Friday, 27 June 2014

Lessons from history #10: How magnesium lost its mojo

Wouldn’t it be great if there was a cheap, non-proprietary, readily available treatment for patients with heart attacks (acute myocardial infarction - AMI)? That’s what doctors wanted to believe, so when they saw the early results of magnesium therapy, they did exactly that. Magnesium therapy for AMI has been labelled a “lesson in medical humility”, but I see it as another example of the pervasive bias amongst researchers, doctors and the public that leads them to overestimate the effectiveness of medical therapies. Put simply, it was another case of ‘believing is seeing’.

Sunday, 22 June 2014

Animal research: just another WOFTAM?

The idea is that experiments are first performed in the lab, are then performed in animals, and these experiments inform the eventual human studies. As a (seemingly) necessary step in this chain, animal experiments are (rightly or wrongly) tolerated based on their eventual benefit to humans. Animal studies however, are not good predictors of human trials, often do not inform human trials, and are methodologically inferior to human trials, so much so, that the results from animal studies are unreliable and biased. In other words, animal studies are often of no benefit to humans. Arguably, they do not benefit humans at all, let alone enough to justify their use. We either need to fix the problem or get out of the animal research game.

Problem 1: Animal research not translating to humans
Often, research just fails to make the cross-species jump to humans. For example, animal studies showing an association between stress and coronary heart disease were not replicated in humans. Biologically, there are many other reasons why findings in one species are not applicable in another (different immune systems, drug tolerances, behavioural traits, etc.). Also, animal studies often assume ‘ideal’ situations that do not take into account the complexities (concurrent diseases, social aspects, concurrent treatments, etc.) of modern human life and healthcare.

The overall failure of animal research to provide benefit to humans is covered in this 2014 BMJ article (here).

Problem 2: The lack of consideration given to animal studies
Examples exist where animal studies were done after clinical (human) trials had already concluded that the treatment was of no benefit. Other examples exist of animal studies being done simultaneously with (human) clinical trials. A good review of the lack of consideration given to animal research can be found in this 2004 BMJ review (here).

In these cases, human benefit cannot be derived from animal research. Therefore, the research is unethical as the animals have been harmed without providing gain to humans. Oh, and by “harmed”, I usually mean killed. And by “killed” I don’t mean sacrificed, as this implies that the death has been traded for some benefit – I just mean killed.

Problem 3: The lack of quality of animal studies
We often consider studies done in a laboratory to be scientifically superior; to be ‘pure’ or ‘basic’ research’, as opposed to applied or clinical research done in humans, which is (supposedly) complex and harder to control. The opposite is true. Given the regulatory and ethical oversight of clinical research and advances in research methodology, clinical research is now of a very high scientific standard. It isn’t always, but it is getting harder to do bad research, and the overall standard continues to rise.

Animal research is methodologically inferior to human clinical research. The 2004 BMJ review (here) showed that the standards demanded of clinical research are not routinely applied in animal research. For example, animal studies are often not randomised, not blinded, not registered, underpowered (too small), and prone to selective reporting bias and publication bias. Consequently, they are ripe for biased interpretations and p-hacking from the researchers. If human research is meant to be informed by animal research, then the humans had better watch out.

To be blunt, the results of animal research are more likely to be wrong than human research. There is considerable room for improvement in the quality of animal research, but these recent reviews (here and here) tell us that despite efforts to improve animal research, things are still bad.

The bottom line
Animal research either needs to improve or stop. In saying this, I have not considered animal ethics, partly because it is a difficult area, and partly because my argument doesn’t need it. Animal research is methodologically poor, the results unreliable, often not transferable to humans and largely ignored but despite this, it still gets funded because it is considered ‘pure’ research. Animal research should be reduced and refined, and be replaced where possible (the “3 Rs”) Otherwise it is just another WOFTAM whose benefits are, you guessed it, overestimated.

Note: this post is about animal research in which animals are harmed, because in order to balance that harm, you need to have a potential benefit. My argument is that the benefit is either non-existent or much less than we supposed. I have no problem with non-harmful animal research.

Sunday, 27 April 2014

Surgery for shoulder impingement

When you raise your arm, the top of your humerus, where the rotator cuff tendons attach, “impinge” against your acromion. When this hurts, it is called impingement syndrome. “Decompressing” the joint by taking some bone off the acromion (an "acromioplasty”) makes sense, and seems to work well. The operation has been around for a long time, and there have been many studies looking at different ways of doing this operation, but very few studies looking at whether or not it works better than not operating. Interestingly, all of the studies that have been done conclude that this operation adds nothing.

