Does smoking weed really result in brain abnormalities? Maybe not.

554px-Cannabis_leaf_2.svgA study purporting to find that marijuana use (even casual marijuana use) may be associated with brain abnormalities has been getting a lot of press lately. You can check out some of the coverage at CNN Health, the Huffington Post, and Fox News. And you can check out the original paper in the Journal of Neuroscience, Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users by Gilman et al., here.

Shortly after the study came out, Lior Pachter posted an analysis of some major problems with the study on his blog. I’m posting a link to his post because I think it’s a great example of something science bloggers do very well: they share important information about the quality of recent studies in real time. This is essential stuff you just don’t typically see in media coverage.

I’d also like to note that the statistical issues he points out are very basic ones. Adjusting p-values for multiple testing is something that I think most researchers understand they have to do even after an introductory stats class. So I’m having a difficult time understanding how this manuscript sailed through peer review in its present form. The Journal of Neuroscience is not some fly-by-night journal! I hope that journal editors will see what happened here and realize that if a manuscript contains statistics, it’s probably a good idea to choose at least one reviewer with knowledge of statistics. Failure to control for multiple testing appropriately is something I see over and over again in the articles I review. There is definitely a need for the statistics police in the peer review process.

Vaccine refusal: it ain’t nothing new

imgres-1I’ve been fascinated by vaccine refusal for a long time, but for whatever reason I had never thought much about its history–at least not stretching back more than a few decades.

Perhaps it shouldn’t be surprising, but turns out that powerful anti-vaccine sentiment has been around for a long time! I just finished Pox: An American History by Michael Willrich, which explores the anti-smallpox vaccine movement during the last major epidemic in the US. Around the year 1900, smallpox emerged from the American South, where it had been festering, and started rampaging across the country, sparking epidemics in major cities like New York and Boston.

Desperate public health officials imposed mandatory vaccine drives. When people didn’t want to be vaccinated–and a lot didn’t–they risked being fined, thrown in jail, or physically restrained while somebody gave them the vaccination. Of course, vaccination laws were applied very differently depending on whether someone was wealthy or poor. In New York’s tenements, brute squads literally chased down and vaccinated every person they could find, breaking down doors and tearing children out of the arms of their mothers. The same was not true on Park Avenue.

All kinds of people joined anti-vaccine societies around the country. Celebrities weighed in too, although at that time people like Mark Twain and Williams James were voicing anti-vaccine sentiments. A little different from today, when anti-vaccine stars tend to be people like Jenny McCarthy and  Jim Carrey. It’s also striking how little the reasons for vaccine refusal have changed in 100+ years. Parents then were primarily concerned about their children’s safety. They cited all sorts of cases in which vaccines had been followed by death or terrible illness. Many believed that it was better to risk smallpox (especially in its milder variola minor form) than to receive the vaccine.

Of course then they had a point. People had very real reasons to worry about vaccine safety. Although local governments could compel people to be vaccinated, they could not guarantee the safety of the vaccines being administered. In the early days, when people were vaccinated with material from the lesions of another vaccinated person, the risk of some unwanted pathogen being transmitted alongside the vaccine virus was significant. In a particularly awful example from 19th century Italy, 63 children were vaccinated with infectious material taken from an infant who appeared to be healthy. Forty-four of those kids developed syphilis. Some also infected their mothers and nurses. And keep in mind this was before we had antibiotics–when syphilis often proved a death sentence.

Later, cows were used to produce the smallpox vaccine, which really helped ramp up production. It also meant that anyone with a cow and access to some virus could join the vaccine business–small, filthy operations were literally operating out of backyards in places like Brooklyn. There simply was no quality control or regulation.

Not surprisingly, vaccines at that time were often horribly contaminated. The vaccine site often became infected. A man or woman might lose days or weeks of work due to their inability to use the vaccinated arm–and the family that depended on them would suffer. That was sort of a best-case scenario, though. A number of children died of tetanus or other infections after vaccination. You can imagine how that stoked fear of the vaccine! It also horrified many of the doctors who unwittingly administered tainted vaccines and saw their patients suffer the results. Eventually, the attention these cases drew to the lack of quality control in vaccine production would revolutionize the way vaccines were produced, and quality control would become one of the industry’s major concerns. The government would also eventually recognize that it had a responsibility to regulate vaccine production and care for people harmed by vaccines.

