Monthly Archives: May 2015

When talking about cancer screening, survival rates mislead

I have been on about this topic quite frequently. All is not as it seems. Refer to my section headed : “Breast cancer screening- mammography” on this web-site. These issues need to be carefully considered by women (Benefits vs risks) of mammography. There are many who now say it does more harm than good. Read the evidence before coming to your own conclusion.
28 January 2015, 6.22am AEDT

When talking about cancer screening, survival rates mislead

Cancer screening is beneficial when it’s able to prevent people dying from cancer. And it should clearly be adopted where there’s evidence showing this. But using cancer survival rates to promote screening…

If we want to know whether screening saves lives, we need to show a reduction in the cancer death rate rather than an increase in the survival rate. Steven Depolo/Flickr, CC BY-SA

Cancer screening is beneficial when it’s able to prevent people dying from cancer. And it should clearly be adopted where there’s evidence showing this. But using cancer survival rates to promote screening, as is often done, is misleading.

For screening to prevent people from dying early, simply finding cancers is not enough; we need to find progressive cancers that would kill if left untreated. What’s more, we need effective treatment for these cancers. And the therapy has to be more likely to cure if administered earlier (when cancer may be detected by screening) than later (when cancer may be detected by the patient or doctor without screening).

Yet many screening advocates – often with the best of intentions – use survival rates to make their case. These statistics may appear as legitimate evidence to support screening, even to medical professionals. But they’re highly misleading as they always make screening look worthwhile, even if it isn’t actually doing any good.

The wrong emphasis

Consider breast cancer screening. The high survival rates for this cancer are used around the world to impress the apparent benefits of screening on people.

Australian research on the topic published last year, for instance, reported improved survival among women whose cancers were found by screening compared to those whose cancers were found because they developed symptoms. An accompanying press release claimed that “the findings show the survival benefits of mammography screening”.

The world’s largest breast cancer charity (and the creator of the “pink ribbon”) is US-based Susan G. Komen. Until recently, its website promoted breast cancer screening by noting that:

early detection saves lives. The five-year survival rate for breast cancer when caught early is 98%. When it’s not? 23%.

By highlighting the higher survival rate of women whose cancer was detected by screening, these examples imply screening prolongs lives. But survival rates actually tell us little about longer lifespans.

In fact, research shows that, between 1950 and 1995, the increases in survival rates after cancer diagnosis weren’t associated with decreases in cancer death rates over the same period. What’s more, cancers that showed the largest increases in five-year survival didn’t have the largest decrease in deaths. Although five-year survival increased for all cancers over the study period, the death rate for some of them also actually increased.

How it works

People whose cancer is detected by screening will show a higher survival rate than those who detect their cancer themselves or have it diagnosed by their doctor, even when screening has not prolonged any lives, because of two types of statistical bias.

The first is known as lead time bias. This is where the detection of cancer through screening at an early stage does nothing but advance the date of diagnosis. The figure below shows hypothetical outcomes for a person with cancer for different screening scenarios.

Figure one: improved survival due to lead-time bias
Click to enlarge

Here’s how to read the three scenarios:

  1. No screening – does not participate in screening; cancer is diagnosed because the person developed symptoms and the person dies four years later. The five-year survival rate for this cancer is 0%.
  2. Ineffective screening – participates in screening; cancer is detected but earlier treatment does not alter natural disease progression. The five-year survival rate for this cancer, which is caught early, is 100% – even though screening has made no difference to how long the person actually lives.
  3. Effective screening – participates in screening, cancer is detected and treatment is able to prolong life. The five-year survival rate is 100%, although screening actually only prolonged the person’s life by two years.

Survival time from diagnosis is substantially longer in both screening scenarios, even though only in the last is there a real benefit.

The second statistical distortion results from what is known as length time bias. This is where the detection of cancer through screening picks up slowly growing cancers, which have a better prognosis than cancers presenting clinically (detected by the doctor or the person when they get ill).

The extreme of this is over-diagnosis, where the cancer would never cause symptoms during that person’s lifetime, or death. Unfortunately, progressive and non-progressive cancer cells appear the same under the microscope – all are labelled as cancer.

