A Whole New World - Honesty in Paediatrics

Paediatrics is a specialty where lying about a diagnosis is normal practice.  It's not because we're bad people.  When you think about the challenges of diagnosis in children combined with the expectation of a diagnosis, it is completely unsurprising.  The adult accompanying the child would like a diagnosis (please and thank you) and the clinician would very much like to give one (you're welcome).

While that all seems very reasonable, in child health it often isn't entirely truthful.  It is one of the mantras of medicine that the diagnosis is going to come from history and examination in most cases.  Hurrah for clinical diagnoses.  In paediatrics, the history is often from a third party and will have an inevitable element of bias.   The examination will also contain more uncertainties more of the time.  You have to accept a significant lack of information when interpreting examination finding in children.

The result of this is that clinical diagnosis is more challenging in paediatrics.  Here's the paradox: clinical diagnosis is the default position in child health.  Why?  Because we don't want to do tests on children or give them treatments "in case" unless these investigations or therapies are very likely to benefit the child.

This week, something big happened and it didn't even hit the news.  The General Medical Council released some new and updated guidance: "Guidance on professional standards and ethics for doctors Decision making and consent."  While much of the content is old news, there is a new emphasis on honesty when there is diagnostic uncertainty that is hugely relevant to paediatric practice, thanks to the fact that uncertainty is where we work.

So, when are we lying to our patients or the adults that accompany them?  The truth is that there is a spectrum of how far what we tell people lies from the truth.  What we should probably do in the light of the new GMC guidance is to re-evaluate our approach to a variety of clinical presentations and ask, "Should I change what I say about this?"

You could argue that nothing is certain in medicine, so what are the thresholds of uncertainty that decide when we should be honest in this way?  That's a fair comment.  We need to apply some measure here - enter the certometer.

The certometer takes the things that we are already using in our diagnostic approach and gives us an idea of how truthful it is to give that diagnosis.  Last week, I asked the medical Twitter world for a few suggestions of diagnoses that we could feed into the Certometer and this seems like a good time to give this contraption a go.

First up is an intriguing suggestion:  Diagnosis - Viral illness.

In my experience this diagnosis is usually given to children with a fever and signs or symptoms of upper respiratory tract infection without signs or symptoms of a more specific diagnosis.

Let's imagine a common scenario then: a 2yr old previously healthy child with a fever for 2 days.  They have a runny nose but no cough.  They have no respiratory abnormality.  Pharynx and both tympanic membranes are inflamed.

The pre-test probability of this being a viral illness is high. It's a child with a fever so the probability that the illness is viral is around 90%.

Positive predictors of a viral cause do exist and include wheeze and urticarial rash in children. This child has none of these things.

Good negative predictors of a diagnosis of viral illness in this sort of case would be some signs of suppurative complications such as mastoiditis.  We haven't seen any signs to suggest this.

So having looked for something specific that truly discriminates and found none, what you are left with is your pre-test probability, dialled down slightly by virtue of the absence of signs of another diagnosis.  In other words, all we have truly achieved is to rule out complications.  Since complications are rare, we're essentially no more certain this is a virus than before we started.

Calling it a viral illness implies that we've added some certainty to the underlying cause that in reality, we haven't.  In fact, by calling it "a virus" we have admitted that there are no specific finding identifying a particular viral illness.

What we have done is far more important.  We have looked for signs of complications and more serious infection (sepsis, meningitis etc) and found none.  What we can say with honesty and certainty is that this is an uncomplicated upper respiratory tract infection.

To emphasise the point about how often the lack of specific signs and symptoms is the norm in paediatrics, I'll give a couple of examples of common, clinical diagnoses that are usually made with enough certainty to be considered completely honest.

• Croup
• Chickenpox
• Febrile convulsion
• Vasovagal syncope

Yep, that's pretty much it.  Most other common problems are really labels given with real uncertainty due to the lack of specific signs or symptoms with good positive or negative predictive value.

Here are a few other examples of diagnoses that are commonly given in what is in reality a great deal of uncertainty that this problem is causing the symptoms or signs.

• Infant reflux disease
• Cow's milk protein allergy (non-IgE)
• Asthma
• in the under 5 yr old child
• where the diagnosis is based on chronic cough without wheeze
• Mesenteric Adenitis
• Hypermobility

Then there's a whole new level of diagnostic uncertainty.  At the beginning I used colic as an example.   Let's try feeding a classic colic presentation into the Certometer.  You see a three week old baby whose only symptom is "crying all the time".  The pregnancy and birth were uncomplicated.  The baby examines normally and is thriving.  They are feeding well and passing urine and stools normally.

What is the pre-test probability that this is colic?  Unfortunately there's no good answer to that because it's not an actual disease.  There is no pathology or treatment.   Colic is simply a label to be given to crying infants that have no pathology.  If you try to put this through the Certometer, you will break it because you can't have any certainty of something that doesn't exist.

It is often argued with colic that the label is therapeutic.  The new GMC guidance should give us an opportunity to re-evaluate that approach.  What would be wrong with telling the parent of the infant described above that their baby is normal and healthy?  That would be honest and potentially just as therapeutic.  We could then use the time that we might have spent (explaining a condition that doesn't exist) on being supportive and encouraging to the parent.  The crying excessively phase does settle and in the meantime, it's all about making sure that it doesn't break the parent.

