Category Archives: Science

Falling into a black hole

To honour Roy Kerr and the first picture of a Black Hole, I have used the wonderful “rayshader” package in R to render the photo into 3D. It’s a bit like an extraordinarily hot volcano. Don’t fall in.

Thanks NASA for the photo (https://www.nasa.gov/mission_pages/chandra/news/black-hole-image-makes-history).

Cheesecake files: A new test to rule out heart attacks in just a few minutes.

Your chest hurts, you go to the hospital (good move), you get rushed through and a nurse takes some blood and measures the electrical activity of your heart.  A doctor asks you some questions.  While she does so, the blood is being tested – the results are back already! Yeah, they are negative and everything else is OK, it’s not a heart attack – you can go home.  This is the likely scenario in the near future thanks to new blood test technology which we, in Christchurch hospital’s Emergency Department, have been fortunate to be the first in the world to trial in patients. The results of our pilot study have now been published ( in a Journal of the American Medical Association (JAMA Cardiology).

About 65,000 patients a year are investigated for heart attacks in New Zealand emergency departments, yet only about 15% of them are actually having a heart attack.  New Zealand leads the world in having become the first country in the world in which all patients are assessed by an accelerated diagnostic pathway that enables rapid evaluation of the patients and can send people home after two blood tests taken two to three hours apart (see here for more).  This means many patients who once-upon-a-time would have been admitted to hospital overnight, are now able to be reassured after 4-6 hours that they are not having a heart attack and can go home.  Nevertheless, there are enormous advantages for both patient and health system to being able to come to the conclusion that the pain isn’t life threatening earlier. The cork in the bottle preventing this happening is the time it takes for a blood sample to be analysed for signs of damage to the heart. These blood tests typically take 1 to 2 hours from the time of sampling (within ~15 minutes of arrival in the ED) until the results are available for the doctor to review.  Because doctors are dealing with multiple patients at a time, their review and decisions around whether to allow the patient to go home, or to be admitted for more investigation, are further delayed.  A point-of-care test is one that happens with a small machine near the bedside and can produce results available to the doctor even while they are still examining the patient.  Until now, though, the precision of these machines has not been good enough to be used in emergency departments.  When one manufacturer told us that their new technology may now have sufficient precision we were keen to test it,  so we, in a first-in-the-world study, undertook a study in patients entering the emergency department of Christchurch hospital whom the attending doctor was investigating for a possible heart attack.

Thanks to the volunteer patients (I love volunteers) who gave some extra blood we measured the troponin concentration by this new point-of-care test (called the next generation point of care troponin I: TnI-Nx). Troponin comes from the heart muscle and is released into the blood during a heart attack. When the troponin concentrations in the blood are very very low we can be confident that the source of the patient’s discomfort is not a heart attack.  Low concentrations require a very precise measurement test. Often, a very low concentration means the patient can safely go home. In 354 volunteers we measured troponin with the TnI-Nx assay when they first came to the emergency department.  Their treatment didn’t change, and all clinical decisions were based on the normal laboratory based troponin (measured on entry to the emergency department and again 2 hours later). From the blood samples we collected and measurements we made, we could work out what could have happened if we had used the TnI-Nx results instead.

In our study the TnI-Nx troponin measurement was as good as, and possibly slightly better, than the laboratory based troponin measurement at ruling-out a heart attack. We found 57% of the patients being investigated had troponin concentrations measured with TnI-Nx below a threshold at which we could be confident that they were not having a heart-attack.  All 57 patients who were actually having a heart attack had higher concentrations.

When implemented our results may mean that instead of waiting 3-6 hours for a results, half of patients being investigated could know within about 30 minutes of arriving at the ED whether they are having a heart attack or not.  This early reassurance would be a relief to many, as well as reducing over-crowding in the emergency department and freeing up staff for other tasks.  But before we implement the new test, we must validate it in more patients – this is a study we are carrying out now.  Validation will enable us to more precisely determine a threshold concentration for TnI-Nx for clinical use which we can, with a very high degree of certainty, safely use to rule-out a heart attack.

