phrase “beyond reasonable doubt” and that they only be allowed to publish the article if in the methods section they define what p value they choose to represent “beyond reasonable doubt” and they defend why they have chosen this value and not another.  “Beyond reasonable doubt” is a term used in the New Zealand judicial system where those charged with a crime are presumed innocent (Null hypothesis) until proven otherwise.  Perhaps those of us in science could learn something from our lawyer friends.

Fat Mate: Fat chance lost

I expect New Zealand tax dollars science spending to be better than what I read in the media this morning. Headlined in the Press was “Blenheim ‘fat mate’ loses 13.5kg in 8 weeks.”  The story was of someone on a trial of a locally produced diet supplement having lost weight.  So far nothing to peak my interest, but then I came across the statements “Satisfax was the result of $12 million research over four years with support from Crown Research Institute Plant & Food Research.” (Satisfax is the trademark)  and “Huge demand for the trial saw it expanded from 100 “fat mates” to 200.”  The second of the links goes to an October article in the Marlborough express which includes the statement that “The trial had been approved by the Health Ministry’s health and disability ethics committee and was partially funded by Callaghan Innovation.

So, your and my taxes are being spent by Callaghan Innovation on a trial of a diet pill the development of which received other tax dollars through Plant & Food. Worth a little more investigation.  The trial went through an ethics committee – big tick.  It was also (a little late) registered on the Australia New Zealand Clinical Trials network (here) – tick.

BUT, it fails miserably as an efficacy trial.

There is no control group.  ie the pill is not compared against a placebo. I can think of no practical reason why there was not a control group taking a placebo (randomised and blinded of course).  Instead, the trial just looks at the average change in weight change over eight weeks and tries to establish if this is non-zero.  Given that these people are doing something hoping to loose weight, there may well be an average loss of weight that has nothing to do with the pill. The press article suggests a biostatistician is going to somehow “account” for the placebo affect (something not mentioned on the trial registration).  I pity the biostatistician as this is involves trying to convince someone that a study run elsewhere with a placebo group, at a different time, under different circumstances could actually serve as a control for this study.

Incredibly, that is not the only major issue.  I read that part way through the trial the publicity was such that there was a demand from people to enter the trial and so they doubled the number of participants from 100 to 200.  Ahhhhhh….. this is classic introduction of bias and should never have been allowed.  Those extra 100 people are not the same as the first group… they have elevated expectations that may well bias the results.  Furthermore, it is always dangerous to talk about the trial efficacy part way through as this may influence the behaviour of those already in the trial.   Grrrrr….

In short – a chance lost and waste of Plant and Food & Callaghan Innovation funding.  There is hope though – a proper randomised controlled trial could be conducted.  But, I won’t be holding my breath.

ps.  The Marlborough Express and Press should be ashamed of such blatant product placement – diet pills on January 2nd are so cliche.  I wonder if it was the reporter or the company who initiated this piece?

Cheesecake files: Just how deadly is it?

Everyone said it did, but how did they know and by how much?  Statements like

“The development of AKI [Acute Kidney Injury] after CPB [Cardiopulmonary Bypass Surgery] is associated with a significant increase in infectious complications, an increase in length of hospital stay, and greater mortality.” (Kumar & Suneja, Anaesthesiology 2011 14(4):964)

are common place in the acute kidney injury literature.  When I started to look at the references for such statements I realised that they were all to individual, normally single centre, studies and that the estimates of the increased risk associated with AKI after CPB varied considerably.  Furthermore, the way AKI is defined in these studies is quite varied. This lead to two questions?

  1. Just how deadly is getting AKI after CPB?
  2. Does it matter how we define AKI in this case?

These questions are important as the answer to them helps a surgeon and patient to better assess the risk associated with choosing to have cardiopulmonary bypass surgery and what the importance is in monitoring kidney function after such a surgery.  To answer these questions required a meta-analysis the results of which I have just published (a.k.a earned a cheesecake).  A meta-analysis involves systematically searching through the literature, a sentence which takes seconds to write but months to serve, for all articles reporting an association between AKI and mortality after CPB.  Then there is learning how to put all the, sometimes disparate, data together (I had to learn a lot of R for this one) and to report on it.  As this was my first meta-analysis, I was fortunate to have the assistance of two highly competent scientists & nephrologists with meta-analysis experience, namely Dr’s Matt James of Calgary, and Suetonia Palmer of my own department in the University of Otago Christchurch.

So – what did we find?

  1. If you get AKI after CPB you about 4 time more likely to die compared to if you do not get AKI after CPB even after accounting for things like age, diabetes, and other risk factors.
  2. Somewhere between 37 and 118 lives per 10,000 CPB operations could be saved if we could find a way to eliminate AKI.
  3. How AKI was measured did not make any difference to the results.
  4. AKI after CPB was also associated with increased risk of stroke.
Figure 1 from Pickering et al, AJKD 2014

A teaser of a figure from Pickering et al, AJKD 2014

Pickering, J. W., James, M. T., & Palmer, S. C. (2014). Acute Kidney Injury and Prognosis after Cardiopulmonary Bypass: A Meta-analysis of Cohort Studies. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. doi:10.1053/j.ajkd.2014.09.008

ps. Sorry about the paywall folks, but as I’ve said before, if we want to put this data in front of the people it is most relevant to we haven’t the budget to always make them Open Access.