The book also draws attention to a major divide in the medical community that was emerging at the time. Homeopaths and other alternative medicine practitioners were very active in the anti-vaccine movement. At the same time, allopaths were coming out strong in favor of vaccination and consolidating their hold over the medical profession. This is another source of tension that seems to have changed very little during the last century.

Willrich gives a sympathetic portrayal of the very real conflicts posed by mandatory vaccination as he follows the outcomes of court cases challenging mandatory vaccination laws. What are the rights of the individual weighed against the many? Especially when the risk of bodily harm to the individual is real? It’s interesting that a lot of passionate vaccine critics then were also active in the women’s rights and civil rights movements of the day. He makes a good case that society’s struggles with vaccine refusal have helped shape our understanding of civil rights. It’s a fascinating book, definitely worth a read!

Why are parents refusing the Vitamin K shot for their babies?

images-2Between February and August of this year, 4 babies in Nashville developed brain hemorrhages or gastrointestinal tract bleeding. Luckily, all of them survived. Not all babies have been so lucky. There was a case, in Australia in 2011, in which the vitamin K shot was refused by the parents and a baby died.

Nashville-area physicians report that an increasing number of parents are refusing vitamin K shots for their babies. Although the percentage of parents refusing the shot is only about 3% at local hospitals, almost 30% of parents refused at birthing centers. And this isn’t just a Nashville thing. Over 20% of parents at a St. Louis-area birthing center refused the shot as well, and I’m sure the stats for hospitals/birthing centers in other places are similar.

Why would parents decline the vitamin K shot? Maybe because of misinformation like that present on Joseph Mercola’s website. Mercola warns of three risks.

1. Inflicting pain on the newborn (in the form of a shot). He warns that the momentary prick of the shot may have long-term effects on the baby’s wellbeing and may jeopardize the success of breastfeeding. I’ll let you judge for yourself whether you think this sounds reasonable. I don’t, and there is certainly no good evidence to support it.

2. The amount of vitamin K injected is 20,000 times the needed dose and contains toxic preservatives. Wow, 20,000 times the necessary dose? Toxic preservatives? What is his source for this dramatic claim? A peer-reviewed journal article? Nope, I’m afraid not. It’s a website called Giving Birth Naturally. This website, in turn, gives no sources at all. Solid stuff, Dr. Mercola!

3. Babies run the risk of acquiring an infection at the injection site. This is true of any injection, but the chances of infection are so, so small. Even a hypochondriac like me thinks this is a pretty minimal risk. Infinitesimally small–I can’t even find reliable numbers on how often it happens, it’s so rare. For what it’s worth, I haven’t been able to find a single reported case of a baby developing an infection at the site of a vitamin K injection.

Now even Mercola acknowledges that the vitamin K shot doesn’t cause cancer. Unfortunately, not everybody has gotten that memo. Check out this website: the Healthy Home Economist. Although the author DOES eventually point out that the vitamin K-leukemia link has been debunked, she buries this acknowledgement in the comments, where no one will read it. Nice. The same uber-outdated information is also found in Mothering Magazine’s Natural Family Living Guide to Parenting. If you’d like to take a look at some of the articles debunking this association, you can check out this one in the New England Journal of Medicine (from way back in 1993!) or this more recent one, from the British Journal of Cancer.

Many of these anti-vitamin K shot websites give suggestions for what parents can do in lieu of the shot. Unfortunately, they are not well thought out.

1. Why not just request an oral dose of vitamin K for your baby? Because it doesn’t prevent hemorrhaging, that’s why. While it sounds totally reasonable, single oral doses just don’t do the trick.  Comparisons of “failure rates,” i.e. the rates of hemorrhaging, in countries that use different methods to administer vitamin K  demonstrate that a limited number of big oral doses just doesn’t work as well as the shot. Daily, low doses may be as effective as the shot–but to the best of my knowledge, those aren’t an option in the US.

2. Eat a lot of vitamin K-rich foods and breastfeed your baby. Again, not a great strategy. Very little vitamin K makes it into breastmilk, even when a mother eats a lot of it. Very little can cross the placenta beforehand either, even if the mom has a great diet. That’s why the shot is necessary.

You would never realize it from the scare-mongering articles out there on the internet, but in reality the risks associated with the vitamin K shot are negligible compared to its potential benefits. It’s true that the chances of any one baby developing vitamin K deficiency-related bleeding are small–but when such a great way to avoid this risk is present, why not use it? A vitamin K shot may not be natural (meaning it didn’t exist tens of thousands of years ago). But neither are vaccines. Or carseats. And these inventions save lives. For any given child, the risk of dying from a hemmorhage or measles or a car accident may be small. But at the population level, these easy fixes make a difference–they save lives.

