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Entries in Medicine (16)


A misguided attempt to regulate homeopathy

Source: Homeopathic remedies may only be prescribed by a qualified doctor, dentist or midwife under a new law agreed by federal ministers last week, and only by those qualified personnel with a diploma in homeopathy

Sigh. I appreciate the desire to control homeopathy, I really do. It is, pure and simple, a scam, and even by their own admission homeopaths are just selling pure bottled water. But this new law seems to completely miss the point. By restricting homeopathy to medical professionals you only cut out 20% of the market, and if anything you lend credance to their absurd claims. How is an untrained layman meant to discern real medicine from fake medicine when both are being prescribed by a qualified* doctor? 

Homeopathic medicines are a real problem in Belgium, being available in many pharmacies. Lydia even accidently bought homeopathic medicine for me once when I had severe ear pain. She was looking for a particular topical corticosteroid ear-drop and the pharmacist said they don't have that one, but she can give an alternative. Lydia was livid when she got home and translated the bottle to read that it was just over-priced water sold as real medicine. As much as I despise the scam artists who profit from homeopathic medicine, I would still let them operate, but I would propose two alternative regulations:

  1. All medical claims need to be supported by clinical trials audited and approved by the FDA, EMA or NICE. For homeopathic medicines this means that no medical claims can currently be made.
  2. Homeopathic "medicines" or any medicine not supported by clinical trials should not be permitted to be sold by any medical professional, as this carries an implicit endorsement of medical efficacy.

In other words, while well-meaning, this new law is the exact opposite of what the government should have done.


* "qualified" in the legal sense. In the practical sense, any doctor who prescribes homeopathy is clearly unqualified to prescribe real medicine. 


Pray for you? We can do a damn sight better than that!

I just listened to a BBC documentary called "The Marriage Breakers of Bangladesh". It is about an interesting NGO created and run by children. The NGO seeks to eliminate child marriage, which is already illegal in Bangladesh, but which often occurs anyway within the poorest and least educated parts of the population. Child marriage is about the worst thing that can happen to a young girl - it is institutionalised legal rape, it ends her education along with her childhood and guarantees the next generation will be born to young uneducated women - with the attendent negative prognosis that confers.

One of the less well-recognised catastrophes of child marriage is obstertic fistula. This use to be quite common, but now it is basically absent from the developed world, due to the increased age of women at birth and the better medical care. In regions where child marriage is common, however, obstertic fistula are also common - probably 100,000 new cases a year, with 2 million women living with a fistula. It is truly a horrible condition. A young girl, pregnant before she is mature, gets the baby stuck in the birth canal during delivery. Labour takes hours, even days, and the tight squeeze cuts off the blood circulation. The baby is born, but the tissue between the vagina and rectum is now dead, and rots away in her body. Scar tissue forms imperfectly, creating a constant leak of fecal waste from the rectum into the vagina. Unable to control her waste, the girl reeks and is divorced from her husband in shame. With no money, no education and often branded as a witch, the girl will typically try to return to her family. If she is very lucky, they take her back, but force her to live with the animals due to her smell. More often she is unlucky, and is stoned to death for witchcraft or slowly starves to death as a social outcast on the edges of the village.

The BBC journalist interviewed one thirteen year-old girl, married and then cast off with a fistula. She was resigned about her life and could not see any escape. She ended by just asking the journalist to "Pray for her". As the journalist panned to the next conversation I was furious. He should have shouted to that little girl, "Pray for you? We can do a damn sight better than that!" A fistula is highly treatable. The Fistula Foundation repairs tens of thousands of fistulas. The cost of the BBC repairing that girl's health and dignity? $450. Surely the BBC budget would cover $450 for a hard-hitting interview? Surely they are ethically obliged to? How dare they swan in, take the soundbites they need, and then leave that girl to her misery? I applaud the BBC for bringing attention to the plight of the millions who suffer from fistulas, but I shake with rage at the thought of them turning their back on that one poor little girl.


Are all homeopaths evil?

This homeopath, who "diagnosed" fake cancers and then used alternative medicine to rape patients while pretending to cure the clearly evil:m

[One] victim, who had experience of and was interested in alternative therapies, told the court that Mr Gill had examined her internally before telling her she had cancer and that he could "get rid of most of it today".

He then inserted an instrument inside her which gave her electric shocks. The court was told that after 20 minutes Mr Gill removed the machine and he and Mrs Gill rubbed oil on her chest before using another machine on the same area.

Initially the victim had told police that she didn't think Mr Gill was getting any sexual gratification but she later said his heavy breathing suggested he was.

This guy goes beyond contemptible, even for a homeopath, but it does raise the question as to whether there are any good homeopaths. Obviously the science is clear - homeopathy is a sham - and it is also clear that being encouraged to take homeopathy instead of actual medicine is causing harm. But what I wonder is whether the homeopaths causing this harm have good but misguided intentions, or whether they are all con-artists, preying on the gullible. [In the case above, which belief is the more gullible, a) you need a man to suck your nipples every day to cure your cancer; or b) you need to drink this vial of pure water with no a molecule of active ingredient to cure your cancer?]

I guess it would be nice to assume that on the whole homeopaths are well-meaning people who just have no clue about the scientific method or medicine and honestly believe that they are helping rather than causing harm. But if that was the case, shouldn't we see lots of homeopaths out there trying to bring their cures to the world? Where is "Homeopaths Without Borders"? Where are the homeopaths volunteering to work in prisons? No "Flying Homeopaths"? No homeopaths working in the forgotten tribes that have no medical care? Pharmaceutical companies are not known for their altruism, but drugs that are off-patent typically have a profit margin of less than 10%, and most of the larger companies provide discounted drugs to the least-developed countries. By contrast, the profit margin of homeopathic "drugs" is nearly 100%, so if homeopaths honestly thought their drugs worked, wouldn't they be dropping their prices to reach out to the masses?


