Why has no one told me this before? Confirmation bias - It lies to you. It lies to everyone. What has it been telling you about children? (Part 1)

Recently, after I had explained why something was a medical myth, a colleague in Primary Care looked at me and with genuine exasperation said, "Why has no one told me this before?"

Good question.  The answer to this is complicated.  A lot of the time there is a big 'Emperor's New Clothes' factor.  Declaring a myth to be untrue requires someone to burst the bubble and it is not always the case that someone is listening or that anyone wants to change their belief.

Myths start for various reasons but only persist if they are fed.  For example, very few people actually believe in the existence of fairies.   Seeing a fairy or hearing from someone who claimed to see one might change that.   People do however believe that mice like cheese without any good evidence to support this.  Where does this belief come from?  Surely we can't all have taken Tom and Jerry cartoons at face value?  Since there was never any reason to doubt what we were told we continued to believe it. Well, it turns out that, whatever the basis for the belief, it is wrong when tested scientifically (Yes, this has been researched and published!).

The best ingredients for a myth are plausibility and confirmation.  Take the old chestnut about not being allowed to use adrenaline with anaesthetic in fingers as an example.  This myth originated when lidocaine and adrenaline were commonly mixed with various things to aid anaesthesia and asepsis.  The mix often contained cocaine, procaine and boric acid.  When skin necrosis developed in fingers, the cause was not isolated, but the idea that a vasoconstrictor (adrenaline) was the cause was credible.  In fact, the other ingredients were probably to blame.  Thus a myth  has persisted for roughly a century was created by a plausible theory and repeated episodes which seemed to confirm this theory. (1)

Confirmation bias comes in several forms.  It affects how we search for, interpret and retain information.  They have been responsible for misleading us about quite a few things in paediatics.  There are so many, in fact, that it would be ambitious to put them all in a single post.  Instead I will divide them roughly into two groups - those where we have been misled about cause and those where we are misled about effect.

• We tend to consider what the cause of something is when we witness an event.  
• We concentrate on an effect when we think we can influence events.

For now, I am going to run through some examples of presumed cause.  Lets start with the things that you may have been told are caused by something else, but probably are not.  It works like this:

Of course sometimes, the presumed cause is real.  We have confirmation bias for a reason and in most cases it is teaching us, not lying to us.  Assumption has a bad name for itself, but is a necessary part of how we work and learn.

(No disrespect to Mrs. Sullivan, who taught me that to assume makes and ass of you and me.  Mrs. Sullivan was an English teacher and the spelling mnemonic is valid even if the statement is completely wrong in the context of exploratory learning.)

In certain circumstances, the reality is very different from our assumptions.  This is usually due to a factor that is not as obvious as the two that we have associated.

There are several examples of this below.  The one that often surprises many people is finding out that it is a fallacy that fever causes febrile convulsions.  I know, right?  I mean it's in the name and everything!  It makes sense that fever causes febrile convulsions since a child develops a fever and then has a convulsion.  We even see a correlation between febrile convulsion and fever that comes on particularly quickly (or so we think).

The only problem is that the evidence goes against this being true.  When children are treated for their fever, it seems that they have the same number of fits.  (2) So what is the cause of the fits?  Probably badness.  Badness is the stuff that infections make which causes the fever, the flu symptoms and all that.  You know, chemicals and stuff.  So even when we treat the symptoms of the infection, badness still causes the seizure to occur.  We can't get rid of viral badness.  In most cases we just make children feel better until they make themselves well.

How does this change our practice?  When I found this out, it completely changed my approach to children who had suffered a febrile seizure.  I no longer worry that treatment needs to be focused on the fever rather than the child's wellness.  Most importantly, I now tell parents that the seizure was not preventable.  Often, the parent blames themselves for failing to treat the fever adequately.  They need to know that this convulsion was not their fault.


Next up is the apparent epidemic of allergy to amoxicillin.

We have to work this one backwards from the evidence.  Approximately 95% of children who have a label of amoxicillin allergy have no allergy when tested or challenged. (3) The explanation for this poor correlation is that children of a certain age frequntly develop a rash (which is often urticarial) while ill with a virus.  Viral and bacterial infections are difficult to tell apart, so it is not uncommon for a child to be given antibiotics while unwell with a viral illness.  When a culprit is sought for the rash, the antibiotics may be blamed, though the reality was that the virus caused it.