The test also should allow people living in rural areas to get just as good care as in emergency departments because it could be deployed in rural hospital and general practices.  This would save many lengthy, worrying, and expensive trips for people to an urban emergency department.

This study was carried out by the Christchurch Emergency Department research group (director and senior author Dr Martin Than) in conjunction with the Christchurch Heart Institute (University of Otago Christchurch).  My colleague, Dr Joanna Young did much of the hard yards, and we thank our clinical research nurses and assistant for all they did to take blood samples, collect data, and lend a hand around the ED.  The manufacturer of the blood test, Abbott Point-of-care, provided the tests free of charge, but they were blinded to the results and all analysis was conducted independent of them.

How we envisage TnI-Nx may be used in the future to allow very early rule out of heart attacks

Please note – patients experiencing sudden onset chest-pain should always seek immediate medical attention.

I am fortunate to hold a Senior Research Fellowship in Acute Care sponsored by the Canterbury Medical Research Foundation, the Emergency Care Foundation, and the Canterbury District Health Board which enables me to participate in these studies.

ps.  You’ll have to read some of my older posts if you want to know why “Cheesecake files”

 

The wrong impact

“We just got a paper in an Impact Factor 10 journal … and hope to go higher soon.”  That’s a statement made to me last week.  It is wrong on so many levels, but does it matter?   Nobel Prize winners think so. This video from nobelprize.org appeared in my twitter feed on Friday.  Before you watch it, consider this, academics in NZ are being encouraged in promotion applications and in preparing for the next round of NZ Performance Based Research Fund (PBRF), which will allocate millions of dollars to academic institutions, to include a metric of the ranking of the journal.  The Impact Factor is the most common metric available.

 

ps. I would not allow a student working with me to present a raw mean of a highly skewed distribution because it so very poorly represents the distribution.  However, this is exactly what the Impact Factor does (for those who don’t know the most common impact factor for a journal in any given year is simply the sum of citations of articles from the preceding two years divided by the total number of articles published.  The citation distribution is usually skewed because the vast majority of articles receive very few citations in such a short time, but a few receive a lot).  There are numerous other problems with it, not the least that it can’t be used to compare “impact” between different disciplines.

An even quicker way to rule out heart attacks

The majority of New Zealand emergency departments look for heart muscle damage by taking a sample of blood and looking for a particular molecule called a high-sensitivity troponin T (hsTnT).  We have now confirmed that rather than two measurements over several hours just one measurement on arrival in the ED could be used to rule out heart attacks in about 30% of patients.

What did we do?

We think this is a big deal. We’ve timed this post to meet the Annas of Internal Medicine timing for when our work appears on their website – here.  What we did was to search the literature to find where research groups may have measured hsTnT in the right group of people – namely people appearing in an emergency room whom the attending physician thinks they may be having a heart attack. We also required that the diagnosis of a heart attack, or not, was made not by just one physician, but by at least two independently.  In this way we made sure we were accessing the best quality data.

Next I approached the authors of the studies as asked them to share some data with us – namely the number of people who had detectable and undetectable hsTnT (every blood test has a minimum level below which it is said to be “undetectable” in hsTnT’s case that is just 5 billionths of a gram per litre, or 5ng/L).  We also asked them to check in these patients if the electrical activity of the heart (measured by an electrocardiogram or “ECG”) looked like there may or may not be damage to the heart (a helpful test, but not used on its own to diagnose this kind of heart attack).  Finally, we asked the authors to identify which patients truly did and did not have a heart attack.

What did we find?

In the end research groups in Europe, UK, Australia, NZ, and the US participated with a total of 11 studies and more than 9000 patients.  I did some fancy statistics to show that overall about 30% of patients had undetectable hsTnT with the first blood test and negative ECGs.  Of all those who were identifiable as potentially “excludable” or “low-risk” only about 1 in 200 had a heart attack diagnosed (we’d like it to be zero, but this just isn’t possible, especially given the diagnosis is not exact).

