Category Archives: Dr Malcolm Kendrick

I am a GP living in Macclesfield, having graduated from Aberdeen medical school many moons ago. This blog is my best effort at providing some balance to the increasingly strident healthcare lobby that seems intent on scaring everyone about almost everything. Is there a foodstuff that is safe to eat anymore? Is there any activity that does not cause cancer or heart disease? Sausages…..get thee behind me Satan.

Calling All Physicians: The Salt ‘Debate’ Must Stop

My last blog highlighted the bully boy tactics used to silence critics of mainstream medicine. Normally by threatening anyone who dares question the experts of ‘killing patients’, or words to that effect. It is a well-worn tactic which, surprisingly, seems to work every time.

‘If you dare to question breast cancer screening, women will die.’

‘If you question the use of statins, millions will die.’

‘If you….’ well you get the general gist.

There are of course slightly more subtle versions of this. However, when a medical ‘expert’ deigns to address mere mortals, we know what they mean when they say ‘The salt ‘debate’ must stop.’ What they are saying, albeit indirectly, is that if you don’t stop questioning what I say, millions will die. Maybe billions…..over the years, perhaps an entire Google.

On this note, several different people pointed me at a recent debate at the conference of the European Society of Hypertension (ESH) and the International Society of Hypertension (ISH) in Athens. Well, not a debate really, more of a tirade. Here is one part of the report

‘Any “controversy” over whether dietary salt is a cause of heart disease and stroke is the result of weak research methodology or commercial interference, Dr Norm Campbell (Libin Cardiovascular Institute of Alberta, Calgary) and Dr Graham MacGregor (Wolfson Institute of Preventive Medicine, London, UK) argued here….’1

I shall translate their statement. If you do not believe that excess salt consumption is a cause of heart disease and stroke you are a flawed and misdirected scientist (weak research methodology), or you are corrupt (commercial interference). No other explanation is, of course, possible. You are either an idiot, or corrupt, and therefore – by definition – should be ignored. Or perhaps stoned to death for being an unbeliever.

Ah well, that put me in my place. Along with anyone else who dares to disagree with the mighty Norm Campbell and Graham MacGregor. Now Graham MacGregor makes great play of the fact that grubby commercial companies are pushing hard to get us to put more salt in his food. He, of course, has no commercial affiliations.

Hold on. Is he not on the board of the Blood Pressure Association? An organisation that receives funding from various different sources……

You may like to know that we have been very fortunate to have received substantial funding from a number of organisations who have helped the Association get off the ground. These Founder Members are listed below:2

  • Astra-Zeneca UK Limited
  • Bristol-Myers Squibb Pharmaceuticals Limited
  • Merck Sharp & Dohme Limited
  • The Community Fund
  • Omron Healthcare UK Limited
  • Pfizer Limited
  • Servier Laboratories Ltd
  • Solvay Healthcare Limited

Would some of these companies not be pharmaceutical companies? Would some of them make tablets to lower blood pressure? Well, gosh, let me think….

Astra-Zeneca, just to look at the first company on the list. They make:

  • Candestartan
  • Lisinopril
  • Felodipine
  • Metoprolol
  • Atenolol

Well, that’s only five blood pressure lowering agents. Which means that Astra-Zeneca clearly have little interest in blood pressure lowering….not. If you were being a little cynical, you would think that an organisation almost entirely funded by pharmaceutical companies might be considered to have a dog in this fight? You might think that Graham MacGregor could, just possibly, have a little conflict of interest going on. No, surely not.

As for Norm Campbell.

‘Dr. Norm Campbell has given talks sponsored by Bayer, Sanofi Aventis, Biovail, Bristol Myers Squibb, Pfizer, Novartis and Merck Frosst and also has been on advisory boards for Novartis, Pfizer, Servier, Boehringer Ingelheim and Schering Plough.’ 3

As per usual. Seek the commercial conflicts, and ye shall find. You don’t get to be the sort of professor who gets to stand up, command the stage, and intone your words of wisdom at an international medical conference without a little background helping hand from a few pharmaceutical companies. Anyway, what were these two saying about commercial interference again? Difficult to think with the sound of all these cash registers ringing in my ears.

Of course, if confronted, these two will state that all the money they receive goes to charity, or that any funding makes no difference to what they say….or suchlike. As Robbie Burns once remarked. ‘Oh wad some power the giftie gie us, to see ourselves as others see us.’

You, are corrupt because you have accepted money from a commercial source; I, on the other hand, am not. Because I am a superior being incapable of being tainted by money.’

However, the main point here is the fact that we have more bully boy tactics going on. Two ‘grand fromages’ take the stage to beat the opposition into pulp.

‘When a member of the audience pointed to the PURE analysis showing that most of the world eats much higher levels of sodium than those recommended by most international organizations, MacGregor and Campbell leaped on this as an example of a study that had radically failed to measure salt in an appropriate fashion, even devising a new “formula” to estimate salt intake because even spot urine testing had been inadequate. “Please let [PURE principal investigator Dr] Salim Yusuf [McMaster University, Hamilton, ON] know that he should stop using spot urine analysis,” MacGregor said curtly.’

I do hope that everyone in the audience made their own minds up about what they were hearing. I suspect the reporter had their own view, by including the word ‘curtly’.

May I make, yet another, plea for medical experts to stop, cease and desist, attempting to bully into submission anyone who dares disagree with them. It is demeaning.

References (may require site registration or membership to access)

1: http://www.medscape.com/viewarticle/826970?src=emailthis

2: http://www.surgerydoor.co.uk/advice/living-with/living-with-high-blood-pressure/what-blood-pressure-association-do-for-you/

3:http://archive.cme.mcgill.ca/html/videos/2009.rural_en/20090923_JacquesGenest/homeblank.html

You are killing patients

(Who me?)

Debate in science is essential. You would hope it were the very lifeblood of progress. One would also hope that researchers could disagree with each other in frank and open debate. But it has become increasingly obvious to me that if you criticise the experts in medical research you can expect a very rough ride indeed. You certainly risk being stomped into silence.

I have witnessed this quite a lot recently, and have found that the ‘stomping’ game is very simple. If a critic of an area of mainstream medicine seems to be gaining some traction with the public, they are very rapidly accused of ‘killing patients’ by various professors a.k.a. ‘experts.’

Sadly, it has become an article of faith that ‘experts’ cannot be argued with. For they have attained the status of demi-gods. Recently, I was reading an article about Daniel Kahneman, Nobel Prize winner in economics. He was discussing the irrationality of the financial system. He made many interesting points. For example:

The way scientists try to convince people is hopeless because they present evidence, figures, tables, arguments, and so on. But that’s not how to convince people. People aren’t convinced by arguments, they don’t believe conclusions because they believe in the arguments that they read in favour of them. They’re convinced because they read or hear the conclusions from people they trust. You trust someone and you believe what they say. That’s how ideas are communicated. The arguments come later.’

Slightly later on, he talks about his own belief in global warming:

‘Why do I believe global warming is happening? The answer isn’t that I have gone through all the arguments and analysed the evidence – because I haven’t. I believe the experts from the National Academy of Sciences. We all have to rely on experts.’

We all have to rely on experts? So says Daniel Kahneman. A man whom I generally greatly admire. In this case though, I could not disagree more violently. In one breath he states that people aren’t convinced by arguments; they’re convinced because they read or hear conclusions from people they trust. Then he says that we all have to rely on experts. But he does not link these two thoughts together to ask the obvious question. Just how, exactly, did the experts come to their conclusions?

By listening to people they trust? And who might they be? Other experts presumably. And how did they come to their conclusions….by listening to other experts. And how did they come to their conclusions. Hold on, it seems we are trapped in a loop of self-reinforcing logic. There is no escape.

In this area, I tend more to go along with Professor David Sackett:

According to the founder of Evidence Based Medicine experts are hindering the healthy advancement of science.

Writing in this week’s British Medical Journal (BMJ), Canadian-based researcher, David Sackett, said that he would “never again lecture, write, or referee anything to do with evidence based clinical practice”. Sackett is not doing this because he has ceased to believe in evidence based clinical practice but, as the BMJ comments, because he is worried about the power of experts in stifling new ideas and wants the retirement of experts to be made compulsory.

Sackett claims that the prestige of experts (including himself) gives their opinions far greater persuasive power than they deserve on scientific grounds alone.”Whether through deference, fear, or respect, others tend not to challenge them, and progress towards the truth is impaired in the presence of an expert,” he writes.

He also argues that expert bias against new ideas operates during the review of grant applications and manuscripts. “Reviewers face the unavoidable temptation to accept or reject new evidence and ideas, not on the basis of scientific merit, but on the extent to which they agree or disagree with the public positions taken by experts on these matters.” 1

My rather cynical view is that experts can be compared to those men (usually men) who have grabbed hold of the microphone at the front of a mob during a protest march. With this simple act they have managed to gain status and authority. Shortly after they become spokesmen for the revolutionary movement, then leaders…then despots.

However, most newspapers, journalists, television producers never ask they question, how did an expert become an expert – what makes them so. Instead, they are completely in the thrall of the ‘expert, and greatly fear their power. Which means that when an eminent professor loads and fires the ‘you’re killing patients’ gun, all hell breaks loose and panic stalks the land. Journalists, newspaper editors, TV producers and suchlike quiver in fear. They instantly retract everything they have ever published on the matter, and promise never to do it again.

The example of Andrew Wakefield is familiar to all. He stands accused of causing the deaths of thousands of children. Fewer people have probably heard to Peter Gotzsche, who is a professor and head of the Nordic Cochrane Collaboration (yet, not an expert). He has long been a critic of a breast cancer screening. Which has not endeared him to many who work in that field. He is regularly accused of killing thousands of women.

He was forwarded a copy on e-mail by a colleague. It has been written to one of his greatest critics Lazlo Tabar by another ‘expert’. It contained this section – which I have reproduced in full from Professor Gotzsche’s book ‘Mammography screening, truth lies and controversy’

‘What is remarkable to me is that this man (i.e. Dr G) calls himself a scientist since he obviously and knowingly ignores the scientific method in order to further his own agenda, whatever that may be. I cannot believe he is so intellectually deficient that he cannot grasp the plethora of evidence that so strongly supports the benefits of screening. What then drives him so blindly in his crusade to convince us that all the world is flat? To become infamous as a contrarian, standing lonely on the curvature of the as he denies is spinning under his feet? Or is it something even more petty? An all-consuming hatred and jealousy of Lazlo Taber, whose impeccable trial facilitated by meticulous Swedish record keeping and a socialist society provides a setting unparalleled in the world for a scientific trial? What is tragic and make G’s ravings sinister is that I am sure his influence has resulted in women’s unnecessary deaths somewhere in the world. The Scandinavians are known for their fair-minded, progressive concern for women, as well as for their intellectual integrity. IN this regard, PG is certainly a Nordic contrarian.’ [G or PG in this case refers to Peter Gotzsche]

Well, that’s very pleasant. However the part that I wish to draw attention to is this short section…’I am sure his influence has resulted in women’s unnecessary deaths somewhere in the world.’ A difficult statement to either prove, or disprove – I would think. However, the weapon is familiar ‘You are killing patients.’

