Thursday, 3 October 2013

Ouch! Why is it so hard to assess children's pain?

The simple answer it is difficult to assess pain full stop, because pain is by definition subjective, the classic definition being that it is whatever the experiencing person says it is.  With children of course there is the added complication of developmental issues, in particular the inability to verbalise pain.

To get round this, there are a large number of different pain assessment tools and scales, ranging in complexity from a straight line with no pain at one end and the worst imaginable pain at the other; to quite sophisticated behavioural tools, which try to identify behaviours associated with pain.  The problem remains though; how do you know when someone who can't verbalise pain is in pain, and how do you know your treatment is working?

A new study has looked at two tools that are fairly commonly used, a 'faces' scale and a colour intensity scale.  The first has faces that reflect differing degrees of discomfort; the second a graduated colour scale, where more intense colour is associated with greater pain.  In my travels around hospitals in the UK, I have to say that I see these scales a lot, but I rarely see them actually used.  Never mind lets press on with the study.

They looked at the reliability and validity of these tools in children aged between 4 and 17 years in the United States who had painful and non-painful conditions; and compared the two tools.  When you are assessing how useful tools such as this are, there are two key things that people look for:
  1. Validity - is it actually measuring what you think it is (in this case is it measuring pain, or might it be measuring something else, such as mood?)
  2. Reliability - how consistent is it, in other words if you measured the same thing twice at the same time, would you get the same answer?
They actually did some quite sophisticated tests here, and found that overall the tools seemed to work quite well.  However, there is a but..

Firstly, the children were quite old; and there was least agreement between the tools in the youngest age-group, which is the very children in which it is hardest to measure pain.  Secondly, validity is context specific.  Just because it works with these children in this place at this time, it does not mean it is going to work elsewhere.  Watch for this one, the famous 'validated tool' which people talk about without often knowing the circumstances of the validation.  For example, a tool validated among old people in New York is not likely to be valid for children in Bolton.  You may think this sounds far fetched (and it is a bit) but I have seen similar claims made.  Lastly just because two tools agree, it doesn't make them right - they could both be wrong.  Often people refer to a 'gold standard' measure and compare a new measure to this, but even then there can be problems, for example the existing standard may itself not be very good.  Everyone 'agreed' about banking 5 years ago - it is just a shame that they were all wrong.

For parents my suggestion is to know your child's pain behaviours, and make sure that when you are with healthcare professionals you make them know that you know!

Tsze (2013) validation of self-report pain scales in children.  Pediatrics 132 e971-979

Wednesday, 25 September 2013

Clinical trials - what do we mean by 'no-effect'?

This is a more difficult question than one might think.  The traditional randomised controlled trial (RCT) randomly selects people from a population of interest; then randomly allocates them to one of two or more treatments, one of which may be a placebo or 'dummy' drug.  The purpose of the placebo is to account for the beneficial (or sometimes detrimental) effect that one sometimes gets just through being given a treatment irrespective of whether it works or not.  So far so good..but..

There is a problem.  In most cases the actual clinical treatment options are not new drug versus dummy drug; but new drug versus some other treatment, which may be something or it may be nothing.  New drug versus dummy drug is almost never the actual option given to patients.  Imagine the conversation with your doctor, "the treatment for condition XXX currently is a drug which we think is of no benefit apart from the fact that it tastes nice and comes in a fancy bottle". 

Traditionally the effect that is seen just by being given something has been termed the 'placebo' effect, Latin for 'I shall please'.  This is a link to the Wikipedia page, (but I did actually know the Latin bit).  In some circumstances the pacebo can be a problem, for example if people just feel better without getting better they may miss treatment that they need.  In studies if they feel better from being given a placebo it may hide a benefit from the active drug (this is termed a Type II error - missing a beneficial effect from a treatment).  There are also ethical issues about people not understanding what they are taking.

However, where the desired outcome is comfort, maybe anything that provides comfort is ok, and if that is a placebo maybe that does not matter.  This may, for example be the case in the treatment of children with a fever, where the desired outcome of treatment is not temperature reduction but relief of discomfort.  If a medicine looks nice, tastes nice, and reduces anxiety in parents and children does it actually matter if it is the active ingredient or a placebo effect?

The reason why this is topical now, is that there is a paper in JAMA Pediatrics which looks at this very subject in the treatment of autism, finding a strong placebo effect compared to the active treatment, indeed in some groups the placebo group actually did better.  Puzzling.. 