VisualAbstract AnnalsIM 170411

Pickering, J. W.*, Than, M. P.*, Cullen, L. A., Aldous, S., Avest, ter, E., Body, R., et al. (2017). Rapid Rule-out of Myocardial Infarction With a High-Sensitivity CardiacTroponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis. Annals of Internal Medicine, 166(10). http://doi.org/10.7326/M16-2562 *joint first authors.

What did we conclude?

There is huge potential for ruling out a heart attack with just one blood test.  In New Zealand this could mean many thousands of people a year can be reassured even more swiftly that they are not having a heart attack. By excluding the possibility of a heart attack early, physicians can put more effort into looking for other causes of chest-pain or simply send the patient happily home.   While not every hospital performed had the same great performance, overall the results were good.  By the commonly accepted standards, it is safe.  However, we caution that local audits at each hospital that decides to implement this “single blood measurement” strategy are made to double check its safety and efficacy.


Acknowledgment: This was a massive undertaking that required the collaboration of dozens of people from all around the world – their patience and willingness to participate is much appreciated. My clinical colleague and co-first author, Dr Martin Than provided a lot of the energy as well as intelligence for this project. As always, I am deeply appreciative of my sponsors: the Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board, and University of Otago Christchurch. There will be readers who have contributed financially to the first two (charities) – I thank you – your generosity made this possible, and there will be readers who have volunteered for clinical studies – you are my heroes.

Sponsors

 

 

To march or not to march?

When I’ve marched in the past it has been to protest or celebrate.  The call for a March for Science, due to take place in New Zealand on the 22nd of April, has me confused as to its purpose.

When I first heard the suggestion of a March for Science in New Zealand I admit I was immediately sceptical (occupational hazard).  The suggestion had come in response to the policies of the Trump administration in the USA.  I am appalled by many of them and by the apparent ignoring of the scientific consensus – but then given the flip-flop on so much that was said in the campaign, it would take a brave person to predict there won’t be a similar flip-flop with respect to climate change policies and the like.  That aside, is the March in New Zealand intended to be a protest against Trump?

Nicola Gaston in a persuasive blog post  writes that with her Bachelor of Arts in her back pocket she will be marching for science and the scientists. Paraphrasing Niemoller she writes “First they came for the scientists, but I was not a scientist, so I did not speak out”. She hit a nerve with me, it is a sentiment that has resonated strongly in me ever since I walked though Auschwitz concentration camp and spent several years living in a country soon after the communists had relinquished power. It is right and proper to speak out for the oppressed, whoever they are and whether we agree with them or not. However, the title of Nicola’s post “Why scientists need to go to the barricades against Trump – and for the humanities” and the first few paragraphs paint the call to march  as a political protest against Trumpian rhetoric and policy.  This, for me, is not an encouragement to march in NZ.  There are many many countries and issues around the world that I abhor and that I think reflect more closely Niemoller’s sentiments– “First they came for the migrants”, “First they came for the children (for the sex trade)”, “First they came for private property” – and I struggle with what I can do about any of them.  However, marching in New Zealand protesting policies in another country is not something I see as effective unless we are demanding action from our government against those countries.

Photo-_Brandon_Wu_(32048341330)

Photo: Brandon Wu 20 Jan 2017 , Wikimedia Commons.