On pretty much the same lines, I reproduce two short sections from a letter written to Dr Uffe Ravnskov by Professor John Kastelein (A big noise in CV research). He is objecting to Ravnskov’s view that raised cholesterol does not cause heart disease:

‘If this was a joke, I could have laughed about your statements heartily, but they are in fact criminal and bordering on the insane….. I insist that you refrain from any advice to any patient anymore. You are lucky not to live in the Netherlands. I would have dragged you to court.’

Once again, a nice polite scientific debate. Accusing someone of being criminal bordering on the insane. More recently, you will have noted the successful attempt to crush the Australian Catalyst programmes. One of which criticised the diet heart/cholesterol hypothesis. The second program was critical of the ever increasing prescribing of statins. I mentioned it in my last blog

The controversial Catalyst program on statins and heart disease, The Heart of the Matter, was attacked by health experts even before it aired last year.

The presenter of ABC radio’s Health Report, Norman Swan, warned “people will die” as a result of the TV program’s messages about heart medications.

Swan, whose criticism of the program has been vindicated by the independent Audience and Consumer Affairs Unit report, had said the program made him “really angry” because it might affect Indigenous Australians, who are especially likely to suffer from high cholesterol.’

Once again the ‘you’re killing patients’ gun was prepped and fired to pretty devastating effect. Both programmes were pulled from the air with humble apologies all round. Even the first episode ‘dietary villains’ was pulled,which was found to contain no errors at all. Guilt by association I suppose.

A similar battle is being fought in the UK between the statin experts, and those who would criticize them. It has been going on for some time. In 2011 the Cochrane Collaboration published a report very critical of the benefit of statins in low risk/primary prevention patients.

Professor Sir Rory Collins, the most eminent statin expert took great affront, and started to pick the paper apart, claiming it was highly dangerous and damaging. At one point claiming it was far more dangerous than Andrew Wakefield’s Lancet paper.

I quote from 2011:

In public health terms it is potentially a far more serious misinterpretation than that of Wakefield and the MMR in the Lancet.’2

He doesn’t state that the Cochrane collaboration is killing patients directly, but by using the example of Wakefield, we know exactly what he means. ‘You are killing patients.’

Professor Collins has warmed to this theme more recently. As you may be aware he has been attacking the BMJ recently for publishing articles about statins which claim that they have significant side-effects. He vehemently protests that they have virtually none. I quote him again, this time from the Guardian:

“It is a serious disservice to British and international medicine,” Collins told the Guardian at the time, claiming that the alarm caused was probably killing more people than had been harmed as a result of the paper on the MMR vaccine by Andrew Wakefield. “I would think the papers on statins are far worse in terms of the harm they have done.”3

He has been recently followed on this theme by Professor Magdi Yacoub (A famous heart surgeon, now retired from this job). Who is pressing the ‘you’re killing patients’ button with great enthusiasm.

Hey guys, engage in scientific debate, or shut up. Accusing people of killing patients is a terrible and horrible insult, and should play no part in any discussions of this sort. It is the tactics of the playground bully. Yes, I mean you.

References (may require site registration or membership to access)

1:http://www.abc.net.au/science/news/health/HealthRepublish_124166.htm

2: http://webappmk.doctors.org.uk/Session/3366252-XXkGXnwQtec5BtkDi3av-aoqmidr/MIME/Trash/146856-02-B/collins%20statins%20exchange%20with%20cochrane.pdf

3: http://www.theguardian.com/society/2014/may/15/statins-bmj-statement-professor-collins-side-effects

The dog that did not bark

Sorry that I have been a bit quiet recently. Just been finishing off my latest book ‘The dangerous book for grown-ups.‘ [Plug]. Anyway, I most amused to see the latest headline from a study that appeared in my inbox. I felt I had to comment.

‘Onglyza offers unparalleled confidence in a broad range of patients with Type 2 diabetes, delivering effective glycaemic control, without the worry of increased risk of CV events.’ This headline was from a site called MDLinx that pushes stuff at me – whether I want it to or not. Actually I did subscribe, as I am always interested in what the pharmaceutical industry is saying about itself.

Onglyza by the way is one a range of new drugs designed to lower blood sugar levels in diabetes. It works in a complicated fashion. However, the bottom line is that is increases insulin release – mainly after mealtimes. Onglyza also goes by the generic name saxagliptin.

Anyway, to return to the main point here. We have this wonderfully positive headline about a new trial on Onglyza, and what could be wrong with that, you may ask yourself? Well, once upon a time, it was assumed that if you lowered that blood sugar you would also reduce the risk of cardiovascular disease. Heart attacks and strokes mainly. This was because a raised blood sugar (or type II diabetes) is seen a very strong risk factor of cardiovascular disease.

Which means that you would kind of expect that if you lowered blood sugar using Onglyza, you might also see a reduction in heart attacks and strokes. instead we have a headline proudly announcing that doctors need not worry about Onglyza increasing cardiovascular risk. My but life does move on.

So what the bloody hell does it do then, exactly? Well, there is much concern that it might increase the risk of pancreatic cancer.  Anything more? Well, here from Wikipedia:

In February 2012, Bristol-Myers/Astra Zeneca distributed additional safety information on saxagliptin use in South Africa. The package insert is to be edited for South Africa. Contraindications will now include a history of sensitivity to saxagliptin (or another DPP4 inhibitor) as well as pancreatitis. Spontaneously-reported adverse events in South Africa have included anaphylaxis, angioedema and acute pancreatitis.

In a cardiovascular outcomes trial, saxagliptin treatment let to a small but statistically significant increase in the risk of being hospitalized for heart failure. http://en.wikipedia.org/wiki/Saxagliptin

Blimey, is there nothing this drug cannot do? Well, one thing it does not do, hooray, is that it does not actually increase the risk of cardiovascular disease. Just as well really, otherwise every effect that Onglyza has would seem to be completely negative. Heart failure, pancreatitis, possibly even pancreatic cancer.

We have reached an interesting point in drug development when the fact that a drug designed to prevent a disease (CV disease) is hailed for not causing an increase in that very disease. Has this really become the limit of our ambitions.

Having thought about this for a while I decided to create my new generic headline that pharmaceutical companies can feel free to use if they wish. Are there no limits to my generosity?

‘A groundbreaking study has found that (insert name of drug here) does not kill people from the disease it is supposed to be preventing. Internationally famous opinion leader (insert name of opinion leader here) says this is a landmark study and strongly recommends that (insert name of drug here) should become the drug of choice for (insert name of disease here)

 

 

$9Bn – open a bottle of Bollinger please

Don’t worry it’s only $9Bn

Last week I noticed that Takeda, and Lilly had just been fined $9bn.

A US jury has fined Takeda and Eli Lilly $9 billion (£5.4 billion) for causing a man’s bladder cancer with their diabetes drug Actos (pioglitazone). The verdict came down hard on the companies after the case unearthed evidence that Japanese company Takeda had deleted emails, at least one of which raised concerns over Actos’ safety. ‘This serves as a wake-up call to those pharmaceutical companies that cut corners and hide or distort the facts rather than openly testing and educating about their drugs,’ Mark Lanier, who represented the plaintiffs, tells Chemistry World.

Takeda was unable to produce files for 46 clinical and sales employees, 38 of which were deleted after it ordered documents be preserved in 2002 ahead of legal action over Actos. ‘The breadth of Takeda leadership whose files have been lost, deleted or destroyed is, in and of itself, disturbing,’ wrote Judge Rebecca Doherty in a January ruling.  http://www.rsc.org/chemistryworld/2014/04/missing-emails-safety-risk-actos-takeda-eli-lilly-fine

I think that most industries would be somewhat shocked at a fine this big, and this truly was a whopper. However, it follows a pattern of massive fines. GSK was fined $3Bn in 2011 for suppressing clinical trial data on increased suicide risk in children, among many other activities, such as paying kickbacks to doctors. Pfizer was ordered to pay $2.3Bn in 2009 for a series of illegal activities, from mis-branding drugs, to bribery and corruption. AstraZeneca had to shell out $523 million in 2010 for illegally marketing Seroquel for use in children. Roche is accused of hiding data on Tamiflu, GSK is embroiled in corruption cases in China and elsewhere. Merck was hit with a $670 million fine over Medicare fraud in 2007. Eli Lilly shelled out $1.4Bn for illegal marketing in 2009…….etc.

These are vast fines, and the activities exposed are very disturbing indeed. Suppressing data on drugs causing cancer, or suicide, is very serious indeed. You would think these fines would be punitive, but clearly they are not. Or they wouldn’t keep happening. Perhaps the companies just see this as the price of doing business?

Say you have a drug that is making $5Bn a year in profit, and half of that profit comes from illegal marketing, or hiding data. It is not difficult to work out that after only five years, you have made an extra $12.5Bn in profit. I assume it takes at least five years for any case to come to court – probably far, far, longer. (Takeda, it seems, started suppressing data as far back as 1993)

I suppose the equation here is very simple, if dreadful. If you get fined a paltry £1Bn for hiding data, then you have made an extra $11.5Bn in profit from acting illegally. Even if you get fined $9Bn, you are still in the money. (Sales of pioglitzazone were very nearly £5Bn in 2010, so this is not an abstract discussion).

In short, if you do not possess a moral compass, and you are only interested in maximizing profit, it makes perfect sense to market your drugs illegally, pay bribes to doctors, suppress data on increased cancer risk – and all the rest of the corrupt and illegal activities that have been exposed in the courts. Why would you not? Any fine you have to pay is going to be smaller than the increased profit.

In my opinion the only real ‘why you would not‘ is if you, the CEO of Takeda, or Merck, or Pfizer can actually be sent to jail if it turns out that the company was acting illegally on thier watch. At present, the greater the profit, the greater the CEO bonus. Fines will usually arrive long after you have left the company, with a massive pay off, and a pat on the back for your great work in boosting shareholder value.

I think it would concentrate the mind if the CEO or Takeda, or Merck, or Pfizer knew that they would go to prison for a long time, if the company they run, or ran, is found guilty suppressing data. At present we are, effectively, rewarding corrupt behavior by pharmaceutical companies. Which is why there have been so many huge fines; and why I predict that there will be many more.

Currently, the situation is one of extreme moral hazard. A pharmaceutical company makes far more money acting illegally, than acting legally. If the activity is exposed, no-one goes to prison and no-one is personally bankrupted. All that is required is  to set aside enough money to pay the fine, if it ever arrives. ‘Don’t worry, dear shareholders, it’s only $9Bn.’ Phew, and I thought profits would be damaged.’

Another point of view

As someone who considers myself to be a scientist, I thought I should present another view to you on statins. This piece (a transcript of a talk) can be seen on Medscacpe1.

Please read on, and see what you think of his arguments:

I am Dr. Frank Veith, Professor of Surgery at New York University Medical Center and the Cleveland Clinic. Today I am going to talk about what I call the “statin witch hunt” and why, despite it, we should give more patients statin drugs.