What to make of this?  Firstly don't underestimate the power of the placebo - it may be as simple as someone taking an interest in the patient making them feel better.  Secondly, as educated informed consumers of research always check, when comparisons are made, to what was the new treatment being compared?  This brings us to a wider point of efficacy v effectiveness - efficacy is can it work in ideal circumstances (as one would see in a RCT) while effectiveness is does it work in practice? - These are often not the same.  Check to see if your new treatment works outside of the lab!

King et al JAMA Pediatr. Published online September 23, 2013. doi:10.1001/jamapediatrics.2013.2698

Tuesday, 17 September 2013

The importance of intellegence - certainly when it comes to influenza.

The complexity of understating the spread of influenza was again highlighted in a paper in Eurosurveillance recently.  In this paper the authors have looked at antibody levels and antibody quality to H3N2 and H1N1 influenza A viruses from pigs that have been known to spread to humans.   H and N; or haemagglutinin and neuraminidase to give them their full names, are two molecules found on the outside of the influenza virus, and it is changes in these molecules which mean that it is necessary to revaccinate against influenza each year.  They constantly change in a process called antigenic drift, and sometimes change suddenly in a process known as antigenic shift; the latter often occurring when an animal virus passes into and then spreads between humans. 

This is a particular problem with influenza because unusually humans share influenza viruses with a variety of animals with which we have frequent contact, namely birds and pigs.  A sudden antigenic shift, as occurred in 2009 with the introduction of a new H1N1 virus into the human population can spread because, being a new virus, there will be little immunity in humans.  The important thing to remember here is that it is not the jump into humans that is the problem (unless you are that human of course); but the subsequent transmission between humans.  That was the difference between avian influenza in 2005 and swine influenza in 2009, the former did not transmit widely between humans and the latter did.  Incidentally the latest virus to worry the world, H7N9 has made the first step, and there are tentative signs that it might have made the second, being transmitted between humans, but so far only a very small number of very close contacts.

Understanding the make-up of the H and N of viruses that are likely to circulate in the human population is important to ensure that vaccine can be made and that preparations can be put in place for health services.  However, it is a bit more complicated than just characterising the H and N numbers, since not all H1N1 for example are the same.

In this study the authors looked at antibody titres (levels) to different strains of influenza of pig origin, remembering that the last pandemic strain came from pigs.  When they looked at a variety of different H1N1 and H3N2 viruses what they found was that there were marked differences in antibody levels in different age groups to different viruses.  For example, those born between 1968 and 1999 had high levels to one type of H3N2, but very low levels to another more recent variety.  These differences reflect exposure to viruses over time, and have been seen before, for example older people tended to be less at risk of catching the last H1N1 pandemic virus because of existing immunity from previous exposure to a similar virus.

What we learn from this is that influenza should probably not be considered to be a single virus, but a large and ever changing family of viruses that can affect different groups in different ways.  The other thing that comes across is that immunity, like knowledge, is a life-long affair.  Just as we learn and collect knowledge, so we learn and collect immunity.  The key is to avoid damage while we are collecting it, which once again emphasises the importance of age and group-specific vaccination policies that reflect the ever-changing world of influenza.  If you want to know more about the UK situation, Public Health England is the place to look.  It is worth keeping an eye on this page, because the situation is constantly changing.

Sunday, 8 September 2013

Guidlines-keep them simple otherwise we won't remember them! The example of weight estimation.

One of the most important variables in paediatrics is development, and one important measure of physical development is weight.  This is used for all sorts of things, including drug doses, fluid calculations and body surface area estimation.  Normally of course we can weigh children, so this should be pretty accurate.

Unfortunately, sometimes we can’t do this, most notably in emergency situations; and in such cases it is necessary to estimate the child’s weight.  While this is never going to be as accurate as weighing the child, a good estimate is the best that can often be achieved.  However, this obviously requires two things: 
  1. A formula for estimating weight
  2. That the person using it can remember it and use it correctly.
A number of methods for estimating weight exist, however a recent letter published in Archives of Disease in Childhood describing a survey among 25 paediatric trainees suggest that this may be a cause of some confusion.   The authors start by reviewing the current Advanced Paediatric Life Support (APLS) Guidelines, which contain three methods of estimating weight:

·         Infants from 1-12 months (0.5 x age in months +4)
·         Children aged 1-5 years (2 x age in years +8)
·         Children aged 6-12 years (3 x age in years +7)

These replace the previous Guidelines which had one formula for children aged 1-10 years, and which still used in some Guidelines.

