"Blausen 0246 ColorectalCancer" by Blausen Medical Communications, Inc. - Donated via OTRS, see ticket for details. Licensed under CC BY 3.0 via Commons - https://commons.wikimedia.org/wiki/File:Blausen_0246_ColorectalCancer.png#/media/File:Blausen_0246_ColorectalCancer.png

Blocked Bowel

The Press headlines this morning claim the Ministry of Health is blocking bowel screening tests. The article itself states the MoH does “not recommend” use of do-it-yourself bowel screening kits.  I can find no MoH press release relating to these kits, so I am a little confused as to whether or not the MoH is blocking anything at all.  This uncertainty aside, the issue has arisen because of the availability of bowel cancer testing kits which are self administered in the home and made available by the charity and advocacy group Bowel Cancer New Zealand/Beat Bowel Cancer Aotearoa (BBCA). There is evidently frustration within this group with respect to the government’s progress towards a bowel cancer screening program in New Zealand (there is currently a pilot underway).  My interest is not the politics, but merely to inform about the test.

The test being offered as best as I can make out is from Clinical Genomics and is their “ColVantage Home” test.  In the information on their website they give two numbers derived from trials which I believe are critical that any potential user of the test understand before they decide to use the test (indeed, not just for this test).  Those numbers are the sensitivity of the test, given as 86%, and the specificity given at 96-98%.  I expect to most those numbers are meaningless, and even to the scientist they are “minimal” in the sense no indication of how accurate these numbers are given (think “margin of errors” given in political polls).  However, let me take the numbers as gospel and let you know what they mean.

The False Positive.  I'd love to acknowledge the source, but I can't locate them.

The False Negative. I’d love to acknowledge the source, but I can’t locate it.

First, a sensitivity of 86%.  This simply means that for every 100 people who actually have bowel cancer, 86 will test positive with the home kit.  The very very important fact to note here is that a negative test does not mean you definitely do not have bowel cancer.  The 14 missed cases are called False Negatives, or Type II errors and are beautifully illustrated by this classic infographic of the doctor failing to diagnose pregnancy.  My concern with False Negatives and a “home kit” is that some people may feel falsely reassured with a negative test.  On the other hand, a test administered by a medical doctor is not simply the test, but exposure to the doctor who may see other signs or symptoms that the test doesn’t pick up.

 

 

 

False positive

False positive

On the other hand a 96-98% specificity means that for every 100 people who do not have bowel cancer 2 to 4 will test positive.  That is, a positive test does not mean you definitely have bowel cancer. The missed 2 to 4 cases are called False Positives, or Type I errors as illustrated by the diagnosis of the man in the image.

Another way of thinking about this is that all of us before a test have a certain probability of having bowel cancer.  We may get an idea of what that probability is by knowing the rates of bowel cancer amongst people like us.  In New Zealand the rates are very high – some of the highest in the world at about 0.3% or 300 per 100,000 adults.  However, risk is higher as people age, hence screening programs are targeted at older adults (over 50s in this case).  There are other risk factors.  Check out the risk calculator here.  A positive test essentially increases your risk, but not to 100%, and a negative test, decreases it, but not to 0%.  If it was me, and I was worried enough to want to have a test because of increased risk factors, I’d go and ask my GP for one.  On the other hand, if I didn’t want my wife to know (duh!) and got a kit, and it was positive, I’d also head down to the GP.

As I stated before – beware of being falsely reassured by a negative test.  However, there is also a major issue with false positives which bedevil any screening program, and even more so one in which the most at risk population are not being targeted (in this case there is nothing stopping 30 year olds having tests).  This requires a bit of maths.  Let’s pretend for a minute that the tests are only being done by people in a population with a very high prevalence of bowel cancer – say 1%.  That means that for every 10,000 people tested 100 will have bowel cancer for whom 86 the test will be positive.   Of the 9,900 who do not have bowel cancer, 198 to 396 will also test positive – ie falsely positive.  ie, in total, 284 to 480 people will test positive.  ie 22% to 30% of those who test positive actually have bowel cancer.  For the individual who started knowing they had (say) a 1% risk, they now know they have a 22 to 30% risk.  Certainly worth checking out more.

Of course, if people have these tests regularly, the proportion of people who end up having a false positive test at some time will increase (along with the proportion of people with bowel cancer who have a positive test).  ie repeat testing will increase sensitivity and decrease specificity.

