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Cantabrians, this is your life John Pickering Feb 27

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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

Tagged: Canterbury, Canterbury District Health Board, Canterbury Medical Research Foundation, Emergency Care Foundation, health, Research

Acute Kidney Injury Following Cardiac Surgery: A Well-studied Cohort of AKI John Pickering Feb 03

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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 John Pickering Jan 15

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.

Tagged: Beyond reasonable doubt, medical literature, medicine, p value, reasonable doubt, significance testing

Cheesecake files: Just how deadly is it? John Pickering Nov 27

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.

 

Tagged: Acute Kidney Injury, Acute Renal Failure, AJKD, AKI, Cardiac Surgery, Cardiopulmonary Bypass, CPB, death, Dialysis, Kidney, RRT

Can Doctors and Nurses help Dialysis patients recover? John Pickering Nov 07

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

Tagged: Acute Kidney Injury, Acute Renal Failure, chronic kidney injury, Dialysis, nephrologists, Nephrology, nurses, Research, survey, UC San Diego

$20bn for Medical Research! John Pickering May 15

Alas, not in New Zealand, but close … our Australian counterparts in medical research appear on the face of it to have scored big in what appears otherwise to be a grim Australian budget.  An AUD$20bn medical research “future fund” is to be established. This effectively means that by 2022-3 there will be twice the current budget available for medical research per annum (i.e. about $1bn).  How this will be divided up remains to be seen, but I note that Prof Mike Daub of Curtin University is suspicious that it is “Medical Research” not “Health and Medical Research.”

If this truly is a massive boost to medical research in Australia, what could it mean to New Zealand?

A negative possibility is that because there are already issues with recruiting medical specialists who wish to undertake research in New Zealand and because the Australian NHMRC already has successful contestable grant funding rates about twice that of New Zealand’s HRC (~16% cf ~7%), I expect there would be more one-way traffic of scientists to Australia. It is imperative that this be avoided, for all our health’s sake.

If, though, the funding recognises the value of collaborative research then it may be possible for New Zealand scientists to work more closely with their Australian counterparts on projects of mutual interest.  To that end, the New Zealand Government has (now) a great opportunity under CER to facilitate collaboration.  Perhaps, a dedicated fund that would support New Zealand researchers financially to play a role in Australian led research.  Apart from the high quality of NZ researchers (!), New Zealand should appeal to Australia because of the better integration of our health systems, especially with respect to tracing patient hospital events nationally, and because of the lower costs of doing research here.  Furthermore, health consumers in New Zealand demand the best (I know I do!) and the best is only available through research – ultimately more research across the ditch will benefit us here.  Thanks Tony.

______

ps. Catching the early flight to Sydney tomorrow to share some Trans-Tasman love and collaborate with my medical research colleagues at the Prince of Wales Hospital and the Royal Brisbane & Women’s Hospital.

Tagged: Australia, budget, future fund, HRC, medical research, NHMRC, Tony Abbott

A day to celebrate John Pickering Mar 13

If it weren’t for your kidneys where would you be?

You’d be in the hospital or infirmary,

If you didn’t have two functioning kidneys.

(with apologies to John Clarke aka Fred Dagg)

Happy World Kidney Day everyone.

This blog started off life as $100 Dialysis because I believe that if we can make a computer for $100 then surely we can do the same for dialysis!  Dialysis is a life saver, yet its cost kills as so many can not afford the treatment.

There’s some good news in the dialysis world.

Schematics of the zeolite nanonfibres and how they may look in practice

Schematics of the zeolite nanonfibres and how they may look in practice

Just last week the MANA – International Centre for Materials NanoArchitectionics announced  they have developed a method to remove waste from the blood using an easy-to-produce nanofibre mesh.  Importantly, they claim it is cheap to produce.  Details were published in Biomaterials Science (free access).  Despite the photograph, there have been no human studies yet, but I expect that won’t be too long in the future.

Dr Victor Gura and the Wearable Artificial Kidney (WAK)

Dr Victor Gura and the Wearable Artificial Kidney (WAK)

In the meantime, the FDA gave approval last month for human trials of a wearable dialysis device produced by Blood Purification Technologies Inc (the WAK).

New Zealand, and Dunedin and Christchurch in particular, lead the way in Home Dialysis.  One Dunedin tradesman has even taken Home Dialysis a step further and turned it into portable dialysis by dialysing in his work van during his lunch hour. Of course, those needing a holiday may go on the road in specially equipped camper vans (http://www.kidneys.co.nz/Kidney-Disease/Holiday-Dialysis/).

Cause for celebration in the New Zealand kidney community was the gong (Office of the New Zealand Order of Merit) given to Adrian Buttimore who for 40 years managed Christchurch’s dialysis service.

These are just a few pieces of good news as doctors and scientists work around the world to improve the lives of dialysis patients.