Here are a couple of other examples of diagnostic labels in children that are without evidence for any disease process.  Neither of these has ever had any pathology associated or been shown to respond to any treatment:

• Growing pains
• Non-specific abdominal pain

Is it time to embrace the idea of greater honesty when we diagnose and explain symptoms in children?  I certainly find that an explanation without a diagnosis is entirely acceptable to families when it comes to a situation where in the past I might have given a non-diagnosis.  Changing that practice is relatively straightforward.  You simply stop saying the thing.

For the situations where we are dealing with an actual diagnosis but there is significant uncertainty, we've got a few options.  The infant with crying and regurgitation of feeds is a good example.  Perhaps we should be stricter about starting off with a label of "possible GORD"?  Perhaps we should go further and start with "Feeding symptoms under observation and follow-up."  Increasingly, I don't give a diagnosis.  Instead I tell the parents that (in the absence of red flags such as fatering growth) "crying and regurgitation can be normal, it can be early symptoms of reflux disease and it can be rarer problems such as allergy.  We don't want to give unnecessary treatments to babies but we also want to treat problems when it's going to help.  This is how we're going to try to get the right balance between those two things..."  

It's a whole new world being honest about our uncertainty but it does work and it works like this:

Edward Snelson
@sailordoctor

Disclaimer: I am not certain about any of that, or that you or I exist.

Reference

General Medical Council UK, Guidance on professional standards and ethics for doctors Decision making and consent, 9 November 2020

COVID question number 6 - What is hyperinflammatory syndrome and how do I recognise it?

At the same time that we are seeing increasing evidence that COVID-19 is less common, less severe and less infectious in children (1), evidence is emerging of a new phenomenon that seems to be related to COVID-19 infection in children: hyperinflammatory syndrome (2).

In a time when people are being encouraged to self-manage febrile illness at home, and primary care has moved to do more remote assessments, the emergence of such a serious clinical entity is worrying.  Although the number of cases remains relatively small, it represents a significant number of seriously unwell children.  Considering how much we focus on the recognition of sepsis in children, current cases of hyperinflammatory syndrome are being reported in numbers comparable to and possibly greater than numbers of children with severe sepsis.

This does not mean that all febrile children should now have a face to face assessment or that all febrile children should be referred to secondary care.  Like sepsis, it is impossible to recognise an entity like hyperinflammatory syndrome before it is clinically apparent.  There is no predictive test.

Like sepsis, we need to be aware of hyperinflammatory syndrome and recognise it where it is manifest, rather than over-diagnose it to the detriment of children with uncomplicated viral illnesses.  So how do we get that balance right?  The answer lies in recognising what is unusual about the illness rather than focusing on the most common features, since these are not necessarily good discriminators.

First, a few FAQs about hyperinflammatory syndrome in children:

What is hyperinflammatory syndrome?
Like sepsis, definitions of hyperinflammation vary and reflect the fact that it is a clinical diagnosis without a binary test or decision tool.  The published literature reflects an uncertainty about pathophysiology but describes a significant number of cases (20 in North London in less than a month) of children with a similar clinical presentation.  The features have been described as most similar to Kawasaki Disease Shock Syndrome (3), a thing so rare that most of us had never heard of it before this recent surge of cases.

Is it caused by COVID-19 infection?
When the initial reports of cases were being circulated without details, it was unclear as to whether this was simply a case of something happening during the COVID-19 pandemic or because of it.  While no official source has yet declared that COVID-19 is definitely the cause, there is plenty of evidence that this is the case.  First, the numbers are highly unusual (4) and there is a pandemic at the moment.  Secondly, many of the children have tested positive for SARS-CoV-2/COVID-19.  While a small proportion testing positive could be explained by the background rate of COVID-19 in the community, the positive test rate in these cases seems too high.  At the moment the sample size is too small to be conclusisve.  Finally, the demographic of affected children mirrors that of severe COVID-19 in adults, with a predilection for males and BAME children.  It therefore seems most likely that these cases are related to the COVID-19 pandemic.

The hyperinflammation syndrome that is being reposted is thought to be a post-infection phenomenon, rather than a complication of acute infection.  The exact mechanism for this is unclear.  Clinically, it has features similar to Kawasaki Disease (for which the mechanism is unknown) and some overlap with toxic shock syndrome (which is seen in bacterial infection) so we're on the back foot when it comes to working out pathophysiology.

How do I recognise hyperinflammation in a febrile child?
The reported features of the children presenting with hyperinflammation are a mixture of non-specific signs and symptoms with a few more unusual elements that may help the front-line clinician.
While gastroenterological symptoms were common, I would suggest that this information is of little help to a clinician who sees acutely unwell children.  Diarrhoea, abdominal pain and painful swallowing were all common features in children who later developed hyperinflammation but are also frequently found in other viral illnesses.

In the case series reported in the Lancet, tachycardia was sometimes present and sometimes heart rate was unremarkable.  This is somewhat surprising since this hyperinflammatory syndrome seems to affect the cardiovascular system most severely.  It is also consistent with other serious paediatric presentations, where heart rate is one of the least specific clinical signs, being both falsely concerning and falsely reassuring on many occasions.

Tachypnoea, also a common feature occurring when the child presented with hyperinflammation is a more specific feature.  Uncomplicated viral illnesses in children do not tend to affect breathing other than in the form of a transient tachypnoea while febrile.  Unexplained, consistently fast breathing should therefore be considered clinically significant.  This was reflected in the Lancet case series, the majority of whom had tachypnoea.  Note that the cases reported did not tend to have pneumonia, thus the qualifier of "unexplained".  Other explanations for fever and abnormal breathing remain more likely.