Finding this out completely changed my practice.  By careful case selection, I take every opportunity to undiagnose penicillin allergy.


Next up: another much maligned medicine - Ibuprofen.   Ibuprofen is often avoided in children who have history of wheeze.  I suspect that this is one of the biggest cases of (wrongly) presumed cause currently in paediatric practice.  You may have been told that ibuprofen causes wheeze or that ibuprofen should be avoided in children with a history of wheeze.  Well, it turns out that this is another myth that has persists despite being disproved.

Once again, the association in space and time of the medicine and the symptoms leads to a very rational fear that it is the ibuprofen causing the wheeze.  When large groups are studied, it seems that Ibuprofen may even be protective against wheeze. (4)  I'll just leave that one with you for a minute...


So after that bomb shell, something a little more palatable but still interesting.  Growing pains are not caused by (wait for it........) growing.  In fact no one knows what causes children to have growing pains.

Feel free to file this under 'how does that change my practice?'  I just think that it is interesting that we feel the need to have an explanation for a symptom which has no known cause and no effective treatment - a bit like colic really!


Next up is something a bit more meaty.  Based on the sessions that I do for GPs here and there, I would approximate that roughly three quarters of primary care clinicians are aware that there is a concern about using ibuprofen for children with chickenpox.  I also know that the basis for this concern is poorly understood.

The truth is that this concern was raised based on a cluster of cases of children who developed severe complications of secondary infection about 20 years ago (5).  No causal link has ever been convincingly shown and the fact that huge numbers of children continue to have ibuprofen in this context makes me think that more robust evidence would have emerged if there was genuine cause and effect.

Invasive streptococcal infection during varicella infection is something that all clinicians should know about.  It is also true that most children who have chickenpox are not very unwell and so paracetamol should be all that is needed.

So why does this matter?  It matters when someone is blamed for something based on poor evidence.  So, let's be clear.  The Emperor appears to be naked, but if anyone else can see that he's got clothes on, I am prepared to be convinced.

Edward Snelson
@sailordoctor
Non-steroidal guardian of the year 2014-2016

Disclaimer- I would never use any of the treatments listed above.  For many years now I have only used fairy magic to treat my patients and any prescribed medication is a pretence.  No one can prove to me that fairies don't exist. 

References

1. Bradon et al, Do Not Use Epinephrine in Digital Blocks: Myth or Truth?, Plastic & Reconstructive Surgery, February 2001
2. A Sahib El-Radhi, W Barry, Do antipyretics prevent febrile convulsions?, ADC, Volume 88, Issue 7, 2003
3. Caubet JC et al., The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge, J Allergy Clin Immunol. 2011 Jan;127(1):218-22.
4. Kanabar et al., A review of ibuprofen and acetaminophen use in febrile children and the occurrence of asthma-related symptoms, Clinical Therapeutics, Volume 29, Issue 12, December 2007, Pages 2716-2723
5. Zerr DM. et al., A case-control study of necrotizing fasciitis during primary varicella, Pediatrics. 1999 Apr;103(4 Pt 1):783-90.

The Internet Has Ruined Everything (Easter Egg - Things You need to Know About Chickenpox)

Things were so much easier when life consisted of being told something by an authoritative figure, after which you could go on indefinitely, believing that fact to be true.  That is how most of medicine has been taught and learned.  The trouble is that much of what we are told is either untrue or unfounded.  Of course to ruin it all, there in now a way to check up on what you are told.  That has made life very difficult for anyone in a medical educational role.

Let me give a non-medical example to illustrate my point.  A few years ago, after watching the film Guardians of the Galaxy, I was commenting on the way that Vin Diesel's role as an animated character was a departure from his roots in gritty action thrillers.  My daughter politely told me that this was untrue, since he had played the title role in the rather brilliantly animated Iron Giant film (1999).  Since I am big and she was little, I felt it only reasonable to set my daughter straight, pointing out that said film was intelligent and Vin Diesel was a hard core meat head who at that stage had not yet begun his career as an actor in any meaningful way.

In my childhood, that would have been the end of the matter.  Faced with such an argument I would have accepted my wrongness or at least agreed to differ with said parent.  This is no longer how these things play out and I was confronted immediately by my wiki-error and proved wrong.

Imagine if we should start to do that with what we think we know about anything in medicine.  Take chickenpox for example: Let's explore some of the things that you might have been told about one of the most common childhood infections.

