Tuesday, April 30, 2013

So you found some science on the Internet... (Part 2)


10 amazing findings about placebos

In part 1 of the series I brought up placebos briefly and I promised you more. It’s important to discuss placebos because many successes of health products and interventions that are not supported by the medical community can at least be attributed in part to the placebo effect. Your brain is a powerful machine and the effects of the placebo can be extremely convincing. Here are some interesting facts about placebos:

1.     Placebos can be somewhat of a self-fulfilling prophecy: if someone is told a placebo acts as a muscle relaxant, their muscles actually relax.

2.     For some conditions (such as mild depression, or some coughs), placebos work just as well as drugs with active ingredients. 

3.     Rats experience the placebo effect.

4.     The placebo effect can work even if the patient is told they are taking a placebo (but keep in mind: in this kind of trial, it’s impossible to blind the participants!).

5.     The placebo effect works better if the intervention is more invasive or severe. The placebo effect is stronger and works on more people when a fake drug is injected with a needle than when it's simply swallowed in pill form.

6.     To properly control for the effect of certain surgeries, clinical trials are sometimes conducted with a group receiving a sham (fake) surgery. The ethics of doing this are often debated (your thoughts in the comments!).

7.     Pills with a visible, well-known name brand work better than pills that look generic.

8.     The placebo effect can work in reverse: if given a placebo and told it will produce negative side effects (like headaches), nearly 1 in 5 people will experience those side effects. This is called a nocebo.

9.     The color of placebo pills matters: “hot” colors like red and orange work better as stimulants, and “cool” colors like blue and green pills have a tranquilizing effect.

10. In some countries, doctors can prescribe placebos. A common use case? Placebo antibiotics for… viral infections*!

References: 
Flaten MA et al. (1999) Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosomatic Medicine 61(2):250-5. 
Pittrof R (2011) Placebo treatment in mild to moderate depression. The British Journal of General Practice 61(584):222. 
Nolan TA et al. (2012) Placebo-induced analgesia in an operant pain model in rats. Pain 153(10):2009-16. 
Kaptchuk TJ et al. (2010) Placebos without deception: a randomized controlled trial in irritable bowel syndrome. Plos one 5(12):e15591. 
Kaptchuk TJ et al. (2006) Sham device v. inert pill: randomized controlled trial of two placebo treatments. British Medical Journal 332(7538):391-7. 
Dowrick AS and Bhandari M (2012) Ethical issues in the design of randomized trials: to sham or not to sham. The Journal of Bone and Joint Surgery 94(suppl 1):7-10. 
Branthwaite A and Cooper P (1981)Analgesic effects of branding in treatment of headaches.British Medical Journal 282(6276):1576-8. 
Rosenzweig P et al. (1993) The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Clinical Pharmacology and Therapeutics 54(5):578-83. 
de Craen AJ et al. (1996) Effect of colour of drugs: systematic review of perceived effect of drugs and of their effectiveness. British Medical Journal 313(7072):1624-6. 
Hrobjartsson A and Norup M (2003) The use of placebo interventions in medical practice – a national questionnaire survey of Danish clinicians. Evaluation and the Health Professions 26(2):153-65.

*Avid Scientific Chick readers will know that antibiotics cannot treat or cure infections caused by viruses.

Sunday, April 21, 2013

So you found some science on the Internet... (Part 1)


Cats and science together on the Internet
The Internet hosts a wealth of information, and, for those concerned with their health and well-being, this can be both a blessing and a curse. I’ve recently come across a website that promotes various health and nutrition measures under the label of “science” (and even “real good science”!) all the while discrediting the work of some academics. While it’s obviously not the first time I’ve seen this sort of thing, this particular website hit home because it targets a community that’s close to me. The truth is, you can find science to support nearly anything, but not all science is created equal. I can’t prevent people from using “science” to support their claims, but I *can* tell you about what actually is “real good science”, how to spot it, and how to make informed decisions.

For this first post in the series, I want to introduce you to the gold standard for scientifically proving that something works (for example, that a drug treats a disease, or that a diet makes you lose weight): the double-blind, randomized controlled trial. Let’s start at the end:

A controlled trial means that the intervention you are testing (for example, a pill to treat stomach ulcers) is compared with a control intervention. The control can be a placebo (a fake intervention), like a sugar pill. You might think that anything works better than a sugar pill. Not so! Placebos are very effective for many conditions (for more on placebos, stay tuned for Part 2!). That’s why it’s very important to make sure that the effectiveness of your pill for stomach ulcers is not due to the placebo effect.