The study found that only 2 of the participants (8%) were able to correctly apply the new formulae to examples that they were given, and that around half used the old formula.  The extent to which this matters is debatable, but clearly someone thought it was worth changing the guidance on this, and this is what is now taught, so one would expect that paediatric trainees at least would know them.

The lesson from this is that Guidelines should always be as simple as possible if we expect people to remember them.  For parents, it might be worth knowing roughly how much your child weighs!

Wednesday, 4 September 2013

What to do about young men?

This is somewhat out of my normal comfort zone of infections, but a recent review in Pediatrics looks at the subject of health in adolescent boys and young men, and makes some suggestions about activities that might be undertaken to improve their health through screening and other measures.

The paper itself is American, and does not necessarily translate directly to a UK or European setting, but much of it does.  The list of conditions that young men might suffer is quite extensive, and in addition to the various medical conditions there are many other issues such as violence and suicide that while they may differ in degree, are definitely issues for many young men.  The other really interesting issues are those surrounding sexuality and the role of men in society.  This struck me because many of the regular drama programmes in the UK (particularly EastEnders) have a really negative image of men, they all seem to be crooks, emotionally unstable, or generally not very nice.  While this is only drama, the drip, drip, drip effect of negativity may be significant.

One of my jobs here in the College is to run the HIV Course, and the assignment for this includes planning a health education intervention.  A lot of the students decide to target gay men; but when asked how they will access them they only seem to know about gay men in terms of those who go to nightclubs and bars.  Now while many gay men do, I am pretty sure there are many who don't frequent nightclubs and bars, so how best to access them?  The same problem occurs with young men, how do you access them, and when you do what interventions actually work?

Since writing the NICE Fever Guidelines, and being a fully paid up convert to the idea of traffic light tables, maybe one idea might be to do a traffic light for young men.  What characteristics are indicative of low, intermediate and high risk of morbidity?  I know they have limitations, they are either too sensitive or too specific........but they are a start, and they do make people think about what we know, and more importantly what we don't, what is the level of uncertainty and where does it lie?

One particularly fascinating idea is the concept of the positive development approach, where one acknowledges and promotes the young persons strengths and assets rather than problems and weaknesses.  It seems obvious, but actually we don't often do that, indeed the NHS in the UK often referred to as the National Sickness Service rather than the National Health Service.  Then it struck me, promoting strengths and assets, and being positive; wouldn't it be nice if we could do that to everyone?

Wednesday, 28 August 2013

Diagnosing infection in children – what is the problem?

One of the big problems in terms of treating children is diagnosing the illness in the first place.  In no group is this more of a challenge than in infants with infections, because many of the classical signs of infection, such as inflammation are absent because of their relatively immature immunity.  A similar problem occurs with people of all ages whose immune systems are damaged, either by disease, old-age, or sometimes medical treatment.  The key to diagnosing infection is often not the bug, but the immune response to the bug, and if you don’t have a good immune response it makes it all the more difficult.  Often the only sign of infection is a fever, hence the importance of fever as a diagnostic sign in immunosuppressed people.

The answer to this is to either have a very low suspicion for disease, which might mean over-treating; or to have a higher suspicion, but then risk missing disease.  The problem with the first is that it is expensive, and in the case of antibiotics might lead to the development of resistance; while the latter leads to the risk of missing potentially fatal infections.  It was partly for this reason that the NICE Guidelines on the treatment of fever in children were developed, but many of the symptoms in the amber and red categories are fairly general, and anyway they don’t tell you what infection the child has, just that they probably do have one.

The answer is better and quicker diagnostic tests.  We have a whole range of tests now, but none that are completely accurate.  Additionally, some are highly dependent on the skills of the person performing the tests or on the organism itself: for example, blood cultures, the gold standard test for many infections may become contaminated with skin bacteria, or the bacteria themselves may not grow in the lab.  Even if they do grow, it is not always the case that the bacteria that grow are the ones actually causing the disease; and there may be other organisms, for example viruses or fungi that do not grow in the lab.  Such methods are sometimes referred to as 'phenotypic' - they look for behaviours such as growth or the response to different conditions or chemicals.  If the thing is dead in the test tube or does not grow it won't have a phenotype!

