Infuse, Medtronic and the Yale University Open Data Access (YODA) Project

Good morning.

Yesterday I was interviewed by a journalist from The Age, and it really shouldn’t have come as a surprise to learn that the article hasn’t reflected the message I thought I was quite clearly giving her.

Here’s the background: Medtronic, a large medical device company, brought to the market Infuse, which is a Bone Morphogenic Protein (rhBMP-2 to be precise).  This is soaked into collagen sponge and placed around fusion sites, and it works on the cellular level to transform cells to make bone.  Simple enough.  It has been used widely, by myself and most other spinal surgeons, to help the body fuse a spinal level.

Eugene Carragee, a prominent Stanford surgeon, raised concerns about Infuse in 2011.  In response to those concerns, Medtronic sponsored a large project in order to address these concerns.  In doing so, they set a new standard in “in the emerging era of open science“.  In fact, they exceeded expectations – not one but two independent groups of researchers were granted access to every last morsel of data that the company had regarding Infuse.  Completely independently, the two groups analysed the data and published their findings recently here and here.

It gives a surgeon and any researcher interested in Infuse confidence knowing that two independent groups produced such similar results, and yet at the same time, each group emphasised different aspects of their results.

In summary, they found:

  • it’s as good as bone graft to create fusion – that’s the key message to take home people.  When a patient’s own bone can’t be used, then we now know that without a doubt Infuse will do as good a job.
  • When used in the anterior neck, it’s associated with increased complications – surgeons have know about this for many years now and it’s no longer used there.
  • complications such as retrograde ejaculation are about as common with Infuse as with bone graft.
  • there is no appreciable increase in the risk of cancer with Infuse – this was a great concern, and although the cancer rates were very slightly higher in the Infuse patients compared to bone graft, it was not higher than the normal population, and after four years there was no difference at all.  I suspect this will turn out to be a statistical anomaly.  Medtronic are continuing to research this area.

If you’ve had a fusion with Infuse, there is not need for concern.  I will continue to use it, as well as similar products, when appropriate, with the patient’s consent.  The journalist and the editors clearly have a newspaper to sell, and boring science is always outweighed by sensationalism.

Medtronic should be commended on what they have done with the YODA project.  With complete transparency, they have opened up their data for not one but two independent reviews, and the results are difficult to argue with.  They have set the standard by which other companies must now live up to – a new era of open science.

Conflicts of interest

Further to my last article “Can back pain be cured with antibiotics?”, remember how I said talk of a Nobel prize might be premature, and that we need to see if these results can be repeated?  Well, today I came across this article:

http://www.theage.com.au/national/health/back-pain-study-fails-to-declare-link-20130526-2n5cz.html

Unfortunately, the authors of the two papers discussed apparently didn’t declare a conflict of interest.  No matter how small it may appear to themselves, any conflict should always be declared when authoring a paper.  Whilst it doesn’t necessarily mean that we should ignore their results, it does raise a shadow over their results.  Many people have unfortunately made this mistake previously, notably Andrew Wakefield, when he failed to declare his financial interest in a mono-valent vaccine that stood to profit by discrediting the MMR vaccine that was in use.

Declaring a conflict of interest does not negate that conflict, but it does, at least, make it public knowledge.  The bigger sin is to not declare it.  Now, unfortunately, this paper has lost some credibility.

As I said before, let’s wait and see if it can be repeated.

John

Can back pain be cured with antibiotics?

Over the next few months many of you will hear about a paper that has just been published in the European Spine Journal. The study, from the University of Southern Denmark, suggest that back pain can be cured with a 100 day course of antibiotics, and certainly they provide some good evidence for that.  Certainly some surgeons are calling for a Nobel prize, but I don’t think it’s that significant yet.  Maybe if you operate on a lot of people with back pain it’s significant, but those of you who know me, know that surgery for back pain is a last resort.

So, what about the study?

Well, it looked at people who had Modic type 1 changes on their MRI after having a disc herniation, whether or not they had surgery for the herniation.  A prior study from the same team, and others, showed that many disc herniations (about half) are infected with a very low grade bacteria called Proprionibacterium acnes which also causes… yep – acne.  It has a peculiar ability to be benign enough not to produce an acute inflammatory reaction, but at the same time it produces propionic acid, which is known to be able to dissolve bone.  Wow.  What a bug.

Now, modic type 1 changes are only about 10-40% of modic changes, the other types being 2, the most common, and 3, the least common.  Modic type 1 changes appear dark on the T1 films, and bright on the T2 films, and represent oedema.  One way of remembering this is that type 1 changes appear the same as the CSF.  See below.

Modic Type 1 changes

An example of Modic Type 1 changes

Anyway, back to the study.  They randomised the participants into three groups.  One group received a placebo, and the other two received the antibiotic (amoxicillin–clavulanate (500 mg/125 mg) tablets three times a day, at 8 h intervals, for 100 days) in two difference doses.  They found that the antibiotic subjects improved remarkably well, usually beginning at 6-8 weeks after commencement, after 100 days, and it appears that the improvement lasted out to one year – well after the antibiotics had ceased being taken.  Within the placebo group not much changed at all.  In addition, the amount of modic change visible on their MRI’s also decreased, which supports the notion that it is due to a chronic low grade infection.

Were there problems with the antibiotics?  Mostly gastrointestinal of nature – loose bowel movements and increased flatus.  Thanks for asking.

