Thursday, April 22, 2010

Stent or surgery?

Two-month old news but I just heard about it. The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) was a 9-year, multicenter, mega trial with over 2,500 patients randomized to either stenting or endarterectomy. Adjudicators of the outcomes were blinded. Results shows that placing a stent to dilate a blocked carotid artery and surgical removal of the blockage--the traditional treatment--both have nearly the same efficacy and overall safety.
The overall safety and efficacy of the two procedures was largely the same with equal benefits for both men and for women, and for patients who had previously had a stroke and for those who had not. However, when the investigators looked at the numbers of heart attacks and strokes, they found differences. The investigators found that there were more heart attacks in the surgical group, 2.3 percent compared to 1.1 percent in the stenting group; and more strokes in the stenting group, 4.1 percent versus 2.3 percent for the surgical group in the weeks following the procedure.
The study also found that the age of the patient made a difference. At approximately age 69 and younger, stenting results were slightly better, with a larger benefit for stenting, the younger the age of the patient. Conversely, for patients older than 70, surgical results were slightly superior to stenting, with larger benefits for surgery, the older the age of the patient.

You'd think that's the final word on the matter. However, in March this year the results of the International Carotid Stenting Study (ICSS) came out. ICSS is a multicenter mega trial with over 1,700 participants randomized to either stenting or endarterectomy. As in CREST adjudicators of outcomes were blinded. Unlike CREST the objective of the European study did not include comparison of efficacy, only safety. Researchers found that surgery is safer overall. Incidence of stroke, death, procedural myocardial infarction, and risk of any stroke and all-cause death were all lower in the endarterectomy group. The three heart attacks that occurred during stenting were all fatal, while all four that occurred during endarterectomy were nonfatal. On the other hand,
There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group.

Possible reasons for the difference in findings: the ICSS employed only symptomatic patients (ie., those who've had minor strokes or transient ischemic atttacks) while CREST included both symptomatic and asymptomatic patients; unlike ICSS, CREST limited itself to physicians who had a "high degree of proficiency and safety."

Wednesday, April 21, 2010

95% of chiropractic sites make unsubstantiated claims

On the heels of Simon Singh's victory, we have the following assessment of chiropractors' claims on the Internet by Ernst and Gilbey.
RESULTS: We found evidence that 190 (95%) chiropractor websites made unsubstantiated claims regarding at least one of the conditions. When colic and infant colic data were collapsed into one heading, there was evidence that 76 (38%) chiropractor websites made unsubstantiated claims about all the conditions not supported by sound evidence. Fifty-six (28%) websites and 4 of the 9 (44%) associations made claims about lower back pain, whereas 179 (90%) websites and all 9 associations made unsubstantiated claims about headache/migraine. Unsubstantiated claims were made about asthma, ear infection/earache/otitis media, neck pain, CONCLUSIONS: The majority of chiropractors and their associations in the English-speaking world seem to make therapeutic claims that are not supported by sound evidence, whilst only 28% of chiropractor websites promote lower back pain, which is supported by some evidence. We suggest the ubiquity of the unsubstantiated claims constitutes an ethical and public health issue.
Ethical and public health issue. What good can we expect from quackery?

Monday, April 19, 2010

Ruse gives Church a two thumbs down

Philosopher Michael Ruse isn't exactly a fan of the Four Horsemen even as he is very much against creationism and its current evolutionary descendant Intelligent Design. Apparently, however, the continuing revelations of sexual abuses and cover-ups in the Catholic Church has pushed Ruse into Dawkins' camp, at least in the matter of wishing for the the Fall of the Catholic Church.
Richard Dawkins, wrote a highly emotive piece for the Washington Post, in which he derided the present pope and expressed glee and satisfaction that such a person was now leading the Catholic Church. In Dawkins's judgment, not only was this no less than the Church deserved, but such leadership could only hasten the Church's demise. I thought at the time that Dawkins was over the top and wrong. I now think that he was right and that it was I who was wrong. Let me say at once that, unlike Dawkins, I don't necessarily want to see this as the end of religion or even of the Catholic Church in some form. I stress that although I cannot share the beliefs of Christians, I respect them and applaud the good that is done in the name of their founder. But I do now think that as presently constituted, the Catholic Church is corrupt and should be eradicated.
Great to hear that even a critic of "New Atheism" (I have problems with that term) sees how depraved the Church is.

Friday, April 16, 2010

The spinal manipulators have backed down

The British Chiropractic Association (BCA) has dropped its libel case against Simon Singh. They thought they could intimidate and silence Simon and criticism of chiropractic by suing. Well they took on the wrong guy. Taking the matter to court backfired. Not only has the BCA managed to train the spotlight on them, they've unwittingly initiated moves to reform English libel laws.

Congratulations, Simon!

Wednesday, April 14, 2010

It's World Dilution Delusion Awareness Week 2010

Replace "Dilution Delusion" with "Homeopathy."

Yes, folks, homeopaths are actually celebrating awareness of their 200-year delusion this week. And as others have already done, I'm all for enlightening the yet unaware about what homeopathy really is. Instead of introducing it let me direct you to these fabulous resources:

Segment from Richard Dawkins' 2007 TV series Enemies of Reason
Talk by James Randi
Homeopathy: The Ultimate Fake, by Dr. Stephen Barrett of Quackwatch
Prof. Robert Carroll's comprehensive article 

Edzard Ernst, former homeopath who practiced for many years and is the first Professor of Complementary Medicine in the UK, along with science writer Simon Singh have this to say about homeopathy's effectiveness:
We suggest that you ignore the occasional media hype and instead rely on our conclusion, because it is based on examining all the reliable evidence - and the evidence suggests that homeopathy acts as nothing more than a placebo. For this reason, we strongly advise you to avoid homeopathic remedies if you are looking for a medicine that is more than just make-believe. [Simon Singh & Edzard Ernst, Trick or Treatment: Alternative Medicine on Trial, Bantam, 2008, p.140-141]
I just went to the Cochrane Library and found a handful of systematic reviews of homeopathy: attention deficit/hyperactivity disorder or hyperkinetic disorder, chronic asthma, dementia, induction of labour, adverse effects of cancer treatments. The authors conclude that the evidence is either absent, insufficient or unconvincing.