Indian medical scams

There are a lot of excellent clinicians in India, struggling to provide top level medical treatment under resource-constrained conditions. Listening to the work of Dr Revathi Raj at Apollo Speciality Hospital in Chennai was inspirational, the work they do under such limitations is amazing. The financial constraints cut both ways, with equipment and medicines limiting in the hospitals, and with much of the population unable to afford even a basic level of care. India runs on private health care, which kills the rural poor, especially young girls. A poor rural family will use up a substantial proportion of their income on a single doctor's visit, so they tend to wait far too long to see a professional. If the sick family member is a young girl, they tend to wait even longer - a death sentence in serious cases, and part of the reason why the sex ratio is reversed in India compared to Europe. Access to medicines is higher, because generics are allowed even for medicines under patent in the rest of the world and no prescriptions are required. But quality is variable due to under-regulation of the generic industry and self-prescription has created an enormous problem in drug-resistance.


Under these conditions, unsafe alternative practices have sprung up, such as this street in Delhi where "dentists" sit by the side of the road and wait for customers. We saw one customer visit and receive the only treatment available - sit on this stool why I pull your sore tooth out with a pair of pliers.

At least these patients where getting some treatment, even if it resulted in many toothless grins. Other street practioners are simply scam artists, such as this street rekki I saw in Chandigarh:

Homeopathic clinics were especially rife, setting up shop all over Delhi and scamming people too poor for real medicine.

Even normal pharmacies stocked large shelves full of junk like this:

It makes me especially angry when fake medicines sit on a shelf next to real medicines, picking up credibility by association. A pharmacist is meant to be a medical professional providing a service, when they sell fake drugs they show themselves to be unconcerned about the welfare of their customers, and concerned only with their wallet.


Modern medicine is not "Western medicine"

Earlier I made the argument that modern values should not be called "Western values". The case for not calling modern medicine "Western medicine" is even stronger. There are two basic ways of thinking about the evolution of medicine, the historical and the methodological, and in neither case is "Western" an appropriate adjective.

The "Father of Paediatic Medicine" (he was not Western)Using the historical perspective, we talk about traditional medicines and modern medicine. Traditional medicines were a diverse set of health practices with a strong regional basis, so it is fair to talk about Indian traditional medicine, Chinese traditional medicine, Aboriginal traditional medicine and so forth. Western traditional medicine was one of these regional practices, and involved practices such as blood-letting, prayer and a bunch of (mostly lethal) herbal treatments. Modern medicine grew out of an algamation of the best practices of all of these traditional medicines, while discarding the worst practices of each.

The centre of modern medicine has shifted over time: it certainly has not always been "Western". Indeed, western Europe was the backwater of medicine for thousands of years - while European doctors were prescribing leeches for every condition the Islamic world was pioneering medicine that we would truly call modern. The foundations of modern paediatrics, pharmacy, surgery and ophthalmology were all set in the Islamic world, drawing on traditions from Greece to Egypt, from Persia to India. Western traditional medicine has probably contributed less to modern medicine than most other traditional medicines. In the 19th century it could be argued that the most advance occured in continental Europe, and in the 20th century in the Anglo-American world, but today modern medicine is truly a global endevour, and the research community is the most international of professions. To call modern medicine "Western medicine" is to cherry-pick that moment in time when the Western world was the leader, ignoring all that came before it and has developed since. Visiting a hospital in China, Ghana, Peru or America you will see the same techniques, philosophy and equipment, making modern medicine "global medicine".

Alternatively, we can talk about medicine using the methodological perspective. Here there have been two major approaches to medicine, the faith-based approach and the evidence-based approach. In general, traditional medicinal practice is based on faith in the effectiveness of the medicines. Western traditional medicine is no different - the use of prayer as a standard healing technique is an obvious example of faith, but equally the adherance of physicians to blood-letting for a thousand years despite all the patients it killed was a sign of faith in the technique, rather than a constant reapprasial of its success. Likewise other traditional medicines are a mismash of techniques, some that work well, some that do nothing and some that can be fatal, but all diligently implemented as the knowledge is transmitted whole rather than critically analysed.

The evidence-based approach to medicine is radically different. It takes hypotheses from tradition or new research, and then simply puts them to the test. If they work they stay, if they fail they are discarded. If anything, the ability to discard failed techniques is the most important aspect of evidence-based medicine, and the key distinction between modern medicine and traditional medicines. Modern medicine continually gets better because it is open to any new ideas but it throws away the ones that don't work. "Alternative medicines" do not throw away techniques that have been proven not to work, so the stagnant approach maintains both harmless voodoo approaches and harmful treatments.

So modern medicine at its best is pure evidence-based medicine, willing to take in any treatment from any tradition, so long as it passes a scientific test. Scientific enquiry is not uniquely Western, it is the shared inheritance of the world and was developed as a global endevour. To call science "Western" is to have a parochial view of science, taught as a school subject where the home-grown heroes are the only figures worth mentioning. We don't call evidence-based engineering "Western engineering", so why do people insist on calling evidence-based medicine "Western medicine"? We don't let self-trained self-proclaimed "alternative engineers" erect skyscrapers, so why do we allow "alternative healers" to treat patients in genuine need?


