Wednesday, 21 November 2012

Statistics and a Big Pinch of Salt


The CF Trust (UK), Cystic Fibrosis Foundation (US) and Cystic Fibrosis Canada all publish annual reports based on the data collected in their patient registries. The statistic that people always focus on is “median predicted survival”.  People talk about it as if it means the same thing as “life expectancy”.

Based on the latest available data, the median predicted survival number in the US, UK and Canada is 37, 41 and 48 respectively. How can it be eleven years higher in Canada than in the US? Patients in both countries have essentially the same treatment options and the genotype profiles are very similar. Also, the number in the US went down slightly from 38 in the previous year. This is very unlikely to be because treatment options got worse year-on-year. It suggests something weird happened in the data and, more generally, that statistics like this should be taken with a hefty pinch of salt.

What exactly is “media predicted survival”?

Median predicted survival is the age beyond which half of the people currently in the relevant CF patient registry are expected to live and below which half are not expected to survive.

Median predicted age of survival is calculated using a standard actuarial method called life table analysis. This is best known for its use in the life insurance industry. It is calculated by looking at how many people are in each“cohort” or group of people born in a given year (say 1975) and finding how many of them survived the past 12 months. That gives an age-specific mortality-rate. Say, at the start of the year, there were 100 people in the database who were born in 1975 and that 90 of them were still alive at the end of the year. Of course, some of the ten that died may have died from something unrelated to CF. Since 90 of the 100 survived, the age-specific mortality rate for that year was 10%. Then the people at the registry will assume all the people born in 1976 (i.e. a year younger than the first cohort) have a 90% chance of surviving the next 12 months (on the basis they will be exactly like the people a year older) and they can work out a life expectancy for each cohort. This process is repeated for all the cohorts.

They then run the numbers and figure out the age above which half of the people currently in the CF patient registry are expected to live and below which half are not expected to live. This is the median predicted survival age. It is specific to the people whose data is currently in the database.  

Is "median predicted survival" the same as "life expectancy"? 

No - median predicted survival is NOT the same thing as life expectancy. Life expectancy is the expected average length of life for someone of a certain age based on currently available data in relation to people of that age. Obviously the average CF baby born today will have a longer life expectancy than the average person with CF alive today but born 30 years ago, as new treatments and earlier diagnosis have made a big difference, but both could be in the same patient registry population. 

Today in Canada, life expectancy at birth is 77 years while the median predicted survival is 48 years.    

Why is “median predicted survival” so different to “median age at death”?

Median age at death is calculated by listing the ages of all the people who have died in a given year in ascending order and finding the middle number (i.e. the number separating the oldest 50% from the youngest 50%). The median age at death is calculated only on the basis of those individuals who have died. In other words, of the ones who died, half of them died younger than the median age of death and half died older than the median age of death. Clearly, this calculation does not tell us anything about the individuals who have not died in that year. You need to know the ages of those still living to get a feel for life expectancy and median predicted survival.

If you think about this in terms of a Formula 1 grand prix, you could look at a particular race in a particular season and make a note of all the cars which crashed and failed to finish. Of those, you could look at how far into the race they each got before they crashed. You might find that more than 50% of the "crashers" crashed in the first 30 minutes of the race. That is fine, as far as it goes, but it would be big mistake to conclude from this that any car starting this race in future would probably crash out in the first 30 minutes. This kind of analysis does not tell the whole story because it fails to take into account the cars which did not crash i.e. the "finishers" and they are very important cars. 

Lies,Damned Lies and Statistics

Another reason for caution is that not everyone with CF is on the registry. Most are now but some people do not consent to have their data included. Others are not on there because they don’t go to clinic often enough to enable the researchers to get the data.I would speculate that the people who are not on the registry are relatively healthy. If that is the case, the statistics based on the data in the registry maybe slightly skewed too much towards the “unhealthy”.  

A more general problem with averages is they only take into account things that have happened in the past. By definition, all the data points used to calculate the average are backward-looking. By the time averages are published they are already out-of-date. Imagine trying to drive a car without being able to look at the road ahead; only being able to look back through your rear-view mirrors. This is essentially what you are doing if you place too much reliance on averages and other statistics. The financial markets have learned this lesson the hard way over the last few years. It is a particular problem with Cystic Fibrosis because the medical science and treatments are improving at a relatively rapid pace. For example, the current data take no account of Kalydeco since it came to market after the end of the period for which data was collected. Other new treatments are coming on-stream all the time. This means the statistics will always lag behind the reality.  

Another problem is that there is often no such thing as the average case (i.e. the statistical average does not actually correspond with anything in the real world) or that it produces something misleading.

If you are 1.6 metres tall and unable to swim, is it safe to cross a river which is 1.2 metres deep on average? Not if the deepest point is actually 2 metres. The average is no use to you in this situation. In fact, it is dangerous. 

Now imagine 10 people each holding a tin of paint. Six of them are holding tins of red paint, four of them green paint.  What is the average colour? You could find the“median” by writing them all down in a list (red, red, red, red, red, red,green, green, green, green) and finding the colour in the middle. Do this by starting at either end and crossing out the items until you get to the middle.  You end with four of each colour crossed out and two reds left in the middle. So the median colour is red.  Does this tell you anything interesting about the colours? Not really. To me, it just begs the question of why some are red and why some are green and why not any other colours.    

