What was I consenting to again?

At 3:52 PM, PmH said…
It seems unreasonable to expect anyone to be capable of signing an informed consent form unless they understand the planned test, the risks and the legal remedies.

PmH quite rightly pointed out that I basically ignored one of the important points of this article:
Guinea pigs do sign “consent forms” that detail the risks; but Tom Edwards, a 21- year-old from Oxford who took part in another Parexel trial, pointed out that his form was 15-pages long. He said he felt “pressured” into signing the form and eventually did so without reading all of it “because I felt like I was slowing everyone down”.

I don’t think anyone could have predicted the side effects of TGN1412, but even ordinary trials can be fairly hazardous. Participants need to understand the potential risks and feel that they can refuse to take part if they feel the risk to be too great — this is basic informed consent.

High school science leaves most of the population ill equipped to deal with a 15-page form which was most likely written in the worst combination of science lingo and legalese imaginable. Tertiary science leaves scientists ill eqipped to write consent forms that the general population can understand, and therefore give informed consent to. Either way, the onus lies on science educators to lift their game and level the playing field somewhat. Obviously there is a need for technical language, and every type of specialty, whether in philosophy or physiology. But there’s a time and a place for it.

On the other hand, the average citizen could use a better grasp of science. The same people who don’t understand consent forms also don’t really understand the science they read in the newspapers, or its implications to their lives (unless the particular science journalist is better than average). Their way of verifying scientific hearsay is to go through their catalogue of anecdotes until they find a situation that confirms or denies the report. And they believe that intelligent design is a plausible alternative to evolution.

For its own good, scientists need to teach better and communicate better; really these are both the same thing.

Sneezy season

The immune system is a mysterious thing. Protective overall, and yet sometimes it backfires. A dramatic illustration of the immune system going wrong was the TGN1412 disaster: six young men given a monoclonal antibody in a clinical trial ended up in ICU with multiple organ failure. One is now showing signs of an aggressive cancer.

Less dramatic, but more aggravating to more people on a more regular basis, are your run-of-the-mill allergies. Almost everyone I know is allergic to something: peanuts, cats, dust, pineapple. I personally have some mild allergies to some animals, but a major reaction to dust mites. When I got an allergy skin test, the swelling that appeared in response to dust mites moved beyond the realm of a few millimetres, which they usually measure, and looked disturbingly like a fat worm under my skin.

It’s bewildering, too, the different things that people say about what causes allergies. It seems that no one can agree on whether it’s over- or under-exposure to the allergen that causes the immune system to go nuts and attack a harmless molecule. Now it’s been suggested that the window of opportunity for avoiding the nastiness of an allergy is pretty small: sometime between six months and nine months of age, at least for food-related allergies.

Personally I don’t think there’s a straight answer to this one and it just highlights the intricacy of the body, which can work against us or in our favour, but is fascinating regardless.

Spotlight on cystic fibrosis

This article was originally published in issue 4 of the MMIM newsletter.

Associate Professor John Wilson began his career with a science degree, followed by a medical degree and a PhD. After working in the United Kingdom for two years, he returned to Australia and is now the head of the Cystic Fibrosis Service, Department of Allergy, Immunology and Respiratory Medicine at the Alfred Hospital, Melbourne.

Cystic fibrosis (CF) is a life-limiting condition characterised by respiratory failure and malnutrition. Although it is caused by an abnormality in a single gene, the expression of the abnormality is highly variable. CF patients’ symptoms range from negligible to severe lung impairment. It follows that other factors must affect how the disease progresses. Wilson is particularly interested in how factors such as gastroesophageal reflux, nutrition, and bone density interact with the cystic fibrosis gene. For example, genes encoding proteins involved in the manufacture of advanced glycation end-products (AGE) are important in diabetic nephropathy, but they also appear to play a role in causing early kidney failure in CF.

Wilson says that MMIM is “very powerful because it helps us direct our research”, which saves time and money by “avoiding fishing expeditions” and ultimately helps his patients. Because Wilson and his colleagues are trying to balance many factors in order to optimise treatment, computer-based analysis is essential. “Constructing models helps us weight the importance of different factors,” Wilson explains.