Facts and Myths about HIV & Circumcision

Fact: Circumcision protects against HIV infection

There are three tiers of evidence for the protective effect of circumcision against HIV infection. Firstly, there are the epidemiological observations, where rates of HIV in circumcised and uncircumcised populations are compared. Secondly, there are the case-control observations, where rates of HIV in circumcised and uncircumcised individuals are compared. And thirdly, there are the randomised clinical trials, where men are assigned to either circumcision or no circumcision and the effect of future HIV infection is compared. 

We can deal with these in turn. The first are the epidemiological surveys. There are multiple relevant studies, all with similar effects, but one of the best designed is the multicentre study set in four cities in different regions of Africa. These studies show a much lower rate of HIV infection in west and north Africa compared to east and south Africa. The infection prevalence closely mirrors the religious border, with lower rates in Muslim Africa and higher rates in Christian Africa. Despite the glee with which certain Muslim scholars touted this as a representation of increased sexual restraint among Muslims, the multicentre study showed very few differences in sexual activity (number of sex partners, prostitution levels, etc). This is not evidence for the role of circumcision in protection against HIV, but it is very strong evidence that something is different between these two communities and that it has a strong role in protection against HIV.

The epidemiological studies lead multiple groups of researchers to investigate the circumcision hypothesis using case-control experiments (comparing the infection rate in circumcised and uncircumcised men). With dozens of different studies, all of various quality, the best way to assess the results is from the systematic reviews that have been performed. General population studies. This systematic review in 2005 looked at all 36 studies into circumcision that had been performed to date. Among the 18 general population studies, seven studies showed a protective effect and two studies showed a harmful effect (right). The difficulty of general population studies is that the rate of HIV infection is low enough that it can be difficult to control for bias and to generate enough statistical power. High-risk studies, by contrast, tend to have higher HIV rates and to have less bias in risk factors, often leading to additional statistical power. Among the 18 high-risk group studies, 13 studies showed a protective effect and no studies showed a harmful effect (left). High-risk population studies Thus, over all, of the 36 studies, 20 showed a significant protective effect, 2 showed a significant detrimental effect, and 14 had insufficient power to draw a conclusion. For anyone who is used to looking at research on inbred mice or the like, this data looks very noisy, however with the immense variation of behaviour and exposure among the human population this type of noise is typical, and the noise in the results are comparable to that observed in condom use studies. One interesting observation is that the studies where circumcision status was actually assessed by the trial nurses showed a stronger (beneficial) effect than the studies where circumcision status was self-reported, other studies show that the error-rate in self-reporting circumcision can be as high as 10%. Overall, the average effect of these trials is a 60% protective effect on HIV infection, again comparable in scope to the average effect observed in condom use studies (~80%).

The key criticism of any case-control study is that there may be confounding effects. When these confounding effects are known (eg number of sexual partners) they can be controlled for, but when confounding effects are unknown they cannot be controlled for. It is therefore always theoretically possible that there is some unknown confounding effect that has a strong correlation with circumcision and is protective against HIV infection. The only way to control for this possibility is to have a randomised clinical trial, where HIV-negative men enroll and are then randomly assigned to either the control group or the circumcision group. In this ideal experiment any confounding factors will be randomised to the two different groups and the effect only of the treatment can be identified. This randomised clinical trial design is the exact experiment performed by three independent groups.  

The study by Auvert et al enrolled a total of 3,274 uncircumcised men in South Africa, tested for HIV and assigned half to be circumcised. The group then followed up both cohorts for HIV status, condom use, sexual activity and so forth, and found a 60% protective effect for HIV infection among the circumcised group. Condom use, sexual activity and the like were nearly identical among the two groups, normalisation for these factors resulted in a 61% protective effect. The study by Bailey et al enrolled uncircumcised 2784 men in Kenya, tested for HIV, assigned half to be circumcised and again followed up for HIV infection and behaviour change. Again, no changes in sexual behaviour were observed and the risk of HIV was reduced by 60%. Finally, the study by Gray et al, with a similar design in Uganda, enrolled 4996 uncircumcised men and found a net protective effect of 60%. All three trials were independently run along best practice guidelines with blinded tested, yet all three trials found the identical effect of 60% protection - which was also the average protective effect observed in the case-control studies. Together, with multiple independent lines of evidence pointing towards the same result, the effect can be considered conclusive, to the point that it is now considered unethical to conduct more clinical trials as it would mean withholding treatment to the control group - the same way that we cannot ethically conduct more clinical trials on proven vaccines.

Several reoccurring criticisms come up for these three clinical trials. The most common objection is that all three trials were stopped early. This is true, however they were specifically stopped early by the ethical board review because the results were clear early on. It is now a built-in feature to clinicial trials that intermittent review will take place and the trials will be halted if adverse events surpass a particular level (so that excess participants are not exposed to the treatment) or if the protective effect surpasses a particular level (because it is considered unethical to withhold the treatment from the control group at this point). This is not a unique feature of the circumcision trials and is an agreed upon compromise between getting perfect scientific results and treating the participants of the trial in an ethical manner. The other main criticism that is raised is that the control group for circumcision is not like a traditional placebo - the trial doctors are blinded but the participants are not, and those assigned to the circumcision group may drop out at higher rates, creating a bias. While theoretically possible, each of the three studies investigated this possibility by looking at the drop-out rate. For example the Gray study found that out of 4996 enrollments, only 37 dropped out (24 in the circumcision group and 13 in the control group), not enough to create any substantial bias.

One further comment. The direct protective effect of circumcision is only known to protect men during vaginal intercourse. It is also likely to protect men during anal intercourse, but this has not been studied. It provides little to no direct protection to the woman, however mathematical modelling suggests that when the take-up of circumcision reaches 50% the "herd immunity" effect would reduce HIV infection among females and uncircumcised men by 25-30%. While not exactly a "silver bullet", this would make an impact to millions of people within southern Africa, where existing circumcision rates are low.