Finally, if you have a history of bowel cancer in your family then don’t hesitate to ask your GP for tests and advice on what you can do to minimise your risk through improving your life style.

NZBRI_CMRF

Two minds about funding heart research

Recently I had a knock on the door from an enthusiastic young man talking about heart research. Given that has been the focus of my research for the last 18 months or so I was delighted that someone was out there trying to raise money for research. However, my delight was, in retrospect,was tempered somewhat when I realised that the man was not representing a New Zealand based research group.

The man was collecting donations for the Heart Research Institute, an independent research group based in Sydney Australia. This is a substantial and credible organisation. I would be happy to collaborate with any of their team leaders. Looking at their website I noted one (of 12) research groups mentioned New Zealand collaborators.   I’ve written to ask if they have more. The HRI have a very professional New Zealand website which gives information on heart disease statistics in New Zealand. They indicate that they support scholarships and fellowships for New Zealanders to work with their Australian counterparts. However, I am in two minds about this group door knocking in New Zealand – one mind thinks “great” they are keen to raise money for heart research, what a good cause. The other thinks “hmmm,” don’t we have some wonderful New Zealand based heart research groups and charities – why another (not New Zealand based) one in a crowded field seeking money from a limited pool of discretionary spending?

Perhaps, to help the people of Canterbury and wherever else funds are being solicited from to make up their own minds, I can remind people of four great charitable organisations supporting heart research in New Zealand.

Heart Foundation of New Zealand: This is a wonderful organisation with a long history of supporting research in New Zealand as well as supporting individuals within New Zealand. They are the group behind the “Heart Foundation Tick” on food labels. Their website is really worth checking out… I just learnt about the “Two Ticks” now appearing on some labels. For the likes of a researcher like me they provide small, but very important, grants that enable important questions to be answered. Indeed, I have just had a paper published which a Heart Foundation grant made possible. In that paper we show that one of the latest guidelines on how to use a blood marker (used in most New Zealand hospitals) to rule out someone having a heart attack are flawed. I note, that they have in large letters on their web site that they do not do door to door fund raising.

Christchurch Heart Institute: CHI is a research group and charitable organisation within my own department, the Department of Medicine, at the University of Otago Christchurch campus (known to most Cantabs as “the med school”). Headed by Professor Mark Richards it is a world renowned group. I have the privilege (a little daunting given just how incredibly intelligent these people are) to collaborate with CHI on a number of clinical projects. The publication I mentioned was one of them. Another project, just kicking off, is investigating markers of acute kidney injury within people who have acute heart failure. They have recently expanded into social media – so you can follow them on facebook.

Canterbury Medical Research Foundation:  CMRF is a wonderful organisation – they are one of the three major sponsors of my own fellowship. My own prejudice aside, CMRF have been supporting research in Canterbury for over 50 years. One aspect of the CMRF that really impresses me is that they understand the need to support researchers and just “let them get on with it.” Cantabrians may recognise their recent campaign that has included some impressive billboards. One important plank of CMRFs work in Canterbury is their subsidiary the New Zealand Brain Institute which does important research into stroke, Alzheimer’s and Parkinson’s disease.

Emergency Care Foundation: The ECF supports research in the Emergency Department of Christchurch hospital including research into the rapid rule-out of heart attacks for patients presenting with chest pain.  I’m fortunate enough to be involved in that research and the role out of new diagnostic pathways to all emergency department in the country.  ECF also support research into the health affects of the Christchurch earthquakes.  ECF are another of my major sponsors.

Some logos of the great local charitable organisations supporting heart research

The transplant smile

Source Deviant Art

Source Deviant Art

“His mega-watt smile could power the Auckland grid” was how Herald columnist Wynne Gray so eloquently described this morning Joeli Vidiri after his kidney transplant.  In the meantime across the Tasman my long term colleague and head of Nephrology at Prince of Wales Hospital in Sydney, Prof Zoltan Endre, is celebrating 50 years of the transplant unit. There is a lovely story of a smiling Carolyn Hochkins who has survived 42 years with a kidney transplant.  Invaluable!

Transplants have become “normal” and rarely make the news unless it is of a famous face or a celebration such as in Australia this week.  They are far from “normal” for the recipients.  They are life changing – not simply a change from being tied to a dialysis machine for many hours a week, but better all round health.  The machine is merely supportive and it doesn’t manage to do everything a kidney can do.

Congratulations Joeli, Congratulations Carolyn, Congratulations all you donors and donor families, Congratulations all you dedicated nephrologists and surgeons that have made the kidney transplant a routine life changer.