The question of whether to give statins to more healthy patients is one of considerable interest to the public and considerable debate in both the medical community and the lay press. In November, the American College of Cardiology (ACC) and the American Heart Association (AHA) released their long-awaited new guidelines on the treatment of blood cholesterol to reduce the risk for adult atherosclerosis. T

This guideline, among other recommendations, guided physicians to expand the number of patients being treated with statin drugs. The guideline was greeted with many objections in both the medical community and the lay press. Most notable was a November 14 New York Times op-ed by 2 respected experts, Drs. John Abramson and Rita Redberg, titled “Don’t Give More Patients Statins.”

Other New York Times articles about Drs. Paul Ridker and Nancy Cook, and another by Gina Kolata, expressed similar reservations about the ACC/AHA guideline recommendation to broaden statin administration. All three of these New York Times articles were part of what I call the “statin witch hunt” which has generated much confusion among the public.

The op-ed by Drs. Abramson and Redberg makes the case that the recent ACC/AHA cholesterol guideline is incorrect to advocate the expansion of statin usage to more patients because such expansion “will benefit the pharmaceutical industry more than anyone else.” They state that the guideline’s authors were not “free of conflict of interest.” In addition, they claim that “18% or more” of statin recipients “experience side effects” and that the increase in statin administration will largely be in “healthy people” who do not benefit and who would be better served by an improved diet and lifestyle.

Although the latter is true for everyone, Drs. Abramson and Redberg convey the wrong message. Statins are the miracle drug of our era. They have proven repeatedly and dramatically to lower the disabling and common consequences of arteriosclerosis — most prominently heart attacks, strokes, and deaths in patients at risk. Statins avoid these vascular catastrophes not only by lowering bad blood lipids but also by a number of other beneficial effects that stabilize arterial plaques.

 They have minimal side effects, most of which are benign. In several controlled studies, the patients who did not receive statins had an incidence of side effects equal to those who received them. Serious side effects are rare and manageable. Moreover, healthy patients are only healthy until they get sick. Many individuals over the age of 40 take a daily aspirin.

Statins are far more effective than aspirin in preventing the heart attacks and strokes that often occur unexpectedly in previously “healthy people.” Clearly it would be worthwhile for such healthy people to take a daily statin pill with few side effects, if it would lower their risk for such vascular catastrophes and premature death.

In contrast to what is implied in the Abramson-Redberg article, these drugs are an easy way for people to live longer and better, and statins cannot be replaced with a healthy lifestyle and diet — although combining the latter with statins is a good thing.

Lastly, with respect to the comments about the pharmaceutical industry benefiting from statin prescriptions, and the guideline authors’ conflicts of interest, both are less important than patient benefit, which has been demonstrated dramatically and consistently in many excellent and well-controlled statin trials. Moreover, most statins are now generic, so the cost for obtaining these miraculous drugs need not be prohibitive, and the guideline’s authors are experts who are eminently qualified to write them.

The statin witch hunt is a bad thing, and more patients should be on statin medication. I am Dr. Frank Veith, and that is my opinion.

1: http://www.medscape.com/viewarticle/822145?nlid=51963_1985&src=wnl_edit_medn_card&spon=2

(You will need to subscribe to Medscape to see the talk, and transcript. It is fairly straightforward to gain access. The site is www.medscape.com It is one of the biggest medical websites.)

I though you should know if Frank Veith has any conflicts of interest. He works at the Cleveland Clinic, so he probably doesn’t, as most of the medical experts who work there state that they give all of their income from working with the pharmaceutical industry to charity. Steven Nissen, a man of whom you may have heard me speak on a regular basis, is the chairman of Cardiovascular medicine at the Cleveland Clinic.

Here, for example, is Steven Nissens conflict of interest statement

Dr Steven Nissen
Medical Director
Cleveland Clinic Cardiovascular Coordinating Center

Dr. Nissen has received grant/research support from AstraZeneca Pharmaceuticals, Atherogenics; Eli Lilly and Co., Lipid Sciences, Pfizer Labs, Sankyo Pharma, sanofi-aventis, and Takeda Pharmaceuticals North America with all reimbursement directed to the Cleveland Clinic Cardiovascular Coordinating Center; and has been a consultant for Abbott Laboratories, AstraZeneca Pharmaceuticals, Atherogenics, Bayer Corp., Eli Lilly and Co., Forbes Medi-tech, GlaxoSmithKline Pharmaceuticals, Haptogard, Hoffman-LaRoche, Isis Pharmaceuticals, Kemia, KOS Pharmaceuticals, Kowa Optimed, Lipid Sciences, Merck/Schering Plough, Novartis Pharmaceuticals Corp., Novo-Nordisk, Pfizer Labs, Protevia, Roche Pharmaceuticals, Sankyo Pharma, sanofi-aventis, Takeda Pharmaceuticals North America, Vasogenix, Vascular Biogenics, Viron Therapeutics, and Wyeth Pharmaceuticals, all fees are paid directly to charity with no reimbursement paid to Dr. Nissen; and has served on the speakers’ bureaus of AstraZeneca Pharmaceuticals and Pfizer Labs, all fees are paid directly to charity with no reimbursement paid to Dr. Nissen.

Cleveland Clinic physicians and scientists may collaborate with the pharmaceutical or medical device industries to help develop medical breakthroughs or provide medical education about recent trends. The collaborations are reviewed as part of the Cleveland Clinic’s procedures. The Cleveland Clinic publicly discloses payments to its physicians and scientists for speaking and consulting of $5,000 or more per year, and any equity, royalties, and fiduciary relationships in companies with which they collaborate. The Cleveland Clinic requires its doctors to approve the public disclosures of their scientific collaborations with industry. As of 3/21/2014 the review process regarding Dr. Veith’s disclosure had not been completed. Patients should feel free to contact their doctor about any of the relationships and how the relationships are overseen by the Cleveland Clinic. To learn more about the Cleveland Clinic’s policies on collaborations with industry and innovation management, go to our Integrity in Innovation page.

A ghost in the machine

I suppose most people missed this story about life expectancy in the UK. If you didn’t pick it up, this article comes from the Doctors net website. A site for doctors registered to practice medicine in the UK.

Life expectancy fall alarm 14/02/2014

The life expectancy of England’s elderly population has fallen for the first time, it was reported last night. Women at the age of 75 can expect to live a little less longer than they would have at the beginning of the decade, according to new figures.

The figures for 2012 are still provisional and represent a reduction of two and half months in life expectancy for women at the age of 75.There was no change in life expectancy for men, who could expect to live 11.3 years.

The Department of Health calculations, obtained by the Health Service Journal, show that life expectancy for women at that age fell from 13.2 years to 13 years. The figures may reflect the growing problems of caring for an elderly population – or simply growing numbers of elderly people.

John Newton, of Public Health England, told the journal: “Life expectancy reflects what has happened in people’s lives, and these people were born in wartime, when there were profound changes in diet. We have seen an unprecedented increase in life expectancy and it’s possible that is coming to an end.

“But we do also expect fluctuation. As we have an older population, the proportion of deaths that will fluctuate due to flu and cold weather is greater.

So it seems that life expectancy in the UK is falling amongst elderly women, and it is staying stationary for elderly men. Which is rather the opposite of what was supposed to happen, and reverses many years of increasing life expectancy.

Why is this happening? Ten years ago the UK Government embarked upon the most expensive, and extensive, initiative ever undertaken in preventative medicine. The Quality Outcome Framework (QoF). This was launched with a great fanfare.

QoF is a system whereby GPs have to screen the entire population for conditions such as diabetes, high blood pressure, chronic kidney disease, high cholesterol, etc. etc.

Once any early stage diseases had been picked up, treatment is instigated. Then there is regular monitoring to ensure that targets for blood pressure lowering, blood sugar control, and suchlike were met. This system has cost billions upon billions of pounds.

It was supposed to stop people dying prematurely from diseases, or conditions that could be properly ‘treated’ and ‘controlled.’ Because the elderly are, by the nature of being elderly, far more likely to have various early stage diseases, and are therefore at highest risk, this is the population that has been most tightly monitored and ‘treated’.

I work, part-time, in Intermediate Care. A unit where elderly people who have had an accident, broken a hip, or suffered other acute illnesses are cared for. Our job is to get them as fit as possible to return home. There are nurses, physiotherapists, occupations therapists, and me, sorting out underlying medical conditions such as anaemia. Some patients arrive from the community, others from hospital.

I did a small audit last year, and found that the average number of drugs that our patients are taking when they arrive in the unit is ten point three. That is, ten point three different drugs. Some of which are taken three or four times a day. So, a total of twenty or thirty tablets a day, in many cases.

This is the very definition of polypharmacy. And how much harm could polypharmacy do? Well here is a study from Israel, looking a study where people in nursing homes had drugs discontinued [They stopped as many drugs as was considered ethical]. Here is the abstract of the paper.

The war against polypharmacy: a new cost-effective geriatric-palliative approach for improving drug therapy in disabled elderly people.

Background:

The extent of medical and financial problems of polypharmacy in the elderly is disturbing, particularly in nursing homes and nursing departments.

Objectives:

To improve drug therapy and minimize drug intake in nursing departments.

Methods:

We introduced a geriatric-palliative approach and methodology to combat the problem of polypharmacy. The study group comprised 119 disabled patients in six geriatric nursing departments; the control group included 71 patients of comparable age, gender and co-morbidities in the same wards. After 12 months, we assessed whether any change in medications affected the death rate, referrals to acute care facility, and costs.

Results:

A total of 332 different drugs were discontinued in 119 patients (average of 2.8 drugs per patient) and was not associated with significant adverse effects. The overall rate of drug discontinuation failure was 18% of all patients and 10% of all drugs. The 1 year mortality rate was 45% in the control group but only 21% in the study group (P < 0.001, chi-square test). The patients’ annual referral rate to acute care facilities was 30% in the control group but only 11.8% in the study group (P < 0.002). The intervention was associated with a substantial decrease in the cost of drugs.

Conclusions:

Application of the geriatric-palliative methodology in the disabled elderly enables simultaneous discontinuation of several medications and yields a number of benefits: reduction in mortality rates and referrals to acute care facilities, lower costs, and improved quality of living.

The first thing to say here is that, if there ever was a ‘war’ against polypharmacy, then polypharmacy won a long time ago…at least in the UK.

For those who find scientific papers somewhat opaque, the key point from this paper is the following

The one year mortality in those who did not have their medications reduced was 45%

The one year mortality in those who did have their medications reduced was 21%

This is a fifty three per cent absolute reduction in overall mortality risk in a year. Which is a better figure than I have seen for any drug intervention, ever, anywhere. So it would seem that the best possible drug treatment discovered…. is to stop taking drugs. As an added bonus you save lots of money, and make the patient feel much better, all at the same time.