So what does that mean?  Well, if I had type 1 modic changes and back pain, I’d be considering this study carefully.  However, as a public health measure, we need to realise that this isn’t the cure for ALL back pain – maybe only 10 to 40% of back pain patients.  We know that back pain has many causes, but I think it’s just amazing that this subset may have found a cure.  Of course, we need to see that these results can be repeated.  Hold back on the Nobel prize for now…

John

Updated Patient Information page

Hi there.
Well after some time I’ve managed to put together a page of what I think is some of the best information on the spine available.

http://www.cunningham.com.au/about-the-spine/

There’s information on spinal conditions, prevention, exercises for your back, and descriptions of operations. There’s text pages, videos and brochures. I ask you to have a look and give me some feedback. Too much? Anything else you’d like to see? Can you find things easily, or not?

I hope you get something out of it.

John

4WD’s and driveway safety

My car was recently in getting some work done and we had a Ford Territoy as a loan car.  Having not driven civilian 4WD’s much before, I was disappointed to see how much space around the car you can’t see.  There’s huge blind spots front and rear, and not much help without a reversing camera.

These three deaths investigated all involved 4WD’s.  These may have been prevented with a little more care.

PLEASE please please if you have to own a 4WD, be careful when reversing out of your driveway. And PLEASE think about if you really need to have that 4WD in the first place.

John

How to look after your spine – updated!

Hi all.

Some of you will remember my four rules about looking after your spine. Four rules never really sat too well with me. Even though it’s an even number and the square of two, it needed to be five – i’m a decimal kind of guy after all. So after much deliberation, and some common sense, I’ve figured out my FIVE rules for looking after your back.

1. Don’t smoke.

2. Lose weight.

3. Do “Core” Exercises.

4. Maintain good posture, and lift things with a good technique, and at last

5. Avoid aggravating activities. This is the one that took me some time to realise needed to be in here. How many times do people say that their back is fine until they do gardening / lift an engine block / etc. It sounds simple, but if you can avoid those activities that cause back pain, then that’s a very simple and drug free way of looking after your back. Some activities can’t be avoided, sure, but try and not do the things that hurt. Does that mean you’re getting old? Well, how do I say it? I know – I wont.

All the best,

John

Isthmic Spondylolisthesis

Hello.

Many young people suffer from back pain but it is usually the kind of pain that gets better by itself over a few days to weeks. Occasionally, though, back pain can persist and it may become worth investigating, especially if it is associated with leg pain, or “sciatica”. A particular condition that can cause lower back pain and sciatica in younger people is isthmic spondylolisthesis. Well what on earth is that, you ask.

Isthmic spondylolisthesis, or IS, for short, is a condition that you might think of as a stress fracture in your lower back. It usually develops when you’re a teenager, and it occurs more frequently in sportspeople that perform a lot of extension activities like gymnasts, fast bowlers and baseball pitchers, but it can occur in people who don’t play any sport either. If it is picked up when you’re really young sometimes the problem, or “defect”, can be repaired. Unfortunately, it often goes unrecognised and only later in life becomes symptomatic.

The defect is in a part of the spine called the “isthmus”, or “pars interarticularis” (pars for short). It is most common at L5, and most commonly leads to a spondylolisthesis, or “slip”, or L5 on the sacrum.

The progress of isthmic spondylolisthesis

isthmic spondylolisthesis

As you can see in the diagram to the right, the pars links the L5 vertebra to the sacrum. If this is broken, the L5 vertebra is only held onto the sacrum by ligaments, and these over time stretch and may fail. This includes the disc between L5 and the sacrum. If you think about it, the whole weight of your upper body – your head, arm, thorax and abdomen – is all bearing down on this segment of your spine, so it’s no surprise that over time, if there’s no bone holding them together, that the ligaments will fail.

So that’s what it is. What can be done about it? You’ll have to wait for my next post…

John

How to look after your spine

In many ways, this post may be the one to put me out of business, but it’s also the post which I’m sure should be my first – how to protect and look after your back.  In medicine the preference is always prevention over cure, yet many of us forget to emphasise the benefits of spine health.  In other words, how can we all look after the health of our spine in order to prevent injury, reduce the symptoms of spinal degeneration, and lastly to speed recovery following injury or surgery.  Let’s get to the point, and keep it simple.

1. Don’t smoke.  There is nothing healthy about smoking, and it is known that smoking leads to accelerated disc degeneration.  It also increases your chances of an adverse event during and after surgery, and may contribute to failure of spinal fusion surgery in the neck and lower back.  http://www.ncbi.nlm.nih.gov/pubmed/11339862

2. Lose weight.  Every kilo your carry leads to an extra 8 kilo’s of force going through your spine.  Thin people are putting less stress through their spine, and losing weight is often a very effective strategy to lessen the symptoms of a degenerating spine.

3. Exercise. Exercise will obviously help you control your weight, but strength training, particularly of the “core” muscle groups, will also help stabilise the spine and reduce some of the impacts that it sustains.  Some people wear a corset device to help them with their backs.  Improving your core strength works in a similar manner.

4. Maintain good posture.  Maintaining a good posture will allow the spine to take loads in the way that it was designed to.  Good posture also refers to good lifting techniques such as bending your knees, and holding heavy loads close to your body.  Core strength will help you to also maintain a good posture.

Is that all?  No.  Now that you’ve read this, it’s up to you to make a start.  Your GP can help you with quitting smoking, and there’s lots of resources available to you on the internet such as QUIT.  Your GP and physiotherapist can also help you to lose weight in a healthy and appropriate manner – some people are even electing to have “gastric banding”, but that is something you really need to see a specialist about.  Your local physiotherapist will be able to show you good core strengthening exercises, and there’s some available from the Mayo Clinic and the AAOS on the internet.

Some other great resources for learning about your spine are available via the links below:

All the best,

John