Let the children take us to space

44 years ago a feather and a hammer were dropped at the same time on the moon by Commander David Scott of Apollo 15. An experiment that continues to cause wonder and inspire children today. Indeed, it may well have been an experiment children would have dreamed up for the astronauts to do. This post is simply to get the children of New Zealand thinking of experiments and possibilities once more.

We are going to have a rocket launch facility in our own backyard.  Wow!  If that doesn’t excite, then little will.  Rocket Lab inspires not just because big controlled explosions are cool (well duh!), but because those involved are innovative, and commercially savvy. Exactly the qualities I’d like to see fostered in the next generation.

Peter Beck, founder and CEO of Rocket Lab has promised that anyone can reach space.  Well said Peter. Here’s my vision to add to his.

  • Let that anyone be the children of New Zealand.
  • Let New Zealanders launch our first satellite (#NZS1 for want of a better handle)
  • Let that satellite be locally dreamed up and grown
  • Let there be a competition to gather ideas for what NZS1 should do
  • Let our children vote on which idea they’d like to see launched first
  • Let the money be crowd-sourced from within New Zealand (less than $2 each!).
Rocket Lab's vision for their launch facility (used with permission)

Rocket Lab’s vision for their launch facility (used with permission: http://www.rocketlabusa.com)

R_014 R_011

 

A wound in the scientific body: a hypothesis

The social and professional media have had a field day with Sir Tim Hunt’s comments concerning women in the lab. Juxtaposed with that in New Zealand has been a very earnest discussion about the gagging of scientists. The purpose of this post is simply to highlight that the two are not unrelated and how we handle one affects the other.

The reaction to Sir Tim Hunt’s comments has been swift and brutal. It amazes me how 140 characters or a couple of columns in a newspaper cannot only hang, but draw and quarter. It also amazes me how swift such judgment can be without recourse to gathering all the evidence first. The issue of bigotry and bias against women in science are very real and very felt. I do not intend to re-litigate any of those issues. It is the brutal nature of the response that concerns me. Not only has one man been thoroughly lambasted in every corner of the world – something of an overkill – but with him so have vast numbers of others been lambasted as the epithets have spilt over to include whole generations of male scientists. I have also noted a bigoted reaction to those condemning Sir Tim Hunt, equally replete with pithy epithets that do nothing but to wound, raise hackles and expose one’s own prejudices.

What has this to do with gagging of scientists? Simply, that it raises the fear index for anyone thinking of making public comments. I was speaking with a very well accomplished scientist the other day who will not speak to the media about their own work because of the very negative reaction of colleagues when they once did so. I hypothesise that following the response to Sir Tim Hunt’s comments, and the response to that response, that there are scientists who are thinking twice about publically speaking out on their science let alone on a controversial issue – a.k.a. self-gagging. The wound is deep. It must heal, because without those voices then the public debates about such issues as sea level rise, euthanasia, medicinal cannabis, science education etc will be all the poorer for the absence of those voices. The missing ingredient, the only known treatment for the wounds that have appeared, is compassion and forgiveness. Not terms that normally appear in the scientific literature, but universals that can alone heal the wounds and lift people up to where they can empathise with others irrespective of race, sex or creed.

Send them home

New Zealand is the home of Home Haemodialysis and Christchurch the hub. Sending people home to dialyse is not only more convenient for them and more cost effective, but also has been shown to reduce mortality.  However, is this reduction in mortality sustained across changes in dialysis medicine over time?  This is an important question as Home Haemodialysis is now being considered seriously in many jurisdictions across the world.  The question was recently addressed by Dr Mark Marshall and colleagues across New Zealand and Australia in an article which appeared online ahead of print a couple of weeks back in the American Journal of Kidney Disease (see here, sadly behind a paywall).

What they did

Step 1 was to extract data from 1998 to 2012 from the Australia New Zealand Dialysis & Transplant Registry which prospectively collects information for all long term renal replacement therapy patients. This is a very important registry and the study highlights the importance of keeping data in this way.

Step 2 Placed patients into one of three time periods according to when they started their dialysis: 1998-2002, 2003-2007, 2008-2012.

Step 3: Identified the exposure of the patients to one of: Facility lead haemodialysis (facility HD), Home haemodialysis (home HD), or Peritoneal dialysis (PD).