On January 30 2010 hundreds of brave souls in the UK, Australia, New Zealand, Canada, and the US went out on the streets and overdosed on a variety of homeopathic pills. Unfortunately for quackery, none of them died, and no one came down with even a tummy ache. Well, that's the point of the whole 10:23 campaign--to show the world that homeopathic preparations--particularly the allegedly most potent ones--contains no active ingredients.

In February 2010 the UK House of Commons Science and Technology Committee released Evidence Check 2: Homeopathy, a report in which it unequivocally stated that there is no evidence for homeopathy and recommended that the government cease supporting its use.

In October 2009 I wrote about homeopathy in the Philippines. Just an excerpt from that blog entry:
In the Nux vomica oral drops some of the substances are watered down to D1000. How dilute is a D1000? If you had one drop of active ingredient and were to dilute it in one go you'd have to mix that single drop with 101000 (remember, that's "1" followed by a thousand zeros) drops of water or alcohol. How much is 101000 drops? That's equivalent to 6.5 × 10992 cubic meters [see Note 1]. And just how large is that? Well, it's more than the size of our universe. In fact a lot bigger. If a bucket were the size of the universe you'd need 7.7 trillion buckets to end up with 6.5 × 10992 m3 [see Note 2]. After mixing (if you can even imagine achieving that) you can scoop a volume as large as the Earth or the Sun or the Milky Way and the chances of finding a single molecule of the active ingredient would still be exceedingly infinitesimal.
Matt Parker writing in TimesOnline has another illustration of how utterly diluted homeopathic remedies are:
To put homeopathy in a medicinal context, if you wanted to consume a normal 500mg paracetamol dose you would need ten million billion homeopathic pills. Where each pill is the same mass as the Milky Way galaxy. There is actually not enough matter in the entire known Universe to make the homeopathic equivalent of a single paracetamol pill.
The funny thing about these dilutions is that if you remove the labels of two vials containing different high potency homeopathic preparations there is no way homeopaths can distinguish one from the other.

While homeopaths are living in dreamland, the homeopathic industry is an investor's dream.
Somewhere near Lyon, France, sometime this year, officials from the French pharmaceutical firm Boiron will slaughter a solitary duck and extract its heart and liver--not to appease the gods but to fight the flu. The organs will be used to make an over-the-counter flu medicine, called Oscillococcinum, that will be sold around the world. In a monetary sense, this single French duck may be the most valuable animal on the planet, as an extract of its heart and liver form the sole "active ingredient" in a flu remedy that is expected to generate sales of $20 million or more. [US News]
Imagine that. Companies can package pure water and lactose (in pill form), stick a variety of labels on the bottles, market water and sugar pills as having therapeutic efficacy for a host of conditions, make a killing, and get away with it legally!

If that got your goat as it did mine then the following should give you a much needed shot of endorphins. Here are comedians Mitchell & Webb parodying homeopathy and other quackery.

So be aware of homeopathy. And make sure to tell others to be wary of it. It's bizarre. It's bunk. It's bogus. It's balderdash.

Crime and punishment

Well, it's about time someone from the inside spoke up and call for The Rat's resignation.

It's not just a matter of command responsibility; Ratzinger ordered the cover up of sexual abuses! This sleazeball has no business leading an organization which touts itself as a moral authority. I'm with Dawkins and Hitchens. Book this depraved geezer and try him.

Tuesday, April 13, 2010

Something's very wrong when they can't tell the difference

Take a cup of consecrated host and another cup of unconsecrated ones. Pour their contents into a jar, put the lid on and mix well. Now ask the Pope, cardinals, and bishops to sort the wafers. Quite patently, they won't be able to. Both chanted over and untransubstantiated crackers look, feel, taste, weigh, and test exactly the same.

Take ten new empty vials from the same production batch and in a class 1 cleanroom fill nine of them with triple distilled water. Using the same batch of distilled water, using new and ultra clean beakers/flasks and pipettes/droppers, and in the same clean 1 room, proceed to make a 30X homeopathic remedy. Doesn't matter what type so long as you end up with a 30X dilution (that is, the amount of active ingredient is 1 part in 1,000,000,000,000,000,000,000,000,000,000). In a double-blind test have homeopaths determine which vial is the homeopathic dilution. They can use whatever instrument, equipment, machine, and laboratory they want. Have this test performed many times. You can bet that as more trials are done, homeopaths' performance will converge toward 1X--they will get it right 10% of the time, which is the probability of being right by chance alone.

Being a fan of James Randi I naturally tend to look at weird and pseudoscientific claims from the perspective of testing them in a controlled fashion. Prof. Chris MacDonald on the other hand looks at homeopathy from the point of view of business and consumer protection. Although he doesn't believe it to be so, for the sake of argument he assumes that homeopathy actually works. He then asks,
How do we detect phoney homeopathic preparations? In order to protect consumers, we need to be able to detect fake remedies — fake versions (sold by counterfeiters) that are really just inert look-alike copies of genuine remedies. In an age of international trade and Internet-based pharmacies, phoney pills are a big problem. So, is there any way to test a homeopathic preparation to verify that it is genuine? If I buy homeopathic tablets, is there any test that can be done to see if they’re real or counterfeit? If authorities suspect a criminal organization of selling fake homeopathic tablets, how can they tell the difference between the criminal organization’s tablets and those manufactured by an honest homeopathic pharmacy?
I'd very much like to hear the dilutionists' answer to this as well.

Repeat after me: Sham = placebo

Yesterday I mentioned Linde et al.'s 2009 Cochrane review and how the authors noted that having needles  anywhere on the skin is as effective as sticking them in the "official" acupuncture points. Here's a recent news item on their eureka discovery:
The researchers conducted two sets of tests on patients with chronic migraine pain. In one test, acupuncture needles were applied in strict adherence with established practice. But in the other test, the needles were inserted either in the wrong positions or else the needles did not penetrate the skin at all.
And as the authors concluded: "Collectively, the studies suggest that migraine patients benefit from acupuncture, although the correct placement of needles seems to be less relevant than is usually thought by acupuncturists."

Lead author Klaus Linde explains these results:
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.
Well that's a clarification/qualification I'm more comfortable with. Noting that the observed reduction in headaches are due to "non-specific needling effects" and "powerful placebo effects" calms me down.