Friday, 25 April 2014

Book/Web review: Testing Treatments

Title: Testing Treatments 2nd Ed, 2011
Authors: Imogen Evans, Hazel Thornton, Iain Chalmers, Paul Glasziou
Publisher: Pinter and Martin, London

Testing Treatments is a book, and Testing Treatments Interactive ( is a website that contains the book, with live links and added information. It is a valuable reference tool for the layperson and also useful for health practitioners who are not well versed in evidence-based medicine. The book tells you why it is important to test treatments, how this type of testing should be done, and how to make research better and more useful to future patients.

Sunday, 16 March 2014

Manufacturing significance

What if I could produce an experiment that concluded that listening to an old song could make you younger? Not feel younger, but be younger. Impossible, of course, but the story of how this can be achieved is a great example of how easy it is to produce statistically significant findings in science. All you need is enough 'wriggle room' in the data and a pre-conceived notion of what the results will be. Like ghosts in The Sixth Sense, scientists often only see what they want to see.

Monday, 10 March 2014

When the antivenoms don’t work, you gotta start asking questions

As a junior doctor in Australia, the country with the deadliest snakes and spiders in the world, you quickly learn where the antivenoms are kept. Now it appears that the deadliness of these critters is less than we thought, and the benefits of the anti-venoms are under question, or have been proven to be ineffective.

Sunday, 23 February 2014

The Hope Peddlers

When treatment choices are limited or when true effectiveness is not clear, patients want hope: they want to have a chance to get better. Doctors hold this valuable commodity, and dispense it on demand, for a fee, after which they claim any perceived improvement as being due to their efforts. Even when a treatment is not proven to be effective, or when it is proven to be no better than placebo, doctors too easily fall into the role of hope-peddler, without considering the hidden costs or unintended consequences.

Friday, 24 January 2014

Does removing breast cancer affect survival?

Allow me to make an assertion: breast cancer survival is not influenced by surgical excision of the primary tumour. This goes against the prevailing wisdom that cancer is cured by removing it, but that kind of thinking is simplistic and at odds with much of the evidence. Lets walk through that evidence.

Thursday, 2 January 2014

Knee arthroscopy for a torn meniscus

I have previously written that knee arthroscopy for osteoarthritis is no more effective than alternatives, including placebo. One criticism of those studies was that arthroscopy is usually done for a torn meniscus (often incorrectly called a torn cartilage) rather than arthritis, despite the facts that the original sham trial of arthroscopy included patients with meniscus tears, and later comparative studies looked specifically at patients with torn menisci. Now, however, we have evidence from a placebo-controlled trial of arthroscopic surgery performed specifically for a torn meniscus in patients without arthritis. Evidence that shows that while most patients improve after surgery, they improve equally well after placebo surgery.

Friday, 20 December 2013

Lessons from history #9: mastectomy

In the early days of surgery, surgeons tried to out do each other in their ability to perform bigger operations, and mastectomy was no exception. For breast cancer, excising the tumour seemed like logical treatment, at least for local control. It also seemed logical that if some excision was good, more excision was better. So simple tumour excision soon gave way to simple mastectomy, which gave way to total mastectomy, which gave way to radical mastectomy, which gave way to things like the ‘extended’ radical mastectomy and the ‘supra-radical’ mastectomy (which included excising the chest wall, amongst other things). Yet, all of this effort was done without properly evaluating the effectiveness – it was all based on what seemed like a good idea.

Friday, 29 November 2013

Book review: The Doctor's Guide to Critical Appraisal

Title: The Doctor’s Guide to Critical Appraisal, 3rd Ed (2012)
Authors: Narinder Gossall, Gurpal Gossall
Publisher: PasTest

This book is not an opinion piece and it holds no new information, but it is as important as any other book I have reviewed because it aims to narrow the gap between practice and evidence in medicine by teaching doctors the science of medical practice; in other words, how to recognise and weigh error, and objectively appraise the scientific evidence for clinical practice.

Monday, 18 November 2013

The map is not the territory

Another version of this saying is “Treat the patient, not the X-rays”, but try as we might, we still end up treating the X-rays, even when the evidence is to the contrary.

Sunday, 10 November 2013

Clot filters

It seems I will never run out of examples of treatments that sound obviously effective in theory, fall into common use based on the strength of the biological mechanism, and yet they fail to show a significant benefit when put to the test. The story of the IVC filter is one of these.

