Download Lectures on Biostatistics (1971). Corrected and searchable version of Google books edition
Download review of Lectures on Biostatistics (THES, 1973).
Acupuncture in the BMJ
A new review appeared in the BMJ today. It is by Madsen et al., from the Nordic Cochrane Centre, Copenhagen. Here are the conclusions.
- The analgesic effect of acupuncture is small and cannot be distinguished from bias resulting from incomplete blinding.
- The analgesic effect of placebo acupuncture is moderate but very variable as some large trials report substantial effects.
- The effect of acupuncture seems to be unrelated to the type of placebo acupuncture used as control.
The results confirm, yet again, that there is essentially no difference between “real” acupuncture and sham acupuncture. All that talk about meridians and Qi really is so much mumbo jumbo.
The average effect (the diamond at the bottom) is essentially zero.
It has often been supposed that acupuncture is a theatrical placebo, but because of the placebo effect it produces more pain relief than (non-blind) controls. This study confirms that there is likely to be such an effect, but it also finds that the size of the placebo effect is too small to be useful to patients. Here is the comparison between sham acupuncture and no acupuncture at all.
The results of different trials are very variable, but the average effect (diamond at the bottom) favours sham acupuncture over no acupuncture at all.
But how big is the effect? The numbers along the bottom of the graph are ‘standardised mean differences’. The average value of -0.42 (95% confidence limits -0.6 to -0.23) between ‘no acupuncture’ and ‘sham acupuncture’ corresponds to a difference of about 10 points on a 100 point scale. This difference is big enough to be real, in the sense that it isn’t just chance. But is it big enough to be useful to the patient? Probably not. Madsen et al conclude
“a consensus report characterised a 10mm reduction on a 100 mm visual analogue scale as representing a “minimal” change or “little change”. Thus, the apparent analgesic effect of acupuncture seems to be below a clinically relevant pain improvement.”
This makes nonsense of the Pittilo report. Notice that these results, yet again, make nonsense of the proposals in the gamma-minus Pittilo report, to pseudo-regulate acupuncture, and to have degrees in the subject.
Cochrane reviews of Acupuncture : and a bad report from BBC
Two new Cochrane reviews appeared last week, Acupuncture for tension-type headache, and Acupuncture for migraine prophylaxis.
You can’t blame subeditors for the appalling title of the BBC’s report on Acupuncture ‘works for headaches’. The content is pretty misleading too. (The link is to a version saved at 19.35 on 21 January 2009.). Furthermore, like far too many of the BBC reports, it is anonymous. One has no idea to blame This is important, if only because the BBC news site is so influential. Twelve hours after posting the misleading title has been copied all round the world.
In the Guardian, Ian Sample had a much better report, Even’fake’ acupuncture reduces the severity of headaches and migraines. Sadly the print edition had the title “Acupuncture aids migraines, researchers
find”, but that can be blamed on subeditors who have a problem with reading (in fact Sample had seen neither title).
The BBC report seemed to call for a complaint. This is what I sent.
| I wish to complain about the report on acupuncture at http://news.bbc.co.uk/1/hi/health/7838231.stm
The title itself was highly misleading “Acupuncture works for headaches” is precisely the opposite of what was shown, namely that it is no better than sham acupuncture controls. The article goes on to say
It is not said that there isn’t the slightest reason to think this is true (or even means anything) , and that the work which is being reported is strong evidence that it’s not true
That is wrong. University of Salford , for example has just closed its acupuncture course after a number of us have pointed out that it is teaching things that aren’t true
It is exactly the opposite of an endorsement. It is one more nail in the coffin of acupuncture as generally understood. This article, I contend, is partial and misleading. Unfortunately it is anonymous. |
Follow-up
Today’s BBC report on the BMJ paper is almost as partisan as the one that I just complained about. “Confusion on acupuncture benefit ” exaggerates greatly the amount of confusion. Worse still, it quotes only two well-known advocates of acupuncture, people who make their living from it. No independent scientific voice is to be heard.
One of those cited is Adrian White. He is described as “a researcher into acupuncture at the Peninsula Medical School”. There is no mention of the fact that he is also Editor in Chief of the journal Acupuncture in Medicine. The other person who is quoted is Mike O’Farrell, the chief executive of the British Acupuncture Council. What do you expect him to say?