The other feature that was most consistent and helpful in discriminating from uncomplicated viral illness was an unrelenting fever.  In children with an uncomplicated viral illness, pyrexia can be dramatic and associated with alarming features such as shivering, cold peripheries, blue lips and mottled skin.  Typically, this is followed by a dramatic improvement, often with the aid of antipyretic medication.

In the cases reported with suspected hyperinflammation secondary to COVID-19 infection, the fever was noted to have been persistently high (38-40 C/ 100.4-104 F) which is much less commonly seen in uncomplicated viral illness.  This may therefore be one of the more useful ways of telling the two apart.

Other features reported include a "variable rash" and painful extremities.  Rashes and pains are common features of uncomplicated viral infection but in combination with the more specific features may help clinicians recognise the syndrome early.

Recognising hyperinflammation (presumed to be related to COVID-19 infection in children) early may therefore be a case of recognising the unusual, looking for alternative explanations such as pneumonia and if no other pathology explains how unwell the child is, looking at how many of the less specific symptoms are present.  If that sounds familiar, that's because it is a similar approach to recognising Kawasaki disease.

The disease then tends to progress to a phase with more significant cardiac involvement, with a profound effect on circulation in many cases.  Shock refractory to fluid boluses is a commonly reported feature.

If signs of shock develop, this will make it more straightforward to recognise that the child does not have an uncomplicated viral illness.  Distinguishing hyperinflammatory shock syndrome from sepsis and other similar presentations brings its own challenges for emergency medicine and acute paediatrics.

Edward Snelson
@sailordoctor

References

1. Munro APS, Faust SN, Children are not COVID-19 super spreaders: time to go back to school Archives of Disease in Childhood Published Online First: 05 May 2020. doi: 10.1136/archdischild-2020-319474
2. Riphagen S., Gomez X., Gonzalez-Martinez C., Wilkinson N., Theocharis P., Hyperinflammatory shock in children during COVID-19 pandemic, Lancet, May 07, 2020 doi:https://doi.org/10.1016/S0140-6736(20)31094-1
3. Kanegaye JT, Wilder MS, Molkara D, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics. 2009;123(5):e783‐e789. doi:10.1542/peds.2008-1871
4. HEALTH ADVISORY: PEDIATRIC MULTI-SYSTEM INFLAMMATORY SYNDROME POTENTIALLY ASSOCIATED WITH CORONAVIRUS DISEASE (COVID-19) IN CHILDREN, 06 May 2020, New York State Department of Health (NYS DOH) Bureau of Communicable Disease Control (BCDC)

The Everest-Lifeboat Test (Easter Egg - Investigating apparent faints in children)

Paediatric guidelines always have to take into account one of the most important maxims of Child Health - the test or treatment must always be in the best interest of the child.  This means a particular discernment about the value of a test or treatment.  Guidelines rarely discriminate between which treatments and tests are essential and which are simply recommended.  When writing a guideline, it is relatively easy to put in a recommendation, often giving the impression that it is a must-do when this is simply not the case.

One of the things that I am most often asked (whether at work or giving and educational session) is "Do I have to do X?  The guideline says to but..."  So how does one discriminate between the must-do's and the would-be-good-if we-could recommendations?  That's easy - apply the Everest-Lifeboat Test.

The Everest-Lifeboat Test is simply a two part thought exercise.  The first part is to ask the following question:  If the person involved was at an advanced stage of climbing Everest, should they turn back to get this test or treatment or could they reasonably continue to the summit?  This part of the test asks if we are doing something just because we can rather than because we have to.  We are purely focusing on the immediate need at this point.

The second part is the lifeboat question:  Imagine that this patient was in a lifeboat, drifting across the ocean.  When they are rescued several weeks later, would they most likely be fine despite their current clinical situation?  This part of the Everest-Lifeboat Test forces us to look forward and consider the medium and long term consequences of action versus inaction.

Let's try this on a fictional patient.

A 10 year old child is brought to you having had an unexplained collapse.  The history given to you is vague and there is no first hand account of the episode as it happened in front of classmates at school.  However, in your further history taking, you find that this child has been having headaches that are worse in the morning.  Also, teachers have noticed that there has been a deterioration in performance at school over the past four weeks.  The child is slightly ataxic and has nystagmus on examination.

Concerned, you discuss the need for further investigations.  In response, the parents say that they are happy to get the tests done but could it please wait a few weeks?  They were just coming to get a medical opinion before they catch a plane to go away for a couple of weeks for their holiday.  They were assuming that this was just a fainting episode and really only came to get their child checked because grandma told them to.

So, what do you think?  This seems like a clear fail of the Everest-Lifeboat Test to me.  I wouldn't be happy to put investigations on hold, despite the obvious inconvenience to the family.

How about this scenario?:

A 12 year old girl comes to be assessed.  She was in school and had been stood in the heat when she began to feel sweaty and nauseous.  Her vision went black and she slumped to the floor.  She was reported to look pale and floppy.  She was unresponsive for a few seconds and then came around slowly over a few minutes.  A few hours later, she feels fine.  There is no history of unexplained deaths in her family.  When you examine her, all is normal.