Myth: the foreskin must be functional or it would have been eliminated by evolution

This myth comes in two flavours. The first is that because it is present it must be functional, the second that if it actually was detrimental in HIV infection it would be selected against. As to the first, evolution does tend to result in the loss of anatomical features with no function, however there are strong exceptions for sexually dimorphic features. Thus a male nipple has no function, but there is strong sexual selection to keep the female nipple. In the absence of selection to create a suppressive pathway against nipple development in males, the useless male nipple is maintained. In all likelihood the foreskin is similar to the male nipple, as the male relic of the female labium. As to the second argument, it must be remembered that evolution is responsive, not predictive. Prior to the entry of widespread HIV infection there would have been no evolutionary pressure against the foreskin. If HIV had been a common infection for millions of years, the continued existence of a foreskin would indeed be a mystery, but this is not the case.


Myth: HIV protection is just a matter of cleanliness

A commonly stated myth about circumcision is that the HIV protection is simply due to the ease of keeping the circumcised penis clean and that good hygiene would replicate the effect. As a starting hypothesis, this is not an unreasonable model to test. A prediction of this model would be that circumcision would protect against a broad range of sexually transmitted infection (STIs), as the "cleanliness hypothesis" would not predict any special status for HIV protection. The ability of circumcision to protect against multiple STIs has been tested in epidemiological studies and randomised trials and so far no effect has been reliably measured for any STI other than HIV. It is possible that for some rare STIs in addition to HIV there may be protective effects and also possible that there is a weak effect against HSV, but to date the evidence against the "cleanliness hypothesis" is very strong - the protective effect of circumcision does not appear to be due to differential cleanliness and is almost certainly due to the unique biological properties of HIV outlined below.


Myth: there is no known biological mechanism to explain the protective effect of circumcision on HIV

The gold standard for incorporating a technique into evidence-based medicine is success in randomised clinical trials, as already proven for circumcision. However medical researchers prefer to understand the mechanism of protection for any intervention, as it allows optimisation or replacement with simpler strategies. It is sometimes claimed that there is no plausible mechanism by which circumcision protects against HIV, however a review of the literature demonstrates that the known biology of HIV suggests an optimal infection route via the foreskin. Unlike some sexually transmitted viruses, like HPV, that are able to directly infect through the skin, HIV is an exceptionally poor virus at crossing the epidermal barrier - purified HIV placed on the skin will remain safely external. Instead, HIV has to rely on two different mechanisms to breach the epidermal barrier - microabrasions and cellular trafficking.

Microabrasions are small tears in the skin barrier which expose the inner tissue and blood to the environment, allowing a direct passageway for HIV to enter. One common cause of microabrasions are sexually transmitted diseases, which often form small ulcers to allow increased shedding. These ulcers allow the reverse infection of HIV, which is why the transmission rate of HIV increases 100-fold with coinfection with other sexually transmitted infections (such as HSV-2). This accounts for the recent data suggesting that anti-HSV-2 treatment programs may reduce HIV spread. The skin of different organs is more or less prone to microabrasions. The mucosa of the anus is the thinnest, followed by the vagina, followed by the oral cavity, followed by the penis, which correlates with the increasing risk of HIV acquisition per sexual act (anal receptive > vaginal receptive > oral receptive > insertive).


The second mechanism is that of cellular traffic. HIV infects through the CD4 receptor, using the coreceptors CCR5 and CXCR4. The expression pattern of these receptors limits the infection of HIV to CD4 T cells, macrophages and dendritic cells. Typically, these cells are found in circulation (which is why intravenous injection of HIV in contaminated blood provides the highest efficiency infectious route), but activated CD4 T cells and naive dendritic cells also circulate into the tissue. In the skin, the top layer is a keratinised barrier with dead cells, with the living tissue deep below this layer. The mucosa is quite different - as a functional interface it requires living cells to directly border the environment. While most of these cells are epithelial in origin, and hence not infected by HIV, dendritic cells lie just below the surface. The reason for this is the role of dendritic cells in antigen sampling, ironically a defense mechanism against common mucosal pathogens. Critically, these dendritic cells do not only lie just below the surface, but the also push thin dendrites through the epithelial cell barrier so that they directly contact the surface (right). We even know exactly how the dendritic cells form these dendrites, as a key paper in Science demonstrated that dendritic cells that lack the chemokine receptor CX3CR1 still home to the epithelial cell surface, but they are unable to produce the dendrites that penetrate to the surface (left).

With regards to circumcision, the key risk is the region of the inner foreskin, which has more in common with the mucosal surface of the vagina than with the keratinised surface of the rest of the penis. During an erection the inner foreskin of the uncircumcised penis is exposed (right), creating a region of relatively thin tissue that does not exist on the surface of an erect circumcised penis. This is the tissue that is thinner and populated by surface level dendritic cells, so it is also the tissue which is most prone to microabrasions and to cellular trafficking via infected dendritic cells. In the circumcised penis this tissue is absent, with the region covered in a thicker layer of non-mucosal skin. It is therefore likely that the biological mechanism of circumcision protection is simply the removal of this mucosal surface during intercourse.


Fact: Condoms are more protective than circumcision

The protective effect of circumcision on HIV is around a 60% lifetime protection. For single event condom use the protective factor is around 99% (with a 1.6% slippage factor), which results in an 80% protection rate. When condom usage is accompanied by sex ed classes on how to use a condom correctly the lifetime protection rate goes up to 95%. Clearly a correctly used condom is more protective than circumcision.