There are many new diagnostic techniques that avoid such problems being developed, some of which are reviewed in a recent paper in JAMA Pediatrics.  In particular these are tending to use molecular methods to either identify the pathogen directly, such as those which look for the genes of the organism; or to identify the host response to the organism.  The latter is helped by the rapidly increasing knowledge of the human immune system and genomic techniques. These methods don’t rely on culturing (‘growing’) the organism in the lab, and so avoid many of the problems inherent in observing growth or behaviour, but they bring their own issues, not least of which is expense.  One method, known as PCR(Polymerase Chain Reaction) which looks for pathogen genomes has been used for some time, and is widely used to diagnose HIV in young children, but is not widely used elsewhere for diagnostic purposes.  Molecular is definitely the way forward, but it may not be a quick journey.

The lesson from this is that testing is fine, but it must not replace the clinical judgement of either parents or healthcare professionals.  Even if you have the best diagnostic test in the world…..ever, it still relies on someone to notice that the child is ill in the first place.  Parents and clinicians are both, in their own ways, generally quite good at this, and so should trust their instincts.  Incidentally, if you want to know if someone really understands this stuff ask them: if they say yes - they probably don't!  There is much of the immune system, and our relationship with micro organisms that we don't understand and probably never will.

Sunday, 11 August 2013

More children being admitted to hospital in the UK - why and what can be done?

According to a study recently published in Archives of Disease in Childhood it appears that more children are being admitted to  hospital (Gill et al 2008 Arch Dis Child 98 328-334).  While the figures are a bit rough and ready, the trends presented are fairly clear and include:
  1. A fairly continuous increase in the number of admissions since 2003; in the preceding 4 years (1999-2003) it was fairly static.
  2. Overall the increase in admissions since 1999 is 28%: in those under 1 year of age it is 33% which is the highest, the lowest was in the 10-14 year age group which was only (!) 13%.
  3. This increase is not because children are getting much sicker, as mortality fell over the same period.
  4. Much of the increase is the result of infectious diseases and other conditions such as asthma that could be managed in the community.
  5. Admissions for chronic conditions fell a little.
  6. Most of the increase was for very short stays, the largest increase being among children admitted for less than one day.
This presents a challenge, because this is clearly not sustainable, and is not good for the children concerned.  It is now over 50 years since the Platt Report which said, should only be admitted to hospital when "the medical treatment they require cannot be given in other ways without disadvantage."  Ironically, the report goes on to say "This may seem obvious but ...... evidence submitted to us suggests that it is still often overlooked."

What is even more perplexing is that over this same period there has been a strong emphasis upon caring for children in the community; provision of alternative methods of getting health care advice such as NHS Direct, the introduction of Children's Centres, and the publication of guidelines such as the NICE Fever Guidelines.

The authors give a long list of possible reasons for this increase.  These seem to fall into 3 categories:
  • Social - parents are less able or willing to look after children at home; or their threshold for seeking hospital advice is lower.
  • Clinical - more children are being sent to hospital by NHS Direct/GPs; hospitals are not as good at triaging as they were; or practice is becoming more defensive, leading to more children being admitted to be on the safe side
  • Organisational - admitting children to avoid breaching A&E targets by observing for longer; changes in contracts and financial incentives that reward admission.
Positives are that the increase in shorter stays may be party due to the fact that we discharge quicker.  That is about it for the positives!

Whatever the reason, this is not good and we must find a way of changing this trend.  One example of innovative thinking is the Traffic Light contained within the NICE Fever Guidelines which splits symptoms into categories (red, amber, green) which is designed to help divide symptoms into those indicative of high; low and intermediate risk of serious illness.  More is needed.  This may be an area where pharmaceutical companies can help, using their marketing expertise to produce quality parent friendly information.

Wednesday, 7 August 2013

How accurate are the doses of medicines given to children?

An interesting letter in Archives of Disease in Childhood published online ahead of print publication goes some way to answering that very question, and the answer is, in many cases not very.

An audit of children's wards at two hospitals in England looked at the doses of liquid medicines that were prescribed, and how easy these were to give using the syringes available on the ward.  For example, one 1.48 mg dose of morphine which came in a concentration of 10 mg/mL should have been 1.48 mL - a dose that was not possible to give accurately with either a 1 mL or 2.5 mL syringe, requiring either rounding up/down, or the use of two syringes.