Let's be clear that the placebo group is there for comparison. If and when the experimental group does not perform any better than the control group then the conclusion ought to be: the modality under test isn't effective. If acupuncturists tell us that the needles should break the skin and that certain points need to be manipulated instead of others in the the treatment of condition X, and if the sham procedure does not meet these criteria, and if there is no statistically significant difference in the results between the two procedures then the conclusion is simple: acupuncture doesn't work.

Sure, we can do a comparative test of placebos and find out which are comparable to placebo X and which elicit placebo effects better than others. But let's keep in mind that they're placebos.

The picture that's coming out of acupuncture studies is that needling anywhere and even jabbing without penetrating the skin (unbeknownst to the particpants of course) all elicit similar or the same effects. One wonders then whether touching, pinching, fondling, scratching, spanking, "hickey-ing," licking, tapping, ... would likewise trigger the same. The only problem is blinding the participants as to which procedure they're receiving. I would guess, however, that being kissed, licked, and fondled by persons the participant finds "interesting" would have much greater, uhh, clinical benefit than being poked with needles.

A journalist for science

Michael Specter of the New Yorker talks about how science is essential, how the antiscience sentiment is misplaced.

Best line: We run away from Big Pharma and leap into the arms of Big Placebo.

Chinese studies now to be taken with a ton of salt

It's worse than I thought. The problem of publication bias in China is nothing compared to this
Ghostwriting, plagiarizing or faking results is so rampant in Chinese academia that some experts worry it could hinder China's efforts to become a leader in science.


"Academic fraud, misconduct and ethical violations are very common in China," said professor Rao Yi, dean of the life sciences school at Peking University in the capital. "It is a big problem."


Fang Shimin, an independent investigator of fraud, said he and his volunteers expose about a hundred cases every year, publicizing them on a Web site titled "New Threads." "The most common ones are plagiarism and exaggerating academic achievement," Fang said.

Monday, April 12, 2010

WHO not to be trusted with review of CAM

In Pricks I posted a list of diseases that according to Chinese herbalist and acupuncturist Shenrong Liu are some of the conditions which the World Health Organization (WHO) says are treatable by acupuncture. Here's the complete list from the WHO website. WHO lists the diseases/symptoms/conditions under four categories: 1.those for which acupuncture has been proved to be effective. 2. those for which the therapeutic effect of acupuncture has been shown but for which further proof is needed. 3. those for which there are only individual controlled trials reporting some therapeutic effects. 4. those for which acupuncture may be tried provided the practitioner has special modern medical knowledge and adequate monitoring equipment. 
1. Diseases, symptoms or conditions for which acupuncture has been proved-through controlled trials-to be an effective treatment:

    Adverse reactions to radiotherapy and/or chemotherapy
    Allergic rhinitis (including hay fever)
    Biliary colic
    Depression (including depressive neurosis and depression following stroke)
    Dysentery, acute bacillary
    Dysmenorrhoea, primary
    Epigastralgia, acute (in peptic ulcer, acute and chronic gastritis, and gastrospasm)
    Facial pain (including craniomandibular disorders)
    Hypertension, essential
    Hypotension, primary
    Induction of labour
    Knee pain
    Low back pain
    Malposition of fetus, correction of
    Morning sickness
    Nausea and vomiting
    Neck pain
    Pain in dentistry (including dental pain and temporomandibular dysfunction)
    Periarthritis of shoulder
    Postoperative pain
    Renal colic
    Rheumatoid arthritis
    Tennis elbow

2. Diseases, symptoms or conditions for which the therapeutic effect of acupuncture has been shown but for which further proof is needed:

    Abdominal pain (in acute gastroenteritis or due to gastrointestinal spasm)
    Acne vulgaris
    Alcohol dependence and detoxification
    Bell’s palsy
    Bronchial asthma
    Cancer pain
    Cardiac neurosis
    Cholecystitis, chronic, with acute exacerbation
    Competition stress syndrome
    Craniocerebral injury, closed
    Diabetes mellitus, non-insulin-dependent
    Epidemic haemorrhagic fever
    Epistaxis, simple (without generalized or local disease)
    Eye pain due to subconjunctival injection
    Female infertility
    Facial spasm
    Female urethral syndrome
    Fibromyalgia and fasciitis
    Gastrokinetic disturbance
    Gouty arthritis
    Hepatitis B virus carrier status
    Herpes zoster (human (alpha) herpesvirus 3)
    Labour pain
    Lactation, deficiency
    Male sexual dysfunction, non-organic
    Ménière disease
    Neuralgia, post-herpetic
    Opium, cocaine and heroin dependence
    Pain due to endoscopic examination
    Pain in thromboangiitis obliterans
    Polycystic ovary syndrome (Stein-Leventhal syndrome)
    Postextubation in children
    Postoperative convalescence
    Premenstrual syndrome
    Prostatitis, chronic
    Radicular and pseudoradicular pain syndrome
    Raynaud syndrome, primary
    Recurrent lower urinary-tract infection
    Reflex sympathetic dystrophy
    Retention of urine, traumatic
    Sialism, drug-induced
    Sjögren syndrome
    Sore throat (including tonsillitis)
    Spine pain, acute
    Stiff neck
    Temporomandibular joint dysfunction
    Tietze syndrome
    Tobacco dependence
    Tourette syndrome
    Ulcerative colitis, chronic
    Vascular dementia
    Whooping cough (pertussis)

3. Diseases, symptoms or conditions for which there are only individual controlled trials reporting some therapeutic effects, but for which acupuncture is worth trying because treatment by conventional and other therapies is difficult:

    Choroidopathy, central serous
    Colour blindness
    Irritable colon syndrome
    Neuropathic bladder in spinal cord injury
    Pulmonary heart disease, chronic
    Small airway obstruction

4. Diseases, symptoms or conditions for which acupuncture may be tried provided the practitioner has special modern medical knowledge and adequate monitoring equipment:

    Breathlessness in chronic obstructive pulmonary disease
    Convulsions in infants
    Coronary heart disease (angina pectoris)
    Diarrhoea in infants and young children
    Encephalitis, viral, in children, late stage
    Paralysis, progressive bulbar and pseudobulbar