However, it is important to note that this does not mean that circumcision has no added value. In the randomised control trials men were still advised to wear condoms, but as you might expect 100% condom usage was not achieved (total condom usage was the same in both groups). The protective effect of circumcision in these trials is therefore an additive effect on top of typical condom usage. Public health is an experimental science and it needs to differentiate between the ideal effects of a treatment and the actual effects of implementation. For example, assuming that all sex was consensual (clearly not the case), voluntary abstinence would block the transmission of HIV. The ideal effect is therefore 100% protection. What happens when abstinence advice is rolled out as a campaign? Absolutely nothing. Circumcision may provide little additional protection when combined with ideal condom use, but in terms of public health what matters is that it provides substantial protection when combined with actual condom use.


Myth: Religious circumcision originated because of the health benefits

A number of religious supporters have lept upon the scientific evidence for the protective effects of HIV as support for ritual religious circumcision. They tout the proposition that the religious tradition of circumcision is validated by the scientific evidence, which therefore validates other aspects of their religion. This is by far an overly generous idea, for several important reasons:

1. While the western world tends to think of circumcision as the removal of the entire foreskin, anyone familiar with men would not be surprised to find out that religion has found many weird ways to manipulate the male penis. For example, there is the dorsal slit circumcision, where the foreskin is cut only along one side of the penis, leaving it flapping below. In some places it is then common to create a hole in the free foreskin and fold it back over the penis, sometimes called the "cowboy cut" as the result looks a little like a cowboy hat. While most of these traditional circumcisions have not been tested for protective effects, based on the biological mechanism of HIV protection, it is highly likely that only the full foreskin removal will result in substantial protection.

2. HIV only originated within the past 100 years, so any protective effect of circumcision would have been non-existent at the time these practices originated. As circumcision has little to no protective effect to other STIs, there is currently no scientific basis on which to claim the practice was beneficial at the time they originated.

3. Ritual circumcision in traditional contexts is highly dangerous. These surgical operations were carried out in non-sterile circumstances by untrained religious leaders. This stands in stark contrast to the modern non-surgical approach to circumcision, where typically a band is used to cut off blood circulation to the foreskin so that it falls off - in exactly the way the umbilical cord is removed, leaving behind the belly-button. While modern (secular) circumcision has extremely low rates of complication (on the order of 1.5% minor events such as swelling, 0% severe events), traditional/religious circumcision can have much higher rates of complication (with adverse event reports of over 10% reported, including severe events). The cost-benefit ratio of religious circumcision was therefore almost certainly a net negative, while the cost-benefit ratio of modern secular circumcision produces a net positive.


Myth: Circumcision reduces the pleasure of sex

This is a very common myth used in opposition of circumcision, often accompanied by an anecdote of some man they know who has a "botched" circumcision and now has pain during sex (anecdotes of uncircumcised men who have pain during sex are duly ignored). Fortunately, in science we can actually go beyond anecdotes and look at some hard data on sexual pleasure.

Who needs a peer-reviewed study when you have a placard and a website?Firstly, what are the effects of circumcision on subsequent adult sexual pleasure?

* when 1410 American 18-59 year old men were asked if they had "trouble achieving sexual gratification" in the past 12 months, around 45% of men reported sexual dysfunctional, with slightly higher rates in uncircumcised men. This small decrease in sexual dysfunctional in circumcised men remained significant even after controlling for variables such as race, age and sexual preference.

* the same study found that circumcised men had a more varied sexual practice, with more masturbation and oral sex, inconsistent with a hypothesis that sex is less enjoyable to circumcised men.

* Payne et al directly tested the sensitivity of circumcised and uncircumcised penises by measuring the response to touch on the ventral and dorsal surfaces. No difference was observed in sensitivity between the two groups.

* most studies are performed on men circumcised as infants, with relatively few men being circumcised as adults. The recent push for adult circumcision in Kenya has allowed a survey of men before and two years after adult circumcision (with a randomised control group). No increase was observed in sexual dysfunction and most men actually reported an increase in sexual pleasure (64% said their penis was "much more sensitive" and 55% said it was "much easier" to reach orgasm). A Ugandan study found that men circumcised as infants were more likely to have earlier and more promiscuous sex than uncircumcised men.

Not all studies find such strong results as the Kenyan survey, which suggests a strong increase in sexual pleasure. Indeed, the three randomised clinical trials for HIV protection found no change in sexual behaviour. Thus the conservative reading of these studies would be that there is no decrease in sexual pleasure among circumcised men, whether circumcised as infants or adults. The only plausible exception may be within the group of men who have religious-traditional (non-modern) circumcision, where relatively little study has been performed.


Myth: Circumcision is the male equivalent of female genital mutilation

Female genital mutilation is the practice of scraping away part or all of the external genitalia of a woman, typically the removal of the clitoris and labium. While it is euphemistically called "female circumcision" it has almost nothing in common with male circumcision. Sexual dysfunctional, while not ubiquitous, is increased in women who have been genitally mutilated, and sexual pleasure is generally decreased. Multiple health risks are associated with the practice, especially increased risk of complication and even death during childbirth. Female genital mutilation is not protective against HIV, and may even increase the risk of HIV infection, either during the mutilation procedure itself or due to additional tissue damage during sexual intercourse. Male circumcision should never be compared to female genital mutilation, a procedure that is more akin to penectomy.


Do parents have a right to circumcise an infant, or should they wait until he can make his own decision in adulthood?