You check a relevant guideline and see that it recommends that you perform a 12 lead ECG. She flatly refuses to have this test done and will not be persuaded.  What should you do?

Applying the Everest-Lifeboat test would go like this:

Would you advise abandoning the final attempt on the summit?  Well, she had an obvious precipitant and prodrome for her apparent faint.  We can advise how to avoid precipitants and what to do if a prodrome is recognised.  The event appears to be a classical vasovagal syncope without red flags in the history or examination.  So, forcing the issue seems to be unnecessary.

Would a few weeks in a lifeboat be an issue?  This brings us back to the guidelines that recommend investigation.  What are they trying to protect us from?  Much of the practice of ECG screening comes from adult medicine, where pathology is much more likely.  In paediatrics, there are a few arrhythmias that we need to worry about, but a standard 12 lead ECG is not the perfect screening test that we might hope it is.  The sensitivity and specificity of 12 lead ECGs in children is poor (1).  Ask yourself why the guidelines don't say, "Don't bother with history and examination.  The ECG is the crucial bit of information."

A quick look at the guidelines gives some useful insights to help us with the Everest-Lifeboat Test.  The NICE guideline "Transient loss of consciousness (‘blackouts’) management in adults and young people" (2) actually only relates to the over 16 year-olds.  This in itself acknowledges that an adult approach cannot be extrapolated to the child who has had a collapse.

Then there is the European Society of Cardiology's guideline for the diagnosis and management of syncope (version 2009). (3) It does take the view that children and adults can be investigated similarly and recommends ECG for all children who have had a faint.  However, this recommendation seems to be based on the assumption that an ECG is clearly useful additional information and fails to consider the possibility that a thorough history and examination gets you to a point where and ECG would not add value.

The American College of Cardiology/American Heart Association guideline (4) does seem to consider this possibility.  There is a strong emphasis on the value of a good history and examination.  Regarding ECG, it points out that ECG is a simple and available test that might identify a tendency to arrhythmia.  However it also states: "Despite the benefit of identifying a likely cause or potential clue about the cause of syncope from the ECG, prospective studies did not conclude that ECG findings significantly affected subsequent management.  The prognostic value of an abnormal ECG in patients with syncope has been questioned as well."

So there it is.  An honest declaration that, while the experts would recommend that we all do a test, it is unclear what the value of the test is.

I know that it might seem as though I just want to avoid doing work here, but there are genuine risks with tests.  The first risk is that they stop us from thinking.  If the sensitivity and specificity of history and examination is excellent, while that of ECG is poor, why introduce a deceptive piece of information?  The second risk is that of getting information that I don't want.  If I do an ECG on a child, it is almost always to look at the rate, rhythm and QT interval.  While those things are usually fine, the diagnostic report usually sports a bit of LVH and right atrial enlargement.  Of course the child has neither of these things, but the machine is just trying to make sense of the voltage it has been given.  If I were to take these things seriously, I might cause unnecessary anxiety for the child and parents.

So, what does my patient really need?  I need to take a good history and establish that the episode that sounds like a faint truly sounds like a faint.  This means asking about the three P's of vasovagal syncope.

If it sounds like a classic faint, I still need to make sure that I consider my red flags.

If the history given is of a straightforward faint, without red flags, I think that allowing the child to refuse the ECG passes the Everest-Lifeboat Test.

When we are forced out of our normal process, it is a good time to evaluate our routine practice.  If a deviation from the norm passes the Everest-Lifeboat Test, I would question the norm.  You may just have discovered that you are doing a test or a treatment that you don't believe in.  Here is a little list of things that have passed the Everest-Lifeboat Test for me at various times in the past (i.e. I was going to treat, something got in the way of that and I went with the the no treatment option):

That's a short list of times when the option of doing nothing became the right thing despite what was routine practice.  In the case of umbilical granuloma, I am pleased to say that doing nothing is now becoming the norm.

I hope that you find the Everest-Lifeboat Test useful at some point.  As to whether every child who has had a faint needs an ECG, versus it is good to get one or it is simply not needed unless there is a specific reason - this is a debate that is lacking input from the good people of the primary care and emergency medicine communities.  My solution?  Stick a cardiologist, a paediatrician, an emergency medicine doctor and a general practitioner in a lifeboat and leave them there till they've sorted it out.  I'm fairly sure they'd be fine...

Edward Snelson
Precordiologist
@sailordoctor

Disclaimer: The Everest-Lifeboat Test was originally described in 1055 by Egbert the Uncertain, a monk who died at the Battle of Hastings before writing down his idea.  I therefore take full credit for inventing the test myself.

1. Kapoor WN, Evaluation and outcome of patients with syncope, Medicine, 1990 May;69(3):160-75.
2. NICE guideline "Transient loss of consciousness (‘blackouts’) management in adults and young people"
3. Diagnosis and management of syncope, European Society of Cardiology, European Heart Journal (2009) 30, 2631–2671
4. Guideline for the Evaluation andManagement of Patients With Syncope,  A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society

The Random Goldfish - When confirmation bias met affective bias

In the previous post, I explored how confirmation bias can lead us to believe that something is causing a problem when really it isn't.  Although sometimes unexpected, this kind of news is not unwelcome.  Finding out that fever doesn't really cause febrile convulsions is a surprise to many, but usually a good one.  Telling people that their treatments don't work is much less popular.

