Category Archives: Science

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.

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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.

 

Cheesecake files: A world second for heart attacks

Going to the Emergency Department with chest pain no longer means an almost certain night in hospital.  Friday saw the publication online of our randomised controlled trial comparing two different strategies to rapidly rule-out heart attacks in people who present with chest pain to hospitals.  Here’s a précis:

What’s the problem?

  • Chest pain is common – 10% or so of presentations to ED are for chest pain.
  • Heart attacks are not so common – only ~10-15% in NZ (and less overseas*) actually have a heart attack.
  • It is devilishly difficult for most chest pain to rapidly rule out the possibility of a heart attack.
  • Consequently, most people get admitted to hospital (in 2007 93% of those presenting with chest pain).

But – led by Dr Martin Than in Christchurch and an international group including Dr Louise Cullen in Brisbane – a series of observational studies and one randomised control trial have resulted in a gradual increase in the proportion discharged.  The trial was the first of its kind, it compared standard practice at assessing chest pain to a purpose built accelerated diagnostic pathway (ADP), which we called ADAPT.   In that study 11% of patients in the standard practice (control) arm and 19.3% in the ADAPT ADP arm (experimental arm) were discharged home from ED within 6 hours.  A great improvement which led to that ADP being adopted in Christchurch hospital.

So why another study?

Two reasons: First, 19% still means that there are many patients being admitted who potentially don’t need to be in hospital.  Second, the ADP was based around a risk assessment tool designed to rule-in heart attacks rather than rule-out.  In the meantime, the team had constructed a purpose build risk assessment tool that in observational studies looked like it could rule out 40-50% of patients.

What is the study just published?

The world’s second randomised controlled trial of assessment of chest pain compared the ADAPT ADP in use (now the control arm) with a new ADP based on the new Emergency Department Assessment of Chest pain Score (EDACS)[the experimental arm].  The only difference between the two arms of the study was the risk assessment tool used. The tool gave a risk score. Patients with a low score, no unusual electrical activity in the heart, and no elevated heart muscle injury proteins in either of two blood samples measured 2 hours apart, were considered low risk.

An important aspect of the study was that it was pragmatic.  This means that the doctors didn’t have to follow the ADP and could decide to send a patient home, or not send them home, based on any factors they thought clinically relevant.  This makes it very tough to run a trial, but it makes the trial more “real life.”

What were the results?

558 patients were recruited.  They all volunteered and are marvellous people.  I love volunteers.

The primary outcome was the proportion of patients safely discharged home within 6 hours.  We assessed safety by looking at all medical events that happened to a patients over 30 days to check to see if any patients discharged home had a major cardiac event that could potentially have been picked up in the ED.

34% of the control arm and 32% of the experimental arm were discharged within 6 hours.  In other words, there was no difference in early discharge rates between the two arms.  The surprising feature of this is that between 2012/3 (when the first trial was run) and 2014/15 the proportion of patients the first ADP ruled out increased from 19% to 34%.  This was unexpected, but pleasing. There were no safety concerns with any patients.

The secondary outcome was simply the proportion each arm of the study classified as low risk (ie not considering whether this led to early discharge or not).  The control (ADAPT ADP) classified 31% and the experimental (EDACS ADP) 42%.  This was a real and meaningful difference which suggests that there is “room for improvement” in early discharge rates as the clinicians become more familiar with the EDACS ADP.

Since 2007 in Christchurch hospital over three times more patients who present with chest pain can be reassured from within the ED that they are not having a heart attack and discharged home (see the infographic).EDACS infographic v2

What was your role?

My role: I managed aspects of the data collection for the later 2/3rds of the patients recruited, did the statistical analysis and co-wrote the manuscript.  In reality, there were a lot of people involved, not least of whom were the wonderful research nurses and database manager who did a lot of the “grunt work”.

What now?

Over the last year all EDs in New Zealand have implemented or in the process of implementing an accelerated diagnostic pathway.  The majority have chosen to use the EDACS pathway.  I am part of a team nationwide helping implement these pathways and monitor their efficacy and safety.

_________________________________________________________________________

This study was funded by the Health Research Committee of New Zealand. The work was carried out with the collaboration or the University of Otago Christchurch, Christchurch Heart Institute, and the Canterbury District Health Board Emergency Department, Cardiology Department, General Medicine, and Canterbury Health Laboratories. My salary is provided through a Senior Research Fellowship in Acute Care funded Canterbury Medical Research Foundation, Canterbury District Health Board and the Emergency Care Foundation.

*Not because we have more heart attacks, just an efficient and well funded primary care sector that keeps the very low risk patients out of the ED.

**Featured Image: Creative Commons Share-Alike 3.0 http://tcsmoking.wikispaces.com/heart%20attack

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What’s going on at the UOC?

Q. What has Mars, Epidemics, Heart Disease, Infection, and Pacifika got in common?

A. They are all central to research project at the University of Otago Christchurch (UOC).

Here are some excerpts for the UOC summer newsletter (Written by UOC communications manager, Kim Thomas).