While placebos can be the ideal control, it’s not always practical, or ethical, to conduct a trial using a placebo. If for example you are testing a new cancer drug, you don’t necessarily want your control group to receive a placebo, and so go drug free, for the duration of the trial. Another type of control would be to use a drug that is already on the market, has known effects, and has already been tested thoroughly.

Randomization in the context of a controlled clinical trial means assigning participants randomly to either the new intervention group or the control group. Why is randomization important? It helps avoid a phenomenon called bias. Imagine that researchers really believe the new pill for stomach ulcers will work better than anything that already exists. They might be tempted to assign the sickest participants to the intervention group and the others to the control group. Seems like the right thing to do, yes? Unfortunately, not so. It’s possible that as stomach ulcers progress, they respond differently to various drugs, and by not assigning the participants randomly you might mask or exaggerate the effects of your new product. Well-designed trials should be randomized whenever possible.

In a double-blind randomized controlled trial, two groups of people are “blinded”. The participants are blinded in that they don’t know whether they are receiving the new intervention or the control, and the experimenters are blinded in that when they are analyzing the data, they don’t know who received what. Blinding a study really helps to limit the biases. That said, it’s not always possible to blind everyone. Sometimes an intervention (like an exercise program) is pretty obvious. But like randomization, it should be done whenever possible.

Double-blind, randomized controlled trial are pretty much as  
good as it gets when you’re trying to prove something – they 
are the most reliable form of scientific evidence because they have all the possible elements in place to avoid false cause-and-effect evidence. Let’s look at one last example. Say I’m trying to prove that a special diet involving eating large quantities of bacon helps people lose weight. So I recruit 10 overweight participants and I closely monitor their diet, making sure they eat their extra-large amounts of bacon. At the end of my study, I find that 6 out of 10 participants lost weight. What does this mean? Pick the right answer:  

a) Bacon is an effective weight-loss tool (60% success! Is  
    that a lot?) 
b) Bacon didn’t change anything – had the participants just    
    gone on with their regular diet, 6 of them would have lost  
    weight anyway  
c) Bacon worked as a placebo for 6 of the participants  
d) The experience of being monitored closely by researchers 
    led the participants to pay closer attention to their diet and 
    exercise, and 6 of them lost weight because aside from 
    bacon they improved their die
e) Bacon worked as a weight-loss tool for 2 participants and 
    4 participants experienced the placebo effec
f) The researchers secretly worked for the Bacon  
    Consortium and this whole thing was a marketing exercise
g) We have no idea what this means because the  
    experiment was not designed well.

That’s right.

Double-blind randomized controlled trials are not entirely without flaws (no scientific method is!). They typically take a very long time to come together and are very expensive to conduct, which can sometimes (but not always) mean that relatively wealthy organizations pay for them (for more on who pays for science, stay tuned for a later installment in this series). Other flaws are shared with many different types of research. That said, while these trials are not perfect, they are still the gold standard. So the first thing to look for when you are researching a health intervention online is whether a double-blind, randomized controlled trial has been done.

 Stay tuned for part 2, on the placebo effect!

Saturday, March 23, 2013

Save your brain cells


I’m not the most coordinated person on this planet. You know that kid who could never tap on her head and make circles on her belly at the same time? That was me. While I can hold my own on the mountain bike trail and poke at mice brains, there are certain things I will never do well, like dancing. Don’t even get me started on “zumba”. So naturally I was a little nervous when I joined a new gym class recently, especially since it involves learning new movements. I’m always so envious of those who seem to learn new things effortlessly, whose bodies respond immediately to what their brains are saying. So I was very excited when I found out about new research that suggests all my pain and suffering might pay off in the end.

It’s a common misconception that adult brains don’t grow. For a long time, scientists thought adults had a finite number of brain cells, and it was all downhill from there (grim, I know). We now know there is hope for us all – some areas of your brain continue to grow brain cells throughout your entire lifetime, at a rate of 5,000 to 10,000 new cells per day. Good news right? Don’t get too excited. We also know that over half of those new cells die within a few weeks of their birth.

Ok, get excited again (what a rollercoaster!): there are things you can do to prevent the death of those brain cells, and one of those things is learning new stuff.