Across all of the drugs given 34% of antimicrobials, 25% of analgesics; 11% of steroids and 5% of sedatives were not accurately measurable using the syringes available.  This leads to two issues:
  1. The technical issue of whether an unmeasurable dose that is rounded up/down, and so which is  not really correct, is a prescribed wrongly or administered wrongly.  In crude terms 'whose fault is it?' (in a no blame, new open NHS kind of way).
  2. Secondly, and of course much more important, is does it matter?  That depends on many things, the child; the dose; the amount of the rounding; other medicines that the child may be on....the list could go on and on.  Also when rounding up, do you round up to the line on the syringe, go half way through it, or go to the top of the line?
The other interesting thing that the authors speculate on is if it is like this in hospital, what might be going on in homes?   To this I would add the issue of crushed tablets; never recommended but it probably still goes on.

Does it matter?  Probably not in most cases, but the authors do conclude that research into the clinical implications of this would be helpful.  Probably the most important thing is not the variation per se, but the judgement of those giving the medicines.  The dangerous people are those who don't know what they don't know.

Wednesday, 31 July 2013

Influenza vaccination for children - Fluenz

Sorry - not even August and another influenza story but this is a big one.

It has been a busy few days in the world of childhood vaccination.  Fresh on the heels of advice from the Joint Committee on Vaccination and Immunisation (JCVI), the body that advise the Department of Health about vaccination policy not to introduce meningococcal type B vaccine yet, we now have details from the Department of Health about routine influenza vaccination for children over the age of 2 years.
Essentially it is to be offered to all children who are aged 2 and 3 years on the 1st September; and to older children up to the age of 10 years in some pilot areas.  There are a number of things about this that need to be highlighted:
  • Influenza is not always a mild illness, and it can lead to more serious infections.
  • Vaccination has two effects, it protects the individual, but by reducing the risk of them catching the disease it also protects other people.  So if your child doesn’t get the flu then they can’t give it to siblings, grandparents…etc.  This is the same thing that I discussed previously with regards to taking time off work reducing the spread of influenza.  So even if you are not worried about your child, what about their grandparents and other contacts?  What about that child at nursery who has asthma?  I don’t want to lay it on too thick, but there are a lot of people around who can become very ill with the flu.
  • This is not the same as the normal seasonal flu vaccine.  That is an inactivated vaccine (note inactivated – it can’t give you the flu!); this is a cold attenuated live vaccine.  This means that it is alive (as much as viruses can be described as ‘alive’) but has been altered so that it can only grow in cool environments – such as the nose, which is much cooler than the lungs and respiratory tract.  This also raises the interesting prospect of the altered strain circulating in the community, that people could ‘catch’ the vaccine virus and become immune that way (which would be a good thing!)
  • It is not an injection but a squirt up the nose (two squirts actually, one up each nostril).
  • If you or your child is in a risk group, this does not replace the need for annual vaccination, it is an additional layer of protection.  You (or your child) still need to be vaccinated as normal.
  • Finally, immunity is not immediate; you need to give the system a good 2 weeks for immunity to develop.
 There are a few children who should not have it: those under 2 years, those with egg allergy, children who are severely immune suppressed and other children who live in their house, and children with asthma who are wheezy at the time of vaccination.
Although this is a new vaccine to the UK, the Americans have been using it for some time.  For people who are worried about it I would just say this, if you are not convinced of the need for your child to be protected; if you are not convinced by the part that this will play in reducing the spread of flu, and I respect (but disagree with both of these); it can’t be worse than catching the flu anyway – because that is all it is, but in a form that is much, much, much less likely to cause disease.

The advice from the JCVI is here; the guidance that healthcare professionals use (the 'Green Book') is here, always check before use as  it changes quite regularly; and the letter from the Department of Health is here.

Monday, 22 July 2013

Vaccination works!

Perhaps not such a surprising headline; but it is nice to see it demonstrated.

One of the wonderful things about vaccination is that as an intervention it works at multiple levels, most notably at the individual and popluation levels.  What that means is that when you vaccinate an individual, as long as that vaccine has worked they should be protected against infection - that is the individual level protection.  Furthermore, because fewer people are catching or carrying the disease; it does not spread so much within the population, giving some degree of protection to people who are not immune.  This is a concept known as herd immunity, and it is particularly powerful when vaccination coverage is high.  This is based on a number known as R0, which I discuss a little here, in summary to find the crucial proportion needed to achieve herd immunity the calculation is 1-1/R0 (so if the R0 is 10, the cacluation is 1-1/10 or 0.9 or 90%.