1. Chickenpox (varicella) is a benign, self limiting viral illness

While that is mostly true, Chickenpox has a surprisingly bad track record.  here are a few chickenpox stats that may surprise you:

• Hospital admission rate of up to 6 per 1000 cases (2)
• Mortality of 2-3 per 100,000 cases (1,2)
• Risk of death four times higher in infants (2)
• 70% of deaths occur in otherwise healthy cases (2)

What causes these admissions and deaths?  It turns out that chickenpox has an alarming number of potential complications.  The most common complication of chickenpox infection is secondary bacterial infection.  This can be the obvious culprit: stapphylococcus aureus.  However probably more commonly and certainly more significantly, group A streptococcal (GAS) infection is the real enemy.  Children with chickenpox are particularly prone to this infection which accounts for the majority of varicella associated deaths.

Other acute and serious complications include encephalitis and pneumonia.  The morbidity and mortality of all of these has been significantly reduced where varicella vaccination has been introduced.

2. You should not give Ibuprofen to children who have chickenpox

If you haven't come across this chestnut then I apologise for being the bearer of bad and rather confounding news.  There has been a controversy about ibuprofen and chickenpox for a long time.  Around the same time that Vin Diesel was voicing the Iron Giant (1999), there was a case controlled study published in which a significant number of children with chickenpox developed necrotising faciitis. (3)  For whatever reason, the authors suspected a link with ibuprofen use and indeed found an association.

This has led many to recommend that ibuprofen is not used as an antipyretic for children with chickenpox.  I believe that the case for this avoidance is based on flawed information.  Firstly, there is the confirmation bias of the original work.  Some of the cases in the study were the same cases that led the authors to ask the question: 'Is there a link?'  Secondly, although it was a case controlled study, the children in the control group had less fever.  Could that be a confounder when looking for an association with an antipyretic one wonders...  Indeed, at the time ibuprofen was a prescribed drug.  In many ways, you could say that the conclusion could easily have been 'Children with chickenpox who were sick enough to see a doctor had a ten times greater risk of developing necrotising faciitis.'  Finally, the association (if there was one) was mainly with ibuprofen being given after there were signs of invasive GAS infection.

The case for avoiding ibuprofen in children with chickenpox is far from convincing.  I certainly don't think that anyone should be accused of bad medicine if they have used ibuprofen for a child with uncomplicated chickenpox.

My advice is this:  Use paracetamol as first line treatment for fever in children with chickenpox.  If a second antipyetic is being considered, ask 'Why does this child need a second medicine?'  Symptoms of uncomplicated chickenpox are normally controllable with one antipyretic.  If the child is unwell despite this, consider the possibility of a secondary infection.

3. Chickenpox causes a rash for a week and a fever for a few days and then it gets better

Except when it doesn't...

While the vast majority get better without complications, chickenpox causes a suprising number of children to get a rather unusual neurological condition: cerebellitis (also called post viral ataxia).  This is a post-infective phenomenon which tends to present in the weeks immediately after the infection, often as the lesions are well crusted or even fading.  Typically the child presents with ataxia.  Other symptoms include clumsiness and difficulty maintaining posture.  Nystagmus and other cerebellar signs may be obvious.  There is no treatment needed but children should be assessed by a specialist to confirm the diagnosis.  Imaging is not needed as long as there are no atypical features and the symptoms begin to improve after a couple of weeks. (4)


So, the internet ruins any attempt to hold onto our faith in simple facts.  This is partly because facts are rarely simple and often wrong.  All of the three bold statements above were things that I was told and believed at some point in my career.  Finding out the truth takes a little looking and a lot of thinking but you get to find out some worthwhile things along the way.  Or, you could just let an expert tell you the facts...

Edward Snelson
So very not an expert
@sailordoctor

References

1. Atkinson, William (2011). Epidemiology and Prevention of Vaccine-Preventable Diseases (12 ed.). Public Health Foundation. pp. 301–323. ISBN 9780983263135
2. Heininger, U., Varicella, The Lancet, Vol 368, Iss 9544, 14–20 Oct 2006, p1365–1376
3. Zerr DM. et al., A case-control study of necrotizing fasciitis during primary varicella, Pediatrics. 1999 Apr;103(4 Pt 1):783-90.
4. Nussinovitch M. et al., Post-infectious acute cerebellar ataxia in children, Clin Pediatr (Phila). 2003 Sep;42(7):581-4.