In one recent experiment, scientists had three groups of rats undergo a procedure called eyeblink conditioning. This experiment is based on Pavlov’s work – he’s the one who found out that if you ring a bell shortly before you feed your dog every day, eventually just ringing the bell will be enough to activate the dog’s saliva glands. Eyeblink conditioning is very similar – it involves ringing a bell and then stimulating the rat’s eye, leading to a blink. Eventually the rat learns to blink when it hears the bell without the need for the actual stimulation.

The researchers carried out the eyeblink conditioning with three groups of rats. One group received a drug that prevented them from learning anything, one group received a drug that made learning easier, and one group didn’t get any drug (that would be the control group). After the rats went through learning (or attempting to learn) the eyeblink procedure, the researchers looked at how many new brain cells had been saved by the process.

The rats that received the drug that prevented from learning predictably didn’t learn anything and also predictably didn’t save any new brain cells. The rats that received the drug that helped them learn saved new brain cells, but no more and no less than the group of rats that learned without any drug. Pretty boring results so far, yes?

But wait! The researchers then closely looked at all the animals that learned the task and reanalyzed how many new brain cells they saved based on how long the rats took to learn to blink. What they found was most intriguing: the longer a rat took to learn the task, the more new brain cells it saved, regardless of whether it received the drug or not.

What this means is that the best way to save a maximum amount of new brain cells is by having a hard time learning something but ultimately being successful.

Now don’t go bragging about being a slow learner just yet - for one thing, the timing of the experiments I described above is very tricky (especially the timing between the eyeblink conditioning and when new cells are counted). We also know very little about the role of those new brain cells and whether they get integrated in existing networks in the brain, and I don’t need to remind you that results obtained in rats don’t necessarily apply to us. That said, it’s well proven that learning is good for your overall brain health, so go ahead and join that zumba class. 


Reference: Curlik DM and Shors TJ (2011) Learning increases the survival of newborn neurons provided that learning is difficult to achieve and successful. J Cogn Neurosci 23(9):2159-2170.

Saturday, December 15, 2012

Wait for it


My commute, on a good day
On most days I bike to work. It’s my way of “walking the walk” – I write enough about the benefits of exercise, it would be a little embarrassing if I were a couch potato. Riding in involves climbing a big hill early(ish) in the morning, but I usually just get into a low gear and think about stuff and I barely notice it.

Not this morning.

This morning, there was a headwind. A cold headwind. It felt like I was pedaling against a wall. I was trying to convince myself that I was enjoying it – looking at the view, trying to feel the oxygen in my brain. But at some point I let out a big sigh and thought “who am I kidding, this is miserable!”.

Even so, I knew full well that tomorrow, I would be back on the bike first thing in the morning. So I wondered – why do I continue to bike in, even in the winter, in the rain, in the cold, up the hill – even though I sometimes don’t derive any immediate pleasure or benefit? The answer, of course, is that rationally, I know that no matter how miserable it is at the moment, in the long run it’s good for me – it’s good for my health, my weight, my ability to prevent and fight illness, and, as anyone who reads this blog knows, my ability to ward off cognitive decline as I get older.

This process of holding off on immediate rewards (driving in to work in a warm car with some Christmas music playing) to benefit from later rewards (health) is called delayed gratification. It was most famously studied using marshmallows: in a well-known study, young children were given the choice between eating one marshmallow immediately, or waiting a few minutes and receive two marshmallows (giving rise to some pretty hilarious antics). The researchers followed-up on the children many years later, and found those who were successful in displaying delayed gratification (and so resisted eating the one marshmallow) were doing better on several outcomes such as academic success and ability to handle stress.

In a more recent study, a team of researchers investigated whether there is a link between the ability to delay gratification as a child and weight in adulthood. They found that one’s performance on a delayed gratification task (similar to the marshmallow experiment) was associated with his or her body mass index (BMI) thirty years later. In short, the kids who were able to wait the longest for a bigger reward had lower BMIs as adults. Interestingly, another study found that children who already have a high BMI score poorly on a delayed gratification task – a nice convergence of evidence from different sources.

Avid Scientific Chick readers can no doubt point to an important limitation of this study. Repeat after me: correlation does not imply causation. The fact that kids who did well at delayed gratification later had lower BMI’s does not mean that being good at delayed gratification causes one to have a lower BMI. There are several potential confounders here, some of which were not controlled for, such as the BMI of the participants as children. That said, the findings remain interesting – it’s not completely out of the park to think that improving self-regulation and self-control could have an impact on weight.

There is a little coda to my earlier story about biking against a wall of wind.