_________________

Hot off the Press… I couldn’t resist adding this…. Pee, the answer to the world’s energy problems. http://www.bbc.com/future/story/20140312-is-pee-power-really-possible

 

Tagged: Dialysis, Home dialysis, Kidney, Nephrology, pee, Urine, Wearable Artificial Kidney, World Kidney Day

How Academia Resembles a Drug Gang John Pickering Dec 02

John Pickering:

Worth a read for those interested in how academia works.
In the NZ context, I wonder how people see this. Is there a small cartel controlling the lives of the rest who plug away looking for grants in the hope of making the breakthrough?
Note: The increase in percentage of PhDs between 2000 and 2011 in NZ in the graph in this article is distorted by the large influx of international students in the late 90s and early 00s. This was further exacerbated by the change in rules to allow international PhD students to pay domestic and not international fees.

Originally posted on Alexandre Afonso:

In 2000, economist Steven Levitt and sociologist Sudhir Venkatesh published an article in the Quarterly Journal of Economics about the internal wage structure of a Chicago drug gang. This piece would later serve as a basis for a chapter in Levitt’s (and Dubner’s) best seller Freakonomics. [1] The title of the chapter, “Why drug dealers still live with their moms”, was based on the finding that the income distribution within gangs was extremely skewed in favor  of those at the top, while the rank-and-file street sellers earned even less than employees in legitimate low-skilled activities, let’s say at McDonald’s. They calculated 3.30 dollars as the hourly rate, that is, well below a living wage (that’s why they still live with their moms). [2]

If you take into account the risk of being shot by rival gangs, ending up in jail or being beaten up by your own hierarchy, you…

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Should scientists respond to pseudo-science? John Pickering Sep 11

Do not answer a fool according to his folly, or you yourself will be just like him.

Answer a fool according to his folly, or he will be wise in his own eyes. (Proverbs 26:4, 5 NIV)

The editors of this particular list of proverbs were not fools – they knew they appeared contradictory.  Their purpose is to get us chewing over how we decide when we should speak up and when we shouldn’t.  When I heard these proverbs on Sunday my mind wandered (sorry Rev) immediately to my fellow science bloggers and the choices we make to respond or not respond to pseudo-science.  When we respond we do so wth hope.  Hope that the second proverb applies and the fool will recognise their own folly rather than keep on believing in their own wisdom.  A question I have for my fellow bloggers, how often does this actually take place?  I suspect, rarely.  At what point are we casting “pearls before swine”?  How do we know?

Perhaps more importantly, other than wasting our own time, could we be doing more harm than good (the first proverb)? By putting our scientific standing behind our reponses could we be enhancing the reputation of the pseudo-scientist in their own eyes or, worse, the eyes of readers? I think scientists are still paying the price for the over-confidence in science as solution to the world’s problems.  This has lead to some skepticism and a willingness to look at solutions that are not “main-stream” (especially if government funded or big-pharma).  By responding to the obvious nonesense, do we merely spread it further?

Some pseudo-science is addressing issues which also have non-scientific ethical issues that need to be respected.  Furthermore, the pseudo-science proponent may hold similar hopes to their scientist critic – eg hope for improved health.  I’m thinking particularly of issues such as vaccination or additives to food or water in which we need to weigh up the rights individuals with our responsibilites to others. Here, a scientist may express their opinion and their methodology of arriving at that opinion, but they need to tread very carefully not to appeal to Science with a capital “S” as if that is the ultimate standard against which all ethical decisions should be measured.

Here endeth the sermon.  Let us chew.

Tagged: proverb, pseudoscience, Science

Prostate cancer and omega 3 John Pickering Jul 12

The media is in a feeding frenzy with reports of a link between Omega 3 and Prostate Cancer.  Here’s a sample:

Link Between Omega-3 Fatty Acids and Increased Prostate Cancer Risk Confirmed (Science Daily)
Omega-3 supplements ‘could raise prostate cancer risk’ (Telegraph)
Omega-3 supplements linked to prostate cancer (Fox)
Omega 3 could increase cancer risk (TV3)

So, what’s the fuss?  The fuss is about a study published online yesterday in the Journal of the National Cancer Institute:

Brasky, T. M., Darke, A. K., Song, X., Tangen, C. M., Goodman, P. J., Thompson, I. M., et al. (2013). Plasma Phospholipid Fatty Acids and Prostate cancer Risk in the SELECT trial. Journal Of The National Cancer Institute, 1–10. doi:10.1093/jnci/djt174/-/DC1

The article is behind a paywall, so I’m not sure how many of the journalists have bothered to read it instead of relying on press releases.  I’ve access to the paper through my university, so here is a synopsis for the lay reader (bearing in mind I am not an expert in either omega 3 or cancer).

The thinking in the general public: Prostate cancer bad, Omega 3 good, therefore Omega 3 may prevent/delay prostate cancer

The thinking of the scientists: Is there a link between phospholipids (including omega 3) and prostate cancer?