The Declaration of the Rights of the Child upholds the right of children to have autonomy as individuals. This does not, however, preclude parents making decisions in the interest of the child, as a child cannot be considered to be truly autonomous. There are multiple examples that are widely accepted for parents making decisions for a child - such as in the area of education. The best comparison to infant circumcision is that of vaccination: both confer protection to infectious disease, both are irreversible and both result in a small chance of minor side-effects (such as swelling for a few hours to days). While this provides a basis for parental right to circumcision, it does not provide an unrestricted mandate - the least damaging form of intervention must be used (ie, non-surgical sterile circumcision over religious circumcision) and the benefits need to be placed in context to alternative (eg, if a vaccine for HIV is successfully generated the rationale for circumcision will be lost, just as the eradication of smallpox eliminates the rationale for the smallpox vaccine - a procedure with more complications than infant circumcision).

Another version of this objection, with somewhat more validity, is that since HIV is generally a sexually transmitted disease the protective effects do not kick in until the child reaches adulthood and has sex, at which time he can decide for himself. Well... perhaps, although it would be naive to assume that all men wait until they are 18 to have sex. Even if you were to wait until the age of 16, the surgical advice for adult circumcision is to have no sexual intercourse or masturbation for at least two weeks following the procedure. That may be quite a hard sell to a 16 year old boy, while being entirely irrelevant to an infant. Again, the best comparison is to vaccination. We have available an outstanding vaccine against human papilloma virus (HPV), which provides substantial (but not 100%) protection against cervical cancer in women who catch HPV. As HPV is a sexually transmitted disease you could advocate that this procedure should also be delayed until the age of 18, but with such mild side-effects as tenderness for a couple of days why not vaccinate all children as young as possible? Several Christian groups object to the HPV vaccine of girls on the basis that it will create "moral hazard" and promote promiscuous sex, but there is no actual evidence to suggest that girls are refraining from sex due to a fear of cervical cancer, and no evidence to suggest that the vaccine changes the rate of sexual activity.


The verdict on Andrew Wakefield: Fraud

In 1998 Andrew Wakefield published a paper which has severely damaged public health in the last ten years. Based on his observations of only twelve children, nine that he claimed had autism, and without a control group, he concluded that the measles/mumps/rubella vaccine caused autism. As a hypothesis, this was fine, unlikely, but not impossible. He saw nine children with autism, reported that their parents linked this onset with the MMR vaccine, and put it in the literature. Why on earth on underpowered observation like this made it into the Lancet is beyond me, but there is nothing wrong with even outlandish hypotheses being published in the scientific literature. Was it a real observation, or just an effect of a small sample size? Was it a causative link, or just due to coincidence in timing?

As with any controversial hypothesis, after this one was published a large number of good scientists went out and tested it. It was tested over and over and over again, and the results are conclusive - there is no link between the MMR vaccine and autism.

In itself, this was of no shame to Andrew Wakefield. Every creative scientist comes up with multiple hypotheses that end up being wrong. People publish hypotheses all the time, then disprove them themselves or have them disproven by others. If you can't admit being wrong, you can't do science, and it is in fact the mark of a good scientist to be able to generate hypotheses that others seek to knock down. Ten of the thirteen authors on the study were able to see the new data and renounce the hypothesis.

The shame to Andrew Wakefield is not that his hypothesis was wrong. No, the shame he has brought upon himself was by being unscientific, unscrupulous and unethical:

  1. Firstly, Wakefield did not present his paper as a hypothesis generator, to be tested by independent scientists. Instead he went straight to the media and made the outrageous claim that his paper was evidence that the MMR vaccine should be stopped. This is not the way science or medicine works and was a conclusion unsupported by the data. Worst of all it was a conclusion that many parents without scientific training were tricked into believing. Vaccination rates for MMR went down (autism rates have remained unchanged) and children started dying again of easily preventable childhood diseases. A doctor does not see half a dozen children that developed leukemia after joining a football team and then hold a press conference telling parents that playing sports causes cancer in children, which is the direct equivalent of Wakefield's actions.
  2. Secondly, it has now been conclusively demonstrated that his original data was fraudulent. Interviews with the parents of the original nine children with autism show that he faked much of the data of the time of onset, taking cases where autism started before the MMR vaccine and reversing the dates to suggest that the vaccine started the autism. Analysis of the medical records of these children show that as well as the timing being incorrect, many of the symptoms were simply faked and non-existent. The evidence on this charge alone makes Wakefield guilty of professional misconduct and criminal fraud.
  3. Thirdly, unknown to the coauthors of the study and the parents of the children, Wakefield had a financial conflict of interest. Before the study had begun, Wakefield had been paid £435 643 to find a link between vaccines and disease as part of a lawsuit. Every scientist must disclose their financial interests in publication so that possible conflicts are known - Wakefield did not. If he had disclosed this to the press conferences the media may have been slightly more skeptical about his outlandish claims.

These last two issues, scientific misconduct and financial conflict of interest, are the reason why the paper was formally retracted by the Lancet. Studies that are wrong don't get retracted, they just get swamped by correct data and gradually forgotten. Instead, the retraction indicates that the Wakefield paper was fradulent and should never have been published in the first place. Likewise, the British General Medical Council investigated the matter and found that Wakefield "failed in his duties as a responsible consultant" and acted "dishonestly and irresponsibly", and thus struck him off the medical registry.

The worst part about this sorry affair is that it is still dampening down vaccination rates. Literally hundreds of studies, with a combined cohort size of a million children, have found no link between the MMR vaccine and autism, yet one fraudulent and retracted study of nine children is still talked about by parents. Some parents are withholding this lifesaving medical treatment from their children, and their good intentions do nothing to mitigate the fact that cases of measles and mumps are now more than 10 times more likely than they were in 1998, and confirmed deaths have resulted. And Andrew Wakefield, the discredited and disbarred doctor who started this all? Making big money in the US by selling fear to worried parents, and deadly disease to children who have no say in it at all.