I’ve just sent another complaint, about today’s BBC report. The more the merrier.
The BMJ itself published an editorial on the Madsen paper. It seems very odd that they should have chosen the editors of the BMJ-group journal, Acupuncture in Medicine, to comment on a paper that sounds the death knell for the subject from which they make their living. Needless to say, the editorial attempted to wriggle out of the obvious conclusions. Worse still, the Health editor of the BBC web site referred to the editorial in his defence, in response to my complaint.
Channel 4 News does a lot better than the BBC, or the BMJ editorial, with its report Acupuncture ‘fails to relieve pain’
“Claims that acupuncture can relieve pain have been undermined by the results of a new study.”
“senior researcher Asbjorn Hrobjartsson said: “Our findings question both the traditional foundation of acupuncture…and the prevailing theory that acupuncture has an important effect on pain in general”. “
The Daily Telegraph also, like almost everyone else, did better than the BBC, with “Acupuncture ‘has almost no effect in relieving pain’”
“The pain relieving effects of acupuncture are so small that they may be clinically irrelevant, according to a review of research into the treatment.”
Even Metro, the free London Newspaper, is more accurate then the BBC. They carry a short report “Acupuncture ‘has no medical point’.”
“The pain-relieving effects of acupuncture compared with a placebo are so small they may be clinically irrelevant.”
New review puts in doubt traditional foundation of acupuncture. Believe it or not, that is the title of the report on Madsen et al from the Prince’s Foundation for Integretad Health! Don’t get too excited though. They haven’t even bothered to look at the original paper, but merely cite the dreadful BBC report. Much prominence is given to the acupuncturists, White and O’Farrell, and the important finding isn’t mentioned at all. Another gamma minus.
35 Responses to More nails in the coffin for acupuncture: and some bad journalism
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I have complained several times over misleading stuff on the Beeb’s website and never so much as had a reply. I have concluded that they don’t care.
Some more nails in the coffin for acupuncture appear if you take into account the results of two other recently published Cochrane reviews. One quantifies publication bias in clinical trials
http://www.cochrane.org/reviews/en/mr000006.html
and the other reviews acupuncture for migraine prophylaxis (“There is no evidence for an effect of ‘true’ acupuncture over sham interventions …”)
http://www.cochrane.org/reviews/en/ab001218.html
DId you try leaving the complaint in the “style, accuracy and grammar” feedback form. This might be more successful than lodging a full-blown complaint. But I do agree, the authorship issues does need to be redressed by the BBC. But they hide behind “the editor takes full responsibility….” and ignore complaints.
It seems it is not just chief executives and editors-in-chiefs or poor reporting that we should be concerned about. It is always assumed that the Cochrane reviews are above any sort of criticism, because of their objectivity and rigour.
We may occasionally need to look more closely.
Some of the funding of the Cochrane review, cited by DC, of acupuncture and headaches is interesting. The Cochrane Collaboration policy on commercial sponsorship is pretty clear. Here are extracts from the 2005 version of the policy, revised, as I understand it, after concerns being expressed about funding for some reviews.
“By ‘commercial source’ we mean any for-profit manufacturer or provider of health care, or any other for-profit source with a real or potential vested interest in the findings of a specific review. ………………..
“By ‘sponsorship’ of a review, we mean a sum of money given to a reviewer or group of reviewers to prepare, or update, a Cochrane review. Such sponsorship could include not only commissioning of specific systematic reviews, but also, for example, funding of a sabbatical period to work on a Cochrane review.
“ People with a direct financial interest in a particular intervention should not be involved in a review of that intervention, either as reviewers, editors or peer reviewers”.
The funding for the acupuncture review is as follows:
• NIAMS Grant No 5 U24-AR-43346-02, USA.
• • International Headache Society, Not specified.
• For administrative costs associated with editorial review and peer review of the original version of this review.
• • National Center for Complementary and Alternative Medicine (NCCAM), USA.