 

Can Doctors and Nurses help Dialysis patients recover?

In the case of dialysis dependent acute kidney injury patients this is a question which Dr Dinna Cruz  and colleagues (University of California San Diego) are asking and seeking opinions from both nephrologists and non-nephrologist doctors and nurses involved in care of dialysis patients.  It was a question which arose out of discussions at this year’s Continuous Renal Replacement Therapies conference (CRRT 2014). Personally, I think it is a brilliant starting point for research to go out and seek the opinion of those “at the coal face” actually treating patients. If that includes you, please take a moment to complete the survey. If it includes someone you know, please pass this request to participate on.  Here is Dr Cruz’s request:

Currently there is much interest regarding the recovery aspect of AKI. A specific area of interest is how to enhance recovery in patients who remain dialysis-dependent at the time of discharge. It is hypothesized that patients with potential for renal recovery may require a different care plan than the “usual” ESRD patient.

Therefore we are asking your opinion regarding the post-discharge care of such patients, using this short survey. It will take only a few minutes of your time, and represents a starting point for developing potential strategies for these patients. We think it is very important to have the input of specialists from different healthcare settings and countries to give a more balanced view.

Kindly complete the survey appropriate for your specialty, then please share both these links with other colleagues so we get more responses from around the world

For nephrologists:

https://www.surveymonkey.com/s/postdischAKIcare_neph

For non-nephrologists, including acute and chronic dialysis nurses:

https://www.surveymonkey.com/s/postdischAKIcare

Thank you very much for your help!

Source: Anna Frodesiak-Wikimedia Commons

Source: Anna Frodesiak-Wikimedia Commons

Publication police and how to choose where to publish

“I confess, I published behind a paywall.  I’m sorry, sir, I didn’t want to, but but but I’m almost out of funds and and …..<suspect’s voice fades>”             Publication Police files, Nov.3 2024

Will peer pressure eventually lead to discrimination against those who publish behind a paywall?  Is it now a moral imperative that we publish everything open access?  If so, is that not simply morality by majority (a dangerous proposition at the best of times), or worse, morality by the most vocal?

I’m often asked “Where should I publish this?” and I must admit that “In an open access journal” is not my first response.  This is simply because there is a higher standard than mere open access (as great as that is).  Where to publish is first and foremost the answer to the question “Where will it get the attention it deserves?”  Of course, this is where ego can raise its ugly head and, worse, I have colleagues who think this means the journal with the highest impact factor, but those distractions aside, it is still the most important question.

Most of our science is simply an incremental step building on what is going before.  Most of the time it is of interest to a relatively small group of fellow researchers or those whose profession is impacted on by the research.  Furthermore, it will probably be of interest only for a short period of time before someone else builds upon it. The “attention a paper deserves” is the attention that these people for whom it has most meaning give it.  For this reason, it should be published in a manner which makes it easy for these people to read about it and access it. This will probably mean one of the professional society journals and/or one of the most read journals in the field.  In the fields of Critical Care and Nephrology where I’ve published most recently this will probably mean a European or American journal which has high readership in those jurisdictions because this is where most of the research is being done.    Of course, this does not mean my manuscript will necessarily be accepted by those journals, but if I deem it has something important to say, then that is where I should send it first.

Comparatively few of those journals are open access only, but all offer an open access option.  This tends to come with a publishing fee in the range of US$1500 to US$3000.  My budget does not stretch to paying such a fee for every publication. I am forced to be pragmatic. If my manuscript is accepted into one of those more high profile journals I have to pick and choose.  The more important I think the findings the more likely I will take the open access option.  Also, if I think the message has immediate application for clinicians (i.e. not just the narrow group of researchers in my field) I am more likely to choose open access.

There is, of course, the option to publish in more general online journals (PlosOne, PeerJ, F1000 etc) and I have done so.  However, my impression at this stage it that these do not rapidly reach the inbox of most of the very very busy researchers and clinicians in the fields I publish in.  A few (like myself), may have set up automatic search strategies or use social media to follow journals in their field, and, of course, if people are conducting PubMed or the like searches they may come across those articles.  However, their lack of specialisation and reliance on someone making more effort over and above reading the specialised professional journals they have always read, mitigates somewhat their usefulness to me to “getting the message out.”  Of course, I could choose to be a “early adopter” or “pioneer” and publish in a low cost open access journal (if my fellow authors would let me) with the hope that this will change the publishing culture of paywalls and high publishing fees elsewhere.  However, it would be at the cost of less exposure of my research to those who are most interested and active in the field.  For some of what I publish I must balance my obligation to advance the field the most by maximising the chances of exposure amongst those for whom it is likely to be of immediate interest with the more philosophical desire for open access to all and sundry from now to eternity.

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