Just counting those in categories 1 & 2 there are a total of 91 conditions that WHO claims to be treatable by acupuncture. That by merely sticking needles in various points on the skin can treat such a wide range of diseases and conditions is already suspect. So we shouldn't be surprised that the WHO review is rather flawed. According to Singh & Ernst the WHO committed two major errors in their review. First, WHO set the bar too low for clinical trials it admitted as evidence. "[T]he WHO had taken into consideration almost every trial ever conducted, because it had set a relatively low quality threshold." And so low quality trials (which are more prone to producing positive findings) skewed the review. Secondly, WHO included a large number of studies from China. This wouldn't be a problem if not for the fact that "careful statistical analyses of all the Chinese results ... demonstrate beyond all reasonable doubt that Chinese researchers are guilty of so-called publication bias." We saw the evidence for this bias in our survey of the studies by Vickers et al., Pan et al., and Tang et al. Given the low admission threshhold and the fact that published Chinese studies are more biased against negative results, the WHO review cannot but come to a very positive conclusion of acupuncture. Garbage in, garbage out. As if that's not enough to weaken the review, the report was "drafted and revised by Dr Zhu-Fan Xie, who was Honorary Director of the Institute of Integrated Medicines in Beijing, which fully endorses the use of acupuncture for a range of disorders." This conflict of interest is more reason to be suspicious of the WHO's glowing findings. [Singh & Ernst p.71-73]

Let's now compare the WHO report with the studies by the Cochrane Collaboration. Why Cochrane? Well, because it's committed to "adhering to the principles of evidence-based medicine" [Singh & Ernst p.74].
The Cochrane Collaboration is practically obsessed with producing high quality, unbiased reviews, given that quality and the avoidance of bias are as important in conducting reviews of trials as they are in conducting the trials themselves. In fact, the organization will not add a review to its database that does not comply with its voluminous set of regulations and safeguards, the most important of which from our perspective is that the quality of the trials must be factored into a succinct, bottom-line conclusion. [W]hile organized medicine might be susceptible to accusations of bias toward CAM, the Cochrane Collaboration is not. The entire reason for the organization's existence is to provide the public and the medical profession with unbiased assessments of what works and what does not work, and it takes this mission very seriously. [Bausell p.202]

The comparative analysis is pretty straightforward. I first searched for all Cochrane reviews with "acupuncture" in the title. I then culled those reviews which had matching diseases/conditions in the WHO report. The results are summarized in the table below. Note that I did not include any findings for electroacupuncture or other forms other than manual needling. And I was tendential toward results for real versus sham acupuncture rather than other types of controls. To my mind the only way to know whether acupuncture is in fact not merely a placebo is to compare it with the results of blinded sham needling.

WHO category
Cochrane Collaboration review
Depression 1 "We found insufficient evidence to recommend the use of acupuncture for people with depression. The results are limited by the high risk of bias in the majority of trials meeting inclusion criteria." [source]
Headache 1 "[T]he available evidence suggests that acupuncture could be a valuable option for patients suffering from frequent tension-type headache." [source]  Note: this review is for tension-type headache.
Induction of labor 1 "There is insufficient evidence describing the efficacy of acupuncture to induce labour." [source]
Low back pain 1 "The data do not allow firm conclusions about the effectiveness of acupuncture for acute low-back pain. For chronic low-back pain, acupuncture is more effective for pain relief and functional improvement than no treatment or sham treatment immediately after treatment and in the short-term only." [source]
Nausea and vomiting 1 Acupuncture did not reduce the proportion of acute vomiting from chemotherapy. [source]  Note: this review is for chemotherapy-induced nausea or vomiting

"Compared with sham treatment P6 acupoint stimulation significantly reduced: nausea ...; vomiting ..., and the need for rescue antiemetics." [source]  Note: this review is for post-operative nausea and vomiting.
Neck pain 1 "There is moderate evidence that acupuncture relieves pain better than some sham treatments, measured at the end of the treatment ."[source]
Rheumatoid arthritis 1 "From the little evidence that there is, acupuncture does not appear to improve the symptoms of rheumatoid arthritis." [source]
Stroke 1 "There is no clear evidence of benefit from acupuncture in acute stroke." [source]

"There is no clear evidence of the effects of acupuncture on stroke rehabilitation." [source]

"There is not enough evidence to make any conclusion about the therapeutic effect of acupuncture for dysphagia after acute stroke." [source]
Tennis elbow (lateral elbow pain) 1 "There is insufficient evidence to either support or refute the use of acupuncture (either needle or laser) in the treatment of lateral elbow pain." [source]

Bell's palsy 2 "The quality of the included trials was inadequate to allow any conclusion about the efficacy of acupuncture [source]
Bronchial asthma 2 "There is not enough evidence to make recommendations about the value of acupuncture in asthma treatment." [source] Note: this review is for chronic asthma.
Cocaine dependence 2 "There is currently no evidence that auricular acupuncture is effective for the treatment of cocaine dependence." [source]
Female infertility 2 "The data from this meta-analysis suggests that acupuncture does increase the live birth rate with in vitro fertilisation (IVF) treatment when performed around the time of embryo transfer. However, this could be attributed to placebo effect and the small number of trials included in the review." [source]
Insomnia 2 "The small number of randomised controlled trials, together with the poor methodological quality and significant clinical heterogeneity, means that the current evidence is not sufficiently extensive or rigorous to support the use of any form of acupuncture for the treatment of insomnia." [source]
Osteoarthritis 2 "Sham-controlled trials show statistically significant benefits; however, these benefits are small, do not meet our pre-defined thresholds for clinical relevance, and are probably due at least partially to placebo effects from incomplete blinding." [source]
Schizophrenia 2 "We found insufficient evidence to recommend the use of acupuncture for people with schizophrenia." [source]
Tobacco dependence 2 "Acupuncture and related therapies do not appear to help smokers who are trying to quit." [source]
Vascular dementia 2 "There is no evidence from randomized controlled trials to determine whether acupuncture provides any effect when treating people with vascular dementia." [source]

Irritable bowel/colon syndrome 3 "There is no evidence to support the use of acupuncture for the treatment of irritable bowel syndrome." [source]

In the above table the only conditions for which Cochrane reviews found evidence of efficacy are tension-type headache, neck pain, short term relief of chronic low back pain, and nausea and vomiting (but not those that are chemotherapy-induced). Of the nine conditions in the table above which according to the WHO are most certainly treatable by acupuncture (category 1), only four are supported by Cochrane reviews and even then the evidence is far from overwhelming.