"Alternative medicines" are not just ineffective, they kill

I hate this fluffy thinking that divides medicine into "alternative medicine" and "Western medicine". Rubbish. "Alternative medicine" just means medicine that has either a) not been proven to work, or b) has been proven not to work. Anything that works is evidence-based medicine, or (as we call it in the trade) "medicine". Traditional medicines from around the world have been tested, and the ones that actually work get incorporated. Yes, willow bark actually helped with headaches, hence aspirin. Yes, cinchona bark actually worked for fevers, hence quinine. Others didn't work, such as the stupid habit of opening the veins of people and bleeding them out for food poisoning, raping virgins to cure HIV or eating crushed tiger bones for male impotence. Medicine gets better and better every year, because it incorporates every therapy that works, whatever the source. By contrast, "alternative medicines" get worse and worse every year, because anything that has an ounce of truth behind it gets refined, improved and turned into actual medicine.

Yet the massive multi-billion dollar industry of medical fraud is stronger than ever, because it promises whatever people want the most. The fraudsters are either completely self-deluded, with illusions of grandeur, or as cold and calculating as any Nigerian lottery scam artist. I don't like seeing these people make a cent from conning decent people, but the general attitude seems to be "oh, it can't do any harm". I beg to differ. "Alternative medicines" do a lot of harm.


"Alternative medicines" kill

There seems to be this odd idea that "alternative medicines" couldn't possibly do any harm because they are natural. Yeah, so are nightshade and foxglove, and they are deadly. Most "alternative medicines" won't kill a healthy person on the spot (or even the most avid fan might learn), except of course they are sold to people with underlying disease, who are exactly the people that can have a fatal reaction against a compound that most of us could take without consequence. One example is royal jelly, touted as a cure-all and sold to asthmatics, yet it can cause fatal anaphylaxis in asthmatics - the target clientele. Acupuncture, harmless, right? Well no, at least 86 people have been directly killed by acupuncture, due to punctured organs, damaged arteries, shock, infection, pneumothorax and haemorrhage. Even new-age rubbish that doesn't involve drugs or needles can kill, such as the pseudo-psychology of "rebirthing" where children are traumatised and occasionally killed.


"Alternative medicines" get in the way of real medicine

Of course, the number of people dying due to acupuncture, rebirthing, royal jelly and the like are a drop in the bucket compared to the number of people who die because they used ineffective "alternative medicines" instead of real medicine. Who knows how many people have died because they stayed home and took aromatherapy instead of going to the doctor? Or they used the "power of crystals" to try to cure that headache for months, before a hopsital visit found that brain tumour too late. Or who replaced effective vaccines with over-priced fruit juices, putting both themselves and their community at risk? I would love to think that the use of "alternative medicine" had no impact on the uptake of real medicine, but we know that is not true - for example people who believe in divine healing are less likely to stay on their HIV medications, certain death for them and a recipie for the generation of antiretroviral resistance HIV strains. Those harmless peddlers of placebos have a lot to answer for.

From Saturday Morning Breakfast Cereal


2010s worst failure in peer review

Even though it is only August, I think I can safely call 2010s worst failure in the peer review process. Just as a sampler, here is the abstract:

Influenza or not influenza: Analysis of a case of high fever that happened 2000 years ago in Biblical time

Kam LE Hon, Pak C Ng and Ting F Leung

The Bible describes the case of a woman with high fever cured by our Lord Jesus Christ. Based on the information provided by the gospels of Mark, Matthew and Luke, the diagnosis and the possible etiology of the febrile illness is discussed. Infectious diseases continue to be a threat to humanity, and influenza has been with us since the dawn of human history. If the postulation is indeed correct, the woman with fever in the Bible is among one of the very early description of human influenza disease.

If you read the rest of the paper, it is riddled with flaws at every possible level. My main problems with this article are:

1. You can't build up a hypothesis on top of an unproven hypothesis. From the first sentence it is clear that the authors believe in the literal truth of the Bible and want to make conclusions out of the Bible, without drawing in any natural evidence. What they believe is their own business, but if they don't have any actual evidence to bring to the table they can't dine with scientists.

2. The discussion of the "case" is completely nonsensical. The authors rule out any symptom that wasn't specifically mentioned in the Bible ("it was probably not an autoimmune disease such as systemic lupus erythematousus with multiple organ system involvement, as the Bible does not mention any skin rash or other organ system involvement") because medical observation was so advanced 2000 years ago. They even felt the need to rule out demonic influence on the basis that exorcising a demon would be expected to cause "convulsion or residual symptomatology".

This really makes me so mad. The basis for getting published in science is really very simple - use the scientific method. The answer doesn't have to fit dogma or please anyone, but the question has to be asked in a scientific manner. How on earth did these authors manage to get a Bible pamphlet past what is meant to be rigorous peer review? Virology Journal is hardly Nature, but with an impact factor of 2.44 it is at least a credible journal (or was, until this catastrophe). At least the journal has apologised and promised to retract the paper:

As Editor-in-Chief of Virology Journal I wish to apologize for the publication of the article entitled ''Influenza or not influenza: Analysis of a case of high fever that happened 2000 years ago in Biblical time", which clearly does not provide the type of robust supporting data required for a case report and does not meet the high standards expected of a peer-reviewed scientific journal.

Okay, Nature has also made some colossally stupid mistakes in letting industry-funded pseudo-science into their pages, but in the 21st century you would hope that scientific journals would be able to tell the difference between evidence-based science, and faith-based pseudo-science.


A breakthrough for HIV prevention?