The bogus HPV vaccine article that just won’t die

vaccinationI came across this article on Facebook today: Lead Developer of HPV Vaccines Comes Clean, Warns Parents & Young Girls It’s All A Giant Scam. It was published on some entertainment website called back in July, but it just won’t die. It’s got 198,000 Facebook likes, and it’s been tweeted 631 times. It claims that Diane Harper, a scientist involved in the clinical trials for Gardasil, one of the HPV vaccines, did a 180 and decided that the vaccine is no good. According to the article, she announced this abrupt change of face at the 4th International “Converence” on Vaccination in Reston, Virginia. She came clean to the audience so she “could sleep at night.”

The article conveniently makes it very difficult to distinguish between the (supposed) paraphrasing of what Harper actually said at that meeting and the interpolations of other people. It says scary things like “44 girls are officially known to have died from [HPV] vaccines.” Uh, really? Wouldn’t that death toll be all over the newspapers? Well, maybe not, since it’s not at all true.

You might wonder how this website can get away with printing things that are demonstrably false. Yesterday somebody pointed out to me the website’s disclaimer: “ contains published articles, speculation, assumptions, opinions as well as factual information. Information on this site may or may not be true and is not meant to be taken as fact.” And the author? Is he a vaccine expert? Nope, his name is Brent Lambert. As it happens, he is also Editor-In-Chief of this fabulous website, and you can reach him at his gmail address. Super professional.

Where did this article come from, you ask? Almost word for word, it was taken from an article that appeared on the website LifeWise in June. This article, in turn, seems to have drawn on a 2009 article in the Sunday Express by Lucy Johnston. (Note: The Sunday Express may sound respectable, but it’s actually a British tabloid.)  Their claims that Diane Harper said all this stuff were debunked back in 2009, the very week that they came out. Ben Goldacre of the Guardian talked to Diane Harper himself. In Harper’s words:

“I did not say that Cervarix was as deadly as cervical cancer. I did not say that Cervarix could be riskier or more deadly than cervical cancer. I did not say that Cervarix was controversial, I stated that Cervarix is not a ‘controversial drug’. I did not ‘hit out’ – I was contacted by the press for facts. And this was not an exclusive interview.”

The original article was promptly taken off the Sunday Express website, and Harper complained to the Press Complaints Commission.

How did this whole brouhaha start? For whatever reason, Harper decided to speak at the 4th International Public Conference on Vaccination, held by the National Vaccine Information Center in Reston Virginia. Sounds bland enough, right? But as it happens, the NVIC is one of the largest, most vocal anti-vaccine groups out there. Why would she attend such an event? I guess it’s possible that she was tricked, that she didn’t realize what she was getting into. Working in the vaccine field, it seems she would have to be familiar with the NVIC, though. Maybe she was trying to engage vaccine critics, hoping that a little education would bring them around. Perhaps we’ll never know. But not surprisingly, it appears that attendees twisted her words in the press.

So how did all the same 2009 tabloid junk get recycled in a 2013 article? And why do people take it at face value? Lord only knows.

I frequently see people post articles like this in places like Facebook after adding something like, “C’mon, people. Do your research. Vaccines are dangerous.” I am all for people doing research about vaccines. There is so much great vaccine research available that if most vaccine skeptics really delved into it, I think they would rapidly change their minds. But does anyone really consider reading an article like this research? Even if the lack of any citations didn’t clue you in, and you didn’t know about the backstory for this chunk of lies, wouldn’t the misspelled words, the disclaimer that says the website contains  information that “may or may not be true,” and the Editor-in-Chief’s gmail address give you reason to pause? Is this really where you want to get the information you use to make medical decisions? C’mon people. Do your research. For real.

If you’re interested, more information about this particular zombie anti-vaccine meme can be found on the Respectful Insolence and Skeptical Raptor blogs.

What are you getting when you buy herbal supplements?

1741-7015-11-222-3Well, this is frightening!

An article in the New York Times a few days ago reported on the huge mess that is the supplement industry. When you buy herbal supplements, you may not be getting what you paid for… and sometimes the substitute materials are potentially dangerous!

Briefly, a group of researchers from Canada bought a lot of popular herbal supplements from the U.S. and Canada and used DNA barcoding to figure out what they had actually gotten. In lieu of St. John’s Wort, they got rice in one bottle and Alexandrian senna, a powerful laxative, in another. In place of Gingko biloba, they got black walnut–potentially deadly for people with nut allergies.