The figure below shows hypothetical outcomes for a population with different screening scenarios.

Figure two: improved survival due to length time bias
Click to enlarge

Here’s how to read it:

  1. No screening – all cancers are diagnosed because the person develops symptoms, which means all are progressive. The five-year survival rate without screening is 20%.
  2. Ineffective screening – additional non-progressive cancers are detected by screening; cancers that are progressive may be detected earlier than with no screening, but earlier treatment makes no difference to natural disease progression. The five-year survival rate is “pushed to” 43%, even though screening has made no difference to how many lives are saved.
  3. Effective screening – additional non-progressive cancers are detected by screening; cancers that are progressive are detected earlier than with no screening and treatment is able to prolong life.

Five-year survival from diagnosis is substantially higher in both screening scenarios, even though only in the last is there actually a real benefit.

When is screening worthwhile?

If we want to show that screening saves lives, we need to show a reduction in the cancer death rate, which measures the number of people dying of the cancer within a population over a period of time.

Unlike survival rates, death rates don’t use the time the cancer was diagnosed in their calculation. And the total number of people in the population is considered, rather than just those diagnosed with cancer.

To work out death rates, the number of people dying over an equivalent period of time might be compared in screened and unscreened groups. Or compare a population before and after a screening program is started. Or different populations that are otherwise similar except that one has screening and the other does not can be compared.

The figures below shows death rates are not affected by lead time or length time biases.

Figure three: death rates not affected by lead time bias
Click to enlarge
Figure four: death rates not affected by length time bias
Click to enlarge

Here’s how to read the three scenarios:

  1. No screening – the person in the first table above dies during the study period, so the death rate is 100% (first panel, Figure 3); 400 of the 5,000 unscreened population in the second table die before five years, so the five-year death rate is 8% (first panel, Figure 4).
  2. Ineffective screening – the person dies during study period, so the death rate is 100% (middle panel, Figure 3); 400 of the 5,000 screened population die before five years, so the five-year death rate is 8% (middle panel, Figure 4)
  3. Effective screening – the person survives to end of study, so the death rate is 0% (bottom panel, Figure 3); 350 of the 5,000 screened population die before five years, so the five-year death rate is 7% (bottom panel, Figure 4).

Death rates are improved only where screening has led to a real benefit; they are unchanged where screening has no effect on natural disease progression.

Survival statistics, even when they are used by well-meaning advocates who misinterpret them as a measure of the success of cancer screening, are misleading. They tell us nothing about lives saved and the potential value of screening programs

Why mosquitoes seem to bite some people more

26 January 2015, 6.09am AEDT

Health Check: why mosquitoes seem to bite some people more

There’s always one in a crowd, a sort of harbinger of the oncoming mosquito onslaught: a person mosquitoes seem to target more than others. What is it about these unlucky chosen few that makes them mosquito…

There are up to 400 chemical compounds on human skin that could play a role in attracting mosquitoes. sookie/Flickr, CC BY-SA

There’s always one in a crowd, a sort of harbinger of the oncoming mosquito onslaught: a person mosquitoes seem to target more than others. What is it about these unlucky chosen few that makes them mosquito magnets?

There are hundreds of mosquito species and they all have slightly different preferences when it comes to what or who they bite. But only females bite; they need a nutritional hit to develop eggs.

Finding someone to bite

Mosquitoes are stimulated by a number of factors when seeking out a blood meal. Initially, they’re attracted by the carbon dioxide we exhale. Body heat is probably important too, but once the mosquito gets closer, she will respond to the smell of a potential blood source’s skin.

Studies have suggested blood type (particularly type O), pregnancy and beer drinking all make you marginally more attractive to mosquitoes. But most of this research uses only one mosquito species. Switch to another species and the results are likely to be different.

There are up to 400 chemical compounds on human skin that could play a role in attracting (and perhaps repulsing) mosquitoes. This smelly mix, produced by bacteria living on our skin and exuded in sweat, varies from person to person and is likely to explain why there is substantial variation in how many mozzies we attract. Genetics probably plays the biggest role in this, but a little of it may be down to diet or physiology.