While the Cochrane review for acupuncture for IVF does say there is evidence in its favor, the authors are cautious given the small number of trials. More importantly that 2007 review has to be tempered by the large RCT by So et al. (2009) employing 370 participants, which found that "placebo acupuncture was associated with a significantly higher overall pregnancy rate when compared with real acupuncture." In other words, real acupuncture is no better than sham. Moreover, a meta-analysis of 14 clinical trials having a total of 2670 subjects published in 2010 by Cheong et al. found "no evidence of benefit in the use of acupuncture during assisted conception." Thus, none of the category 2 conditions listed in the table have any good evidence in their favor.

Although only a minority of the diseases/conditions in the WHO report have corresponding Cochrane reviews the trend is apparent--Cochrane reviews paint a much sober picture of acupuncture's effectiveness. Except for some four conditions, there is currently a dearth of good evidence for the efficacy of acupuncture. This is further drummed in when we consider the fact that the findings of other Cochrane reviews of acupuncture which have no matching conditions in the WHO report are all negative:

Uterine fibroids: "There is no reliable proof of effectiveness of acupuncture for uterine fibroids due to lack of randomized controlled trials up to now."
Migraine prophylaxis: "There is no evidence for an effect of 'true' acupuncture over sham interventions, though this is difficult to interpret, as exact point location could be of limited importance."
Epilepsy: "The current evidence does not support acupuncture as a treatment for epilepsy."
Glaucoma: "At this time, it is impossible to draw reliable conclusions from the available data to support the use of acupuncture for the treatment of glaucoma."
Shoulder pain: "There is not enough evidence to say whether acupuncture works to treat shoulder pain or whether it is harmful."
Restless legs syndrome: "There is insufficient evidence to determine whether acupuncture is an efficacious and safe treatment for RLS."

One would think that this blunder by the WHO is an isolated case. Unfortunately, it seems that CAM has a special place in its heart. In 2005 the British medical journal Lancet reported that
a draft report on homoeopathy by the World Health Organization says the majority of peer-reviewed scientific papers published over the past 40 years have demonstrated that homeopathy is superior to placebo in placebo-controlled trials. Furthermore, it says that homoeopathy is equivalent to conventional medicines in the treatment of illnesses, both in humans and animals.
Looks as if the WHO yet again made no effort to separate chaff from grain and instead admitted any Tom, Dick and Harry study into their review of homeopathy.

We're talking about the World Health Organization here. This is suppose to be an organization which has the health of the human population in mind. Needless to say, it ought to promote and suggest treatments that work, treatments that are backed up by good science and good evidence. Patently, there is no good scientific rationale undergirding acupuncture and homeopathy. And the best evidence at hand refutes them.

There may be hope, however. In 2009 as a response to an open letter by the Voice of Young Science network WHO officials came out stating that WHO does not recommend homeopathy for the treatment of AIDS, tuberculosis, malaria, and diarrhea in infants. While laudable, I'd rather hear them announcing that the WHO does not recommend homeopathy for any and all conditions.

An interesting aside:

In the above Cochrane review of acupuncture for migraine prophylaxis, Linde et al. posit a strange hypothesis. Given that there was no statistically significant difference between real and sham acupuncture the authors muse that the "exact point location could be of limited importance," that "correct placement of needles seems to be less relevant than is usually thought by acupuncturists." What they seem to be saying is that sham acupuncture is as therapeutic and efficacious as real acupuncture. In the above study by So et al. the authors also make a similar a comment after finding that sham performed significantly better than real needling: "Placebo acupuncture may not be inert." Dr. Steven Novella has this to say:

It is just a form of special pleading to argue after a negative trial that placebos work also. In this study the authors are left trying to justify the conclusion that placing the needles in the “correct” locations had a disadvantage over placing them in random locations, which would also mean that expertise in acupuncture is a disadvantage.
One wonders how Linde, So, and their team members would react if after a new drug fails to perform any better than the placebo control the authors of the trial hypothesize that the placebo they employed may not be inert.



R. Barker Bausell. Snake Oil Science: The Truth About Complementary and Alternative Medicine. Oxford Press, 2007.
Simon Singh & Edzard Ernst. Trick or Treatment: Alternative Medicine on Trial. Bantam, 2008.

Sunday, April 11, 2010


What do you call a treatment modality that is effective against a gamut of human diseases including Bell's palsy, arthritis, post stroke paralysis, sciatic pain, neuralgia, migraine headaches, insomnia, dizziness, neck and shoulder and back pain, anxiety disorders, depression, mood swings, asthma, colds, flu, allergies, bronchitis, sinusitis, hypertension, angina pectoris, arteriosclerosis, anemia, acute/chronic diarrhea, constipation, indigestion, gastritis, ulcers, irregular/painful menstruation, PMS, hormonal imbalance, infertility in men and women, menopausal symptoms, UTI, prostatitis, bladder/kidney dysfunction, sexual dysfunction, fatigue, tinnitus, diabetes, immune deficiency, debilitating disorders, bed-wetting, seizures, tobacco and alcohol addiction?*

It's called a panacea. Some, including myself, would describe it as snake oil.

Now think of a tested and proved treatment, whose biological/biochemical mechanism is supported by, among others, in vitro studies, which is able to address all of the above conditions. If there is one, I'm all ears.

Let's look at some of the most common proven treatments. Because of their "wonder drug" nature antibiotics immediately spring to mind. But even they are only effective against bacterial infections not viral, and each antibiotic has its limits as to which species it can lick. Worse, antibiotics are limited by the fact that evolution favors those freaking bugs eventually outsmarting our weapon of mass decimation. The sheer number of bacteria and their extremely fast reproductive cycles means selection forces can act within years instead of millennia and longer. So as life-saving and indispensable as antibiotics are, they still cannot address anything beyond bacterial infection.

Of course there's a slew of other drugs such as statins, NSAIDs/analgesics/antipyretics, SSRIs, H2 blockers and proton pump inhibitors, beta blockers, calcium channel blockers, anticoagulant/antiplatelet drugs, insulins, ... Yet none of them claim to be able to treat the above encyclopedia of diseases. (Even SSRIs whose efficacy is controversial aren't claimed to be effective against infections, asthma, diarrhea, etc.; in fact they may have adverse side effects)

What about surgery? Well, obviously there is a whole range of surgical procedures depending on the disease/condition one is addressing. Heart surgery obviously is not going to cure a fractured tibia nor will any doctor in his right mind even suggest it. Kidney transplant does nothing if one has healthy kidneys and a brain tumor. Angioplasty certainly isn't called for if one has appendicitis or diabetes or anxiety disorders or infertility or anything in the above litany except for (certain) blockages in arteries.