A shocking 30 out of 44 samples included substitute plants rather than the plants they were supposed to contain. That’s almost 70%! And roughly 60% of the samples contained plants that weren’t listed on the labels.

In the figure shown here, you can see how the results broke down by company. Each company is represented by a different letter along the bottom. Only two companies appeared to be providing what they said they were providing… Other sellers provided consistently contaminated projects. Unfortunately for consumers, the authors didn’t list companies by name.

Shelly Burgess, a spokesperson for the FDA, said “Unfortunately, we are seeing a very high percentage — approximately 70 percent — of firms’ noncompliance,” she said, “and we are very active in taking enforcement actions against such violations.” Come again? If the FDA were “very active” in taking action, then 70% of firms wouldn’t be noncompliant, right?

Here’s a link to the original study, DNA barcoding detects contamination and substitution in herbal products by Newmaster et al.

Bach Flower Remedies: Do They Work?

You’ve probably seen Bach flower remedies at health food stores or new-agey sorts of shops. Or maybe your chiropractor or vet has recommended them. bachproducts-allThey’re recommended for all sorts of maladies, including asthma, hypertension, migraines, eczema, allergies, dyslexia. But do they work?

The story behind Bach flower remedies is pretty romantic. Dr. Edward Bach was a Welsh physician with an interest in homeopathy. He believed that many illnesses are caused by things like fear and despair–not so different from how many researchers today view the effects of stress. He also believed that we could develop a new medical system by focusing on cures found in nature. So he abandoned his London practice and headed out into the countryside to investigate the curative effects of flowers. In addition to abandoning city life, he decided to jettison the scientific method and instead use intuition to guide his work. Wandering the lanes of Oxfordshire, he developed a number of flower remedies–many of which you can still buy today.

While Dr. Bach was initially interested in the dew that collects on flowers, he realized that collecting dew drops wouldn’t be very practical if he wanted to reach the masses. So, as the closest large-scale approximation he could think up, he began to make his remedies by putting fresh flowers into water and then steeping them in the sun or boiling them. He also added brandy as a preservative. It’s highly doubtful that the flower remedies contain pharmacologically significant amounts of any flower-derived chemicals–instead, the flowers are supposed to transmit their energy to the water and then to you. So, basically, they are supposed to work via the memory-water mechanism on which homeopathy is based.

A few randomized, controlled trials have actually tested the effects of Bach flower remedies. For example, researchers tried using the Rescue Remedy or a placebo on 100 University students about to take exams. Less than half of the students completed the study, but in those who did, no effect on test anxiety was found. A similar study on test anxiety also found no difference between flower and placebo groups (although even taking a placebo helped soothe students). There is one study that has reported a significant effect of Rescue Remedy in reducing stress in a subgroup of students with very high-anxiety… but if you test enough subgroups you are bound to find a positive result eventually, due to chance alone, so I’m not sure I put much stock in these results.

In another study, researchers randomized 40 kids with ADHD to either Bach flower remedies or a placebo for three months. With only 20 kids in each group though, and with half of the kids dropping out before the three month study was complete, the power to detect any changes in behavior was pretty low. The effect of the flower remedies would have to be pretty amazing to show up. I’m fairly certain a study this small couldn’t have demonstrated a significant effect of ANY ADHD medication.

The good news is that nobody has reported any adverse effects associated with the flower remedies. Since they are essentially water, that makes sense! The bad news is there is not much evidence that they work, except for as a placebo. Some flower enthusiasts point out that so far the remedies have only been investigated for anxiety and ADHD. That’s true. It’s also true that most of the studies done so far have been so small, and getting patients to comply with treatment has been so difficult, that even if the remedies DID work, chances are that the trials wouldn’t detect an effect. Unless you buy that water can holds memories, though, it doesn’t seem likely that even a huge NIH-sponsored trial would pick up any beneficial effect of the Bach flower remedies.

That said, it’s not unusual for 30-40% of people given a placebo to report that they feel better. And Bach flower remedies appear to be harmless. So if someone’s feeling bad and they believe in the potential of these remedies to cure, maybe it’s not such a bad idea to give them a try! Since I don’t see how the placebo effect would work on pets, though, it’s hard for me to see how using the remedies on animals would be of much use. I guess that as an owner, maybe your own anxiety about your pet’s condition could be alleviated in a sort of indirect placebo effect.

Bacteriophage therapy: An idea whose time has come?