Just one paper? No, of course not. There are a number of different studies demonstrating that discontinuing medication in the elderly is a good thing to do. A review paper in the Journal of the American Medical Association (JAMA) came to the following conclusions:

‘The finding that simultaneous discontinuation of many drugs is not associated with significant risks and apparently improves quality of life should encourage physicians to consider testing this in larger RCTs (randomised controlled studies) across a variety of medical cultural settings. Polypharmacy may have different faces in different countries or clinics but there is no doubt that the problem is global. This approach has international relevance; it combines our best existing evidence with patient-focused care while actively avoiding extrapolation from inappropriate populations where no evidence exists for treatment in elderly patients.’

In fact, I cannot find any evidence that polypharmacy, however you define it, does anything but harm. In the face of such evidence what did the UK authorities decide to do? Why, they set about create a system designed to drive the biggest explosion of polypharmacy ever seen. What else would you expect them to do?

So why has the mortality gone up in the elderly population in the UK? Well, I know where I would put my money. On the very system designed to stop them dying in the first place.

A sorry little patient tale

Working as a GP in England becomes increasingly difficult as the drive to put more and more people on statins gathers pace. Virtually every day I see a patient taking statins who is suffering a clear adverse effect.

I know that this is a very biased sample, because patients in the area know that I am ‘the doctor who writes stuff about statins.’ So there is a degree of self-selection going on here. People who think they may be having adverse effects choose to see me.

However, there is another degree of self-selection going on here. When I see that a patient is on statins, I tend to be on high alert for any mention of statin related adverse effects. Whilst most other doctors happily dismiss such things as: tiredness, memory loss, joint pains, muscle pains depression, irritability, impotence, stomach pains, skin rashes and the like as ‘nothing to do with statins.’ I tend to think the statin may be the cause.

I then usually say. Stop the statin for a couple of months and see what happens to your, tiredness, memory loss, joint pains etc etc. Very often these symptoms go away. Then what? Then the practice statin prescribing statistics start to look quite bad. The senior partner (who is pretty sympathetic to my cause), has had words. The practice is losing money. I have had to ‘exempt’ more and more patients from the cardiovascular disease indicators.

The prescribing lead from the local Clinical Commissioning Group has also had words. It is clear that my non-prescribing of statins is very much frowned upon. Although nothing concrete has yet happened, the pressure to conform cranks up. At times I wonder why I bother. Should I just focus my anti-statin efforts at a more global level? Writing articles, lecturing, speaking to journalists, writing books, and the like. .What difference can I make with a few patients in the practice?

Yesterday, however, I saw a lady who had been admitted to hospital with severe abdominal pains. So severe that she had scans, tests, and was very nearly taken down to surgery for an exploratory operation. Did she have galls stones, appendicitis, cancer? Nothing could be found.

She was discharged with strong painkillers, and follow-up appointments were arranged. She came to see me between Christmas and the New Year to get more painkillers to tide her over. I suggested that the statin may be causing her stomach pain, and that she should stop them, which she did.

Guess what. Of course, the stomach pains have gone. She also reported that she’d had three episodes of Transient Global Amnesia whilst taking statins. This is where your memory goes, you wonder about as if in a fugue, and can remember nothing of what went on. She had not reported these episodes to anyone, but since being made aware that stains can cause them, she now knows what happened.

Since stopping the statins she also reports that her energy levels are back to normal, and that she feels human again. Her life, her quality of life, has returned.

After thanking me for helping her, she then asked. ‘What do you think I should do, doctor. Should I go back on them again, the other doctors say that I should, but I don’t want to.

Please sign

I just got this as an e-mail this morning.

Friends,

I’ve just heard that companies like Coca-Cola, Nestle and others will be able to claim their products are ‘healthier’ thanks to a new EU regulation on using fructose. But consuming high levels of fructose is a leading cause of obesity around the world.

This decision was made by the EU Food Standards Agency in Parma, Italy. We need to push back on food industry lobbying by demanding the EU Food Standards Agency thinks again.

Can you sign this petition demanding the EU Food Standards Agency thinks again?

http://action.sumofus.org/a/eu-fructose/

So, now, it will be claimed that Coca-Cola is a health food. You really couldn’t make this stuff up, could you? Or if you did you would be accusing of stretching credibility far beyond breaking point.

Anyway, if you feel you can, I would hope that you can sign this petition. It takes about thirty seconds.

For those of you who sometimes feel that big business is now running the world, whilst Governments jerk up and down on their strings. ‘All citizens must now drink Coke for a healthy and fulfilling life…’

“In a way, the world−view of the Party imposed itself most successfully on people incapable of understanding it. They could be made to accept the most flagrant violations of reality, because they never fully grasped the enormity of what was demanded of them, and were not sufficiently interested in public events to notice what was happening. By lack of understanding they remained sane. They simply swallowed everything, and what they swallowed did them no harm, because it left no residue behind, just as a grain of corn will pass undigested through the body of a bird.”  1984

Please protect the community

The primary functions of government are to maintain order, settle conflicts, and protect the community. So I am told.

Generally I am a small state man. In fact I refer to myself, when I don’t think anyone important is listening, as an anarchist. I believe that humans should be allowed as much freedom as is possible, without being allowed to seriously harm others. Rules and regulations and bureaucracy are not really my thing. So I am achingly reluctant to demand that the State gets involved in creating yet another agency, or add to its powers in any way.

But sometimes the State must intervene to carry out one of its three primary functions. Namely, to ‘protect the community.’

Where Governments around the world have to step in, right now, is to gain proper control of the creation of medical guidelines. Something that they have spectacularly failed to do, up to now.

As you may be aware, a row is rumbling under the surface about European guidelines on the use of beta-blockers in surgical operations, guidelines that were based on corrupt research. Doctors following these guidelines have probably killed 800,000 people. Give or take.

Some people have written into this blog stating that the numbers cannot be that high, and that the calculations are probably wrong. They were not my calculations, I hasten to add. My view on this is that many many thousands have certainly died unnecessarily. It doesn’t really matter if it was one hundred thousand, five hundred thousand, or eight hundred thousand.

How many would be acceptable?

The answer is, of course, none. But when guidelines go wrong the potential for killing hundreds, thousands, or even millions, is always there. If, for example, your guidelines state that fifty per cent of the population must take a drug for a condition, and these guidelines are wrong, you can kill millions,.

Recently, I did the back of a fag packet calculation on the number of people who were killed by the advice that patients must be managed with six weeks of strict bed rest after a heart attack. Here is some advice from that era: ‘The patient is to be guarded by day and night nursing and helped in every way to avoid voluntary movement, or effort.’ Thomas Lewis.

According to my figures, and I am not going into them here, strict bed rest for six weeks after a heart attack killed fifteen million people worldwide. Yes, fifteen million. More than died in the fighting in the first and second world wars added together.

This, I hope, gives you some idea of the potential death toll when medical guidance goes wrong. Given this, you would hope that the process that leads to the creation of guidelines would be checked, and double checked, then triple checked, then monitored.

You would also hope that the evidence underpinning the guidelines was free from bias, and corruption. Furthermore, that all data – positive or negative – would be freely available, with no possibility of hiding anything away. You would also hope that those creating the guidelines had no possible conflicts of interest.

The fact is that NONE of these things are true. We have a system that is almost perfectly free from scrutiny of any sort. Many, if not most, guidelines are based on trials that are designed, set up and run by the pharmaceutical companies. They own and control the data, and are under no obligation to let anyone else see it, if they don’t want to. Negative data are regularly buried, never to see the light of day.

A few brave souls e.g. Ben Goldacre, Fiona Godlee (editor of the BMJ), and Peter Gotzsche have been demanding that all clinical trial data are made available for scrutiny, but almost nothing has happened. Currently Roche are refusing to release data on their flu drug Tamiflu. Various studies remain unpublished, no data released. The UK Govt. seems powerless to act. Or maybe it just doesn’t want to, with so much money at stake.

Last year AbbVie and InterMune, two drug companies, took legal action against the European Medicines Agency to stop them releasing any data from clinical studies, and to ensure that no trials data could made available, anywhere, to anyone, ever again. I like to think I helped to kick this monstrous and terrible legal action into touch. But, companies still do everything in their power to ensure that data will not, ever, be released.

Then we have the enormous problem that that ‘experts’ chosen to write guidelines work hand in glove with the pharmaceutical industry. The US guidelines on cholesterol lowering written in 2004 were put together by nine people. Here is a conflict of interest statement. I have put this up before, but I think it bears almost endless repetition:

ATP III Update 2004:  Financial Disclosure

Dr. Cleeman: (Chairman) has no financial relationships to disclose.

Dr. Grundy: has received honoraria from Merck, Pfizer, Sankyo, Bayer, Merck/Schering-Plough, Kos, Abbott, Bristol-Myers Squibb, and AstraZeneca; he has received research grants from Merck, Abbott, and Glaxo Smith Kline.

Dr. Bairey Merz: has received lecture honoraria from Pfizer, Merck, and Kos; she has served as a consultant for Pfizer, Bayer, and EHC (Merck); she has received unrestricted institutional grants for Continuing Medical Education from Pfizer, Procter & Gamble, Novartis, Wyeth, AstraZeneca, and Bristol-Myers Squibb Medical Imaging; she has received a research grant from Merck; she has stock in Boston Scientific, IVAX, Eli Lilly, Medtronic, Johnson & Johnson, SCIPIE Insurance, ATS Medical, and Biosite.

Dr. Brewer: has received honoraria from AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Esperion, and Novartis; he has served as a consultant for AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Sankyo, and Novartis.

Dr. Clark: has received honoraria for educational presentations from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer; he has received grant/research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer.

Dr. Hunninghake: has received honoraria for consulting and speakers bureau from AstraZeneca, Merck, Merck/Schering-Plough, and Pfizer, and for consulting from Kos; he has received research grants from AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, and Pfizer.

Dr. Pasternak: has served as a speaker for Pfizer, Merck, Merck/Schering-Plough, Takeda, Kos, BMS-Sanofi, and Novartis; he has served as a consultant for Merck, Merck/Schering-Plough, Sanofi, Pfizer Health Solutions, Johnson & Johnson-Merck, and AstraZeneca.

Dr. Smith: has received institutional research support from Merck; he has stock in Medtronic and Johnson & Johnson.

Dr. Stone: has received honoraria for educational lectures from Abbott, AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, Pfizer, Reliant, and Sankyo; he has served as a consultant for Abbott, Merck, Merck/Schering-Plough, Pfizer, and Reliant.

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04_disclose.htm

Those companies that I have marked in bold sell (or at the time sold) statins and/or other cholesterol lowering medications. A mere eight members (the chairman was employed by the NIH who was not allowed close ties with industry), and we have almost seventy direct financial conflicts of interest with companies who made, and sold, cholesterol lowering agents.

How we can possibly allow doctors with enormous financial conflicts of interest to create guidelines that will be followed around that world, and will affect hundreds of millions (in this case billions) of people….How can this possibly be allowed.

We currently have a system of guideline creation that relies on three things being true, if they are to be sare – all three things:

1: That the clinical trial data are not corrupt, or biased

2: That negative data are made available when requested

3: That the medical experts tasked with creating the guidelines are completely unaffected by their financial conflicts of interest

The fact is that none of these critical requirements are followed….even remotely.