The same grant from NIAMS appears to have been broad in its support, as there are studies of various CAMs associated with it, including one of acupuncture for idiopathic headache (2008). This was the conclusion of the latter’s review in its ‘Implications for practice’
“Due to the clinical heterogeneity and the poor methodological quality of the included studies, straightforward recommendations for clinical practice cannot be made. Overall, some forms of acupuncture seem to be beneficial, but it is unclear which treatment strategies (points, type of stimulation, frequency, etc.) and which providers may be most promising for particular groups of patients. Though not risk-free acupuncture seems to be relatively safe in the hands of qualified providers. Therefore, we conclude that headache patients who want to try acupuncture should not be discouraged. Existing provision of acupuncture to headache patients also seems justified. Whether acupuncture should be more widely recommended and, if so, which particular type of acupuncture should be offered, are questions that cannot be answered at present.”
What was that about not making straightforward recommendations?
I think I feel a letter to the Cochrane Collaboration composing itself in my brain……
Oh, and Mr Adrian White (above) is one of the authors of the review.
See my previous entry for the rules on financial interest in interventions under scrutiny and see also this from the Cochrane review:
D E C L A R A T I O N S O F I N T E R E S T
This review includes trials in which some of the reviewers were involved, ……………These trials were reviewed by at least two other members of the review team.
Gianni Allais, Benno Brinkhaus and Adrian White use acupuncture in their clinical work. Gianni Allais receives fees for teaching acupuncture in private schools. Klaus Linde has received travel reimbursement and, in two cases, fees from acupuncture societies (British, German and Spanish Medical Acupuncture Societies;
Society of Acupuncture Research) for speaking about research at conferences. Eric Manheimer and Andrew Vickers both received an honorarium for preparing and delivering presentations on acupuncture research at the 2007 meeting of the Society for Acupuncture Research. Adrian White is employed by the British Medical Acupuncture Society as journal editor and has received fees and travel reimbursements for lecturing on acupuncture on several occasions. Benno Brinkhaus has received travel reimbursement and fees for presenting research findings at meetings of acupuncture societies (British, German and Spanish Medical Acupuncture Societies).
Just because they are not part of the pharmaceutical industry……………..
“Mike O’Farrell, the chief executive, said the latest study contradicted the majority of previous research in the area.”
This would be despite the fact that, as a systematic review, the study is based on the majority of previous research in the area. Hmmm.
Also this statement from O’Farrell that: “Acupuncture does work and research results consistently demonstrate the positive outcomes of treatment on patients.”
Even applying the most positive bias in interpretation of the trial data this is beyond reasonable.
Harrumpf.
And look at this for another example of execrable journalistic standards….
“Acupuncture Stops Headaches, But ‘Faked’ Treatments Work Almost As Well
Headache sufferers can benefit from acupuncture, even though how and where acupuncture needles are inserted may not be important. Two separate systematic reviews by Cochrane Researchers show that acupuncture is an effective treatment for prevention of headaches and migraines. But the results also suggest that faked procedures, in which needles are incorrectly inserted, can be just as effective.
“Much of the clinical benefit of acupuncture might be due to non-specific needling effects and powerful placebo effects, meaning selection of specific needle points may be less important than many practitioners have traditionally argued,” says lead researcher of both studies, Klaus Linde, who works at the Centre for Complementary Medicine Research at the Technical University of Munich, Germany.
In each study, the researchers tried to establish whether acupuncture could reduce the occurrence of headaches. One study focused on mild to moderate but frequent ‘tension-type’ headaches, whilst the other focused on more severe but less frequent headaches usually termed migraines. Together the two studies included 33 trials, involving a total of 6,736 patients.
Overall, following a course of at least eight weeks, patients treated with acupuncture suffered fewer headaches compared to those who were given only pain killers. In the migraine study, acupuncture was superior to proven prophylactic drug treatments, but faked treatments were no less effective. In the tension headache study, true acupuncture was actually slightly more effective than faked treatments.
The results indicate that acupuncture could be a used as an alternative for those patients who prefer not to use drug treatments, and additionally may result in fewer side effects. However, Linde says more research is still required, “Doctors need to know how long improvements associated with acupuncture will last and whether better trained acupuncturists really achieve better results than those with basic training only.”
It appears to say clearly that acupuncture is an effective treatment for headache. Ridiculous.
Oh, hang on, it’s from the Collaboration themselves. That can’t be right.
The second BBC report (http://news.bbc.co.uk/1/hi/health/7852882.stm) quotes Mike O’Farrell as saying “Acupuncture does work and research results consistently demonstrate the positive outcomes of treatment on patients.” They don’t. The journalist fails to balance the report with equal dibs from the scientific view point. Also the BBC say that “acupunture is hotly contested”, whereas from a logical pojnt of view there is no evidence to support acupuncture beyond placebo. No contest.