If you wanted to calculate the “mean” average, you could empty all the tins into one big pot, mix it up and then divide it back into the 10 tins. You will get brown paint. But in reality none of them was holding a tin of brown paint.  It is much more interesting and meaningful to take a given tin and look at what is inside.

Of course, published statistics tell you about average outcomes based on past experience across the whole CF population (i.e. for all mutations). They do not even tell you the average specific to your mutation. Not yet, anyway. To date, over 1,600 mutations have been identified and they all have different implications. Even two people with exactly the same mutation, can be affected in very different ways. Every person with CF has their own unique hue and shade. Focus on the colour of the paint in your tin; don’t pay too much attention to these statistical snapshots.

One thing that is clear from the data is that longevity and quality of life for people with CF is increasing significantly and steadily over time as a result of earlier diagnosis (and now newborn screening); better drugs and medication; better transplant options and techniques; more sophisticated physio and airway clearance techniques; and perhaps higher levels of awareness. With little support from governments around the world, this is largely as a result of the work done by the CF Foundation in the US, the CF Trust in the UK and Cystic Fibrosis Canada and the data they present is probably the best available to tell a complicated story. 

For anyone who does want to read the latest patient registry reports they are accessible here (and there is some interesting stuff in there if you read the discussions behind the headline numbers):

UK Data from CF Trust (2010):

USA Data from Cystic Fibrosis Foundation (2011)

Canada Data from Cystic Fibrosis Canada (2010):
Patient Data Registry Report 2010

Monday, 19 November 2012

Adaptive Physio & Why We Should All Learn Italian


When I was younger I did a lot of sport and found my lungs would naturally clear themselves. Now my FEV1 is usually between 30% and 40%, my resting SATS are 92-94% on air but they can quickly drop below 90%. I have to be careful of de-saturating as I now have mild pulmonary hypertension so I use ambulatory oxygen. I try to do as much exercise as I can (on oxygen) but I don’t always have the energy and I have to work much harder at it. So I need a Plan B (and a Plan C and sometimes a Plan D).

I tend to get a very dry, tickly cough so my challenge is to work through my physio without it degenerating into a manic coughing fit and making my airways very tight without actually clearing anything. I also find the gunk tends to be buried deep down and I have to work hard to get it out. I am interested in any techniques that help me clear a decent amount of mucus without exhausting myself too much, giving myself a horrendous headache, feeling sick or all three of these. For me, it’s all about efficiency: clearing the most mucus for the minimum amount of coughing and energy expenditure. I typically do a modified form of autogenic drainage and I also use a PEP mouthpiece. I find the back-pressure helpful in terms of propping open the airways so I don’t get too tight and wheezy (i.e. so I can move sufficient volumes of air to reach and mobilise the deep secretions).

I find my lungs are a bit like the weather - very unpredictable. Some mornings they feel very tight, dry and tickly. Some mornings they are more friendly: more relaxed, more moist, more soft feeling. Different techniques work on different kinds of “lung weather.” So I always have to be quite creative and just keep trying, adapting things until something works.   

After doing Salbutamol and Pulmozyme nebs but before starting on airway clearance, I find doing some gentle stretching is very helpful. This is mostly to do with lengthening and aligning my spine and opening up my chest. I tend to find I get hunchy and this gets worse when I feel worse. It’s a vicious circle though because the more hunchy I get, the worse I breathe. A bit of work on posture each day stops it getting too bad. And I find it’s a good way to focus and relax.

When I was in the Royal Brompton once for a course of IVs there was a singing teacher called Maya  walking around offering to give patients singing lessons. I had done some singing in school but that was 20 years ago and not a note had passed my lips since. I had a go though because I was intrigued and also quite bored. In fact it turned out to be a bit of an eye-opener. It was a lot of fun and it taught me some useful things about breathing and posture. I am not about to enter the X Factor but I do find singing helpful and enjoyable. I also find some of the techniques useful when doing airway clearance which for me is usually some form of autogenic drainage.    

Sometimes during airway clearance, when I am fully exhaling or doing a slow gentle huff trying to mobilise secretions, I find it helpful to imagine I am singing a long deep note but without actually singing. In other words, my mouth, airways and diaphragm all behave as if singing a long deep note but without any involvement of the vocal cords. The feeling of holding the note works really well for me. 

I also experiment with different mouth shapes. As I am doing these slow gentle huffs, if I find nothing is moving I try a different mouth shape. For example, I might start off with my mouth shaped for an “ah” sound but if that is not producing, I might switch to an “eeh” sound or an “oh” shape and so on until something moves.

On other recent occasions, I have found gargling gently with warm water can be effective. The combination of hydrating the throat and the “flutter” effect of the water just seems to do the trick. Then there are the old classics like slowly steaming up a mirror. I have tried using The Vest but I find it difficult to hear and feel what is going on in my lungs/airways so I prefer other methods. If I am really feeling bad and have no energy, I find some old fashioned percussion and postural drainage is the best approach. 