Christchurch in NASA Mars project role

University of Otago, Christchurch, researchers are playing a crucial role in research that will assist in NASA’s mission to Mars.

Screen Shot 2016-02-09 at 10.15.21Thee Christchurch researchers are scanning the brains of explorers who have wintered in Antarctica as part of a NASA /German Aerospace Center project to understand what impact living in extreme environments has on the human brain. The research will be relevant for NASA’s plans to send humans to Mars. The shortest possible return trip to the red planet would take two years.

The international research team is led by the University of Pennsylvania’s Associate Professor Mathias Basner. His team will be scanning the brains of astronauts, while the Canterbury team focuses on those who have wintered in Antarctic’s extreme and isolated environment.

Dr Tracy Melzer is the MRI research manager for the Christchurch campus’ New Zealand Brain Research Institute. He says the research aims to understand whether prolonged periods in these extreme, isolated and hostile environments change brain structure and function.

His international collaborators have already found the hippocampus region of the brain, which is important for memory formation and visual/spatial orientation, actually shrinks during the Antarctica winter.

Dr Melzer and his colleagues will scan the brains of up to 28 international explorers over two years. They are tested before leaving for Antarctica, immediately on their return, then six months afterwards. The Christchurch scans are important because they capture explorers immediately as they return from the ice.

Preparing for future disease epidemics

Christchurch microbiologist Professor David Murdoch has taken part in an invitation-only global think tank aimed at better anticipating future infectious disease epidemics.

The head of the University of Otago, Christchurch’s Pathology Department was one of two Australasians invited to the World Health Organization-led event late last year.

Professor Murdoch says he was privileged to be among about 130 international experts invited to attend, including human and animal health experts, and members of aid agencies and the insurance and travel industries.

“ The big idea was how to better prepare for future epidemics, knowing there definitely will be ones. It also recognized reviews of the Ebola response and a desire to improve on that.”

Acknowledging the importance of collaboration, one key outcome of the event was getting people from diverse areas of expertise together, Professor Murdoch says.

Thee event consisted of six sessions, including ‘Back to the future: learning from the past’, and ‘Preventing the spread of infectious disease in a global village’. Each session consisted of short talks by five experts, then robust discussion.

Professor Murdoch spoke at the event about the relatively new area of microbiomes (the communities of microorganisms that inhabit parts of the human body) and how understanding it could help with preparing for and controlling future respiratory disease epidemics.

Some of the ideas that emerged from the event were that global and public health were getting more political attention than ever, and that health threats increasingly reflected nature, including the animal world, and so acknowledging and understanding its interplay with human health was important.

Contact between children monitored in world first infection study

Christchurch primary school pupils are wearing sensors tracking contact with each other in a world-leading study to better understand a common but serious disease.

The staphylococcus bacterium is a major cause of serious infections such as septicaemia, but also often presents as sores on the skin. Most commonly, though, it is carried harmlessly on skin or in noses, from where it can be passed on to others who might become ill. Very little is known about who passes it to whom in the community.

University of Otago, Christchurch researcher Dr Pippa Scott is testing levels of the bacteria in Linwood Avenue School pupils and, in a world first, monitoring contact between them using ‘proximity sensors’ to better understand how staphylococcus is passed from person to person.

Dr Scott says school-aged children o en spread u and other diseases so could be important to the spread of staphylococcus in the community.

“We asked a lot of schools if they would take part in the study and Linwood Avenue School principal Gerard Direen came back to us quickly and said the school would be really keen to help.’’

Dr Scott says 70 children aged between 8 and 11 were given the proximity sensors to wear clipped to their shirts for around 2 weeks. e sensors are not GPS devices and cannot pinpoint a child’s whereabouts but rather record when children come in contact with each other. They have never before been successfully used in a study linking infectious disease spread to contact in the same individuals.

The study is ongoing but early analysis found almost every child was carrying the bacterium at some stage during the seven times they were tested. More than half the children carried the bacteria at any one test session. Almost all strains the children had were susceptible to commonly prescribed drugs for the condition.

First study of South Island Pasifika heart health

“She was one of the first scientists to demonstrate our cells produce free radicals as part of their normal function.”

It’s well known that New Zealand’s Pacific population suffers higher rates of heart disease than the general population. But until now, evidence has been based on data gathered
in Auckland. University of Otago, Christchurch researcher Dr Allamanda Faatoese is changing that with the launch of the Pasifika Heart study of Christchurch Pacific people.

“Pacific communities living in Auckland have vastly di erence environments than those in Christchurch. We know little about the heart health pro le of Pasifika people in Christchurch,’’ she says.

The Heart Foundation-funded Pasifika Heart study will for the first time measure heart disease risk factors in 200 Pacific Island participants, both healthy people and those su ering from illness. Dr Faatoese is based at the University’s Christchurch Heart Institute but will study participants from across the South Island.

Each participant’s personal and family medical history, blood pressure and body composition will be recorded along with their cholesterol levels, blood sugars and markers linked with kidney function, gout and heart failure.