How special is your patient? (recognising the unwell child with a difference)

The previous GPpaedsTips was all about deciding when a child does not have sepsis. The hierarchy of evidence was put forward as a model for determining what information is most helpful in this process.  Those of you who take the time to read the terms and conditions will have noticed the "this rule does not always apply" clause.

Fig 1 - The hierarchy of evidence used in most cases to determine whether a child does not have a serious infection

The reason that the rules do usually apply is that the majority of children are unlikely to have a serious infection (one that has a reasonable chance of causing morbidity or mortality).  Also, they will usually have some sort of red flag to alert the clinician to serious infection when they are really unwell.

The reason that the rules do not always apply is that some children are special.  They might be special because they are much more likely to have a serious infection.  They might be special because they do not readily alert the clinician when they are significantly unwell.  If they are really special they will do both.

Fig 2 - Legolas from the Lord of the Rings

As explained to me by my daughter, a 'Special'  in a book or film is a character that can only really be taken on by another 'Special'.  Hundreds of unnamed characters might try to kill them without any hope of success.

Contrary to what parents think, most children are not special, at least not in this context.  Most children are predictably ordinary.  They probably have a viral upper respiratory tract infection and if they are developing a more significant infection they will have the courtesy to look and behave as though they are unwell.  Hopefully they will do so enough to convince a clinician that this is the wrong time to assume that the red throat is all the explanation that is needed for the fever.

Fig 3 -  In the Star Trek universe, 'Red Shirts' were never special and had a tendency to be killed off each episode.

So, how do you know when you have a special patient?  You know because they come with labels such as:

• Neonate
• Immunosuppressed
• Immunodeficient
• Pre-existing neurological or muscular disorder
• The child with chickenpox

Neonates (or to be honest, all sprogs under 3 months old) are the biggest group of specials in primary care.  Due to their maternally donated immunity, new-born babies tend to have a few months free of common viral infections.  When infection does occur, the likelihood of bacterial infection and sepsis is therefore much greater. In addition to this they are to give clear signs of illness.  More often the indicators are vague and come in the form of a subtle change in behaviour such as sleeping excessively or feeding poorly.

Children are rarely immunosuppressed but it is increasingly common for a child to be treated with immunosuppressant medication if they suffer from any chronic autoimmune condition.  Ideally these families have direct access to specialist advice when their child becomes even slightly unwell.

Thankfully and despite parental concerns, congenital immunodeficiency is very rare in children.  Having frequent self-limiting viral illnesses is normal as long as the child is otherwise thriving and developing normally.  When a child does have a congenital problem with their immune system they are usually prone to rapid deterioration into serious infections.  One of the best ways of establishing a child’s tendency to do this is to ask what has previously happened in similar circumstances.

If the child has a neurological or muscular disorder they may not be able to look unwell in a way that you will easily recognise.  If in doubt, ask the parents.

Which brings me onto my surprise witness: the child with chickenpox.  Large numbers of children with varicella are seen in primary care every minute of every day.  The vast majority have a self-limiting illness which causes more annoyance than unwellness.  A small proportion of children with chickenpox get secondary infection.  The danger is that someone will assume that this is caused by the logical staph aureus and prescribe flucloxacillin.  In fact Streptococcal infection is the greater risk and infection may be invasive and severe.  Any child who has chickenpox and goes onto be unwell (especially when this occurs late in the usual 7 day course of the illness) has to be presumed to have streptococcal sepsis.

The bottom line is that special children must be treated in special ways.  They are dangerous patients for the unwary clinician.  I have listed the groups that I think might come your way but there will be others.

Fig 4 - Dumbledore could only be taken on by other special characters.  Special children need special doctors when they are unwell.

What does special treatment look like?  It does not comprise giving them all amoxicillin “just to be on the safe side.”  It is useful to go into more detail about past illness in the history and be extra thorough when examining.  It might involve a discussion with a specialist and often requires referral.  Just like in the movies, a special character needs another special character to take them on.  I, like you, am a generalist.  I don’t fancy my chances if I start to free-style the management of a special patient so I phone a friend so that I survive another episode.

Edward Snelson

Fellow Red Shirt

@sailordoctor

 Disclaimer: I am told I am a very, very special doctor.  All generalists are specialists but that is another blog.

 If you found this helpful, you might also like:  The TPR paradox - how do I know if a child might have sepsis?