 

Since Nicola wrote that piece, the March organisers have written about the reasons for the March (here and here).  While what has happened in the US is still very much to the fore, the organisers’ attentions seems to have turned towards a protest against policies of the current government “our current government has and continues to be ineffective in defending our native species and environment” (Geni- Christchurch organiser), “The government believes they are improving freshwater, yet they aren’t utilizing NZ freshwater ecology research outputs or freshwater scientists for these decisions.” (Erin-Palmerston North), “you only have to look at the Land and Water forum to open the discussion about the government ignoring the advice of scientists in regards to water quality.” (Steph-Auckland), and on the March for Science websiteThe dismissal of scientific voices by politicians is perhaps best encapsulated by our former Prime Minister’s dismissal of concerns about the impact of our dairy industry on water quality

 

Critique

The organisers in the spirit of peer review invite critique.  My first thought is that if people want to protest the government’s actions with respect to water quality – then please do so.  But, please don’t dress it up as a “March for Science” as if NZ politicians are inherently anti-science.  It comes across as a belief that the NZ Government is tarred with the same brush as the Trump administration with respect to its treatment of science.  I don’t think that comparison is fair.

As an aside, I believe we must be careful with the generalisation “anti-science”, a phrase I’ve regularly heard from the voices and pens of scientists in the past few years.  The phrase has almost always been used to describe people who take stances in opposition to the scientific consensus on matters such as vaccinations, fluoridation, or climate change.  I don’t believe these people are anti-science per se – indeed, they often try (and fail) to use science to back their views. Furthermore, they may well embrace the findings of science in general.  Troy Campbell and Lauren Griffen’s recent post in Scientific America is a good panacea against the loose and pejorative use of the term “anti-science”.

Another aspects of the call to March that I find difficult is the statement “We acknowledge that in Aotearoa New Zealand the scientific community has yet to live up to the principles of Te Tiriti o Waitangi, and that there is an ongoing process of decolonization required to achieve greater inclusion of Māori in the scientific community.” I admit I’m not entirely sure what this means. However, as a member of the scientific community it sounds like I’m being slapped over the wrist.  Further, I feel it is accusing me of some form of racism.  I’m sure this was not the intention, but it is the impression I get and one I don’t like getting.

This is all a pity, as I’d hoped that the March for Science would be more of a celebration with the added value of standing in solidarity with scientists who have been silenced or disenfranchised.  To be fair, celebration is obviously on the mind of some of the organisers such as Cindy from Dunedin “together to celebrate the quest for knowledge and the use of knowledge to protect and enhance life… hope that the March for Science Global initiative will empower scientists and other knowledge-seekers to continue their important work and to share it widely.”  However, this does not seem to reflect the overall tone of the call.

One of the goals of the March is to highlight that “Good scientists can be political.”  I applaud this sentiment and it is something I have tried to be take on board in the past – twice I stood as a political candidate in the general election (2005 and 2008).  Beyond protest, I would encourage all scientists to spend a few minutes with their local MP explaining why and what they do.  The temptation is to bemoan the lack of funding, but I would suggest that funding follows understanding, and we need to engage with politicians and as we do so to recognise the complexity of the decision making with all the competing interests that they have to make.

I began with a question, to march or not to march?  As I’ve written this, I’ve come to the conclusion that, on balance, the call has not resonated with where I’m at, or with what I think of as effective dialogue with politicians, therefore I will not be marching.  I appreciate that others will disagree, nevertheless I wish them a very positive experience.

Big data + Big science = Big health

Big data and big science are buzz phrases in health research at the moment.  It is not at all apparent what the exact definition of these are or should be and whether they will be short lived in our lexicon, but I think it reasonable to assume that where there is buzz there is honey.

I think of big data in health as information routinely collected by our interaction with health systems, both formal (eg GPs or hospitals) and informal (eg networked devices that continuously monitor our heart beat).  Through ever improving connectivity such data may become available (anonymously) for the health researcher and policy maker.  The statistical tools needed to analyse this volume of data without producing spurious correlations are still being developed and there are some genuine ethical concerns that must be addressed.  Within New Zealand we have a unique alpha-numeric identifier for anyone who has encountered our formal health system.  This is very unusual internationally and puts us in a good position to pull data together from multiple sources and to monitor change over time.  Recently I have used this system to assess the performance of new emergency department chest-pain pathways at multiple hospitals throughout the country.  These pathways had been developed in research programs in Christchurch and Brisbane. Following a Ministry of Health initiative for each emergency department to adopt such a pathway, and with the financial support of a Health Research Council grant (and my personal sponsors), we were able to establish efficacy and safety parameters of the change in practice.  If we had used a traditional model of employing research staff at each hospital the costs would have run into many millions and would simply not have been possible given how health research is financed in this country.  This model of monitoring changes made to how health care is delivered is both pragmatic and affordable.  It is also necessary if we are to be reassured that change is really improving practice. We expect to see more big data used in this way.