This week a breakthrough for HIV prevention was announced in Science. AIDS researchers in South Africa just completed a long-term study of Tenofovir Gel, and found that the gel, inserted into the vagina before sex, results in a 40% HIV protection rate for women. With 900 women being followed up for 30 months, the results look very solid, and potentially even better than the headline figure of 39% protection. As with all such studies, the protection rate given is with average usage, not ideal usage. The average study participant only actually used the gel for ~75% of sexual intercourse occasions. For the "high adherers", the group using the vaginal gel for >80% of sexual intercourse occasions, the protection rate was 54%. How important is this breakthrough? In a way, it is both bigger and smaller than the headlines would suggest.

A new tool to fight HIV spread

In the age of vaccines with efficacy rates of >99%, a ~40% protection rate sounds rather poor. Furthermore, this is currently a form of protection only against heterosexual transmission of HIV to women, with no data yet on any protection granted to males having sex with a HIV+ woman or as an anal gel for male homosexual transmission. HIV acquisition by non-sexual routes, such as intravenous drug use, will of course be unaffected by the gel. This is a very poor efficacy rate when compared to condom use. A Cochrane meta-analysis has determined that consistent use of condoms results in an 85% protection rate against HIV, which can go as high as 95% with correct usage. The protective effect is only on par with that of male circumcision, which multiple randomized trials have found protects males from heterosexual HIV transmission at a rate of around 60%.

Is the new gel then completely redundant? A downgrade from the condom? No, not for a key population group - the women of southern Africa. The ten countries of southern Africa together constitute 35% of global HIV cases, with HIV reaching a hyper-endemic situation with 10-30% of adults infected with HIV. In this region, heterosexual spread is the dominant form of HIV transmission, and indeed the risk factor of greatest magnitude at the population level goes to married women. Condom usage in Africa is generally very poor, with an average of only 4.6 condoms available per man per year, due to low demand. Only 7% of women in southern Africa reported using a condom the last time they had sexual intercourse with a regular partner. In particular, women who are food insecure are 70% less likely to use a condom when having sex, with less personal control over sexual relationships. Other women may not use a condom during sex for more personal reference - such as trying to conceive. A vaginal gel therefore provides (partial) HIV protection for the first time to any women who would not otherwise use a condom during sex, either because of personal choice, lack of sexual control, or through a desire to become pregnant.

The other important consideration is that any protection results in a greater number of cases being prevented than the effectiveness of the protection to the individual. This is because each case stopped also prevents the flow-on cases which would have spread from the infected individual. It has been estimated that a weakly protective vaccine, with only a 50% protection rate and only given to 30% of the population, would reduce new HIV infections by more than half, over 15 years. These figures are comparable to the results for Tenofovir Gel, so if the maximal potential is realized, this breakthrough has the ability to halve new African HIV cases.

A tool that will sit idle?

The problem, of course, is that the potential of this gel will not be realized. In many ways, the HIV epidemic is not a problem waiting for a medical solution, but rather a problem waiting for a social and political solution. Consider mother-to-child HIV prevention. Current medical treatment of HIV+ women during pregnancy and after birth reduces the transmission rate to the child by more than 99%. Even in developing countries, the treatment program has over 98% efficacy. And yet these cases, almost entirely preventable under current treatment, make up 15% of global HIV cases and 40% of HIV cases in southern Africa, since only 33% of pregnant HIV+ women in Africa get any form of anti-HIV treatment, let alone the recommended treatment program.

Other strategies, which are already proven to work, could make similar impacts if broadly implemented. Widespread male circumcision would reduce HIV rates by 60% in males and, by reducing prevalence, 30% in females. Comprehensive sexual education focused on preventing new infections can be highly successful. An aggressive campaign of university HIV testing and near universal antiretroviral treatment would be capable of reducing new HIV infections by 95% within 5 years. Just the simple treatment of individuals with genital herpes with current antiherpatic drugs could be expected to reduce transmission of HIV in southern Africa by 50%.

No, a new tool to fight HIV is not going to stop the virus. Realistically, the current tools available could cut new HIV cases by 99% within the decade, if only they were implemented. The true scourge of HIV is that it attacks the marginalised in society, hitting regions of great poverty, infecting those on the receiving side of racial and sexual discrimination. The people that, quite frankly, too many people feel deserve to be sick. Being interwoven with issues of sexuality, drugs, race and poverty, people in power have not only been slow to move - they have often moved in the wrong direction, such as the $15 billion pledged in aid by George W. Bush, with its focus on replacing effective condom use with ineffective "abstinence only" programs.

A major part of the problem is certainly lack of resources, both funding and public health infrastructure. The response to HIV has been delayed, fragmented, inconsistent and grossly under-resourced. Lesotho launched a national voluntary counselling and testing campaign aiming at universal testing, which fell through due to a lack of resources. In South Africa only 28% of HIV+ people have access to antiretrovirals. In Zimbabwe only 4.4% of HIV+ pregnant women are receiving antiretroviral treatment to prevent mother to child transmission. In Nigeria 10% of all HIV transmission events are due to lack of funds for hospitals to screen transfused blood, a situation which requires only funding to remedy. However, funding is not the only impediment to an efficient HIV prevention campaign. Policy makers have repeatedly failed to spend limiting resources on HIV prevention, concentrating on medical treatment without adequate care and support. This is despite the cost of most HIV prevention techniques being well under the $4770 per infection prevented that it would take to create a cost savings compared to simple treatment. What is needed to end the HIV crisis is, in fact, simple in health terms and is difficult only in political implementation – a coordinated and adequately funded approach to integrate evidence-based HIV prevention strategies, in concert with major social and economic development efforts to eliminate gender disparities, race- and sexuality-based discrimination and extreme poverty.