Forgot to mention we should all complain to the BBC in an effort to correct the record and as a push to improve the BBC’s standards for science reporting. I’m not sure about the equal dibs bit above, as it may entitle any lunatic’s view (including my own!) to an equal share.
[…] acupuncture benefit“! Prof. David Colquhoun (from whom I learned about this latest review) discusses in much more detail the BMJ review and BBC’s below-par reporting in the last couple of weeks in regards to […]
To Andrew:
How come the Collaboration say there may be some ‘non-specific needling effects’ in addition to powerful placebo in their own summary of the research for journalists? If the lead author of the review is saying this, then it must carry weight. It may well be a bad day for the theories behind traditional acupuncture, but the review found that acupuncture in general is a more effective treatment than conventional painkillers. Which, if we dislike acupuncture that much, makes it an even blacker day for the painkiller industry, surely? Placebo it may mostly be, but outcomes are outcomes, and perhaps we should start looking at why the ritual of acupuncture appears, according to the collaboration, to be productive in terms of pain relief. I’m still struggling to see what is wrong with the headline ‘Acupuncture works for headaches’ in the context of the findings of the first Cochrane review. Perhaps, unlike this blogger, the reviewers have managed to get over their fixation with the hocus pocus of traditional acupuncture, which is not supported by this review, and actually tried to compare the effects of simple needle insertion against pharmacological rivals.
Interestingly, there is a type of bias which goes unmentioned in blogs of this type. Confirmation bias. But I’m sure that no-one here suffers from that.
It’s true that the Medical acupuncture people, Adrian White et al. have abandoned the hocus pocus, and seem happy to admit that it doesn’t matter where the needles go. But that was already well-established before these last lot of reviews.
It was also quite well established already that in a non-blind comparison of acupuncture versus no acupuncture, the acupuncture wins.
The really new thing in the Madsen paper is that although acupuncture still beats no acupuncture, the advantage is too small to be much use to patients. So it may be a theatrical placebo, but the placebo effect isn’t big enough to matter in real life.
If this conclusion is confirmed by others, then acupuncture is dead. You can’t even make the (morally-dubious) argument that it’s a good placebo.
This message was entirely missed by the dreadful BBC coverage. Keep complaining.
I’d agree that the second review throws out a different perspective, possibly on the same evidence (don’t know if any of the same trials were included in both). Surely the second headline ‘confusion over…’ reflects the fact that one week you have a review which suggests a reasonable benefit over conventional painkillers, the next you have a review which does no such thing. Both reviews from Cochranes in various guises.
I understand that the findings of the second review are far more in tune with your own beliefs about the value of acupuncture (or lack of it). And, if confirmed by other studies, indeed, acupuncture for these conditions is a gonner. But when balanced against other reviews which suggests a benefit to patients, the argument is not so clear-cut. Hence the ‘confusion’. I wouldn’t have thought you could report the second review without making reference to the findings of a similar review published a week earlier. That truly would be confusing for the audience.
What we need is for Cochrane to do one, overarching review, perhaps, rather than churn out several which appear somewhat contradictory.
That could actually shine a light on this mess.
As far as I can see, apart from the overall findings, there is one major difference between these two reviews. The Madsen review had no specific funding, whilst the review of acupuncture for headache/migraine had funding from CAM (research) organisations. In addition the latter was conducted by people who appear to be ‘provider[s] of health care, ……….. with a real or potential vested interest in the findings of a specific review’.
Can someone help me here.
There seems to be plenty of evidence that “real” needling and “sham” needling are as about as (in)effective as each other and are also about as (in)effective as doing nothing.
The actual differences vary slightly trial by trial but that seems to be the gist of it.
I can certainly understand that needling has a strong placebo effect – it is obviously far more dramatic, invasive and interventionist than some other rubbish quackery like HY or reiki.
BUT, is this study arguing that needlism is more effective than pharmaceutical painkillers (ibuprofen, codeine, aspirin etc). I find that very difficult to believe (so much so that I don’t actually believe it – not least because painkillers undergo proper trials and if they were no better than placebo or nothing then they would not spring into existence).
Is Hamfisted a needlist – if so I find the combination of name and job extremely worrying.