The subjects studied:  Participants were enrolled in a trial of Vitamin E supplementation verse Placebo.  They were all male, from the US, Canada or Peurto Rico, aged 50+ if black (the medical literature uses this description), or 55+ if not, had no history of prostate cancer and with a PSA (prostate-specific antigen) test of <4ng/ml at the start of the study.  They were enrolled between July 2001 and May 2004.  While 35,533 men were enrolled in the trial, in this study only 2273 were studied.  These consisted of 834 patients who had prostate cancer diagnosed prior to 1 January 2008 and 1364 “matched” subjects who had no prostate cancer diagnosed in that time.  This is called a case-controlled study.  The “matching” is a statistical process whereby they make sure the two groups being compared (those with and without cancer) have certain demographic features in common on average.  In this case the groups had similar age ranges and similar ethnicities.  The cancer group was further divided into those with low and those with high grade cancers.

The methods:  Blood samples taken when patients were recruited and the total fatty acid content along with 4 types of Omega-3 fatty acids, 2 types of Omega-6 fatty acids, and 3 types of Trans-fatty acids were measured. The mean (average) proportions of each of the types of fatty acids (compared with total fatty acid) were compared between the No cancer and the Prostate Cancer groups.

The results:  Those with cancer had on average a greater proportion of each of  three of the kinds of Omega-3 fatty acids than those without cancer.  The p values were 0.03, <0.001, 0.006 (see here for an explanation of p values).  The p values for the two Omega-6 were higher (therefore more likely to be arrived at by chance) at 0.17 each.  The Trans-Fatt p values were 0.048, 0.08, 0.002. At this point it is very important to remember that not all those with cancer had high proportions of Omega-3 – it was the average that was higher.  An analysis comparing the 25% of subjects with the lowest Omega-3 (combination of the three Omega-3s) values with those with the highest 25% showed that the risk of prostate cancer was between 9 and 88% greater (with 95% confidence that this was not just by chance), ie a Hazard Ratio of 1.43 (95%CI 1.01 to 1.88).  Considering only those with the highest grade of cancer the Hazard Ratio was 1.71 (95%CI 1.0 to 2.94).

The authors performed a multivariable analysis.  That is when they check to see if other factors may be influencing the results.  They say that for Omega-3:

The continuous multi-variable-adjusted hazard ratios predicting total, …prostate cancer risk, [was] 1.16 (95% CI = 0.98 to 1.36),

This means that Omega-3 proportions changed the risk of getting prostate cancer by between a 2% decrease (100*(1-0.98)) and 36% increase (100*(1.346-1)) when other factors (not stated what) are accounted for.  This is what the 95% CI (Confidence interval) suggests.  The 1.16 is merely somewhere near the middle of the change in risk (16% higher).  It is the confidence interval that matters.  When it crosses 1, as it does here, it is not normally considered very important (ie not “statistically significant” as is often said).

The authors then conducted a meta-analysis for the Relative Risk of getting prostate cancer for two types of Omega-3 (DHA and EPA) and Omega-3 total fatty acid.  A meta-analysis is where they gather up all the studies and combine the results together.  In this case there were 7 studies (including the present one) which reported DHA and EPA and 4 which reported totals.  The results were

EPA:  RR = 1.07 (95%CI 0.95 to 1.21)
DHA: RR=1.16 (95%CI 1.03 to 1.31)
Total: RR=1.14 (95% CI 0.99 to 1.32)

Remember it is the 95% CI that is most important.  In this case only DHA creeps above 1 for the 95% CI.  Remember also that RR (Relative Risk) is a comparison of the rates of cancer between those with the level of Omega-3 among the lowest 20% and among the highest 20%.

The Conclusions:  The authors conclude

…these findings contradict the expectation that high consumption of long-chain ω-3 fatty acids and low consumption of ω-6 fatty acids would reduce the risk of prostate cancer.

This sounds reasonable under the assumption that consuming omega-3 (eg in supplements) actually increases the proportion of omega-3 in the blood.  They also state

It is unclear why high levels of long-chain ω-3 PUFA would increase prostate cancer risk,

What the media said:  TV3 borrowing from Sky, had a graphic with the word “Supplements” prominent and they talked of a 71% increased risk of high grade prostate cancer and 43% increased risk overall.  As we’ve seen these numbers are not what is relevant, the confidence intervals are – this adds a lot more uncertainty to the results (but not such good TV).  Also, they ignored the meta-analysis entirely (numbers not so big or interesting). They said nothing about the age range etc.  Finally, and most importantly, the study was not a study of supplements!  We have no idea why some participants had higher Omega-3 than others.  Some may have been because of supplements, some because of fish eating, some simply because of their own body composition and own metabolism.

My conclusion:  The study did not show that supplementation of Omega-3 is risky.  Nor did it show that supplementation is beneficial. It simply was not a study of supplementation. It did show that elevated proportions of Omega-3 fatty acids are possibly associated with increased risk of prostate cancer in men 50+ (black) and 55+ (non-black). Remember, too, that this is talking about relative risk.  The overall prostate cancer risk during the study period was just 2.35%.  If I’ve done my math right, then those in the top 25% of Omega-3 have an absolute risk of 2.77% (95%CI 2.12% to 3.65%).

 

Tagged: cancer, Fatty acids, Omega-3, Phospholipids, prostate cancer, supplements

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