Anyone who has been a clinician for a reasonable amount of time knows what it feels like to share good and bad news with someone.  When I am teaching about paediatrics in primary care, it sometimes feels like I am saying that very few treatments actually work.  This feels having something taken away form us.  The real headline is that children make themselves better in the vast majority of clinical scenarios.  It is our job as clinicians to do as much nothing as possible while looking for opportunities to give effective treatments.

One question that I am often asked is, "If these treatments don't work, why do people use them?" Good question.  I tend to assume that my sample cohort of co-workers is representative of clinicians and I work with good, conscientious people who want to give children the best treatment possible. Since I don't believe that clinicians are generally unintelligent, malicious or lazy, I will take a risk and say that there must be powerful forces at work if any of us are giving ineffective medicines to children.  The problem that leads us all to use ineffective treatments is our very desire to make children better and parents happy.

If you want something really badly and do something in an attempt to make it come about, when the thing happens, we are likely to believe that this was cause and effect.  This approach would work in a fixed environment,  For example, consider a person trying to solve a puzzle (like a Rubik's Cube).  The puzzle isn't going to solve itself, so if the person tries many different strategies and then something works, they have solved the puzzle.  This assumes that the puzzle has not been solved by chance, which in this case is extremely unlikely.

Now consider someone with a different problem.  He wants a picture of his goldfish next to the castle in the goldfish bowl.  He tries shining a light to get the goldfish to move into position.  He tries tapping the glass, placing some food and tries making waves in the tank.  Whatever he does just before the goldfish moves into position must have done the trick right?  Wrong.

Well, much of paediatrics is like that.  Childhood symptoms often fluctuate or resolve.  We want our treatments to work.  We want to make children better and parents to be happy.  These factors are the perfect ingredients for us to wrongly believe that what we did worked.  Sometimes though, the goldfish just moves.  Because it's a goldfish.

Enough about goldfish. Let's use a really common example of how confirmation bias leads us and our patients to believe in an effect that is not real.

If I tell someone that antibiotics will cure a child's throat infection within a week, you can imagine how that sounds plausible.  Then, the initial belief in my statement will be reinforced when the child does indeed get better.  The true believer does not consider that the alternative is just as plausible - that all (uncomplicated) throat infections get better with time.  You know that guy who still has the viral sore throat he caught when he was two years old?  No?  Neither do I.

Paediatrics is a branch of medicine where most illnesses will resolve with time and many symptoms that could be attributed to a treatable cause.  But we and the parents both want the problem to be treatable.  The problem is, you're too nice.  You want to help and you want everyone to leave happy. This is called affective bias (the thing that reinforces confirmation bias). The end result is that we can easily believe that we are treating a problem, when in fact it gets better on its own.

Now, bias gets a bad name in medicine, but I would like to defend bias.  Clinicians could never learn or make decisions without bias.  We would be permanently uncertain and unable to choose. Without confirmation bias, we would never notice a pattern.  Without affective bias we would never take the parents seriously or care about the child.

Bias is good.  There, I've said it.

Bias is your friend, but friends can be fickle.  The thing about friends is that despite their faults, they're still your friends.  It is good to know what to expect from them.  That way, you don't feel surprised when they do the thing that they always do.  In the case of bias, your friend wants to mislead you and get you do do things you shouldn't do.

So, what are the best examples of the confirmation bias of presumed effect in paediatrics?  I've already mentioned antibiotics for upper respiratory tract infection.  There are many more, but lets just look at one in detail as an example:

Confirmation bias (presumed effect) - 
Example number 2: Treatments for gastro-oesophageal reflux disease in infants

If there was ever a paediatric condition that fitted the brief for this subject, it is feeding problems in babies.  The symptoms that babies present with are so often simply withing normal limits for infancy.   Did you know that straining is a thing that 1 in 6 babies do and that it is called dyschezia, not constipation?  If you add regurgitation of milk (aka 'reflux'), colic and other common gastrointestinal complaints, most babies have some sort of symptom that we could treat if we chose to during the first few months of life.  With a few exceptions, these are normal for being a baby, and will resolve in time.

The cardinal sign of a self resolving problem is that there are treatments available without good evidence of efficacy.  (Cough medicines for children are a good example of this.)  By way of contrast, there are very few treatment strategies for the management of pneumonia.  I'm guessing that you probably use antibiotics.

The evidence for the available treatments for reflux disease is not good.  In many cases the evidence is that they have little effect.  Rather than posting several dozen references, I am simply going to signpost you to the NICE guideline for Gastro-oesophageal reflux disease in children and young people. (1)  In the full document there is an extensive literature review which makes for interesting reading.  The bottom line is that the evidence is usually lacking.  The evidence that we do have form research points toward little or no effect for alginates, H2 agonists and PPIs.  By their own admission, much of the advice in the guideline depends on the experience of the experts involved in the guideline writing process.

Of course the problem is that there are infants with genuine pathology.  These children often begin their visits to healthcare professionals with non-specific presentations which easily fit the bill for what is 'normal for infancy'.  If we are honest with ourselves, the niggling doubt that the child might have a significant problem is one of the factors that pushes us in the direction of pulling out our prescription pads.  After all, it won't look as bad when the child turns out to have a problem later if we were busy trying treatments instead of reassuring the parent that these symptoms are usually part of normal infancy.