Big science is often thought of in terms of hundreds or thousands of researchers in facilities like CERN costing hundreds of millions of dollars. I think big science need not be so large or expensive.  Rather it is large international collaborations whereby sufficient good quality clinical research data is gathered to answer important clinical questions.  The key is “sufficient”.  Because of the prevalence of a disease or the size of a population base any one research group may not be able, in a reasonable time frame, to collect sufficient data to answer the important questions.   Over the past two years I have been involved in several international studies where we have pooled data, some of which our group has led, some of which are led by colleagues overseas.  We are now formalising a “consortium” to further ensure data is well and appropriately used and collected.  This move had been particularly important as even million dollar studies of a thousand patients do not have sufficient data to answer some of the key safety questions around the diagnosis of heart attacks (my current focus).  A criticism of much academic clinical research is that it is just not useful1.  This is in large part because the studies are too small to give results that would change practice.  They are also often not pragmatic enough (eg by excluding significant portions of patients likely to be assessed or treated by the intervention under study).  Recognition that it is through large collaborative studies that useful practical change can occur will lead to more such collaborations.  They require people to be involved with a slightly different skill set than those whose research is purely local – in particular the “people” skills required to form productive and lasting cross-cultural relationships.  They also require flexibility in funding which may lead to how rules for some grants change (eg by allowing some portion of funding to be spent offshore).

The era of Big data and Big science for Big health is both daunting and exciting.  While there will no doubt be blind alleys and false starts as with any research or new venture, there will also be practical and meaningful evidence based changes to health delivery. Something to look forward to.

  1. Ioannidis, J. P. A. (2016). Why Most Clinical Research Is Not Useful. Plos Medicine, 13(6), e1002049. http://doi.org/10.1371/journal.pmed.1002049.t003

Cheesecake files: A little something for World Kidney Day

Today is World Kidney Day, so I shall let you in on a little secret. There is a new tool for predicting if a transplant is going to be problematic to get working properly.

Nephrologist call a transplant a “graft” and when the new kidney is not really filtering as well as hoped after a week they call it “Delayed Graft Function.”  Rather than waiting a week, the nephrologist would like to know in the first few hours after the transplant if the new kidney is going to be one of these “problematic” transplants or not.  A lot of money has been spent on developing some fancy new biomarkers (urinary) and they may well have their place.  At this stage none are terribly good at predicting delayed graft function.

A while ago I helped develop a new tool – simply the ratio of  a measurement of the rate at which a particular substance is being peed out of the body  to an estimate how much the body is is producing in the first place.  If the ratio is 1 then the kidney is in a steady state. If not, then either the kidneys are not performing well (ie not keeping up with the production), or they have improved enough after a problem and are getting rid of the “excess” of the substance from the body.  This ratio is simple and easy to calculate and doesn’t require extra expense or specialist equipment.

A few months ago, I persuaded a colleague in Australia to check if this ratio could be used soon after transplant to predict delayed graft function. As it turns out in the small study we ran that it can, and that it adds value to a risk prediction model based on the normal stuff nephrologists measure! I’m quite chuffed about this.  Sometimes, the simple works.  Maybe something will become of it and ultimately some transplants will work better and others will not fail.  Anyway, it’s nice to bring a measure of hope on World Kidney Day.

This was published a couple of weeks ago in the journal Nephron.