Now mull over whether drugs and surgery are sensible and how plausible they are. Penicillin for instance was discovered by accident in one experiment--where a mold gate-crashed and screwed up a bacterial party. Further in vitro experiments confirmed the action of penicillin. And you can do such petri dish experiments for the current trove of antibiotics and show how they can in fact mess up the colony. Of course just having a chemical kill a dishful of bacteria tells us nothing about how it will do in the human body. Isopropyl alcohol will kill a multitude of microbial species too. But there are good reasons doctors don't prescribe isopropanol for internal use. And so you perform animal studies and clinical trials to ascertain both efficacy and, more importantly, safety at the effective dosages.

All drugs including antibiotics are chemicals. So are food, water, and air. So are hemlock, ricin, botox, and poison ivy. The body is a chemical factory. So it stands to reason that ingesting a chemical or getting it intravenously can and may have an effect on the body.

The action of a host of surgical procedures is common sense. If you place a stent in a blocked carotid artery which restores the diameter of that pipe then obviously you address the constriction and improve blood flow. You can even measure the before and after flow rate using ultrasound. Transplants are just as common sense. They're a direct analogue of parts replacement in machines. Excision of tumors also makes sense, particularly when that tumor is putting pressure on surrounding tissues. Removal of that feckless appendix specially when it's become a bloated home for a million pathogens is just as sensible.

So at least with these common treatment modalities, none of them claim to address a broad sweep of unrelated disorders. And all of them have a physical/biological/biochemical even common sensical basis for how they work and how they are suppose to treat disease.

But there is (at least) one modality that boasts of actually being able treat that long roster of conditions above. And that's acupuncture. A short introduction to the theory behind acupuncture:
In TCM (traditional Chinese medicine), the body is seen as a delicate balance of two opposing and inseparable forces: yin and yang. The concept of two opposing yet complementary forces described in traditional Chinese medicine. Yin represents cold, slow, or passive aspects of the person, while yang represents hot, excited, or active aspects. A major theory is that health is achieved through balancing yin and yang and disease is caused by an imbalance leading to a blockage in the flow of qi. Yin represents the cold, slow, or passive principle, while yang represents the hot, excited, or active principle. According to TCM, health is achieved by maintaining the body in a "balanced state"; disease is due to an internal imbalance of yin and yang. This imbalance leads to blockage in the flow of qi. In traditional Chinese medicine, the vital energy or life force proposed to regulate a person's spiritual, emotional, mental, and physical health and to be influenced by the opposing forces of yin and yang. (vital energy) along pathways known as meridians. Qi can be unblocked, according to TCM, by using acupuncture at certain points on the body that connect with these meridians. Sources vary on the number of meridians, with numbers ranging from 14 to 20. One commonly cited source describes meridians as 14 main channels "connecting the body in a weblike interconnecting matrix" of at least 2,000 acupuncture points.

For illustrations of these meridians go here, here and here among others.

Could "meridians" be just a fancy name for the network of blood/lymph vessels or the nervous system or muscle groups or some other system within the body? Apparently not. Meridians are a completely different phenomenon from anything we currently know of human anatomy. Thus, if we dissect a cadaver and look for meridians, we can mince the whole corpse, but neither we nor acupuncturists will be able to find these channels. You can take a microscope or any other instrument and examine every square micron of the body internally and externally and you won't see these meridians nor will you discover what they're made of. They're not made of nerves, vessels, muscles, or any tissue. We can't see them via dissection or fMRI, X-ray, ultrasound, CAT scan, PET scan, etc.

Dissecting human cadavers was taboo in ancient China [Shapiro p.50, Ernst & Singh p.52]. Needless to say back then they didn't have anything remotely close to any of our imaging technology. So how did the Chinese "know" of the existence of meridians thousands of years ago? They didn't. They merely came up with the idea of a network of energy or vital force conduits and happily took it for granted and passed on the "therapeutic" tradition and its supposed mechanism of operation down the generations.

And what about the vaunted energy form called qi? What kind of energy is this: chemical, mechanical, thermal, electromagnetic, nuclear? Or is it some new form which the ancients knew about but which scientists have been unable to discover? How do you measure this energy? What instruments can be used to detect it? Energy has to come from somewhere. What produces qi? And since energy dissipates where does qi go? We know human biochemistry pretty well. Our energy comes from chemical reactions made possible through the food, water and oxygen we take in. What metabolic processes are involved? It seems these questions can't be answered. Qi is some "energy" that can't be detected, or perhaps can be detected but only subjectively--not unlike the "human energy field" which touch therapists claim to be able to detect. But then 9-yr old Emily Rosa's study--published in the prestigious Journal of the American Medical Association--effectively debunked the claim of practitioners--mostly nurses--that they can sense this energy field. So is qi yet another imagined phenomenon which would be equally debunked if subjected to a blinded test of detection? Will another 9-year old to put an end to thousands of years of nonsense?

There are meridians which can't be seen, qi which can't be objectively detected or quantified. And then there are postulated mechanisms of cure which make little sense: Disease is said to be caused by blocked or unbalanced qi, and acupuncture is the method by which the flow of qi is unblocked or rebalanced. What does unblocking and rebalancing qi mean biologically, physiologically, etc.? What are the physical, physiological, biochemical processes involved? What happens at the cellular level? Can this unblocking, rebalancing of the undetectable qi be detected and measured?

The onus of proof is of course upon those who make the claim for the existence of new postulated phenomena. But no evidence has been provided. On the other hand, we've been looking inside the human body for centuries. And since the last century we've been scanning it too.We've also measured signals coming from it. But meridians and qi are nowhere to be found. Which naturally leads to the question: How then do today's acupuncture proponents know that meridians and qi are not just human constructs, that they in fact have empirical reality? What's the difference, for instance, between unseen channels that conduct some force or energy (poorly and vaguely defined as they are) and unblocking and rebalancing that energy and the claim that all human disorders are caused by undetectable gremlins in the brain and that realigning gremlin aura in a particular way cures the person of their disease? Neither meridians nor gremlins can be found, neither qi nor auras are detectable much less measurable, neither unblocking/rebalancing qi nor realigning auras have been shown to actually occur. These phenomena have no existence beyond the crania of their proponents. Acupuncture (as is our gremlin theory of disease) is pseudoscientific from the git go.

