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To improve outcome for critically ill children, healthcare workers need to be trained to better work together. In addition, guidelines are often quite strict but not always tested by clinical trials. Fluid interventions for critically ill children with severe malaria or sepsis in African hospitals actually worsen the outcome. Researchers working in large consortia can also make better impact for patients and to policy makers.

My name is Kathryn Maitland. I am a paediatrician based at the KEMRI Trust Programme in Kilifi, Kenya, where I have been for the last 20 years. The focus of my research is the critically ill child, particularly the child who’s just presented to hospital. We have been looking at how best to keep that child alive.

First of all, we did a series of what we would call physiological studies, to try and understand what was causing them to be unwell, particularly children with severe malaria. My initial focus was trying to establish, for children with severe malaria who came in a very desperate state, whether they actually had features of what we call shock. We had to underpin the work we subsequently did by looking at the physiology of these children, putting in central venous pressure lines and studying them overtime and over their course of illness. We were able to establish that, like children with sepsis, children with severe malaria also do have shock. That allowed us to be able to justify to do fluid intervention studies as we would normally do in the emergency rooms in the UK.

I went on from that study to do a very large phase III trial, and the results were extremely surprising for all of us; we weren’t anticipating them. They actually showed that although children who had shock – and this was not just children with severe malaria but also children with sepsis – we were able to give them fluid and that corrected shock, but that did not save lives. In fact, it actually worsened the outcome. Children receiving what is normally given in the emergency rooms here actually had a worse outcome than children who didn’t receive fluid boluses. That piece of research was published in the New England Journal of Medicine in 2011 and it caused quite a stir in the world. We are now 8 years following that and people are still trying to understand the results of that trial. But it has not only changed practice in Africa, but it’s also changed practice elsewhere.

If you think about what you do when you first see a very sick child, the first thing that we recognise is that a very sick child comes in and there is chaos, everybody wanting to do something. I think that the most important thing is that all the teams are trained. There is a course called ‘Emergency, Treatment and Triage’ which is ETAT for short, and that has a very significant impact. The course trains teams not only to recognise very sick children, but also to do a standard set of treatments and look after them beyond that. I think getting people to work together in a nice organised systematic way has an enormous effect, and that is before we even start to consider the treatments. The second part of trying to improve outcome is looking at the guidelines, which is what people try to follow, and say well, has this guideline – which often gives very strong recommendations – has this been tested a clinical trial? Because that is the best evidence. As I’ve given you an example with the FEAST trial, it is the only controlled trial that has ever been conducted in the world and the results were quite surprising. We also need to test other interventions that are commonly given in the emergency room.

For example, one of the recent research trials we’ve completed and just published this August in the New England Journal of Medicine was a transfusion trial. This trial was in African children who have severe anaemia, and there is no surrogate population around the world, this is a very specific question for children in Africa. Severe anaemia is a very common problem when they present to hospital, and the WHO guidelines often recommend – because children use a lot of blood from the blood transfusion – not to transfuse children who are less severely ill, even though they are very unwell because they are hospitalised. And doctors don’t believe it, so they transfuse away and that means that they are using up their resource of blood; and often when you get a very sick child, who really does need blood, there is no blood in the blood bank. We’ve conducted the trial that showed that with a haemoglobin between 4 and 6, if the child is stable, you do not need an immediate transfusion. We actually confirmed the WHO guideline, but there is one caveat to that: we were able to show that you must monitor these children, and by monitoring them you will find that nearly half of them will develop severe and complicated anaemia within the next 24 hours, needing a transfusion. We were able to show that you can allocate transfusions according to not just as soon as they come through the door; but if you monitor children, we were able to show that you can preserve the very precious supplies of donor blood.

Over the last decade, I think what’s really been instrumental and making big changes in terms of research and our output is the way people work. It has been recognised that instead of one group of people working in a single centre producing a small piece of research showing A or X and another group saying ‘oh no, we disagree, why’, now people are beginning to work as quite considerably large consortia, which means that you can actually move through research questions in a much more integrated manner. You also have a much bigger impact not just obviously in clinical trials but across huge consortium. I think many of the other people who work in this department have been able to show that when you pull your data, you pull your efforts, you work collaboratively, you can make enormous impact for the populations that you are working with, and also to policy makers, because you come with a very strong body of evidence.

I have often been asked why are you not trying to prevent children from coming into hospital, and trying to save them when they come in because they are very sick? Well, it’s a really important targeted way of reducing child mortality. If you have a very strong evidence base that you are able to show that treating children in a particular way, because you’ve done this in a clinical trial and then that can save lives, it actually is a very cost-effective way of improving outcome. Our research group and the focus of our research group has similarities with the rest of the world in that even in rich emergency rooms within the UK and beyond, many of the guidelines have not been tested. It is not a unique field, people struggle and conducting this type of research has huge ethical challenges and practicality challenges. We’ve been able to address those in Africa, so we think we are an example for the rest of the world.

Our research is almost immediately translatable. Because we do large clinical trials designed to be run in the settings in which the actual guidelines will be taken up; we don’t try to replicate artificial settings. When we come up with a result, and it’s a definitive result, it can be immediately translated into policy and also then put into practice – another word: translation. We think we have a capital T for translation in terms of our research. Thank you.

This interview was recorded in September 2019

Kathryn Maitland

Based in eastern Kenya, Professor Kathryn Maitland leads a research group that have highlighted the unique importance of emergency-care research as a highly targeted and cost-effective means of tackling childhood mortality in resource-limited sub-Saharan Africa hospitals. Her major research portfolio includes severe malaria, bacterial sepsis and severe malnutrition.

Translational Medicine

From bench to bedside

Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.