About halfway up the hill, at the peak of my frustration, almost as if on cue, a huge coyote emerged from the forest, and started trotting along the bike path as I was biking. It was a big fluffy beast, and for a second I was scared, but it was minding its own business, and eventually started making its way across the street. Still excited from my encounter, I turned my head, and there was another equally huge coyote sitting just next to the bike path, in the forest, staring me down. I couldn't believe it. I've seen coyotes before, but never this big, never this close, and never on my way to or from work. They were beautiful creatures and my heart was warmed. Delighted with this turn of events, and with the fact that this morning’s gratification was instant and not delayed, I grinned like an idiot all the way to work. 

Reference: Preschoolers’ delay of gratification predicts their body mass 30 years later. Schlam TR et al. (2012) The Journal of Pediatrics Aug 18 [Epub ahead of print].

Thursday, December 6, 2012

You're not that tired


A few years ago, good friends of mine dragged me to a viewing of Touching the Void, a movie about the extraordinary survival of a mountain climber against all odds. I remember coming out of that movie thinking, “Wow, when I complain that I’m tired, I’m really not that tired – I have so much more in me”. It might sound corny, but over the years, I’ve thought about this movie several times, and it has inspired me in many ways.

Which part of your body decides when you can and can’t go on? In exercise science, the debate has been going on for years. Some researchers think it’s the heart – you can only exert your big muscle so much. Others link stamina and endurance to lung capacity – measures like VO2 max (how much oxygen your body transports and uses during exercise) have been linked to performance in sports. More recently, measures like the lactate threshold (the exercise intensity at which lactic acid starts to accumulate in your blood) have become popular. Professional athletes are poked and prodded to try to figure out what makes a winner, but somehow with each theory comes at least one or two outliers. 

In an effort to investigate what drives people to push themselves and what sets the limits, British researchers came up with an interesting experiment using cyclists.

Each cyclist in their study had to complete four trials of 4 kilometers on a stationary bicycle. The first trial was just to get used to the equipment and the setting. The second trial was the real deal – they had to go as fast as possible, and their time was stored and used as the “baseline” time, or their “personal best”. During the last two trials, the participants “raced” against themselves – an avatar representing them was projected onto a big screen in front of them, and they could track their progress in relation to that of their avatar. The idea is that the avatar on the screen was going at the same speed as the cyclist’s 2nd trial (the one used to set their personal best). The researchers were hoping to learn whether a cyclist could beat their trial time by chasing themselves to the finish line, thus establishing a new best time.

You can probably guess the outcome of the study: all the participants beat their best time when they raced against it. But there’s a twist: in one of the last two trials, the researchers tricked the cyclists: the avatar was actually going 2% faster than their previously established personal best. And every participant beat that time, too! So guess what? It’s not in your heart, or your lungs, or you legs. It’s all in... your brain.

What the study tells us is that you have a little energy reserve, even when you think you’re going all out. Your brain doesn’t want you to tap that reserve, because if you get into that habit, you might use it up and die. So it keeps it hidden. It makes you feel like you’re going to die even though you’re not. But the reserve is available – throw in a little deception and a little competitiveness (or, in the case of the mountain climber, a little actual fear for your life), and you can gain access to it.

So there you have it! Next time you didn’t sleep well and you’ve been going all day at work and running errands and working out and you just feel like collapsing on the couch and having a nap… Dr. Julie says… Collapse on the couch and have a nap. But do it knowing you could also clean the house if you really wanted to.

Reference: Effects of deception on exercise performance: implications for determinants of fatigue in humans. Stone MR et al. (2012) Med Sci Sports Exerc. 44(3):534-41.

Friday, November 30, 2012

It's time to have "the talk"

Please enjoy this cuteness as a reward for reading this post
No, I'm not talking about the "birds and bees" talk. This "talk" is one you should have with your parents, or your partner, not your children. It's not an easy talk. You're not going to want to talk about it. They are not going to want to talk about it. But the discussion is important, and it should take place sooner than later. This "talk" is about advance health care directives.

Essentially, establishing "advance health care directives" (sometimes called a "living will") means deciding ahead of time how you want to be treated if you are no longer able to make decisions for yourself because you are ill (for example, with dementia) or incapacitated (for example, after a car crash). These decisions include things like whether you'd want to have a feeding tube, be treated with antibiotics, or be resuscitated with CPR if your heart fails (and many other decisions!). In general, people go about this in one of two ways: either by appointing someone to make decisions for them should it be necessary, or by writing down instructions for treatment, such as the kinds of treatments they would be ok with and the kinds they wouldn't want. Ideally, the advance directives should be a combination of both.