Even some acupuncturists have already given up providing tangibility to these concepts. A brochure by the China Acupuncture Health Center in Westford, Massachusetts, for instance, admits, "you can't look at [qi] under a microscope, you can't detect it with any scientific instrument. You cannot isolate it in any form or substrate" [Shapiro, p.48]. Just like invisible gremlins and their aura. Felix Mann, founder and president from 1959 to 1980 of the (British) Medical Acupuncture Society, is most explicit and forceful about the nature of these ancient concepts:
Acupuncture points, in the traditional sense, do not exist.... Meridians, in the traditional sense, likewise do not exist. [Mann p.3-4]

Some [researchers] have tried to find acupuncture points or meridians by measurement of the electrical skin resistance. Those with a microscope have tried to find specialised structures in the skin or subjacent tissue. Those who have the use of infra-red photography, Kirlian photography or ultrasound have all diligently searched for the elusive acupuncture point. Some have been "successful" and have described their findings in journals.

If only these researchers had realised that the traditional acupuncture point does not exist! [Mann, p.5]

The meridians of acupuncture are no more real than the meridians of geography. If someone were to get a spade and tried to dig up the Greenwich meridian, he might end up in a lunatic asylum. Perhaps the same fate should await those doctors who believe in meridians. [Mann p.31]

Given how 1. there is not a shred of evidence for the existence of meridians and qi, 2. there is hardly any scientific rationale for how needling the skin can produce the plethora of claimed therapeutic effects, and 3. acupuncture is claimed to be a panacea, with the ability of treat infectious diseases, psychiatric, reproductive,  gastroenterological, musculo-skeletal, respiratory, ... disorders, the prior probability that it is an efficacious therapy is extremely low. Even prior to testing and conducting trials there is no good reason to believe that acupuncture should work, anymore than chiropractic manipulation of the spine or pinching various points on the butt will cure the said litany of diseases.

In fact acupuncture can be likened to that other pseudoscience--chiropractic. It postulates a phenomenon of subluxation or misalignment of the spine. As with blocked qi, subluxations are said to be the cause of diseases. And while needling can unblock and rebalance qi, spinal manipulation can correct subluxations and cure the patient of his ailment. Just a needling is a panacea, realignment of the backbone is touted to be a cure-all.

So can pin pricks treat the host of disorders mentioned above? We should be most skeptical that they can. 


* This list of diseases comes from a pamphlet by Shenrong Liu, an acupuncturist who has a master's degree in Traditional Chinese Medicine from the Academy of Chinese Culture & Health Sciences in Oakland, California. She is (or was) a Chinese Medicine Physician in China and has been in practice for 20 years. She's currently practising TCM in the Philippines. In her pamphlet she writes, "According to the United Nation's World Health Organization, over seventy diseases can be treated effectively with acupuncture, including the following:" The above list of diseases then follows.



Edzard Ernst & Simon Singh. Trick or Treatment: Alternative Medicine on Trial. Bantam, 2008.
Felix Mann. Reinventing Acupuncture: A New Concept of Ancient Medicine, 2ed., Butterworth-Heinemann, 2000.
Rose Shapiro. Suckers: How Alternative Medicine Makes Fools of Us All. Harvill Secker, 2008.

Saturday, April 10, 2010

The lighter side of science

Watch science comedian Brian Malow here and here. Just an example from his repertoire of bar jokes:

Some helium gas drifts into a bar. The bartender says, "We don't serve noble gases in this bar." The helium doesn't react.

What a gas! Malow's jokes I mean.

And to add to his wonderful collection here's my own contribution:

A DNA molecule walks into a bar. The bartender says, "We don't serve double helices in this bar." The DNA  immediately turns around and splits.

Thursday, April 08, 2010

Why studies from China should be taken with a sack of salt

Nothing new in what follows. Actually the studies I cite below are all over five years old. Just that of late I've been in a discussion with a doctor (an MD) who's also an acupuncturist and the topic of publication bias came up. We both agree that Chinese studies are suspect. But then he makes the simplistic claim that studies in the West are also guilty of the same bias. True enough that those in English-speaking countries are also afflicted with publication bias. But just as corruption is more prevalent in some countries than in others so too is publication bias. There is a difference in degree. And this isn't just a prejudice. There is evidence showing that this is a bigger problem among Chinese studies.

For instance, a 1998 systematic review by Andrew Vickers et al. ("Do Certain Countries Produce Only Positive Results? A Systematic Review of Controlled Trials") showed that 100% of acupuncture studies from China, Taiwan, Hong Kong, Japan, Vietnam were positive while of those from English-speaking countries 60% from the UK, 53% from the USA, and 30% from Canada, Australia, and New Zealand were positive [Bausell p.170]. Furthermore,
when Vickers and his colleagues repeated the analyses with a much larger sample of trials involving treatments other than acupuncture (most of which involved conventional medical treatments), they basically came up with the same results: 98 percent of conventional Chinese trials produced positive results, as did 97 percent of Russian trials [Bausell p.169]

In their 1999 "Review of randomised controlled trials of traditional Chinese medicine" Jin Ling Tang et al. noted that besides reporting inadequacies, small trial sizes, limited use of blinding, inappropriate controls (use of a control treatment which in itself has not been shown to be efficacious), etc., there was a preponderance of positive findings among the RCTs which may be attributable to publication bias:
Most trials claimed that the tested treatments were effective, indicating that publication bias may be common; a funnel plot of the 49 trials of acupuncture in the treatment of stroke confirmed selective publication of positive trials in the area, suggesting that acupuncture may not be more effective than the control treatments.

Zhenglun Pan et al. in "Local Literature Bias in Genetic Epidemiology: An Empirical Evaluation of the Chinese Literature" have this to say:
Chinese studies typically suggest much stronger genetic effects than non-Chinese studies, and this may be even more prominent for the few studies that reach PubMed. Although Chinese studies are smaller than non-Chinese studies and thus even more underpowered, surprisingly half of them reach formal statistical significance for the evaluated gene-disease association. This exaggeration is seen across very diverse topics.