220px-PhageBacteriophages are viruses that attack bacteria–their name means “bacteria eater” in Latin. Here, you can see a bunch of bacteriophages on the surface of a bacterial cell. They look sort of like balloons tethered to the surface of the moon. They were discovered near the dawn of the twentieth century, and at first they enjoyed some spectacular therapeutic successes. Felix d’Herelle, one of the men who discovered bacteriophages, treated four dysentery patients with them in 1919. Soon after, he used bacteriophages to treat outbreaks of cholera in India and plague in Egypt. In the U.S., phage trials were performed at Baylor, and the researchers involved were impressed by phage therapy. It didn’t always work so well in practice, though. Phage therapy can be tricky. The organomercury used to preserve phage cocktails often destroyed them instead. Preparations could also be contaminated with exotoxins produced by the bacteria used to grow the phages. Finally, there have been problems in the past with inconsistency. The composition of a phage treatment may vary from batch to batch, with predictable effects on efficacy. Many physicians were less than happy with the results they got with phages. And when antibiotics were discovered, there was really no reason to continue to struggle with this form of therapy.

Things are different today, though. There are so many reasons why bacteriophage therapy makes sense. First, antibiotic resistance is increasingly becoming a problem. The utility of our antibiotics is dwindling, and the discovery of new antibiotics isn’t keeping pace. Antibiotics are static. But bacteriophages can evolve along with their bacterial prey. Instead of  struggling to identify new antibiotics, perhaps we could use phages and let natural selection do our work for us. If we’re lucky, maybe bacteriophages could replace some of the antibiotics we’re losing. In addition, we’re beginning to appreciate how important our microflora are. Wiping out our microbial ecosystem wholesale with antibiotics isn’t desirable, and it can increase susceptibility to pathogens like C. difficile. Bacteriophages, because they target only specific types of bacteria, might get around this problem–killing the problematic bacteria, but leaving everything else intact. Mixtures of phage could potentially be tailored to a person’s specific infection.

One of the reasons that phage therapy has been slow to catch on in the U.S. is that it has been primarily practiced in Eastern Europe and the Soviet Union. Today, phage therapy is routinely being used in Russia and the Republic of Georgia. But over the years, much of the work done was not published in English, so scientists in the West were unaware of it. In addition, many studies didn’t meet the standards that western scientists require. And, of course, getting approval to use a new therapy in the clinic is tough. As a result, companies have been wary of trying out phage therapy in humans and have been using it in different settings instead. Phages targeted to Listeria, a food-borne pathogen, have been approved by the FDA to help sterilize processed foods. Other phage mixtures have been approved to protect crops against pathogens. And more phage treatments are in the works.

Baby steps toward human treatments are being made, though. In the U.S., several safety studies in humans have shown promising results. And the first randomized controlled trial in the West was recently performed by Biocontrol Limited. It targeted adult patients with chronic ear infections caused by antibiotic resistant Pseudomonas aeruginosa; a bacteriophage solution was swabbed on infected ears. The researchers involved reported outcomes that were better than those achieved with a placebo, which is promising! As we have begun to appreciate the ecosystem in our guts, some researchers have proposed that bacteriophage therapy could help us perform more subtle manipulations than the ones to which we’re accustomed–by introducing certain phage, perhaps we could promote the biosynthesis of nutrients or the breakdown of parts of our diet.

Phage therapy faces some of the same major challenges that antibiotics do. Bacteria can develop resistance to bacteriophages. And a given phage can only target a relatively narrow range of bacteria. For these reasons, often a mixture of phage are administered to a patient. In terms of obtaining regulatory approval, this can be tricky, however. Although treating people with multiple phages does prolong the time until resistant bacteria arise, resistance may be inevitable. Therefore, researchers have been throwing around ideas like combining phage and antibiotic treatments (which seems to work especially well), cycling different phage mixtures, or engineering phage that can circumvent mechanisms of resistance.

Delivering the phage to where they need to go can also be tough. They have to spread from the site of application, and they also have to avoid being cleared from the bloodstream. For that reason, researchers have been focusing on infections that are localized (like ear infections and wounds). Over time, it may be possible to engineer delivery systems that will enable phage treatments to be used for more systemic infections. Some researchers have even shown that specially-engineered bacteriophages have the potential to break down biofilms, a gooey layer of protection that bacteria can hide behind.

Bacteriophage therapy may not be ready for primetime yet, but great strides have been made in the past few years. I’m really looking forward to seeing where this alternative type of treatment is going to go!