Avoiding unnecessary treatments is gold standard care.  Alginates are the most frequently used medications for reflux symptoms but in my experience this treatment runs a high risk of causing constipation.  This is far from ideal if you are trying to make life easier for baby and parent alike.   Motility drugs have repeatedly been associated with dangerous cardiac side effects and PPIs have been shown to increase the risk of respiratory tract infection. (2)  The take home message from this is that, although medication is an option, we need to be sure that a treatment is really likely to be better than watchful waiting.

The NICE guidelines focus on consideration of how the infant is affected - severe distress or red flags (faltering growth, feed refusal etc.).  It is also important to consider other possible diagnoses such as UTI.

I said that there were quite a few problems that have a similar story.  Going through all of them in detail would take a long time, but here is a list of some of the treatments that lend themselves to this combined bias effect:

The evidence for all of these treatments in children is that they work rarely (antibiotics for URTI, inhalers for cough alone, suspected CMPA based on colic alone) or never (cough syrups, simethicone or lactase for colic in babies).  All of these clinical scenarios share a common theme- the likelihood that the symptom will resolve in time.

So lets come back to bias.  Confirmation bias will cause us to believe that a treatment is effective while affective bias will make us want to give something even when there is little or no benefit. "But earlier, you said that bias is good.  You said that bias is my friend!" you might well say.  I stand by that.  As long as you know how you expect your friends to behave, any misbehavior can be managed and they can still be your friends.

For confirmation bias, we need to have good evidence to justify treatment that is used for symptoms when the natural course is resolution with time.  For example, I don't need evidence to back up my belief that morphine works for pain when a child has a broken leg.  If the child feels less pain afterwards, it has nothing to do with a goldfish effect.  Conversely, I should want evidence that a treatment is effective for any of the symptoms listed above.

For affective bias, we need to harness our desire to be nice to parents and children.  That means not wasting their time with ineffective treatments or worse still causing new problems. Sometimes, doing nothing is the nicest thing that you can do.  Managing to treat where appropriate and avoid unnecessary treatment is the holy grail of paediatrics.  Ultimately, the child is the patient and we need to only give them medication that is more likely to help than harm.  At least, that's what we should be trying to do despite our biases.

Edward Snelson
Amateur Medical Errorist
@sailordoctor

Disclaimer - I am too biased to be taken seriously, even by myself.

References

1. NG1 - Guideline for Gastro-oesophageal reflux disease in children and young people, NICE
2. Orenstein et al., Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease, J Pediatr. 2009 Apr;154(4):514-520

Your New Year's Resolution - Undiagnose a Child This Year

If you’re wondering what to do for your New Year’s resolution, don’t give something up or join a gym.  Neither will work out anyway.  This year, do something truly worthwhile - promise yourself that you will undiagnose a child or three.

Paediatrics is particularly prone to the pitfalls of overdiagnosis and overtreatment.  Although this is a problem, the reasons for overdiagnosis are actually good ones:

• The tendency for symptoms to resolve with time (e.g. vomiting and crying in infancy)
• In childhood there is usually an illness that can’t be treated which mimics those that should be taken more seriously (e.g. viral urticaria leading to overdiagnosis of antibiotic allergy)

When there are no good tests available to tell between two possibilities, we sometimes give a therapeutic trial to help answer the question.  That is a strategy which will lead to misdiagnosis if symptoms improve despite our treatment rather than because of it.

With therapeutic trials, it is often best to challenge the assumption that it was the treatment that worked.   The two best examples that I can think of are childhood asthma and cow’s milk protein allergy in infants.

Let me give you a case to illustrate what I mean:

A 3 month old has been treated unsuccessfully for symptoms of gastro-oesophageal reflux disease (GORD).  A clinician suspects non-IgE Cow’s Milk Protein Allergy (CMPA) because first and second line treatment for GORD has been unsuccessful and because they notice that the baby has quite significant eczema.  (Click here to see a guide to diagnosing feeding problems in this age group)  The clinician decides to trial an extensively hydrolysed feed.  Over the next few weeks, the child’s symptoms of being unsettled and bringing back feeds improve considerably.  The eczema is responding to topical treatment.

In this situation, it is easy to assume that the change of milk was what made the difference.  Often, this is simply confirmation bias.  Colic, reflux and other symptoms of infancy have a tendency to self-resolve.  Of course the treatment may have been what worked but at this point in time, we genuinely have no idea.

This is the time to stop the hydrolysed formula and reintroduce a standard formula.  (Only do this for Non-IgE CMPA.  IgE CMPA is the kind that has urticaria and wheeze etc.  The children with this type of allergy need to be referred to an allergoligist.)   If the original symptoms of being unsettled and vomiting lots return in the next couple of weeks, the diagnosis is now more robust.  If the child remains well despite a return to standard formula, you have undiagnosed a thing.  Marvellous.

The second clinical scenario is the 7 year old with a nuisance cough.  The cough has been there for somewhere around 2-3 months.   There are no associated symptoms such as wheeze or altered exercise tolerance, but the cough is waking the family up at night.  The chest is clear on examination.

So, what is the likely diagnosis?  Surprisingly, in research land, coughs like this turn out to be caused by pertussis infection more often than asthma or reflux disease. (1,2)  It seems that although the pertussis vaccination is successful, infection is still relatively common.  Instead of causing a more significant respiratory illness, what we see in vaccinated children is often just the cough that lasts 100 days.  There are other, similarly benign reasons for chronic cough in children.  Also, there are plenty of significant pathological causes of chronic cough that are not asthma.