And yes, sites like this probably do have a confirmation bias. They confirm that needlism and other forms of quackery are rubbish and that we quite rightly should be biased against the charlatans who practice this nonsense.
I’d picked up on the BBC’s reporting of acupuncture working for headaches, but I didn’t complain to them about it. This post is a reminder that sometimes bloggers need to be a bit more active in terms of addressing the source of misinformation instead of simply writing about it. Good stuff.
I’m not a needler, as it happens, although the name would probably be a good representation of what would happen if I were!
The reviews appear to be a mixed bag, although the CC clearly states in the first one that acupuncture (true or sham) is superior to painkillers for the specific purpose of headache prophylaxis.
The second review finds no benefit, in a broader range of conditions.
The only weapon you should have against acupuncture is actual evidence from folks such as the CC, not forejudgement that they are quackery and rubbish.
If, somehow, acupuncturists are achieving a very powerful placebo effect, or even a mild physiological effect of unknown mechanism, then it’s worthwhile trying to work out if that’s true, and if so, how it can be harnessed to improve the efficacy of conventional medicines.
I’m all for knowing more about the placebo effect. But the whole point of the Madsen paper is that isn’t a “a very powerful placebo effect” but one that is so weak that I was surprised myself.
At the moment we are in the absurd situation that a GP is not allowed to prescribe a placebo in an honest way (a bottle of “pink water”) but is allowed to refer people to a homeopath for a dishonest placebo. That is just dishonesty made compulsory. An absurd situation, but one that arises naturally when nobody grasps the nettle of deciding what works and what doesn’t.
Wouldn’t prescribing a placebo honestly somewhat defeat the object? It’s an interesting question though. If the flourishes and fibs can improve the outcome, perhaps we should send our doctors to RADA?
Agree with you on the Madsen verdict. It was the original Cochrane review last week which seemed to suggest a clear benefit, composed of powerful placebo plus some hint of physiological impact.
I’m interested as well – if acupuncture works no better than existing painkillers, or is better but to a clinically irrelevant level, how does its side-effect profile and cost effectiveness stack up against the conventional medication, given that, say, for low back pain, you wouldn’t want people on NSAIDs for long periods?
“Wouldn’t prescribing a placebo honestly somewhat defeat the object?”
There’s a very interesting paper available here: http://www.leecrandallparkmd.net/researchpages/placebo1.html that is titled “An Exploration of Neurotic Patients’ Responses to Placebo When Its Inert Content Is Disclosed”.
Hamfisted did you read the first review? It can’t have been the one I read since your conclusion about acupuncture vs painkillers is not borne out in it. The review found that wrt tension headaches (a specific sort, not all headaches) acupuncture reduced the number of days of headaches per month. That is different from acupuncture working better than a painkiller for any given headache which is what you claimed.
Tension headaches can also be relieved by massage, by stress reduction, by contraceptive pills. Taking a painkiller a day will not reduce the incidence of headaches and may in fact induce them, the so-called pain-killer bounce headache.
Mind you when I was on strong NSAIDs for my hands a lack of headaches was a benefit, though I suspect they were simply being masked. I did get a real doozy once and took to my bed reasoning that if it could get through 200mg of ketoprophen I should take it seriously.
The issue of confirmatory bias is important – we are all of us prone to it and should take it seriously. I wonder how I would react if genuinely convincing evidence arose for acupuncture rather than the current picture of predictably poor results accompanied by overwhelmingly positive spin. I would certainly take some convincing but I like to think on the face of it that I would reappraise my position. Plausibility and the existing evidence make it seem unlikely that I’ll be put in that position.
The migraine review strongly suggests what we assumed – that acupuncture is a placebo. Adding the clever term “non-specific needling effects” in addition to plain old placebo borders on sophistry, since not only does it not matter how deep the needle goes in or where, it also doesn’t matter if the needle goes in at all!
The tension headache review requires a little more attention. In terms of both response and reducing headache occurrence only one of the trials showed a clear and significant effect of acupuncture over sham, and since it was the largest trial it had a major effect on the meta-analysis. If one looks at the forest plots the picture is astoundingly unimpressive. The authors acknowledge the major influence of this one trial so fair enough….
