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Team:Groningen:PP:Martini
From 2014.igem.org
Policy & Practice
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Martini Hospital
Visit Martini hospital, a meeting with the medical microbiologist and the medical director
On the thirteenth of August our team visited the burn centre at the Martini hospital in Groningen. We were immediately reminded that we were in a hospital, where due to the vulnerable patients and the increased risk of infections, strict hygienic measures are implemented. This was demonstrated by first moving through a lock chamber, after which we were dressed in blue scrubs to keep unwanted bacteria out of the centre. We were led through the centre, and had a talk with the medical microbiologist and the medical director of the burn centre in Groningen.
Figure 1:
Some of our team members visiting doctor Beerthuizen for an interview.
During the visit we learned things that helped us to put our bandage into context.For example:
If 20% of a patient’s skin is covered with burn wounds, there is a high chance of infections. These infections are mainly caused by Gram-negative bacteria
Groningen does not perform surgery if a patient is infected with Pseudomonas aeruginosa because the chances of this surgery being successful is decreased.
Currently the mostly used treatment method in Groningen is the application of Cerium, it neutralizes the dead skin, and has a positive effect on the inflammatory process and subsequently on the wound healing. Effect of Cerium is diminished if a biofilm is present in the wound.
For colonization caused by Staphylococcus aureus, Bactroban is used. This drug contains Mupirocin, which is an antiseptic.
To assess the chances of an infection, samples of the nose, mouth and wounds are taken from patients. These samples are then grown on five different types of plates that are selective for different pathogens. In this centre they use stamps instead of swaps from the wound. When the stamps show a certain type of growth, the doctor either calls for action or leaves it to be.
In some cases of P. aeruginosa infection, patients are treated with a bath therapy. This treatment reduces P. aeruginosa in the bath, after which the wounds will be left open to the air to dry.
When we asked about application of growth factors in the wound, the specialists indicated that there is a possible benefit in wound healing.
Apart from being informative, this visit brought us back to why we are actually developing this bandage. It also reminded us of all the other factors that need to be addressed in the design (e.g. user comfort and applicability). We are glad that the burn centre allowed us a visit!
First visit to the burn centre at the Martini-hospital in Groningen on the seventeenth of July
We had the idea of developing this new type of bandage to fight infections in burn wounds. A bandage that uses genetically engineered bacteria to detect an infection, and maybe even protect the wound from further harm. We got this information from literature, but were keen to see how our solution to this problem relates to the real world. It might look good on paper, but we had no clue on how the end users, the people in the hospital, would look at it. For these reasons, we arranged a meeting with two Doctors from the burn centre Groningen. During this meeting the whole team got a better view of burn wounds in general. It provided us with some idea how big this problem is, and what the current treatment methods are.
Just to give you an idea of what we learned here;
Based on one year, approximately 0.25% of the Dutch population gets a burn wound
35000 of those people are treated by the family doctor
13000 are treated in the hospital
Around 600 – 800 patients are treated in the Dutch burn centres
Among younger children (until 2 years old) hot fluids are the most common cause of burn wounds
Severity of the burn wound is measured in total burned surface area (TBSA) and the depth of the wound
Depending on the severity of the wound, patients can stay from 1 week to several months at the burn centre to fully recover
The burn centre in Groningen has approximately 10 cases of P. aeruginosa colonization per year
30% of the patients at the hospital have an S. aureus colonization
The Gram-negative bacteria are the most difficult to treat
>This is quite a list, and there was a lot more that we learned that day. The most important message in regard of our project is that there is no ideal bandage for the treatment of burn wounds after the Flammacerium treatment. It is a very good incentive to make a bandage that can protect the wound.
Figure 1:
Getting a tour through the hospital.
Towards an application; an interview with the burn centre at the Martini-hospital
Nearly halfway through our iGEM-adventure of creating an infection-detection-protection dressing for (burn) wounds, we got the opportunity to talk with some experts in the field. Of course, creating a ‘genetically engineered machine’ is what we do, but we want to explore the application further. Having a talk with people who could eventually use our concept in real-life was therefore essential; if there is no need for this type of dressing, then there is no need to develop it!
Marianne Nieuwenhuis is the head of clinical research for the three cooperating burn centres in the Netherlands and is based at the burn centre of the Martini hospital in Groningen. Jakob Hiddingh is also affiliated to the burn centre and is working on clinical research trials. Whenever a researcher is not around, Jakob takes over the responsibilities, making him an expert on the practical side of clinical research trials.
Can you explain something about the burn centres? How do they work? What kind of research should we imagine when you talk about clinical research trials?
‘In the Netherlands there are about 600-800 recordings (annually) of patients in the three burn -centres; Beverwijk, Rotterdam and Groningen. Rotterdam is the largest of these three. The time patients stay at the centre varies from one day to several months. We do research in everything ranging from psychological research to physical issues like itching. On average, patients remain at the centre for 14 days, but as said, this varies a lot depending on the patient and severity of the injury.’