For example, Wilson’s research team found surprising interactions between the most common mutation of the CF gene, ΔF508 (either one or two copies), and bone mineral density (BMD). Carrying this mutation and being male are “powerful risk factors” for osteoporosis, independent of pancreatic disease and vitamin D malabsorption. Because osteoporosis is considered to be predominantly a disease of women, this means that we need to be “extra-vigilant” about BMD screening for men with CF. It also has implications for children with CF, who should have BMD augmented to prevent osteoporosis before it occurs.

This type of work, Wilson says, “will improve the health of Australians” – both with CF and with other conditions. In his role at the Alfred he still sees patients regularly, and is committed to practical research that will “get to the clinical interface” and make a real difference for patients. His approach is to address current clinical guidelines with up-to-date research: it is always important to “evaluate evidence and challenge icons” and determine whether there is a better way to approach treatment.

His overall plan for management of CF is to create an electronic health record, which can be “interrogated” to retrieve information, and “injected” with management plans, creating individual goals for therapy. Treatment can be accelerated if goals are not being met, or wound back if they are ahead of schedule.

Some of the most dramatic advances in CF survival rates in the last two decades have been relatively simple changes, such as an increase to twice daily physiotherapy, and a shift from postural drainage (which causes reflux) to other techniques to clear airway secretions. By studying the current techniques and analysing them statistically (with the help of the MMIM database), Wilson and his research team can make further advances that make a real and timely difference to patients.

Still in the Stone Age down under

Debate is heating up in Australia about the use of mifepristone (RU-486) for medical (as opposed to surgical) abortions. Tony Abbott, who is clearly highly qualified to have an opinion about (a) medicine (he has an Economics/Law double degree) and (b) women (he quite obviously isn’t one), has decided that he should be more cautious than the Australian Medical Association, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, and the World Health Organization and keep mifepristone off the shelves in Australia. Well, that’s his story, anyway. Unfortunately for Mr Abbott, people aren’t stupid and are quite able to see that his views on mifepristone are just thinly veiled anti-abortion views (which go hand in hand with his anti-stem cell research views).

All research and medical opinion points to mifepristone’s safety and efficacy in inducing termination, when combined with a prostaglandin analogue such as misoprostol (which is already available in Australia for other uses). From the reading I’ve done, I can’t see how medical abortion is any less safe than a spontaneous abortion. Both can lead to complications, such as incomplete abortion, which can be taken care of with medical help.

It’s insulting to doctors for Abbott to suggest that they would not be able to deal with the complications that can arise. If they can deal with a miscarriage, they can deal with a medical abortion too. And it’s insulting to suggest that they would prescribe mifepristone unwisely. Any doctor prescribing it would, of course, be there to deal with any adverse effects, same as they would be for any medication they prescribed. Rural doctors, in particular, should be offended at the implication that they can’t handle complications of pregnancy, when they can probably deal with them better than some over-specialised urban doctors. Should they be recommending that all female regional inhabitants relocate to cities for pregnancy care?

Abortion isn’t nice or pleasant but it’s a reality that some women find themselves facing for a variety of reasons. Whether the underlying cause is their own stupidity or the cruelty of rape, no woman should find herself facing the alternative of an unsafe abortion, or an unwanted pregnancy that will produce an unwanted child, who might never receive adequate care or love. And medical abortion makes it easier — some might say too easy, but I feel that the option needs to be there for women in remote areas, or from communities where abortion is not acceptable, and going to the doctor for a pill and pretending that you’ve had a miscarriage might be your only option.

It’s just mind-boggling that this decision is in the hands of one man who’s clearly biased, rather than where it belongs: in the hands of each individual woman.

Fluoride and the thought police

A naturopath I know recently sent me an article entitled Media Reports on Dangers of Fluoride in Your Water. I’ve had fascinating discussions with this woman in the past, which have included gems such as, “pathology tests are really just scientific experiments”.

Even if I usually expected better of her, a quick glance at the homepage would convince me not to take this article seriously. If you sign up for the site’s newsletter, you also get a “FREE must-read bonus report on “The Dangers of Grains and Sugars!” Funny, but I thought that grains and sugars contained something essential for our survival… oh yeah, energy. Clearly, functionality isn’t homoeopathic.

But back to the fluoride. As a much-needed brain exercise, I decided to go through the article and try and pick out the dubious points… without researching. With the internet, it’s too easy to find information, even reliable information. So, curbing my knee-jerk response to look up every health-related concept on NCBI, I tackled quackery at its best.

* Loaded language: before the end of the introduction, there are three loaded phrases used: “dangers of fluoride”; “terrible effects”; and “harm”.