One of the best studied substances contained in sweat is lactic acid. Research shows it’s a key mosquito attractant, particularly for human-biting species such as Aedes aegypti. This should act as fair warning against exercising close to wetlands; a hot and sweaty body is probably the “pick of the bunch” for a hungry mosquito!

Probably the most famous study about their biting habits demonstrated that the mosquitoes that spread malaria (Anopheles gambiae) are attracted to Limburger cheese. The bacteria that gives this cheese its distinctive aroma is closely related to germs living between our toes. That explains why these mosquitoes are attracted to smelly feet.

But when another mosquito (such as Aedes aegypti) is exposed to the same cheese, the phenomenon is not repeated. This difference between mosquitoes highlights the difficulty of studying their biting behaviours. Even pathogens such as malaria may make us more attractive to mosquitoes once we’re infected.

Only females bite because they need a nutritional hit to develop eggs. Sean McCann/Flickr, CC BY-NC-SA

Researchers are trying to unscramble the irresistible smelly cocktails on the skins of “mosquito magnets”. But the bad news is that if you’re one of these people, there isn’t much you can do about it other than wearing insect repellents.

The good news is that you may one day help isolate a substance, or mixes of substances, that will help them find the perfect lure to use in mosquito traps. We could all then possibly say goodbye to topical insect repellents altogether.

Attraction or reaction?

Sometimes, it’s not the bite as much as the reaction that raises concerns. Think of the last time the mosquito magnets in your circle of friends started complaining about being bitten after the event where the purported mosquito feast took place. At least, they appear to have attracted more than the “bite free” people who were also at the picnic, or concert or whatever.

But just because some people didn’t react to mosquito bites, doesn’t mean they weren’t bitten. Just as we do with a range of environmental, chemical or food allergens, we all differ in our reaction to the saliva mosquitoes spit while feeding.

People who don’t react badly to mosquito bites may think they haven’t been bitten when they’ve actually been bitten as much as their itchy friends. In fact, while some people attract more mosquito bites than others, there’s unlikely to be anyone who never, ever, gets bitten.

The problem is that people who don’t react to mosquito bites may all too easily become complacent. If you’re one of them, remember that it only takes one bite to contract a mosquito-borne disease.

Finally, there is no evidence from anywhere in the world that there is something you can eat or drink that will stop you being bitten by mosquitoes. No, not even eating garlic, or swallowing vitamin B supplements.

Perhaps if we spent as much time thinking about how to choose and use mosquito repellents as we do about why mosquitoes bite our friends and family less than us, there’d be fewer bites all around.

Why the modern world is bad for your brain

Why the modern world is bad for your brain

In an era of email, text messages, Facebook and Twitter, we’re all required to do several things at once. But this constant multitasking is taking its toll. Here neuroscientist Daniel J Levitin explains how our addiction to technology is making us less efficient

Daniel J Levitin

Sunday 18 January 2015 19.30 AEST

Daniel J Levitan: ‘When trying to concentrate on a task, an unread email in your inbox can reduce your effective IQ by 10 points.’

Daniel J Levitan

Our brains are busier than ever before. We’re assaulted with facts, pseudo facts, jibber-jabber, and rumour, all posing as information. Trying to figure out what you need to know and what you can ignore is exhausting. At the same time, we are all doing more. Thirty years ago, travel agents made our airline and rail reservations, salespeople helped us find what we were looking for in shops, and professional typists or secretaries helped busy people with their correspondence. Now we do most of those things ourselves. We are doing the jobs of 10 different people while still trying to keep up with our lives, our children and parents, our friends, our careers, our hobbies, and our favourite TV shows.
Our smartphones have become Swiss army knife–like appliances that include a dictionary, calculator, web browser, email, Game Boy, appointment calendar, voice recorder, guitar tuner, weather forecaster, GPS, texter, tweeter, Facebook updater, and flashlight. They’re more powerful and do more things than the most advanced computer at IBM corporate headquarters 30 years ago. And we use them all the time, part of a 21st-century mania for cramming everything we do into every single spare moment of downtime. We text while we’re walking across the street, catch up on email while standing in a queue – and while having lunch with friends, we surreptitiously check to see what our other friends are doing. At the kitchen counter, cosy and secure in our domicile, we write our shopping lists on smartphones while we are listening to that wonderfully informative podcast on urban beekeeping.