So if you are caring for someone who is particularly susceptibe to infectous disease, one of the best things you can do is to ensure that you are fully up-to-date with your vaccines.  This is one of the rationales for vaccinating children against influenza, clearly to protect them, but also to protect grandparents and others at risk of severe influenza illness.

A study from America has looked at this phenomena with regards to hospitalisation with pneumonia (Griffn et al (2013) N Engl J Med 369 155-163).  It looked at three periods: before the introduction of the pneumococcal vaccination into the infant schedule; its early days of introduction; and a latter phase when it was fully embedded.  The findings were stark, among both young and old the numbers of people admitted to hospital with pneumonia was reduced, from period one to three the reduction was 43.2% in those under 2 years of age (who would have had the vaccine) but even more impressively by13% in those aged 75-84 years and by 22.8% in those over the age of 85 years.  Overall the reduction ws 10.5%, in numbers this equated to a reduction of 168 000 hospital admissions in one year.  (When you see percentages or relative risks/odds ratios always look at the actual numbers as well - remember 10.5% of nothing is.....nothing.  These numbers are fairly impressive though).

Now there are loads of issues around these findings: just two of the questions are what else might have happended during this period (they discuss reductions in smoking and influnza vaccines for example) and how reliable are the data?  But however cynical one might be, these are impressive results.  The crucial thing to remember though is that herd immunity, which is what is being seen here, relies on high vaccination levels.

Friday, 19 July 2013

It may be sunny but influenza will soon be here..

As the temperature reaches the low 30°Cs it may seem difficult to imagine, but influenza season will soon be upon us.  One of the many dilemmas of flu season is at what point one should go sick or keep a child at home.  A recent study from the United States has looked at this very subject, but from a public health perspective, what is the effect of someone with flu going to work on the wider community? (Kumar et al (2013) Am J Pub Health 103 1406-1411).
This was a study done using agent based modelling, in other words it was a computer simulation.  Probably the most important thing to do when you look at a model such as this is to check the assumptions made in the model, so for example here they had different scenarios: one where not everyone had access to paid sick leave; one where everyone did; and some where employees were able to take either 1 or 2 ‘flu days’ regardless of access to paid sick leave.  In all models it was assumed that 28% stoically went to work even if they had the flu; and that the R0 (the average number of infections caused by each infected person) was 1.4 – pretty typical of seasonal influenza.  However, in some circumstances, such as schools and nurseries it may be much, much higher.
The results of the modelling showed that the attack rate (the proportion of those without immunity who were exposed and caught the flu) was 11.54% in the mixed sick-leave scenario; 10.86% where paid sick leave was universal; only 8.62% where 1 flu day was allowed; and 7.01% where employees were able to take 2 flu days.  In a simulated population of 575 866, this equates to 66 444; 62 538, 49 611; and 40 386 infections respectively.  That is a lot of numbers, but what it is saying is that the 2 flu day scenario reduced the number of infections at work by 26 059 or 39% from the baseline mixed sick-leave scenario.
So the lesson from this is that it may be better for the economy for people to go off sick rather than go to work when they are ill.  Remember that once one has the flu, you can then infect other people who may be in one of the high risk categories for severe disease, so the impact is almost certainly even wider than this study suggests.  This can of course be mitigated by getting vaccinated - and the flu vaccine is gradually being rolled out to all children aged over 2-years (not this is not an injection!); and others in the high risk categories should already be getting it.  More details here (it is a bit wordy - but keep going - it is on page 10!).
 Now major warnings in interpreting these and similar data:
  1. All models are wrong – the trick is to get the model that is least wrong
  2. Look at the assumptions – do they seem sensible?
  3. Does the model allow for ‘random behaviour’?  These are called stochastic models and while they are more lifelike, they are also much more complicated.  The opposite, where people essentially do as they are told or behave the same are called deterministic models.
  4. In epidemiological studies always be clear about the case-definition; how do you know someone has the flu?  This is crucial, because we need to know that we are talking about influenza and not just a bad cold.  The UK case definition and other epidemiological data are here.
Finally reading this paper I learned a new term, which is ‘presenteeism’ – which is going to work or school when ill, something I may have been guilty of in the past...  More about flu to come, in the meantime enjoy the sun!