Step 4: Compared rates of death for patients starting in each time period for each of the dialysis modalities after accounting for age, sex, ethnicity, primary kidney disease, and glomerular filtration rate at the start of therapy (ie how well the kidney was functioning).

What they found (with my commentary)

there is demonstrable survival benefit associated with recent era irrespective of the landmark initiation time.

Indeed, it was a 25% lower (adjusted) mortality for those starting dialysis in  2008-2012 compared to the 1998-2002.

Well done kidney docs – they are getting better and keeping people alive.

There is significant effect modification by modality [type of dialysis] (P <0.001), and separate models were developed in each subgroup: there is a 23% corresponding reduction for those on facility HD therapy, a 29% reduction for those on PD therapy, and a 46% reduction for those on home HD therapy

In other words, all things being equal, survival was improved more on home haemodialysis than either of the other types.

Hazard ratios for death according to era and mode of dialysis.  Lower numbers are better!  From: Marshall, M. R., Polkinghorne, K. R., Kerr, P. G., Agar, J. W. M., Hawley, C. M., & McDonald, S. P. (2015). Temporal Changes in Mortality Risk by Dialysis Modality in the Australian and New Zealand Dialysis Population. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. doi:10.1053/j.ajkd.2015.03.014

Hazard ratios for death according to era and mode of dialysis. Lower numbers are better! From: Marshall, M. R., Polkinghorne, K. R., Kerr, P. G., Agar, J. W. M., Hawley, C. M., & McDonald, S. P. (2015). Temporal Changes in Mortality Risk by Dialysis Modality in the Australian and New Zealand Dialysis Population. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. doi:10.1053/j.ajkd.2015.03.014

I note patients were only around 60 years old on average when they first initiated dialysis, yet 37% died before the end of the study period or could receive a transplant.  Folks – do your damnedest to avoid kidney disease – starting with avoiding diabetes.

Conclusions

  1. Survival has increased during the past 15 years
  2. Survival of peritoneal dialysis patients has increased more than facility haemodialysis patients
  3. The relative survival of home haemodialysis patients has improved the most

Has home haemodialysis caused people to survive longer?  This study can’t say, because it is an association study not one set out to demonstrate causation. However, it is evidence that supports the continued use and possibly even expansion of home dialysis in New Zealand and Australia.

For further reading, refer to the paper itself:

Marshall, M. R., Polkinghorne, K. R., Kerr, P. G., Agar, J. W. M., Hawley, C. M., & McDonald, S. P. (2015). Temporal Changes in Mortality Risk by Dialysis Modality in the Australian and New Zealand Dialysis Population. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. doi:10.1053/j.ajkd.2015.03.014

Christchurch has breast cancer research hub

Guest post by: Kim Thomas, Communications Manager at the University of Otago, Christchurch

Research Radar UOC

A team of specialist cancer researchers have joined forces to focus on the impact of obesity on breast cancer.

The researchers all work at the University of Otago, Christchurch’s Mackenzie Cancer Research Group. The Group is headed by Canterbury District Health Board oncologist Professor Bridget Robinson, a breast cancer expert.

Researchers Associate Professor Gabi Dachs, Dr Margaret Currie and Dr Logan Walker have previously investigated various aspects of cancer but decided to team up and focus on the significant health issue of obesity.

Associate Professor Dachs says that international studies have shown breast cancer patients who were obese before or after diagnosis are less likely to survive than patients with normal BMI. Risk of dying from breast cancer increases by a third for every increment of 5kg/m2 in BMI.

autumn15obesity

From left to right: A/Prof Gabi Dachs, Dr Margaret Currie, Dr Logan Walker

The three researchers are investigating different aspects of obesity and breast cancer:

  • Associate Professor Dachs is looking at molecular factors associated with obesity in cancer, particularly how fat cells communicate with cancer cells and negatively affect them.
  • Dr Margaret Currie is putting fat and breast cancer cells together to see how the fat cells make tumours more resistant to treatment. She suspects the fat cells provide ‘an extra energy hit’ to cancer cells by providing lipids, or fats, in addition to glucose.
  • Geneticist Dr Logan Walker will investigate whether the obesity-related gene responsible for the amylase enzyme in saliva (AMY1) contributes to breast cancer development. He will also explore the role of key genes that behave differently in breast tumours from obese women.

The researchers’ work is funded by the NZ Breast Cancer Foundation, the Cancer Society of New Zealand, the Canterbury and West Coast Division of the Cancer Society NZ, the Mackenzie Charitable Foundation and the University of Otago.

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