How many other guidelines out there are wrong, damagingly wrong, and horrifyingly wrong? How many millions of people are being put at risk by a system that is wide open to corruption, and bias? I have not the slightest idea, but I suspect many….

The public are most certainly not being protected. We have put the foxes in charge of the chicken coop, with entirely predictable results. Time for the farmer to pull out the shotgun and start blasting away. Time for the state to start doing what it is there to do. Namely, ‘protect the public.’

Guidelines kill 800,000

A few days ago a friend sent me this headline by e-mail.

‘Guideline Based on Discredited Research May Have Caused 800,000 Deaths In Europe Over The Last 5 Years.’

I would replace the word ‘May’ with these two words ‘almost certainly.’ You would think, would you not, that if any other event in the world, at any time, had killed eight hundred thousand people, this would be front page headlines around the world for weeks, probably months, maybe even years.

Governments would spring into action, those guilty dragged into court. Thousands would protest in the streets, petitions would be signed, laws passed.

The reality is, I am willing to bet, that you have never even heard of this gigantic scandal. It will not have appeared in any national television programme, or newspaper. The blogosphere is also, almost totally silent.

Eight hundred thousand people. Please let that figure sink in for a few moments. If you dropped a major thermonuclear device on Manchester (UK) and killed every single living person, this would be roughly equivalent. If you laid the corpses end to end, the line of dead people would stretch from John O Groats to Land’s End (the entire length of the UK). Walking briskly each day, it would take you two months to pass them.

Think on that.

To an extent the actual guidelines themselves are not the most important thing here. They are now in the process of being changed (although they have not yet been changed). Nobody can be brought back to life, those who could have died – are dead. The issue here is that the processes leading to the creation of guidelines, that have almost certainly killed 800,000 people, are still in place, with no prospect of any change.

Those who have read this blog may be aware of my distaste for medical guidelines, and my concerns about their impact. I wrote an earlier blog called ‘Who shall guard the guardians.’ This outlined some of the problems, but even I was overwhelmed by the sheer scale of deaths involved when guidelines go wrong. I could have worked it out, but never did.

Guidelines are based on evidence, and evidence is based on clinical trials. And major clinical trials are, almost without exception, paid for, run, and controlled by the pharmaceutical industry. The great and good of medicine, the ‘Key Opinion Leaders’ KOLs, who put together the guidelines will almost all have very close connections with the industry. In some cases they will have been paid millions by pharmaceutical companies.

Whether they think so, or not, these opinion leaders are biased. Biased in favour of pharmaceutical products that are promoted through biased research, and launched on an unsuspecting world. And there is no-one out there to check what these KOLs and guideline committees are doing. If, to pluck a name from the air, the European Society of Cardiology (ESC) decides to create a guideline committee, how do they do it?

They choose a chairman, who will be on one of their committees. A well regarded, sound chap, with expertise in the area. He, very rarely she, will then decide on which of his friends and colleagues would be most suitable to be committee members.

They will have a few meetings, gather the evidence together, decide on what best practice should be, and produce their guidelines. No other organisation checks on them, or their decision making, or their conflicts of interest. Or, indeed, the evidence itself.

Yet, when the guidelines come out, many countries will slavishly follow them. They will form the basis for instructions to their medical services. Doctors who fail to follow the guidelines can be censured, or lose their jobs. They virtually carry the force of law.

Something this powerful and important and critical to medical care is dealt with in an almost completely cavalier fashion. Which is, frankly, inexcusable.

I suppose you are wondering what these guidelines were? Well, they were on the use of beta-blockers to protect the heart during surgery. To see more on this story go to the Forbes website

I cannot send you to the article published in the European Heart Journal, because one hour after going up on their website, it was pulled. Here is the comment from the authors of this paper, Graham Cole and Darrel Francis, on the decision of the Editor to disappear the article.

‘Our article is a narrative of events with a timeline figure and a context figure. We had not considered it to contain scientific statements, but we admit that it does multiply together three published numbers.

It is not an analysis of individual trials considering design, molecule, dose and regimen. We published last year the formal meta-analysis under stringent peer review in Heart and addressed the questions, including dosing, in that paper and associated correspondence.

The first of our two EHJ articles merely says that our community, which races to take credit when research-led therapy improves survival, must be equally attentive to the possibility of harm.  The leverage of leadership means the magnitude of either may be far from trivial.

Where our article relayed numbers, we made clear that alternative values were possible. The focus for readers was on how serious the consequences can be when clinical research goes wrong.

We thank Prof Lüscher for highlighting the scientifically important point that the pivotal trial, DECREASE I, has not been retracted by NEJM because the investigative committee did not recommend this. Unfortunately the committee could not have done so, because DECREASE I was outside its brief, displayed on the first text page of the first committee report. Can readers suggest why DECREASE I, from the same trial family, was exempted from inquiry?

We admire Prof Lüscher’s diligence in sending for peer review what we thought was merely multiplication. We await the review of the pair of articles. The first narrated one instance of a pervasive problem. The second suggests what each of us can do to reduce recurrences.

We respect the process Prof Lüscher has set in motion. We ask readers to join with us, and the journal, in maximizing the reliability of clinical science for the benefit of patients.’

Well, I am really glad that this article is being sent for peer review, because – as we know – peer review is a jolly good thing. To quote Richard Horton, Editor of the Lancet:

‘The mistake, of course, is to have thought that peer review was any more than a crude means of discovering the acceptability — not the validity — of a new finding. Editors and scientists alike insist on the pivotal importance of peer review. We portray peer review to the public as a quasi-sacred process that helps to make science our most objective truth teller. But we know that the system of peer review is biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong.’

Let me just repeat that last bit. Peer-review is:

….biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong.

Frankly, I wouldn’t hold my breath waiting for peer-review on this matter.

I suppose you may also be wondering how the problem with these guidelines came to light. Well, it turns out that the chairman of the guidelines committee was Prof Don Poldermans. A man who has now been booted out of his job at Erasmus Hospital in the Netherlands for making up his research. The very research that was used to create these guidelines.

Don Polderman’s also had financial conflicts of interest with Merck, Pfizer, Novartis and Medtronic. To name but four. (One conflict of interest statement can been seen here).

Anyway, here is a summary of what has happened:

      • Don Poldermans had financial conflicts of interest with several pharmaceutical companies
      • Con Poldermans carried out corrupt research, supporting the use of pharmaceutical products
      • Don Poldermans was the chairman of an ESC committee that recommended widespread use of drugs to protect the heart during surgery
      • Widespread use of drugs to protect the heart during surgery has killed 800,000 people over 5 years in Europe (alone)
      • The paper outlining the scale of deaths has been pulled by the ESC

I hope the hell there are no more Don Poldermans out there…..but you would have to be a brave man to think so. Personally, I believe there is an endemic problem with bias and corruption in medical research, and we should be very afraid indeed.

How to kill a hypothesis

“Why do people insist on defending their ideas and opinions with such ferocity, as if defending honour itself? What could be easier to change than an idea?” J.G. Farrell.

When the orbit of Neptune was found to be irregular, and not to follow classical Newtonian physics, it was suggested that, perhaps, the laws of physics may break down in deep space. Others, rather more pragmatically, suggested that there was another planet out there, interfering with the orbit of Neptune. It was just too far out, and dim, to be seen.

That planet, no longer called a planet, was Pluto. Once observed, it accounted for the distortions in the orbit of Neptune.

When the orbit of Mercury was found to be irregular, and not to follow classical Newtonian physics, it was suggested that there was another invisible planet orbiting closer to the sun. This planet was named Vulcan.

Of course there was no planet Vulcan. The reason why classical Newtonian physics did not accurately predict the orbit of Mercury is because the mass of the sun bent time and space. Classical Newtonian physics had to be replaced by Einstein’s theory of relativity.

What does this tell us?

It tells us that it is very difficult to know if an apparently contradictory observation actually refutes a scientific theory. It also tells us that you can use ad-hoc hypotheses (there is another planet out there) to support a cherished central hypothesis, and that this is a valid scientific technique.

But at what point do you have to admit defeat? How many contradictory observations can you dismiss before you must accept that the game is up, and that your hypothesis is wrong?

I think about this a lot. Mainly with regard to the cholesterol hypothesis, or the diet-heart hypothesis, or whatever term is now current. I have seen evidence that directly refutes this hypothesis again and again and again and….indeed…again.

If anyone wishes to debate this issue with me, I can produce far more evidence contradicting it, than supporting it. Yet still it stands, untouched. In fact I would suggest more people believe in this hypothesis than at any time in human history. Billions of people also take statins to lower their cholesterol levels. As you can imagine, this is more than a little frustrating.

How can you convince people that this hypothesis is wrong? I have tried in many, many, different ways. As have other members of THINCS (The International Network of Cholesterol Skeptics).

Yes, I have helped to convince many thousands of people that cholesterol has nothing to do with heart disease, or cardiovascular disease, or atherosclerosis, or unstable atherosclerotic plaques…

Indeed, stepping sideways for a moment, one of the major difficulties in this area is that the terminology shifts and swirls in front of you, making it impossible even to pin down what you are talking about.

At one time the experts were quite happy to tell us that a raised cholesterol level caused heart disease. Now we have ‘good’ cholesterol and ‘bad’ cholesterol, and ‘light and fluffy’ bad cholesterol and ‘small and dense’ bad cholesterol (which really should be called ‘evil’ cholesterol, I suppose). We have the ratio of good to bad cholesterol, apob-100 levels, particle numbers, sub-fractions of good cholesterol, dyslipidaemia, LDL particle size, or number,  or…..the list goes on and on.

How can you argue against a scientific hypothesis when the damned thing will not stay still from day to day?

That, however, is a bit of a side-issue, although I have come to realise that this constant creation of new types of cholesterol, and sub-fractions, and ratios, is all part of the game that is played to protect the cholesterol hypothesis from refutation. How can you refute a hypothesis that can change into any shape it likes? Answer, you can’t.

Anyway, in my efforts to work out how to change ideas in the wider population I have spent a great deal of time looking at the history of scientific thought. I wanted to gain any insights I could into how people managed to kill off hypotheses in the past.

As part of my education I have tried not to get too depressed by fellow thinkers on the subject. Such as Max Plank, who said:

‘A scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it.’

In short, his view is that you should forget trying to convince people. They will never, ever, change their minds. Max Plank, by the way, was the man who published Einstein’s special theory of relativity (against great opposition).

Another of my scientific heroes is Wilfred Trotter. A man you are unlikely to have come across. Unfortunately, however, he was not much help either:

‘The mind likes a strange idea as little as the body likes a strange protein and resists it with similar energy. It would not perhaps be too fanciful to say that a new idea is the most quickly acting antigen known to science. If we watch ourselves honestly we shall often find that we have begun to argue against a new idea even before it has been completely stated.’

I could fill hundreds of pages with quotes saying the same type of thing. Essentially, people love the ideas they have grown up with, and become deeply emotionally attached to them. Changing them is painful; they dislike and fear new ideas and, will bring forth all the powers of their intellect to do so.