I have had and continue to get lots of fantastic instruction, help and support from my physios. I think they are the unsung heroes of CF care. But at the end of the day, we are all unique and our lungs are capable of weird and wonderful variations. 

I have learned that I have to be open-minded, try lots of different things, improvise, adapt, never give up and find something that works for me. It may be something nobody has ever thought of before!

Perhaps like learning how to sing in Italian…

An American friend of mine who is a trained opera singer recently told me this:

Listening to and thinking about how an opera singer uses their lungs might help you make your breathing work better for you. When we were babies we happily breathed through our tummy/diaphragm but as we grow older we think we have to breathe through our chest. It is good to rediscover tummy breathing and good use of the diaphragm.

As you inhale, feel the diaphragm flatten (contract) causing the abdomen to bulge outwards. During exhalation, the diaphragm relaxes upward, allowing the ribs to drop down and the abdomen to draw inward again. Feel the movement in your ribs and abdomen. You can feel the movement of your breathing by putting one hand on the side of your torso and the other hand on your abdomen. During inhalation, you will be able to feel your hands move out. During exhalation you will feel your hands move back in.

Italians singers are usually perceived to be the most "natural" sounding. Italian vowel sounds are the purest - have the fewest diphthongs – of all the Western languages. It's why one can sing so quickly in Italian (like Rossini likes to write, Mozart too, sometimes); and also why Italian opera specialized in "bel canto" - beautiful singing - as almost an end in itself. I don't know if this is true, but my old Juilliard Italian diction coach used to maintain that Italians were the most relaxed and kept their breathing channels the most open, especially while they slept. She claimed that Italians (unlike most northern Europeans, or worse still, Americans) never clench their teeth when they sleep or when they are at rest. They have relaxed jaws and open larynxs. And they sing "in the mask" - that's singer talk for projecting with an open throat, feeling like the sound is coming out, not from the mouth, but rather from an area between the upper nose and the eyes.  When it doesn't work well with Italian singers, they can sometimes sound too nasal.  

So while writing this note, I thought it might be fun for you to find an Italian diction coach or even take some singing lessons if it wouldn’t be too much of a strain.

Another thought: do you know something called the Alexander Method? Not really an exercise thing (it's not Pilates); it's used by lots of singers and actors to improve their posture, open up their breath canals, all of that kind of thing.  When I was at "singer camp" there used to be an Alexander teacher attached. Putting one hand on your forehead and one on your belly while you breathe is an old trick, and might be fun to play with. The simple act of being still, concentrating deep breaths on mindless numbers - or whatever you choose - might be a good opening to any breathing exercise.

But at the end of the day, it's all in the way you use your diaphragm. And singing is probably one of the best ways to improve.    

Food for thought!

Sunday, 18 November 2012

Some Brilliant CF Blogs

Here is a list of some top blogs by people in UK, Ireland and Australia with Cystic Fibrosis. These are just the ones I have stumbled across so far and which I think are brilliant. I'm sure there are others and they are in no particular order. 

Updated: 21.11.2012

My Life With CF
Evan (27, Male)

fighttolivelivetofightcf 
Lydia (19, Female)

Cocktails & Creon
Grace (19, Female)

Me, Myself and I (and CF)
Gemma (27, Female)

A Sprog's Life!
George (22, Female, On Kalydeco)

magicbluepill
Genevieve (27, Female, On Kalydeco)


Ludicrous Bunglings
Laura (23, Female, On Liver and Pancreas Transplant List)


The End of My Tether?
Sam (27, Female, On Lung Transplant List)

My Life With Cystic Fibrosis
Katie (14, Female, On Lung Transplant List)

Come Walk in My Shoes
Kerry (20, Female, On Lung Transplant List)

2nd chance @ life?
Kirstie (22, Female, Post-Transplant)

This is my life, and I choose to love it
Emily (26, Female, Post-Transplant)

And last but by no means least...for those of sound and independent mind, who are not easily offended and who appreciate critical thought:

Cyber-Cystic: Diary of a Cultural Bastard
Andy (34, Male)


Another Day on Foulis Ward (at Royal Brompton)


Another day on the ward they call Foulis
I wake up and wonder quite how my bowel is
But in comes the nurse with the morning IV's
My chest feels a bit better, just a little wheeze

I think I've gone paler
I'll try an inhaler

Trundle, trundle – here comes the food truck
Something tasty, with a bit of luck
My belly's still full, I hope it all fits
You can't go wrong with cheese and biscuits

Spirometry, obs, sats and levels
They can all be little devils
They’re bits of a jigsaw along with the sputum
You might not like 'em, but you can't dispute 'em

To help my condition
Here comes the dietitian
As for phlebotomy
I hope they've forgotten me

Now here's comes the physio
I feel a bit dizzy though

And as the day ebbs
I get through my nebs
More IV's
“Hot drinks, please!”

I think they'll soon need to change my line
Left arm or right, they can both be a swine

Tomorrow it’s Ward Round so the pace is frenetic
Must remember my BM's cos I’m now diabetic
They'll fix me soon, I have no doubt
I must get well before the next bout!