Diagnosing ‘cough variant asthma’ is possibly the biggest reason for the current debate about overdiagnosis of asthma in children, fuelled by an article in the BJGP earlier this year. (3)   Many children in the UK are prescribed inhaled steroids for chronic cough symptoms.  If they get better, this is taken as evidence that they had asthma, but there are other possible reasons for this resolution of symptoms.  The evidence suggests that the most likely thing is that the cough has resolved with time rather than with treatment.

This is therefore another opportunity to undiagnose a thing.  As well as stopping inhaled steroids after (Snelson makes up a number quickly…) three months it is probably a good idea to get some sort of objective assessment before, during and after the therapeutic trial.  Peak flows are great if you can get the child to do these well.  In many cases a symptom score (4) is more achievable.  If the only complaint was cough, then a symptom diary is all that is required.

If when you stop the steroids, the child’s cough is still resolved, you have a winner.  Your New Year's resolution is fulfilled.  Of course, once you start, undiagnosing an become a bit addictive.  If you find it becomes a problem, why not join a gym instead?

Edward Snelson
Diagnosectomist
@sailordoctor

Disclaimer: My New Year's resolution is to get a better disclaimer.

References:

1. Marchmont et al, Evaluation and Outcome of Young Children With Chronic Cough, Chest Journal, May 2006, Vol 129, No. 5
2. Wang et al, Whooping cough in school age children presenting with persistent cough in UK primary care after introduction of the preschool pertussis booster vaccination: prospective cohort study, BMJ, 2014;348:g3668
3. Looijmans-van den Akker et Al, Overdiagnosis of asthma in children in primary care: a retrospective analysis, BJGP, 1 March 2016
4. Asthma.com, Child Asthma Control Test

Why bronchiolitis doesn't get better with inhalers and how understanding "why?" is better than "do that!"

There was interesting debate this week about using inhalers for bronchiolitis.  The interesting features included how heated it became (there was mild name calling and much "prove it" involved, rated PG) and how confident people were in expressing their views on social media about their differing clinical practice.  (Take it from me that you should be fairly sure of yourself before you put something out onto the interweb.)  To me what was most interesting was that the views, despite being polar opposites, where seen as fact.  I am going to assume that all involved want to practice the best possible medicine, but someone must be wrong mustn't they?

What do the guidelines say?  The American Academy of Pediatrics and the UK's National Institution of Clinical Excellence along with other institutions, have produced guidelines in the past few years, specifying that beta agonists and ipratopium should not be used, so why are such debates still happening?  I think that there are a few reasons.  One of these is that for medics, knowing what to do is not as powerful as knowing why, especially when it comes to changing practice.  For me, understanding a disease is much more effective as a learning process than being told, "This is the disease and this is the treatment."   I suppose it is because I already understood the reason why I was doing what I was doing (even if the understanding was flawed), so a diktat is not as powerful a persuader as a new and better understanding.

There is a perpetuated myth regarding beta-receptors and infants.  This myth comes from early studies that failed to find evidence of beta-receptors in infants.  Since then, (as early as 1987) research of better methodology (3) has proven that these receptors are there from birth.  The myth persists because (just as the news reports plenty of crises but not so many resolutions) we are often told things, but rarely does anyone untell us something.

Perversely, the beta-receptor folklore has done us no favours when it comes to trying to understand bronchiolitis and viral wheeze.  The uncertainty created by this myth makes clinicians think that a lack of beta receptors has caused the lack of response to salbutamol.  In fact, the child would respond just fine if only they had bronchospasm.

In bronchiolitis, there is no bronchospasm so salbutamol does not help.  In viral wheeze, ipratopium is a poor treatment and the old myth about ipratropium leads some to believe that ipratropium is the first line treatment for this age group when what they really need is plenty of salbutamol if they really do have bronchospasm.

When discussing the management of wheeze in infants, I often get the impression that people believe that bronchiolitis is just what you call viral wheeze in a child under the age of 12 months.  In fact this is not true.  Bronchiolitis is a separate entity, with different histopathology and a unique clinical pattern of illness.  There is a gradual unset of symptoms, peaking at day 3-4 and beginning to resolve at day 7-10.  Doesn't sound very spasmy does it?

Of course the confusion arises from the fact that both bronchiolitis and viral wheeze are caused by a viral illness.  They can both occur in a child around the age of 12 months old and they cause similar symptoms.  There is however a subtle but helpful difference in the way that they present.

The reason for this difference is a difference in mechanism.  While bronchiolitis and viral wheeze share a cause, the pathology is different because the effects on the airways are different.

I suppose that since it is unrealistic to think that all uncertainty can be removed, the question remains, what is the harm in trying a bronchodilator in all every case, just in case?  Here are a few possible reasons why it is going to make things worse if it isn't going to make things better:

It's always difficult when two illnesses have so much overlap, but there are genuinely good reasons to avoid unnecessary treatment for bronchiolitis.  Hopefully understanding why bronchodilators don't work helps the thinking clinicians to decide for themselves, rather than just being told what to do by guidelines.

Edward Snelson
Mytharchivist
@sailordoctor


Disclaimer:  I would like to express my appreciation to the children who allowed me to perform lung biopsies on them during their wheezy episodes.  Science thanks you.