Things are made all the more difficult when you try to convince people who have spent large amounts of their professional life studying a specific area. When someone has become an ‘expert’ in something, and their reputation, and position of authority, is inextricably linked to a certain hypothesis, you are not just attacking an idea, you are attacking them. As noted by Leo Tolstoy:

‘I know that most men, including those at ease with problems of the greatest complexity, can seldom accept even the simplest and most obvious truth, if it be such as would oblige them to admit the falsity of conclusions which they have delighted in explaining to colleagues, which they have proudly taught to others, and which they have woven, thread by thread, into the fabric of their lives.’ Leo Tolstoy

Despite all of this being rather depressing, it has all helped me to establish one clear rule. Do not bother trying to convince people who are ‘experts’ in heart disease that the cholesterol hypothesis is wrong. It is a complete waste of time and energy. The only people who can be convinced are inquisitive people who do not have too much invested in this particular hypothesis.

I have also worked out another rule. Facts are almost completely ineffective at convincing people of anything. Recently, I was reading an article on Daniel Kahneman, Nobel prize winner in economics. He was discussing the irrationality of the financial system. He made many interesting points. For example:

The way scientists try to convince people is hopeless because they present evidence, figures, tables, arguments, and so on. But that’s not how to convince people. People aren’t convinced by arguments, they don’t believe conclusions because they believe in the arguments that they read in favour of them. They’re convinced because they read or hear the conclusions from people they trust. You trust someone and you believe what they say. That’s how ideas are communicated. The arguments come later.’

Once again, if this is true, what can be done? How to change ideas…..

I leave you at this point with a small section of dialogue from the film Inception:

Dom Cobb: ‘What is the most resilient parasite? A bacteria? A virus? An intestinal worm?’

Arthur: ‘Uh, what Mr. Cobb is trying to…’

Dom Cobb: ‘An idea. Resilient, highly contagious. Once an idea has taken hold of the brain it’s almost impossible to eradicate. An idea that is fully formed, fully understood. That sticks, right in there somewhere.’

[he points to his head]

The cholesterol hypothesis is one of the most resilient parasites of all. How to kill it off? All suggestions welcome.

Is medical research now beyond redemption?

Below, I have copied an entire article from the BMJ, written by Dr Des Spence, who is a fellow Scottish GP. We communicate from time to time, and share a general view that medicine is heading in a very unfortunate direction with overdiagnosis and over-treatment/polypharmacy becoming a massive problem.

This is driven, in the main part, by the pharmaceutical industry. An industry that would like to see the entire population of the world taking medication every day….. forever. To achieve this they have, effectively, grabbed hold of medical research and twisted it to their own ends.

Anyway, please read this article. It encapsulates much of what I feel, and I believe it needs a wider audience [I have added a few comments into the text to ensure that I am not breaching copyright]

Evidence based medicine (EBM) wrong footed the drug industry for a while in the 1990s. We could fend off the army of pharmaceutical representatives because often their promotional material was devoid of evidence. But the drug industry came to realise that EBM was an opportunity rather than a threat. Research, especially when published in a prestigious journal, was worth more than thousands of sales representatives. Today EBM is a loaded gun at clinicians’ heads. “You better do as the evidence says,” it hisses, leaving no room for discretion or judgment. EBM is now the problem, fuelling overdiagnosis and overtreatment.

[This is now a major problem for GPs who are increasingly measured and monitored, and funded, according to how accurately we follow guidelines mk comment]

You see, without so called “evidence” there is no seat at the guideline table. This is the fundamental “commissioning bias,” the elephant in the room, because the drug industry controls and funds most research. So the drug industry and EBM have set about legitimising illegitimate diagnoses and then widening drug indications, and now doctors can prescribe a pill for every ill.

[As you can imagine, this makes it difficult not to prescribe statins mk comment]

The billion prescriptions a year in England in 2012, up 66% in one decade, do not reflect a true increased burden of illness nor an ageing population, just polypharmacy supposedly based on evidence. The drug industry’s corporate mission is to make us all sick however well we feel. [Absolutely true mk comment] As for EBM screening programmes, these are the combine harvester of wellbeing, producing bails of overdiagnosis and misery.

Corruption in clinical research is sponsored by billion dollar marketing razzmatazz and promotion passed off as postgraduate education. By contrast, the disorganised protesters have but placards and a couple of felt tip pens to promote their message, and no one wants to listen to tiresome naysayers anyway.

[Speaking as a tiresome naysayer I could not agree more mk comment]

How many people care that the research pond is polluted, with fraud, sham diagnosis, short term data, poor regulation, surrogate ends, questionnaires that can’t be validated, and statistically significant but clinically irrelevant outcomes? Medical experts who should be providing oversight are on the take. Even the National Institute for Health and Care Excellence and the Cochrane Collaboration do not exclude authors with conflicts of interest, who therefore have predetermined agendas. The current incarnation of EBM is corrupted, let down by academics and regulators alike. [If anyone has any suggestion how to improve regulation, please let me know mk comment]

What do we do? We must first recognise that we have a problem. Research should focus on what we don’t know. We should study the natural history of disease, research non-drug based interventions, question diagnostic criteria, tighten the definition of competing interests, and research the actual long term benefits of drugs while promoting intellectual scepticism. If we don’t tackle the flaws of EBM there will be a disaster, but I fear it will take a disaster before anyone will listen.

[There have already been many disasters, but nobody has yet listened mk comment]

Original article can be found here

Sorry about the intrusive comments, but I don’t want the BMJ jumping up and down on me – especially as they are the only major journal that seems keen to criticize the industry.

What Des Spence is saying, is what I have been saying for some time now. Evidence Based Medicine (EBM) could have been a great thing – so long as it was not enforced too rigidly. But the evidence has been manipulated and corrupted all the way along the line. EBM is now almost completely broken as a tool to help treat patients.

Some years ago I stated that I no longer believe in many research papers that I read. All I tend to do is look at the authors, look at the conflicts of interest, look at the companies who sponsored the study, and I know exactly what the research is going to say – before I have even read the paper.

I have also virtually given up on references. What is the point, when you can find a reference to support any point of view that you want to promote? Frankly, I do not know where the truth resides any more. I wish to use evidence, and the results of clinical studies, but I always fear that I am standing on quicksand when I do so.

We are at a crisis point. Medical research today (in areas where there is money to be made) is almost beyond redemption. If I had my way I would close down pubmed, burn all the journals, and start again, building up a solid database of facts that we can actually rely on – free from commercial bias. But this is never, ever, going to happen.

Happy New Year.

 

How to avoid dementia

Most of us fear that we may develop dementia as we get older. I fear that I may have got it already, as my memory for names becomes even worse. One piece of good news is that, for around one third of people, it may be possible to prevent dementia simply by taking three forms of vitamin B. Vitamin B6, B12 and folic acid.

The research work on this was done at Oxford University, and was published earlier this year. I received a copy of the study about a month ago, and I read it with great interest. The key statements from the abstract are, as follows:

‘Our results shows that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD processes and that are associated with cognitive decline.

….we go further by demonstrating that B vitamin reduces, by as much as seven fold, the cerebral atrophy in those grey matter (GM) regions specifically vulnerable to the AD (Alzheimer’s Disease) process.’

Some of you may know that Jerome Burne blogged about this a while ago, which is what attracted my interest in the first place. It immediately fired me into instant action. Several weeks later I got hold of the full paper, which was published in the proceedings of the National Academy of Sciences. It is entitled: ‘Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment.’ Sorry to say that you have to pay to get the entire manuscript.

This study built on earlier work which also demonstrated a significant reduction in brain shrinkage using vitamin B(s) (at lower doses). The brain images themselves look particularly impressive, even to my untrained eye, with far less atrophy to see in the vitamin B treated group.

Unfortunately, this benefit only seems to be available those people who had a high level of homocysteine in their blood in the first place. A level found in about one third of the population.  For the other two thirds, taking vitamins does not seem to help.

Why do vitamin B(s) have this beneficial effect in this group?  Well, it has been known for a long time that people with high homocysteine levels are more prone to developing dementia. It is also known that B-vitamins lower the level of homocysteine the blood (look up Wikipedia if you want more detail on this complex area). However, just because a high level of homocysteine is found in people with dementia, does not mean that it truly is cause. It may be an innocent bystander. An association, rather than a cause.

However, the Oxford group, by lowering homocysteine and slowing brain atrophy, have gone a long way to prove that homocysteine does seem to be an actual cause of dementia. At least in about one third of people who have high levels in the first place. More importantly, the risk of dementia can be significantly reduced using a simple regime of B vitamins. A regime that appears to have no adverse effects – apart from a small degree of damage to the bank balance.

Why, you might ask, is no-one doing anything about this? Last week our glorious UK health secretary, Jeremy Hunt, announced that he was, sorry, we were, going to defeat dementia in twelve years’ time. Or some other such nonsense figure that he plucked from out of thin air. Did he mention research into vitamin B? No, he did not. Why not? Possibly because no-one made him aware of this research. Probably because he has no interest in dementia other than as a career enhancing, five minute, sound bite. He is such a busy, busy, man. Tomorrow he will be curing cancer. Sorry, we will be curing cancer.

A further important reason for the deafening silence in this area is because pharmaceutical companies cannot make money out of vitamins. Vitamins cannot be patented; therefore any profit margin is far too puny to be of interest to them. Which means that there will be no funding from the pharmaceutical industry to support any further research into B vitamins.

Even worse, if vitamins do work to reduce dementia this will significantly erode any pharmaceutical industry profits to be made. In commercial parlance vitamins would be called – ‘the competition’.

And what do we do to ‘the competition’ boys and girls?

We crush it sir?

‘Yes, that’s right, we crush it like an insect under our boot, don’t we boys and girls. Using any means possible……lock and load.’

I am sure a few Grima Wormtongues, sorry pharmaceutical company lobbyists, have already been whispering in various ears, denigrating this vitamin B research. ‘Very preliminary, not very convincing, we need a new approach, you need to support us, the pharmaceutical industry, only we can find a cure…….my precious…..’

Trust in me, just in me
Shut your eyes and trust in me
You can sleep safe and sound
Knowing I am around
Slip into silent slumber
Sail on a silver mist
Slowly and surely your senses
Will cease to resist
Trust in me, just in me
Shut your eyes and trust in me

(Kaa, the python the Jungle Book)

Wake up, wake up!

Of course Vitamin B is not a miracle cure for all forms of Dementia. In fact it is not a cure – in any recognised sense of that word. All that vitamin B(s) can do is to significantly slow the process of brain shrinkage. Once you have lost brain tissue, it does not come back.

In addition, these vitamins only work in about a third of the population, and only for Alzheimer’s Disease.  There are other causes of dementia, and vitamin B compounds will have no effect on them, at all. However, right now, it looks like by far best thing we have got. In fact, it is the only thing we have got. Alzheimer’s meds can slightly improve symptoms, but have no impact on the underlying disease process.

On the other hand, for the sake of a relatively simple blood test, and spending a couple of hundred pounds (or dollars) on vitamins a year, or however much they actually cost you, this decision is a no-brainer (sorry, couldn’t resist the pun).