But there’s a fly in the ointment. Although we think we’re doing several things at once, multitasking, this is a powerful and diabolical illusion. Earl Miller, a neuroscientist at MIT and one of the world experts on divided attention, says that our brains are “not wired to multitask well… When people think they’re multitasking, they’re actually just switching from one task to another very rapidly. And every time they do, there’s a cognitive cost in doing so.” So we’re not actually keeping a lot of balls in the air like an expert juggler; we’re more like a bad amateur plate spinner, frantically switching from one task to another, ignoring the one that is not right in front of us but worried it will come crashing down any minute. Even though we think we’re getting a lot done, ironically, multitasking makes us demonstrably less efficient.

Multitasking has been found to increase the production of the stress hormone cortisol as well as the fight-or-flight hormone adrenaline, which can overstimulate your brain and cause mental fog or scrambled thinking. Multitasking creates a dopamine-addiction feedback loop, effectively rewarding the brain for losing focus and for constantly searching for external stimulation. To make matters worse, the prefrontal cortex has a novelty bias, meaning that its attention can be easily hijacked by something new – the proverbial shiny objects we use to entice infants, puppies, and kittens. The irony here for those of us who are trying to focus amid competing activities is clear: the very brain region we need to rely on for staying on task is easily distracted. We answer the phone, look up something on the internet, check our email, send an SMS, and each of these things tweaks the novelty- seeking, reward-seeking centres of the brain, causing a burst of endogenous opioids (no wonder it feels so good!), all to the detriment of our staying on task. It is the ultimate empty-caloried brain candy. Instead of reaping the big rewards that come from sustained, focused effort, we instead reap empty rewards from completing a thousand little sugar-coated tasks.

Brain

In the old days, if the phone rang and we were busy, we either didn’t answer or we turned the ringer off. When all phones were wired to a wall, there was no expectation of being able to reach us at all times – one might have gone out for a walk or been between places – and so if someone couldn’t reach you (or you didn’t feel like being reached), it was considered normal. Now more people have mobile phones than have toilets. This has created an implicit expectation that you should be able to reach someone when it is convenient for you, regardless of whether it is convenient for them. This expectation is so ingrained that people in meetings routinely answer their mobile phones to say, “I’m sorry, I can’t talk now, I’m in a meeting.” Just a decade or two ago, those same people would have let a landline on their desk go unanswered during a meeting, so different were the expectations for reachability.

Just having the opportunity to multitask is detrimental to cognitive performance. Glenn Wilson, former visiting professor of psychology at Gresham College, London, calls it info-mania. His research found that being in a situation where you are trying to concentrate on a task, and an email is sitting unread in your inbox, can reduce your effective IQ by 10 points. And although people ascribe many benefits to marijuana, including enhanced creativity and reduced pain and stress, it is well documented that its chief ingredient, cannabinol, activates dedicated cannabinol receptors in the brain and interferes profoundly with memory and with our ability to concentrate on several things at once. Wilson showed that the cognitive losses from multitasking are even greater than the cognitive losses from pot‑smoking.

Russ Poldrack, a neuroscientist at Stanford, found that learning information while multitasking causes the new information to go to the wrong part of the brain. If students study and watch TV at the same time, for example, the information from their schoolwork goes into the striatum, a region specialised for storing new procedures and skills, not facts and ideas. Without the distraction of TV, the information goes into the hippocampus, where it is organised and categorised in a variety of ways, making it easier to retrieve. MIT’s Earl Miller adds, “People can’t do [multitasking] very well, and when they say they can, they’re deluding themselves.” And it turns out the brain is very good at this deluding business.
Brain
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‘Asking the brain to shift attention from one activity to another causes the prefrontal cortex and striatum to burn up oxygenated glucose, the same fuel they need to stay on task.’ Photograph: Alamy

Then there are the metabolic costs that I wrote about earlier. Asking the brain to shift attention from one activity to another causes the prefrontal cortex and striatum to burn up oxygenated glucose, the same fuel they need to stay on task. And the kind of rapid, continual shifting we do with multitasking causes the brain to burn through fuel so quickly that we feel exhausted and disoriented after even a short time. We’ve literally depleted the nutrients in our brain. This leads to compromises in both cognitive and physical performance. Among other things, repeated task switching leads to anxiety, which raises levels of the stress hormone cortisol in the brain, which in turn can lead to aggressive and impulsive behaviour. By contrast, staying on task is controlled by the anterior cingulate and the striatum, and once we engage the central executive mode, staying in that state uses less energy than multitasking and actually reduces the brain’s need for glucose.