….but if you go to the original paper of that big trial (Endres et al. 2007), those authors conclude no significant effect of acupuncture by their own predetermined criteria of efficacy (which the review authors also acknowledge). In fact Endres et al. conclude that “the degree to which treatment benefits depend on psychological compared to physiological effects and the degree to which any physiological effects depend on needle placement and insertion depth are unclear.”
So the results are only significant by the criteria applied by the Cochrane reviewers (which they justify and acknowledge).
There are 2 issues that arise from this. One is that the effect is so small that is likely to be fairly irrelevant. The one trial that demonstrates an effect for the review itself concluded that acupuncture was ineffective compared with sham.
The other is one of potential bias. I am not suggesting that there is any overt or conscious effort by the authors to manufacture a result but the reviewers are established acupuncturists and/or advocates of the technique and for all of us bias is impossible to escape. They are to some degree wedded to the idea that acupuncture is a useful and effective therapy. They are members of established active acupuncture research groups, and they could not have set their own a priori criteria of efficacy naïve to the data they would be reviewing. In fact they are likely to have been very familiar with the data when designing the protocol. Which makes it very difficult to design it impartially.
I think there is a case (probably completely impractical) for Cochrane Reviews to be done by people with expertise of reviewing but no clear connection to the therapy of choice. Financial interests are just one part of the puzzle of bias; in fact I suspect that a firmly held belief in the therapy may be more influential.
Of course I could be suffering from “rescue bias”. Ted Kaptchuk describes this as “discounting data by finding selective faults in the experiment”.
I don’t think I am, but then I wouldn’t, would I?
Ref:
Endres HG, Böwing G, Diener HC, Lange S,Maier C,Molsberger A, et al. Acupuncture for tension-type headache: a multicentre, shamcontrolled, patient- and observer-blinded, randomised trial. Journal of Headache and Pain 2007;8 (5):306–14.
Yes, I agree that confirmation bias is a danger. That’s why we have systematic reviews and meta-analyses. And that’s why I said that Madsen et al would signal the end of acupuncture if it is confirmed.
There remains the interesting question of when and how to decide enough is enough. Many people think that there is no point in spending more money on homeopathy research. The question has now been answered with sufficient certainty. The same question must now be asked of acupuncture research. Unfortunately there is no simple way to answer the question.
Most people in research would, I imagine, would prefer to choose a topic where there was a rather bigger chance of a useful outcome than in homeopathy or acupuncture. If the trials continue to come out negative, people will eventually just lose interest.
I agree completely. Pain has always been acupuncture’s biggest claim and the results are convincingly poor.
Unfortunately people will only lose interest when those who research it stop shying away from drawing the appropriate conclusions and the media stop reporting it in such a ridiculously positive light.
This vocal anti-MMR quack has his own spin on this issue:
http://www.cityacupuncture.org.uk/acupuncture.html
“Over the past thirty years there has been considerable scientific research into acupuncture, and we are now beginning to understand how it works. We can be sure that the effects of acupuncture are not all in the mind. It s increasingly being used alongside conventional medicine.”
So, we can all be sure! Now, put down anything breakable before you read the next bit…
“The distinction between complementary, or alternative, medicine and orthodox medicine is becoming blurred as the benefits of acupuncture become accepted by conventional doctors. Acupuncture is used in the vast majority of NHS pain clinics and is being offered by an ever increasing number of GPs and hospital doctors.”
I hope you did put down anything breakable, or your office is likely to look a lot like mine.
Thought I’d heard of Halvorson before so did a Google search.
If you were shocked by city acupuncture (which btw also does bone-crunching and other stuff), have a look at this:
Dr Richard Halvorsen answers the big questions about MMR, vaccines and diseases
http://www.cryshame.com/index.php?option=com_content&task=view&id=68&Itemid=80, where he kindly explains how measles in Africa is quite different from measles in the UK, where children are brought up in ‘nutritionally’ good environments etc etc.. Almost bigger baloney than we saw from the perpetrators of the MMR myths.
It does seem to contrast rather with his disappointment at his practice losing out to United Healthcare for running the Brunswick Centre general practice. Not sure which is worse to be in charge of a general practice, a US corporate giant or an anti-vaccine quack.
Maybe it is time to follow many US states and say ‘No vaccine, no school’, with a requirement for documentary evidence or notary-sworn statements for people who have real grounds for objection.
A fantastic article by Steven Novella on this issue here:
http://www.sciencebasedmedicine.org/?p=413
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