As you may know, we are developing a dressing that is aimed at protecting burn wounds, specifically to detect an infection of S. aureus or P. aeruginosa. Do many problems with infections occur when treating burn wound patients? How do you handle these?
‘There is a clear distinction between an infection and a wound that has some pathogens (harmful bacteria) in it; a colonization. Colonization is when the pathogen is there, but you do not get ill from the presence of these bacteria. When you talk about an infection, many of the classical features occur and these are very harmful for the healing process. In this centre, we typically take a sample of all the wounds once a week to see if there are any harmful bacteria on them. We also take a sample of the throat and nose. ‘
Groningen, and the Netherlands in general, do not have many problematic infections. How is this problem of infection prevention taken care of in the rest of the world?
‘It’s hard to compare numbers because every centre and hospital has its own way of detecting infections. There is a large range of pathogens, but especially S. aureus and P. aeruginosa are the pathogens that cause most problems.’
Figure 2:
Visit to the burn wound centre at the Martini-hospital in Groningen.
If we understood well, Flammacerium (a cream-like substance) is used mostly to keep the wound clean and improve wound healing. How does this treatment work and is it used in other parts of the world?
‘Flammacerium consists of two components, the silver sulphadiazine (also known as Flammazine), and cerium nitrate. The silver sulphadiazine keeps the wound clean, but a serious downside is that it induces hypergranulation after a while (the overproduction of tissue). People have been looking for an alternative for quite some time, but so far nothing really superior is on the market yet. We believe that the cerium nitrate does have a positive impact on the treatment of burn wounds, therefore we keep using Flammacerium. In other parts of the world this treatment method is used to a lesser extent.’
For our dressing, we would like to think a step further than only developing it and then putting the prototype in the fridge. What are the main hurdles to be taken when developing this dressing for burn patients?
‘Keep in mind that for every minor step you want to do when dealing with a clinical research trial, you should write a protocol and all actions should be cleared by the medical-ethical commission. In the Netherlands, this is the case for every WMO-research (research involving humans). For the testing of a new product, such as your dressing, you would need to fill out many forms involving a complete description, how it works, what could go wrong, what is the goal and added value etc. etc. .’
As we are speaking about regulation issues regarding new products, what do you think of our idea once it has gone through all the clinical trials and been proven to work, say in 10 years? Do you see the relevance of having such a dressing? Do you foresee any ethical issues that might arise in the practical application of GMO’s in healthcare?
‘The funny thing is, I never heard of synthetic biology before you came along. I did not realize this project would involve any moral dilemmas that needed to be so seriously addressed. I just thought: that’s great, they are “playing around” to make bacteria do a specific task! As long as the added value is clear, in other words, if it helps the patients to get better, there will be not so much resistance against it. It should be very well regulated though, but this is already under debate. I understand that genetically modified organisms are a bit difficult to use and there is some resistance, but to me this project seems very worthwhile.’
Do you have any advice for us that could help us in the development of our dressing?
‘We are enthusiastic about your idea and think that this is an innovative approach to treating wounds. The idea I like so much is that it goes beyond normal theoretical research, but you are actually making it. It is a quite appealing concept. There is also possibly less resistance as you are trying to make a better treatment for patients with burn wounds. You should have a talk with our medical microbiologist and medical director!’
Visit Martini hospital, a meeting with a nurse practitioner
Nearly halfway through our iGEM-adventure of creating an infection-detection-protection bandage for (burn) wounds, we got the opportunity to talk with some experts in the field. Of course, creating a ‘genetically engineered machine’ is what we do, but we want explore the application further. Having a talk with people that could eventually use our concept in real-life was therefore essential; if there is no need for this type of bandage, then there is no need to develop it!
In this story, we were given the opportunity to talk to a nurse practitioner at the burn centre Groningen. During a regular workweek she guides parents and patients throughout the whole healing process.
During the visit we learned things that helped us to put our bandage into context. For example:
In Groningen, most of the time the treatment starts with Flammacerium for at least three days. Chemical burns cannot be treated with Flammacerium. These wounds are treated with Flammazine instead
After a Flammacerium layer occurs, the wound is treated further with fatty gauze (Jelonet). This can be left in place for two or three days
Drying the wound is a very good treatment. Sometimes we do not need complicated “intelligent” methods, air is very effective as well
On the out patient clinic, S. aureus causes the most common infections. The infection can be treated well with Bactroban, which contains Mupirocin
Believes of people might cause some resistance to this product. Nowadays, for example, some people do not want blood transfusion because of what they believe. Be aware of this. Bacteria in general have negative connotations, this might cause some difficulties for introducing this product
Think about the comfort of the bandage; does it fit nicely, does it look nice and can it be removed and applied in an easy manner?
Keep the benefits and the costs of such a bandage in mind. If it truly is better, than it can be more expensive, but for just a small improvement there will be less room to manouver (financially speaking)
The nurse practitioner indicates that LactoAid will suit the clinical patients the best
Think about how to present your idea to the outside world; that is key to the acceptance
