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.