Indeed, it is such an obvious thing to do that I have started to offer the blood test at my own clinic. (Yes, I suppose this counts as a Disclosure of Interest). Mainly because no-one in the NHS is the slightest bit interested. So someone had to do it.

The daily doses of vitamin B in this study were:

20mg vitamin B6
500mcg vitamin B12
800mcg folic acid

These are considerably higher than the recommended daily allowance (RDA) for these vitamins. But the RDAs for almost all vitamins were established as a bare minimum, many years ago, using virtually zero evidence. They remain unchangeable by any means known to man. I call them the ‘ten vitamin commandments,’ which have been engraved upon stone.

Until a group of idiots…sorry experts, decides to study the benefits of various vitamins in greater depth, we are going to be stuck with RDAs that make no sense, and will certainly not help you to delay, or even prevent, dementia. Until then, get a blood test to check homocysteine levels. Providing, that is, you can find anyone to do it. Then, if it is high, take vitamin B(s).  They can do you no harm, but they could do you a hell of a lot of good. Which is my kind of preventative medicine.

You absolutely cannot be healthy any more – it’s official

I have been waiting for some time now before it became officially impossible to be healthy. In recent years the boundaries of health have been inexorably squeezed tighter and tighter. Recently, they snapped shut. The land of the healthy now no longer exists. Tis but a memory.

I wondered if it would be cholesterol that would obliterate health first, but it turned out to be blood pressure. This was pretty much second favourite in my book.

As with many areas of ‘health’ the definition of a healthy blood pressure has fallen and fallen. A few years ago we had go to the stage of a condition known as pre-hypertension. A state of having a high blood pressure that wasn’t really high, but represented an ill-defined danger of some sort. This pressure was set at 115/75mmHg. Far lower than the average blood pressure in the Western World.

However, with the latest CV prevention guidelines (yes, them again) we have managed to get the optimal systolic blood pressure down to 90mmHg. Underneath, you will see a little graph that I created using the CV risk tool. The tool can be downloaded here:

So you can check out for yourself that what I am saying is true.

CV event risk in next 10 years vs systolic BP

I put in figures for a healthy male, and then only changed the blood pressure level. As you can see, as the blood pressure goes up, the risk of a CV event goes up, and vice-versa. Going from 90mmHg to 150mmHg causes your risk to go up from 2.6% to 6.5%. A 250% increase in relative risk. What this tells us is that 90mHg represents the absolutely optimum blood pressure. Anything higher and your risk increases, and it increases quite steeply.

By definition, this means that a systolic blood pressure of 90mHg is ‘healthy’ and anything above this becomes increasingly ‘unhealthy.’ Now it has to be said that a systolic blood pressure of 90mmHg is low. Pretty damned low. Indeed, I have been asked to check patients out because their systolic BP was 90mmHg, and the nurse was rather worried about them.

I can hardly blame the nurse for this, because the definition of hypotension (dangerously blood pressure), is…yes, you guessed it, a systolic blood pressure of 90mmHg and lower. You can check this ‘fact’ on the National Institutes of Health site.

This means that we have reached a situation whereby a systolic blood pressure lower than 90mmHg increases risk; and a blood pressure higher than 90mmHg increases risk. I suppose you could say that anyone with a blood pressure of exactly 90mmHg is healthy, so the land of health still exists as a microscopically thin sliver of habitable area. But for all intents and purposes, health has gone.

Can it really be true that there is no such thing as a healthy blood pressure?

In order to believe this you have to believe in the linear or log-linear model. A model that can, to a major degree, be laid at the feet of a certain Jeremiah Stamler. He stated that ‘the relation of SBP (systolic blood pressure) to risk of death is continuous, graded, and strong, and there is no evidence of a threshold.’  In short, as BP goes down, risk goes down, and there is no lower limit beyond which this is not true. Well, until you reach 90mmHg, it seems.

This idea is based on mathematics, whereby Stamler took all the studies he could find, matched BP with risk, and then created his perfect curve. You can see how this type of thing is done by looking at a curve created by matching writing score vs. reading score. [I took this example from the internet1]. The dots may seem all over the place, but there is a trend from bottom left to top right.

The curve is a linear model, which smooths out all of the data variations. Excel spreadsheet will even calculate a curve like this for you, if you have a graph with dots which may seem completely random.

log_tr1

In the world of hypertension, the log-linear model rules.

‘This(the log linear model) is the paradigm for the relationship of all cardiovascular risks to blood pressure, and forms the foundation of the current guidelines for hypertension.’ These words from the European Heart Journal in the year 2000, since then the paradigm has not changed, and neither has the model. The latest CV guidelines are based on it.

How could it be otherwise? Do you really think anyone has done a study lowering blood pressure from 100mgHg to 90mmHg? If so, think again. In fact the model was first created from the Framingham study data. This is the world’s longest running, and most cited, study on cardiovascular disease. It has been running since 1948 in a town called, unsurprisingly, Framingham in the US.

Now, this would be all fine and jolly – if the model were actually correct.

In 1980 Ancel Keys, who is not my favourite ever person it must be said, looked at the Framingham data.  He concluded that the linear model, in terms of the relationship between overall and coronary heart disease was unjustified.

Twenty years after this, a group of statisticians from UCLA looked at the data again. And here is what they said:

‘Shockingly, we have found that the Framingham data in no way supported the current paradigm to which they gave birth. In fact, these data actually statistically reject the linear model. This fact has major consequences. Statistical theory now tells us that the paradigm MUST be false for the target population of the study.’2

Was this paper refuted? No, not exactly….

“The National Institutes of Health’s National Heart, Lung, and Blood Institute (NHLBI) issued a statement regarding Port’s findings saying that they found it “thought provoking” but “After careful review of this study, the NHLBI finds that it does not offer a basis for changing the current hypertension guidelines.”

End of.

Which means that we are here. A world where health was finally extinguished by using a mathematical model. A perfect world for the pharmaceutical industry. Everyone is ill, and all shall have medications, for ever.

‘Can you do Addition?’ the White Queen asked. ‘What’s one and one and one and one and one and one and one and one and one and one?’

‘I don’t know,’ said Alice. ‘I lost count.’

 

1: http://goo.gl/ZlJ7tO

2: Port S. et al: ‘There is a non-linear relationship between mortality and blood pressure.’ European Heart Journal (2000) 21, 1635-1638

The most unpronounceable failure yet

Every day a billion things pop into my inbox, and I find my thought dragged this way and that. Mainly, what should I blog on next, and can I be bothered…..so much wine to be drunk.

However, I thought I should give everyone a quick head up on VARESPLADIB. This is the first and last time you are going to hear of this drug, so listen up. The first thing I would like to draw your attention to is the list of authors

Stephen J. Nicholls, MBBS, PhD; John J. P. Kastelein, MD, PhD; Gregory G. Schwartz, MD, PhD; Dianna Bash, RN; Robert S. Rosenson, MD; Matthew A. Cavender,MD, MPH; Danielle M. Brennan, MS; Wolfgang Koenig, MD; J.Wouter Jukema, MD, PhD; Vijay Nambi, MD, PhD; R. Scott Wright, MD; Venu Menon, MD; A. Michael Lincoff, MD; Steven E. Nissen, MD; for the VISTA-16 Investigators 1

Notice anything. Ah yes, Steven Nissen appears once again on a major study. He certainly gets about does our Steven. Another name that means much to me, but nothing to you, is John P Kastelein….he gets about too. Hardly a day passes without these guys running a major clinical trial, and then writing about it. I think they must have been cloned in the past to get through so much work.

Anyhoo,  enough of them. What is, or was, VARESPLADIB, and why should you care. Here from the study itself.

‘Varespladib methyl is a nonspecific pan-sPLA2 inhibitor with favorable effects on atherosclerotic lesions in animal studies. Initial studies demonstrated that varespladib reduced levels of sPLA2-IIA by morethan 90%,in addition to lowering low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP) in patients with stable coronary disease and ACS.’

So now you know. Or maybe not.

Stripped to its basics, varespladib (which I shall PLAD) is an anti-inflammatory drug specifically designed to reduce the inflammatory cascade that is thought to be a major cause/risk factor for heart disease. Not only that, but it reduces LDL ‘bad/naughty cholesterol’ and C reactive protein too – a sign of inflammation in the arteries. Possibly CRP may even be a cause of CHD… in truth you might think it is a cause, if you are idiot.

Some years ago I wrote that we should await the C-reactive protein lowering agents. On the basis that a high CRP levels had been identified as ‘risk factor’ for heart disease. I wasn’t sure if it would happen, but I suspected it would. I predicted that lowering CRP would be a complete and utter waste of time.

Inflammation cannot, I have always said, be the cause of anything. Inflammation is the way that the body heals itself. If you cut yourself you will develop a red and inflamed area around the cut, otherwise known as inflammation. The inflammation did not cause the cut, the cut caused the inflammation.

However, such is the idiotic thinking in heart disease research that various people, led by Paul Ridker, decreed that inflammation causes heart disease (and not the other way around). They then decreed that if you could lower the inflammation that the risk of heart disease would fall. The noise in the background is the mad stampede of pharmaceutical companies rushing off to find drugs to block the inflammatory pathway, lower CRP, and cure heart disease.

Enter PLAD. Here we have a drug that lowers inflammation, lowers CRP, and as an extra added bonus  lowers LDL ‘bad/naughty’ cholesterol, so it should provide a triple benefit. And guess what we find:

‘At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm.’

The conclusions:

‘In patients with recent ACS (acute coronary syndrome – a heart attack to you and me), varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS.’

I am sure that there are a whole new bunch of anti-inflammatory agents out there, being trialled as I write this. I am also sure that they will fail. Hey guys, you could save billions if you read my stuff.

Now, repeat after me. Blocking inflammation blocks healing. Block healing and you die. End of. Time for a glass of wine.

1: Varespladib and Cardiovascular Events in Patients With an Acute Coronary Syndrome The VISTA-16 Randomized Clinical Trial. JAMA. doi:10.1001/jama.2013.282836

They have now, officially, all gone mad?

The Mad Hatter: ‘Have I gone mad?’

Alice: ‘I’m afraid so, you’re completely bonkers, but let me tell you something, the best people usually are.’

Alice in Wonderland

I find myself quoting Alice in Wonderland more and more these days. I now think it was never a children’s book, it was an accurate scientific analysis of human behaviour.

As many of you are aware the American medical authorities have come up with the latest guidelines to reduce cardiovascular risk. A major part of the guidelines is now to inform us all that we should forget about lowering cholesterol (LDL) levels, and just take a statin…. no matter what¹.

This is how the New York Times put it:

First, the guidelines have moved away from achieving target cholesterol levels.
Americans have long been urged to focus on their laboratory numbers. Many people are obsessive about checking their cholesterol levels and pursuing even better numbers. Doctors have been told to focus on these numbers and, in some cases, the quality of their care was assessed by the percentage of their patients with low cholesterol levels.