Deep venous thrombosis (DVTs, clots) in the leg can dislodge, traveling up through the main vein in the pelvis and abdomen (inferior vena cava, IVC), through the heart and then embolise in the lungs (pulmonary embolus, PE), sometimes causing rapid death. An IVC filter is a wire cage placed in the IVC that snares clots that have broken free from the leg veins, before they can travel to the lungs. The device has been used for decades, but without much evidence of benefit, as this recent report tells us.

Thursday, 31 October 2013

Osteoporosis drugs – cosmetic surgery for the bones?

One of the most popular drugs prescribed these days are the bisphosphonates. You may know them as Fosamax (alendronate) or Actonel (risendronate). They have been pitched as the drug that everyone with osteoporosis should take, and if you are a female over 50, you may have been advised to get your bone density measured, in case you need to take these drugs. Worldwide sales of Fosamax alone hit the $3 billion mark before it went off patent in 2008. We know the drugs increase bone density, but that is just cosmetic surgery for the bones. How much of that translates into fracture prevention? And how many people would want to take this drug if they were given an accurate description of the risks and benefits?

Friday, 11 October 2013

The magical “floating” kidney

I started writing this up as a “Lesson from History”, because floating kidney (or “nephroptosis”) was big in the late 19th century, and I thought that the condition was no longer taken seriously. In researching this however, I found that surgery for this condition is having a resurgence thanks to laparoscopic (keyhole) surgery. To a man with a hammer, everything looks like a nail.

Monday, 7 October 2013

Book review: The Role of Medicine: Dream, Mirage or Nemesis?

Title: The Role of Medicine: Dream, Mirage or Nemesis? (1979)
Author: Thomas McKeown
Publisher: Basil Blackwell, Oxford

In a book that is often grouped with Effectiveness and Efficiency (Cochrane) and Limits to Medicine (Illich), Dr McKeown attempts to calculate the role of medicine in the improvement in health seen over the preceding centuries. He also points out the current problems with medicine (in the 1970s, anyway) and makes suggestions for the future of medical practice, education and research.  Fortunately, many of his suggestions have been realised, but unfortunately, the contribution of medicine to the continuing improvement in health remains overestimated.

Friday, 20 September 2013

Why does spine surgery increase impairment?

In the world of compensation and impairment ratings there is a bible known as the AMA Guides to the Evaluation of Permanent Impairment. The “Guides” aren’t perfect, but I have one major criticism: that the impairment rating for spinal conditions is linked to having surgery, such that surgery (that is undertaken in order to reduce impairment) increases the impairment rating. I will take you through the twisted logic, but it makes as much sense as awarding no impairment for someone crippled with knee arthritis, and then awarding a high impairment rating after they have had their knee replaced and their function restored. This paradox is helping surgeons and lawyers, but does little for the patients except to increase their payout.

Tuesday, 10 September 2013

Craniectomy – a no-brainer?

Raised pressure in and around the brain is associated with (notice I didn’t say “causes”) bad outcomes in patients with traumatic brain injury. Management of such patients centres around reducing this pressure, either by managing their breathing and giving drugs, or by surgical decompression of the brain, usually achieved by removing a piece of skull (craniectomy). Craniectomy is common practice, and it has been around for over 100 years. This recent comparative trial showed that craniectomy was successful in reducing the pressure around the brain, but caused (notice how I didn’t say “was associated with”) more harm than good. A case of “the operation was a success, but the patient died”.

Saturday, 31 August 2013

Calcium for healthy bones?

It’s one thing when my patients tell me that they are eating extra calcium to help their fractures heal or prevent new ones, but when my colleagues are advising them the same thing, its time to correct the bias. Taking calcium and/or vitamin D to heal fractures and prevent new fractures is another case of something that sounds good and is easy to believe, but doesn’t work as advertised.

Monday, 19 August 2013

Hiding in the herd

I had a conflict of interest while operating the other day. I had a patient with a hip fracture that needed surgery, and a knee fracture (on the same side) that would normally be fixed surgically but according to my criteria (decent evidence), it wasn’t necessary. I would not have been criticised for doing the surgery (in fact, my trainees had already consented the patient, thinking that I would). Further, I expected some criticism for not doing the surgery, and I would have felt terrible if the result of my non-operative treatment had been poor. The conflict? I would have been paid a lot of money to do the surgery, and got paid nothing for treating it non-operatively. I was tempted to hide in the herd.