Now you're probably sitting there thinking "I'm way too young for this" (aren't we all), or "my parents are well, there's no need". And that's exactly the problem: by the time you need advance directives, chances are it will be too late. Our ability to make decisions for ourselves over our lifetime is like a bell curve: it's pretty low when we're young, still low-ish in our pre-teen/teenage years (hence the need for the "birds and bees" talk), then it peaks in adulthood, and starts declining again as we get older. So ideally we should start this discussion at our peak. I know I'm being a complete bummer suggesting we all sit down and talk about death and illness at our peak. But there's a good chance you'll thank me later.

I'm currently attending the Leadership Program for Physicians and Leaders in Long-Term Care in Vancouver (my talk is tomorrow and I should definitely be preparing for it instead of writing this!). There's a lot of discussion at the conference around advance directives. The main problem is that a lot of people don't have them!

There's some uncertainty over how much physicians actually follow advance directives. In some areas they have to and in others they don't. Really what it comes down to is everyone is better off if they have at least had the discussion - at the conference, one presenter mentioned how older adults who have advance directives tend to enjoy a better quality of life, and a better death. I know, I know. You're don't want to be reading about death on a Friday night. If you need a break, here are some kittens: click here.

As I said before, it's not an easy discussion. "Ah, ok, so, yeah, one day I might have dementia, or be in a car accident and suffer brain damage, and well I think I'd rather...". But hey, a lot of discussions are unpleasant ("Ah, ok, so, yeah, I dropped your brand new iPhone in the toilet"). So just do it. And don't just sit down and write this by yourself, either - speak to a loved one, or a relative, about what your thoughts are, and also involve your doctor - they can absolutely help with this, and may be able to provide you with useful tools. Advance directives should be an ongoing discussion, not a one-time thing - revisit your choices once in a while, and always keep someone in the loop.

I realize this isn't my most uplifting post, but as science moves forward, we face new choices that are important to talk about. So chatter away!

Thursday, November 15, 2012

Go lift some weights and call me in the morning

In my last post I told you that I would reveal the one thing you can do to have a significant, positive and lasting effect on your brain health as you get older. See if you can spot it in the following list:

a) Learn to dance Gangnam style
b) Join a choir
c) Catch a wave
d) Pump some iron

Ok, that was a trick question. All of these answers are somewhat correct, but I was looking for the "most" correct answer (flashbacks to undergrad, anyone?): Pump some iron.

I realize I sound like a broken record - I've already written about how aerobic exercise can promote healthy aging here and here, and I've even already written about resistance training, or lifting weights, here.

So why am I at it again? Because it's important!
I'm fresh out of the 2012 Aging and Society Conference, where researchers came together to discuss what works and what doesn't when it comes to healthy aging. It turns out everyone pretty much agrees that exercise is hands down the most effective intervention to keep your brain cells happy into old(er) age. All sorts of different types of exercise, ranging from simply walking to attending resistance training classes, are associated with different types of improvements in cognition, memory, and even brain size. 

Of course, there are different levels of effort involved with different types of exercise, or even when talking about a single form of exercise. When my friend Jess asks me to go for a walk, she means a power walk: it usually involves going up hills, sweating like a pig (even though pigs, ironically, don't sweat much), and barely having enough breath for girl talk (though somehow we always seem to find it). When my friend Al and I go for a walk, what he means is a "mosey": we stop to look at the view, pet the dog, chit chat with strangers, and have more than enough breath for lengthy discussions about life, work, and the possibility of alien lifeforms. When it comes to brain health, whether you're walking or pumping iron, a little sweating and effort can go a long way. For example, resistance training has been proven to be most effective when the load, or how much weight you are working with, increases over time. So kick the intensity up a notch: there will still be plenty of time for chit chat around a post-exercise, antioxidant-rich mug of matcha (my new obsession - stay tuned).

Now that the obvious has been (re)stated, I want to take this opportunity to discuss the idea that perhaps lifestyle interventions such as exercise could be prescribed by your doctor. We know that exercise can improve cognition in aging but also conditions like depression. Should physicians prescribe lifestyle changes? Or are diet, exercise, and other lifestyle activities choices we should make ourselves? How would you feel if your doctor prescribed you exercise instead of pills? Would you be more motivated to exercise if the prescription came from your doctor instead of from your friendly Internet science blogger? Your thoughts in the comments!

 
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