To make matters worse, lots of multitasking requires decision-making: Do I answer this text message or ignore it? How do I respond to this? How do I file this email? Do I continue what I’m working on now or take a break? It turns out that decision-making is also very hard on your neural resources and that little decisions appear to take up as much energy as big ones. One of the first things we lose is impulse control. This rapidly spirals into a depleted state in which, after making lots of insignificant decisions, we can end up making truly bad decisions about something important. Why would anyone want to add to their daily weight of information processing by trying to multitask?

In discussing information overload with Fortune 500 leaders, top scientists, writers, students, and small business owners, email comes up again and again as a problem. It’s not a philosophical objection to email itself, it’s the mind-numbing number of emails that come in. When the 10-year-old son of my neuroscience colleague Jeff Mogil (head of the Pain Genetics lab at McGill University) was asked what his father does for a living, he responded, “He answers emails.” Jeff admitted after some thought that it’s not so far from the truth. Workers in government, the arts, and industry report that the sheer volume of email they receive is overwhelming, taking a huge bite out of their day. We feel obliged to answer our emails, but it seems impossible to do so and get anything else done.

Before email, if you wanted to write to someone, you had to invest some effort in it. You’d sit down with pen and paper, or at a typewriter, and carefully compose a message. There wasn’t anything about the medium that lent itself to dashing off quick notes without giving them much thought, partly because of the ritual involved, and the time it took to write a note, find and address an envelope, add postage, and take the letter to a mailbox. Because the very act of writing a note or letter to someone took this many steps, and was spread out over time, we didn’t go to the trouble unless we had something important to say. Because of email’s immediacy, most of us give little thought to typing up any little thing that pops in our heads and hitting the send button. And email doesn’t cost anything.

Sure, there’s the money you paid for your computer and your internet connection, but there is no incremental cost to sending one more email. Compare this with paper letters. Each one incurred the price of the envelope and the postage stamp, and although this doesn’t represent a lot of money, these were in limited supply – if you ran out of them, you’d have to make a special trip to the stationery store and the post office to buy more, so you didn’t use them frivolously. The sheer ease of sending emails has led to a change in manners, a tendency to be less polite about what we ask of others. Many professionals tell a similar story. One said, “A large proportion of emails I receive are from people I barely know asking me to do something for them that is outside what would normally be considered the scope of my work or my relationship with them. Email somehow apparently makes it OK to ask for things they would never ask by phone, in person, or in snail mail.”

There are also important differences between snail mail and email on the receiving end. In the old days, the only mail we got came once a day, which effectively created a cordoned-off section of your day to collect it from the mailbox and sort it. Most importantly, because it took a few days to arrive, there was no expectation that you would act on it immediately. If you were engaged in another activity, you’d simply let the mail sit in the box outside or on your desk until you were ready to deal with it. Now email arrives continuously, and most emails demand some sort of action: Click on this link to see a video of a baby panda, or answer this query from a co-worker, or make plans for lunch with a friend, or delete this email as spam. All this activity gives us a sense that we’re getting things done – and in some cases we are. But we are sacrificing efficiency and deep concentration when we interrupt our priority activities with email.

Until recently, each of the many different modes of communication we used signalled its relevance, importance, and intent. If a loved one communicated with you via a poem or a song, even before the message was apparent, you had a reason to assume something about the nature of the content and its emotional value. If that same loved one communicated instead via a summons, delivered by an officer of the court, you would have expected a different message before even reading the document. Similarly, phone calls were typically used to transact different business from that of telegrams or business letters. The medium was a clue to the message. All of that has changed with email, and this is one of its overlooked disadvantages – because it is used for everything. In the old days, you might sort all of your postal mail into two piles, roughly corresponding to personal letters and bills. If you were a corporate manager with a busy schedule, you might similarly sort your telephone messages for callbacks. But emails are used for all of life’s messages. We compulsively check our email in part because we don’t know whether the next message will be for leisure/amusement, an overdue bill, a “to do”, a query… something you can do now, later, something life-changing, something irrelevant.