Those days are over. The new guidelines recognize that for patients who have exhausted lifestyle efforts and are considering drug therapy, the question is not whether a drug makes your lab tests better, but whether it lowers your risk of heart disease and stroke. Studies over the past several years have shown that improving your lab profile with drugs is not equivalent to lowering your heart risks².

One of the most influential cardiologists in the world, Steven Nissen, had this to say:
“The evidence was never there” for the LDL targets, he said. Past committees “made them up out of thin air,” he added.

Past committees made them up out of thin air….. Let me try that statement again…. Past committees made them up out of thin air. Exactly. Ex-bleedingly-zactly.

So, ladies and gentlemen, you have been conned. Utterly, completely and barefacedly conned, for the last thirty years. Your cholesterol level has absolutely no impact on your risk of cardiovascular disease. You think not? Well, that is precisely what they are saying in these guidelines. If not in quite such plain words.

But, of course, I am not being entirely fair to them. The level of LDL may actually matter after all – according to the same guidelines. For, as the New York Times article goes on to say.
There’s one exception to the numbers rule. People with very high levels of the harmful cholesterol known as LDL still need to worry about targets. The new guidelines set that LDL level at 190 milligrams per deciliter – but the principle is that if people have very high cholesterol levels, then their cardiovascular risk is so high that it is likely that treatment to reduce the levels would offset any risks of the drug treatment.

So, your LDL level doesn’t matter in the slightest, unless it is a very high level. Then the level does matter a great deal. Please explain, oh great cardiologists, does LDL, or does it not, cause cardiovascular disease.

Well, it seems that it both does, and does not, simultaneously. Amazingly, we have achieved a quantum state with LDL. It simultaneously exists as a molecule that can both cause – and not cause – CVD. Which means, of course, that the levels must be both lowered, and not lowered. Yes, well, this makes perfect sense. At least it would to a lunatic.

Perhaps if we open the box with the ‘at risk cat’ in it, we will find that this new version of Schrodinger’s cat died of a heart attack caused by LDL. Alternatively, it did not. Before opening the box, it exists in both possible states. It is an interesting variation on a theme.
The most astonishing thing is not that these people are now talking the most complete gibberish. They have been doing this for years. The most astonishing thing is that the vast majority of the population will still listen to what they have to say – and follow their advice.
Well, good luck with that all you billions of mad people, following the advice of these mad scientists Good luck with that indeed. I salute you. Meanwhile I shall attempt to find the answer to a far more important question than what causes heart disease.

“Why is a raven like a writing desk?”

1: http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437740.48606.d1
2: http://well.blogs.nytimes.com/2013/11/12/3-things-to-know-about-the-new-cholesterol-guidelines/

The backlash begins

(Catalyst under fire)

Those who read this blog will know that Maryanne Demasai, a journalist at the Australian Broadcasting Company (ABC), put together two programmes. One questioning the cholesterol hypothesis; the other very critical of the over-prescribing of statins. They can be seen here.

Heart of the Matter Part 1 – Dietary Villains

Heart of the Matter Part 2 – Cholesterol Drug War

Over several months I helped Maryanne to put together the scientific arguments, and I feel proud to have done so. I warned her, though, that she should expect a vicious backlash if the programmes ever went out. Of course, it has happened.

Also, exactly as I told her, the attacks are not on the data. They can’t be, as the science she presented is pretty much spot-on. They are personal attacks on everyone who took part. Those she interviewed are being accused of being “crack-pot quacks”, ‘into earthing’….and ‘snake oil salesman selling vitamins’ etc.

You can see the latest (evidence free attack) here. A programme by media watch, which includes such scientific observations as the fact that Maryanne did not smile when speaking to a conventional ‘expert.’ Off with her head, the biased hussy! http://www.abc.net.au/mediawatch/

Of course none of this surprises me. I knew exactly what would happen, and how it would happen. This is not because I am sort of a genius. It is that I have seen it all before, many times. Here follows a personal testimonial from a Dutch Journalist Melchior Meijer, who had the temerity to criticise statins in the past:

My name is Melchior Meijer. I’m medical reporter for several magazines and newspapers in The Netherlands. Reporting about the many obvious flaws in the cholesterol hypothesis, shedding light on the biologically plausible adverse consequences of statin therapy, is as close to 21st century blasphemy as a medical journalist can come.

I experienced this in 2004, when I wrote an article about statins in a national newspaper. In the article, several doctors and scientists expressed well founded doubts about the safety of statin therapy in the general population. I also presented a few `anecdotal’ cases of statin induced harm, which were extremely easy to find.

The medical establishment reacted in fury and started an aggressive media offensive. Carefully avoiding the arguments in my article, they used their authority to hang me out on TV as a liar, a potential mass murderer. They called for `official measures’ to prevent naive journalists from making similar `tragic mistakes’ in the future.

They also took me to the Press Court, but they didn’t reckon with the fact that the Press Court checks facts and figures. The Court did an investigation and decided that I had just done my job, observing and questioning. [As an aside: the chief of my newspaper, born into a family of influential physicians, was not happy with the Court’s decision. He had already apologized on television for `this tragic mistake’.]

After this statin users started calling and mailing to the media, always reporting the same symptoms: various degrees of (muscle pain) and loss of muscle mass, exhaustion, personality changes and amnesia. But my colleagues didn’t like to take up this serious issue. That is, until last March when the TV-colleagues of TROS Radar, a consumer programme with an average of 2 million watchers (we have 16 million inhabitants), took up the subject.

Dutch cardiologist Dr Paul de Groot expressed his doubts about cholesterol as a causal factor, and postulated that statins sometimes do more harm than good, especially in primary prevention. Dr Uffe Ravnskov, who by the way was honoured yesterday with the prestigious Leo Prize for independent science, pointed out the many flaws in the cholesterol hypothesis.

The programme also interviewed people who had experienced devastating side effects from statins, which quickly disappeared upon discontinuation – although sometimes they did not. I was on the programme to explain how Unilever had succeeded in keeping an unfavourable article about its cholesterol lowering spread Flora out of the press.

When the shit hits the fan…

My time is limited, so I will make it short. Radar was vigorously attacked from all directions. Professors Martijn Katan and John Kastelein used various media outlets to shamelessly fire irrelevant, slanderous attacks on Dr Ravnskov. As usual, they did not address any of the scientific arguments. Radar invited Katan and Kastelijn for a public debate with Drs Ravsnkov and Kendrick, but they declined.

The Dutch Cardiologists Association, together with the Healthcare Inspectorate – and this is critical – announced official guidelines for medical journalists who plan to cover `delicate medical matters.’

History, you see, does repeat itself, and so I can predict what now happens in Australia. There will be calls to bring in ‘official guideline for medical journalists who plan to cover ‘delicate medical matters.’ This is also known as press censorship. It has been popular in various dictatorships over the years. Currently, North Korea is the best place to see this in action.

Believing in impossible things – there is a trick to it

At times, all you can do it shake your head in amazement, and wonder at the ability of people who think of themselves as scientists to make statements that are impossible to reconcile with reality, or logic….or pretty much anything to do with science.

Yesterday, I was sent a copy of a paper called ‘High coronary plaque load: a heavy burden.’ Published in the European Heart Journal in August 2013. It looked at the use of statins to reduce the volume of plaque in arteries. I include three verbatim quotes from the paper:

  • Of particular interest, neither LDL cholesterol levels at baseline nor those after high dose statin treatment could independently predict major adverse cardiovascular events (MACEs)
  • One of the most striking results of this study is the fact that LDL levels at baseline or after statin treatment showed no predictive value for MACEs. This could lead to doubt about the beneficial effect of LDL-lowering therapy. However, as also discussed by the authors, there is overwhelming evidence for the beneficial effects of statin therapy on plaque progression and MACEs.
  • Currently statin therapy is so fundamentally established in clinical practice that its beneficial effect is beyond doubt. Even though it has been demonstrated that in patients receiving statin therapy LDL levels have no additional prognostic value, further lowering of LDL cholesterol levels with novel PCSK9 monoclonal antibodies could further reduce the residual risk in these patients1.

So, the researchers discovered that LDL (‘bad’ cholesterol) levels did not predict major coronary events:  angina, heart failure, heart attacks and suchlike. Neither did the degree of LDL lowering with statins have any correlation with coronary events. At this point, having very clearly established that their research flatly contradicts the cholesterol hypothesis, they finished off by remarking that when the new cholesterol agents arrive, which will lower LDL levels even more than statins, they will ‘further reduce the residual risk in these patients.’

I shall try to reduce this paper to its ineluctable essence.

  • We have found that LDL levels have nothing to do with cardiovascular disease
  • We have found that the degree of LDL lowering with statins does not correlate with cardiovascular events
  • We think we need to the lower the LDL more to prevent cardiovascular disease

‘Alice laughed. ‘There’s no use trying,’ she said. ‘One can’t believe impossible things.’

‘I daresay you haven’t had much practice,’ said the Queen. ‘When I was your age, I always did it for half-an-hour a day. Why, sometimes I’ve believed as many as six impossible things before breakfast. ‘Lewis Carroll – Alice in Wonderland.

I suppose it becomes easier to believe in impossible things if you have a few conflicts of interest to help you along the way…..smooth the pathway of belief, so to speak. Here follows the conflict of interest statement from the paper:

Conflict of interest:

J.W.J. receives research grants from and was a speaker at meetings sponsored by Astellas, AstraZeneca, Biotronic, Boston Scientific, Bristol-Myers Squibb, Cordis, Daiichi Sankyo, Eli Lilly and Company, Medtronic, Merck-Schering Plough, Pfizer, Orbus Neich, Novartis, Roche, Servier, the Netherlands Heart Foundation,the Interuniversity Cardiology Institute of the Netherlands, and the European Community Framework KP7 programme. M.A.dG. has no conflicts to declare. The Department of Cardiology received research grants from Biotronik, Medtronic, Boston Scientific

Corporation, St Jude Medical, Lantheus Medical Imaging, and GE Healthcare.

For those paying attention, you may have noticed the mention of PCSKP monoclonal antibodies earlier.  What are these, I hear you cry. These are the next monstrous regiment of cholesterol lowering agents that are waiting in the wings, engines running smoothly. If you thought statins were heavily promoted – you ain’t seen nothing yet.

You may not be astonished to learn that one or two of the companies listed in the conflict of interest statement of that paper are developing PCSK9 monoclonal antibodies. I wonder if that could have anything to do with the statement……’further lowering of LDL cholesterol levels with novel PCSK9 monoclonal antibodies could further reduce the residual risk in these patients.’

And if that thought depresses you, as it does me, here is a little poem by W.H. Auden to cheer you up:

‘Give me a doctor partridge-plump,
Short in the leg and broad in the rump,
An endomorph with gentle hands
Who’ll never make absurd demands
That I abandon all my vices
Nor pull a long face in a crisis,
But with a twinkle in his eye
Will tell me that I have to die.’

1: Michiel A. de Graaf and J.Wouter Jukema. ‘High coronary plaque load: a heavy burden.’ European Heart Journal (2013) 34, 3168–3170