* “Water fluoridation then spread across the United States despite concerns by respected doctors and scientists that adding it to public water supplies could cause serious health problems that would only become evident years later.” How prophetic of them. I wonder, also, if these doctors have names…

* “According to a 2001 study released by the Centers for Disease Control and Prevention (CDC), it was found that by age 12, kids who live in fluoridated communities averaged only 1.4 fewer cavities that those in non-fluoridated communities.” If this is true, it’s probably because the anti-fluoride lobby has succeeded in getting people to filter their water.

* Under the heading “Dental Fluorosis Running Rampant”, Mesquita makes use of the dodgiest statistics I’ve ever seen: he decides that of the 32% of US children that have some form of fluorosis, all of these must come from cities where the water is artificially fluoridated. He uses this assumption to increase the percentage from 32% to 53%, conveniently forgetting all other factors that could cause fluorosis in other cities (too much toothpaste? Fluoride happy dentists? Naturally occurring fluoride?).

* “A 1991 study by the U.S. Public Health Service found a strong link between fluoride exposure and bone cancer in boys. They found there was a 79 percent increase in osteosarcoma in fluoridated communities and a 4 percent decrease in non-fluoridated communities.” I wonder what made the non-fluoridated communities have a decrease in bone cancer? There must be some other factors here, even if these statistics were true (see below).

* Apparently 50% of ingested fluoride is deposited in your bones. I’d like to know how they determine this kind of thing. I don’t think I’d like to be part of the study… sounds painful. Also, fluoride not only causes bone cells to grow, it also causes them to mutate. Multi-talented little ion really.

* Apparently the FDA requires warning labels on toothpaste stating that if more than used for brushing is accidentally swallowed, one should seek medical advice. Of course, nowhere in the article do they mention how much fluoride is found in toothpaste and whether this is more or less (I’m suspecting A LOT more) than is found in water.

* At the end of the article there’s an advertisement (well, that’s what it looks like to me) from the owner of the website, for a water testing company — he helped them develop their product. Can anyone spell conflict of interest?

* This article has no references, and even the studies and “facts” referred to within the text would be difficult to find without an extensive search, because no author’s name is given. There’s no accountability, which is obviously the way this kind of writer likes it. You’re not meant to think about it, you’re just meant to be scared and above all, buy their product. So if the facts are faked and the statistics are dubious, hopefully you won’t notice until it’s too late (if at all).

Well, that’s as much as I could think of off the top of my head. Now for some research.

According to Quackwatch, fluoride use was much better investigated and researched than Mesquita would have you believe. It was first studied by comparing the dental hygiene in different cities; eventually naturally occurring fluoride was found to improve dental hygiene (Peterson J. J Hist Dent. 1997 45:57-61). The ideal amount of fluoride in water was found to be one part per million (ppm).

Addition of fluoride to water supplies was tested much more broadly than the Mesquita article mentions; 21 cities in four US states, not just two states, were studied before the concept was rolled out to other states and countries (Dean HT. Nutrition. 1990 6:435-445).

The article claims that in 2001, the Centers for Disease Control and Prevention (CDC) found that fluoridation of water only marginally decreased the amount of cavities in 12-year-old children; but in the same year the CDC continued to recommend use of fluoride toothpaste and water fluoridation (MMWR Recomm Rep. 2001 50(RR-14):1-42). Mesquitea also claims that fluoridation of water increases fluorosis (MeSH definition); but a 2002 study showed that children in areas where fluoride occurs naturally in water were more likely to suffer fluorosis, due to the higher amounts that can occur in the water (Beltran-Aguilar ED et al. J Am Dent Assoc. 2002 133:157-165). According to Mequita, 84% of the population in places with over 3.7 ppm fluoride have fluorosis; he doesn’t mention that no city would ever add that much, since 1 ppm was found to be optimal; higher amounts are due to naturally occurring fluoride.

I couldn’t find a study from 1991 that showed a link between fluoride and bone cancer; however I found a couple from 1991 that said there was no link (McGuire SM et al. J Am Dent Assoc. 1991 122:38-45; Mahoney MC et al. Am J Public Health. 1991 81:475-479). A more recent review concurred (Cook-Mozaffari P. Community Dent Health. 1996 13 Suppl 2:56-62.)

My conclusions: I’ll keep drinking fluoridated water, and be glad I’ve got it (and a brain to suss out what’s what).