The larger genetic effects in Chinese studies are unlikely to reflect genuine heterogeneity in the effects of genetic risk factors across various "racial" descent populations. Heterogeneity due to ancestry should not have led always to larger effect sizes in all probed gene-disease associations. Therefore, the most likely explanation is publication bias against "negative" results or other selection biases in the chase for statistically significant findings. This explanation is further supported by our analysis of the expected number of statistically significant findings. Even if the average genetic effects in the Chinese studies were indeed as large as those observed, one would expect far fewer Chinese studies to have reached formal statistical significance on their own, given their small sample sizes. The alternative explanation that Chinese investigators may be targeting high-risk populations with particularly strong genetic effects is unlikely given these data.

In his November 22, 2005 PLoS article "Selection Bias in Meta-Analyses of Gene-Disease Associations" JL Tang comments on the above study by Pan et al:
In their study published in this issue of PLoS Medicine, Pan and colleagues compared genetic studies conducted in mainland China with those from other places. The researchers identified 12 gene-disease associations and compared a total of 161 Chinese studies and 309 non-Chinese studies. The Chinese studies were on average smaller in sample size than non-Chinese studies and appeared in the literature a few years after the first non-Chinese studies. Chinese studies in general reported a stronger gene-disease association and more frequently a statistically significant result. These two characteristics were more likely to occur in Chinese studies identified through PubMed than in those accessible only locally.

These findings suggest a variation or heterogeneity in the strength of the gene-disease association (often expressed in an odds ratio) observed between Chinese and non-Chinese studies. These studies are primarily case-control studies. Many factors may contribute to the variation in the estimate of odds ratio across such studies, such as the genetic make-up of the population studied, the type of patients included, the selection of controls, the quality of the study design, and the quality of the laboratory work. These factors could lead to either over- or under-estimation of the true odds ratio. However, it is difficult to conceive that any single factor, or combination of these factors, could consistently cause the exaggerated odds ratio in Chinese studies in all the topics (gene-disease associations) examined by Pan and colleagues. Selective publication is therefore a very likely and worrying explanation for their findings.

Selective publication can cause publication bias, which in turn could lead to false gene-disease associations in meta-analyses. It would be a disaster if a genetic screening program (in which healthy people are tested for a gene and offered a treatment if they test positive) were based on such a false association. Even if such a false gene-disease association were only subjected to further related investigations, this would be a waste of valuable resources for medical research.

Selective publication of positive studies in China and a few other Asian countries has been observed in clinical trials of acupuncture. However, selective publication by no means exists in only the Chinese literature. It is probably a common phenomenon in the entire field of biomedical research. Given the fact that positive studies are more likely to be published than negative ones, and given the pressure on researchers worldwide to publish in indexed journals (especially in international journals with high impact factors), selective publication is likely to continue in the foreseeable future. As compared with English-speaking countries, selective publication is perhaps more likely to occur in non-English-speaking countries where there are a small number of indexed journals to publish local studies.
That last line bears repeating: "As compared with English-speaking countries, selective publication is perhaps more likely to occur in non-English-speaking countries where there are a small number of indexed journals to publish local studies."



R. Barker Bausell. Snake Oil Science: The Truth About Complementary and Alternative Medicine. New York: Oxford University Press, 2007.

Wednesday, April 07, 2010

A dozen apples a day will likely not banish cancer risk away

Just in: An analysis by Paolo Boffetta et al., (Fruit and Vegetable Intake and Overall Cancer Risk in the European Prospective Investigation Into Cancer and Nutrition) concludes that there is "a very small inverse association between intake of total fruits and vegetables and cancer risk." The study used data from over 142,000 men and 335,000 women who had a high intake of fruits and vegetables.

Apparently, this mega prospective analysis supports the findings of previous studies:
In an accompanying editorial, Walter C. Willett, M.D., Dr.P.H., of the Harvard School of Public Health, notes that "this study strongly confirms" the findings of other prospective studies that high intake of fruits and vegetables has little or no effect in reducing the incidence of cancer, although it has been shown to affect the risk of cardiovascular disease.
That last point has to be emphasized. Just because eating more fruits and vegies has negligible impact on cancer risk doesn't necessarily imply it's worthless or doesn't have significant consequences for other conditions.

Saturday, April 03, 2010

Courts of science vs courts of law

Just learned from Andy Lewis of Quackometer that General Electric had sued Danish radiologist Henrik Thomsen for supposed inuendo concerning GE's MRI contrast drug Omniscan. Apparently GE did not like what Thomsen had to say about their product even if he was merely expressing safety concerns given that there was reasonable evidence to be wary of Omniscan. GE had a taste of its own medicine when Thomsen countersued. The giant probably didn't expect that. Well, last February GE had a change of heart and change of mind and dropped its libel suit. What the heck was it thinking in the first place when it tried to silence Thomsen?!

As you may know, journalist and author Simon Singh had also been sued for libel by the British Chiropractic Association (BCA) over his use of "bogus" in  the April 19 2008 edition of the Guardian.
The British Chiropractic Association claims that their members can help treat children with colic, sleeping and feeding problems, frequent ear infections, asthma and prolonged crying, even though there is not a jot of evidence. This organisation is the respectable face of the chiropractic profession and yet it happily promotes bogus treatments.
The judge who heard the case sided with the BCA. Singh appealed and after a costly battle a celebration is in order. Yesterday, the judges presiding over the appeal dealt a coup de grace to BCA's breathtaking inanity.

Among other things in their decision is this: 
We would respectfully adopt what Judge Easterbrook, now Chief Judge of the US Seventh Circuit Court of Appeals, said in a libel action over a scientific controversy, Underwager v Salter22 Fed. 3d 730 (1994):
"[Plaintiffs] cannot, by simply filing suit and crying 'character assassination!', silence those who hold divergent views, no matter how adverse those views may be to plaintiffs' interests. Scientific controversies must be settled by the methods of science rather than by the methods of litigation. … More papers, more discussion, better data, and more satisfactory models – not larger awards of damages – mark the path towards superior understanding of the world around us."

    So we've had both quacks and Big Pharma try to stifle critique by enlisting the courts. But as Easterbrook says scientific matters are not settled through litigation. Science has its own courts for arriving at the truth.