This uncertainty wreaks havoc with our rapid perceptual categorisation system, causes stress, and leads to decision overload. Every email requires a decision! Do I respond to it? If so, now or later? How important is it? What will be the social, economic, or job-related consequences if I don’t answer, or if I don’t answer right now?

'Because it is limited in characters, texting discourages thoughtful discussion or any level of detail, and its addictive problems are compounded by its hyper-immediacy.'
‘Because it is limited in characters, texting discourages thoughtful discussion or any level of detail, and its addictive problems are compounded by its hyper-immediacy.’
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‘Because it is limited in characters, texting discourages thoughtful discussion or any level of detail, and its addictive problems are compounded by its hyper-immediacy.’ Photograph: Alamy

Now of course email is approaching obsolescence as a communicative medium. Most people under the age of 30 think of email as an outdated mode of communication used only by “old people”. In its place they text, and some still post to Facebook. They attach documents, photos, videos, and links to their text messages and Facebook posts the way people over 30 do with email. Many people under 20 now see Facebook as a medium for the older generation.

For them, texting has become the primary mode of communication. It offers privacy that you don’t get with phone calls, and immediacy you don’t get with email. Crisis hotlines have begun accepting calls from at-risk youth via texting and it allows them two big advantages: they can deal with more than one person at a time, and they can pass the conversation on to an expert, if needed, without interrupting the conversation.

But texting suffers from most of the problems of email and then some. Because it is limited in characters, it discourages thoughtful discussion or any level of detail. And the addictive problems are compounded by texting’s hyperimmediacy. Emails take some time to work their way through the internet and they require that you take the step of explicitly opening them. Text messages magically appear on the screen of your phone and demand immediate attention from you. Add to that the social expectation that an unanswered text feels insulting to the sender, and you’ve got a recipe for addiction: you receive a text, and that activates your novelty centres. You respond and feel rewarded for having completed a task (even though that task was entirely unknown to you 15 seconds earlier). Each of those delivers a shot of dopamine as your limbic system cries out “More! More! Give me more!”

In a famous experiment, my McGill colleagues Peter Milner and James Olds, both neuroscientists, placed a small electrode in the brains of rats, in a small structure of the limbic system called the nucleus accumbens. This structure regulates dopamine production and is the region that “lights up” when gamblers win a bet, drug addicts take cocaine, or people have orgasms – Olds and Milner called it the pleasure centre. A lever in the cage allowed the rats to send a small electrical signal directly to their nucleus accumbens. Do you think they liked it? Boy how they did! They liked it so much that they did nothing else. They forgot all about eating and sleeping. Long after they were hungry, they ignored tasty food if they had a chance to press that little chrome bar; they even ignored the opportunity for sex. The rats just pressed the lever over and over again, until they died of starvation and exhaustion. Does that remind you of anything? A 30-year-old man died in Guangzhou (China) after playing video games continuously for three days. Another man died in Daegu (Korea) after playing video games almost continuously for 50 hours, stopped only by his going into cardiac arrest.

Each time we dispatch an email in one way or another, we feel a sense of accomplishment, and our brain gets a dollop of reward hormones telling us we accomplished something. Each time we check a Twitter feed or Facebook update, we encounter something novel and feel more connected socially (in a kind of weird, impersonal cyber way) and get another dollop of reward hormones. But remember, it is the dumb, novelty-seeking portion of the brain driving the limbic system that induces this feeling of pleasure, not the planning, scheduling, higher-level thought centres in the prefrontal cortex. Make no mistake: email-, Facebook- and Twitter-checking constitute a neural addiction.

© Daniel J. Levitin. Extracted from The Organized Mind: Thinking Straight in the Age of Information Overload, published by Viking (£20). Click here to buy it for £16.