References

1. Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis, American Academy of Pediatrics, October 2014
2. NG9 Bronchiolitis in children: diagnosis and management, NICE, June 2015
3. A Prendiville et al., Airway responsiveness in wheezy infants: evidence for functional beta adrenergic receptors, Thorax. 1987 Feb; 42(2): 100–104.

Asthma, Overdiagnosis, Underdiagnosis and all that

A storm is coming and it's set to be a force 10.  There is much debate about how asthma should be diagnosed in children.  There are two opposing views and (guess what?) they are both right.  This conundrum, which occurs whenever a diagnosis is complex, is always the perfect setting for the perfect storm as clinicians struggle with the "right way" to diagnose an illness.

This week an article was published in the BJGP, talking about the overdiagnosis of asthma.

Overdiagnosis is an issue close to my heart because it causes morbidity through tests, treatments and time spent being medicalised, none of which are necessary because the patient does not have the disease.  In paediatrics there is a particular tendency to overdiagnosis due to the lack of precise information (what does the abdominal pain feel like to a 2 year old? It would really help to know!) and the desire to make the child better.  Being cute will have that effect.

Of course overdiagnosis is also at risk of distracting from the real diagnosis, thus robbing the patient of treatment that would be beneficial.

The above mentioned article contains some results that will make most of us sit up and take notice. Set in the four Dutch primary care centres, they found that in "more one-half (53.5%, n = 349) of the children the signs and symptoms made asthma unlikely and thus they were most likely overdiagnosed."

Very well, so essentially this shows that when you apply a new diagnostic pathway (retrospective analysis of signs and symptoms plus a generous use of tests including spirometry), it disagrees with the old diagnostic pathway, which was presumably based mainly on history and examination.  That doesn't feel very applicable to the 'real world' of diagnosing childhood asthma in a front line clinical setting.  Well get ready, because your 'real world' may be about to be rocked.

Earlier this year, NICE published a draft guideline for the diagnosis of asthma, including children.  This contains one particular proposed recommendation that surprised me: "Do not use symptoms alone without objective tests to diagnose asthma. (in children from the age of 5)"  Boom.

So, a six year old comes in with an acute wheezy episode.  This was not triggered by a cold.  It started when they visited an animal shelter.  The child has eczema and the parents are both atopic. When you see them, the child responds to the salbutamol that you give.  In further history the parents had noticed that the child coughs at night quite a lot.  Time to do some tests?

I await the final version of the NICE guideline with interest.  Meanwhile I am a big fan of the British Thoracic Society guidelines which stratify into three groups - low, intermediate and high probability of asthma.  These guidelines list the features that make asthma more likely:

• More than one of the following symptoms - wheeze, cough, difficulty breathing, chest tightness
• Personal history of atopic disorder
• Family history of atopic disorder and/or asthma
• Widespread wheeze heard on auscultation
• History of improvement in symptoms or lung function in response to adequate therapy.

And the features that make asthma less likely:

• Isolated cough in the absence of wheeze or difficulty breathing
• History of moist cough
• Prominent dizziness, light-headedness, peripheral tingling
• Repeatedly normal physical examination of chest when symptomatic
• Normal peak expiratory flow (PEF) or spirometry when symptomatic
• No response to a trial of asthma therapy
• Clinical features pointing to alternative diagnosis

Testing with spirometry etc. is reserved for times of diagnostic subcertainty.

Does this approach lead to overdiagnosis?  I am sure that it does, for the reason that that children with intermediate probability of asthma still might not have asthma.  While tests can add to the available information, the diagnosis of asthma remains clinical.

So how bad is overdiagnosis?  If I could avoid overdiagnosis then I would, but in medicine that is just not possible unless there is a perfect test available.  In most cases we have to set ourselves the challenge of being rigorous with our diagnoses without being overcautious.  Cautiousnesses leads to underdiagnosis  which is also problematic, depending on the burden of the disease.  I am happy to overdiagnose sepsis in babies for example.  I know that the alternative is disastrous. I am equally happy to underdiagnose colic.  Colic is not harmful and there is no effective treatment.

When it comes to asthma, there is a huge morbidity and mortality associated with this disease.  So while I agree with the study authors about the burden of unnecessary treatment when a child does not have asthma, I believe that the effect of moving our diagnostic goalposts needs to be considered carefully.  Will there be more underdiagnosis as the pendulum swings away from making the diagnosis of asthma on clinical grounds?  That is a real possibility and as far as I can tell no-one has looked at the burden of that change.

The bottom line is that asthma is a diagnosis that can be overdiagnosed and yet underdiagnosis is equally detrimental.  However, without turning to complicated investigations, overdiagnosis and underdiagnosis can both be avoided by considering all the factors that make a diagnosis more or less likely as per the BTS guidelines.

Edward Snelson
Over and under most days
@sailordoctor

This post has been all about diagnosing asthma in the 5-15 year old age group.  If you would like to find out more about the under five year olds you might like to read:

• How is your wheezer wired? Asthma vs Viral wheeze in the under 5 year old.
• High Voltage - What the diagnosis plus severity means for management of viral wheeze

References

1. Looijmans-van den Akker et Al, Overdiagnosis of asthma in children in primary care: a retrospective analysis, BJGP, 1 March 2016
2. Draft NICE Guideline for Consultation: Asthma: diagnosis and monitoring of asthma in adults, children and young people
3. British Thoracic Society /Scottish Intercollegiate Guidelines Network - British guideline on the management of asthma (Quick Reference Guide)