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                     <h1>Human Practices - Silver</h1>
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                     <h1>Human practices</h1>
                     <p style="text-align:justify" ;>In earlier discussions with specialists, we gained first insights on how our project would influence the treatment of patients. But what do they themselves think of our idea? In order to investigate this, we proposed to invite several patients to discuss our project. However, talking to patients is not something you go over lightly.
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In HEKcite we create an oscillating HEK-cell, but for what purpose? Therapeutic drug monitoring is our answer. In the treatment of multiple severe diseases, a stable concentration of drugs is crucial. Steady blood levels determine therapeutic outcomes and increase survival rates. Currently, the most common therapeutic drug monitoring technique is blood sampling. For patients who need lifelong observation, the numerous hospital visits and frequent blood samplings can have a negative effect on the quality of life.
                        After receiving approval from the ethics committee of the UZ Leuven, we planned the overall course of the interviews in detail. The proposed questions were then reviewed by professor Monbaliu, who has already helped us earlier in the project. By performing patient interviews, we have gained insights in the daily lives of patients and learned of their opinion about HEKcite and the device, which would enable them to check the level of immune suppressants continuously. This information helped us frame the impact of our project, allowed us to adapt the project to patients’ needs and may be interesting for stakeholders in the future. In earlier discussions with specialists, we gained first insights on how our project would influence the treatment of patients. But what do they themselves think of our idea? In order to investigate this, we proposed to invite several patients to discuss our project. However, talking to patients is not something you go over lightly. After receiving approval from the ethics committee of the UZ Leuven, we planned the overall course of the interviews in detail. The proposed questions were then reviewed by professor Monbaliu, who has already helped us earlier in the project. By performing patient interviews, we have gained insights in the daily lives of patients and learned of their opinion about HEKcite and the device, which would enable them to check the level of immune suppressants continuously. This information helped us frame the impact of our project, allowed us to adapt the project to patients’ needs and may be interesting for stakeholders in the future.
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Therefore, we develop a system that allows patients to determine the level of drugs at home. Furthermore, the ease of these measurements allows for daily or even continuous analysis.</p>
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Using this dynamic data collection instead of the static measurements performed in hospitals today, we might increase both therapeutic outcomes and quality of life of patients. In order to investigate the different views on our projects we talked to specialists in several fields where therapeutic drug monitoring is of great importance: transplantations, psychotics and epileptics. Three specialists have provided insights in how they expect our project will influence the lives of their patients and future treatments. We used this information to further shape our project.
 
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                    <h2>Patient interviews</h2>
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                    <p>Introduction about our team and an explanation about the iGEM competition.</p>
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                                 <h3>Professor Diethard Monbaliu</h3>
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                                <p>Professor Monbaliu is a reputable abdominal transplant surgeon, at the department of microbiology and immunology at UZ Leuven. He is also responsible for a course on topographical and radiological anatomy and supervises several thesis students.</p>
                                 <h3>Question 1: What is your experience using immune suppressants?</h3>
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                                <p>Professor Monbaliu confirmed our expectations that there is a need for a more dynamic measurement. In addition, he suspects that it could lead to a better evaluation of patients’ compliance. Together, these advances could result in fewer transplant rejections. He has also brought our attention to a novel and more prevalent immunosuppressant drug, tacrolimus. Finally, he mentioned that patient variability is an issue in his field, and that our device should take this into account. Want to learn more? Press for more details.</p>
                            <p style="text-align:justify">All participants have the same answer: There is more to organ transplantation than meets the eye. After the surgery, not all problems are solved as you would expect, but new ones arise. Some of these issues are side effects, caused by immune suppressants. Among the most frequent side effects are insomnia, easy bruising and bleeding, a tingling sensation on the skin, infection of the joints, et cetera…</p>
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                                <h3>Question 2: Would you like to see a decrease of the amount of blood samples that needs to be drawn?</h3>
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                            <p style="text-align:justify">Most participants answered that they experience only mild discomfort from drawing blood. This is explained by the fact that blood drawings serve many purposes: When the participants go to medical consultations for blood drawings, the concentration of immune suppressants is just one of many variables analysed. This means that our device would most likely not reduce the total number of hospital sessions and the discomfort of blood drawing. This raises the question whether the device would be helpful for transplant patients. Luckily, this question was answered in the continuation of the interview.</p>
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                                Before this meeting, we were investigating the immunosuppressant cyclosporine, as we thought this compound was commonly used after transplantations in order to reduce the chance of rejection. However, professor Monbaliu clarified that this is no longer the case. Instead, he brought our attention to the compound tacrolimus, which has taken cyclosporine’s place in transplantation medicine. Both drugs have the same mode of action, but tacrolimus has a better clinical outcome and less side effects. We were interested in using this novel drug for our research, but unfortunately, the compound is too expensive for us to use. Therefore, considering our financial situation and the input of the professor, we chose to use cyclosporine in our experiments. </p>
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                                <p>Lastly, according to professor Monbaliu, a possible reduction of blood sampling could be a great advantage. However, he mentioned that every patient is different, which means that finding the optimal concentration of immunosuppressant for each patient could a challenge. As a result, our device should be calibrated individually for every patient. Together with professor Monbaliu, we suspect that the individual differences and the problems that go with them could be assessed during clinical studies. As soon as different patients and their different values can be assembled, it can lead to the procedures needed to determine the optimal drug concentration and calibrate our device.
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                    <p>After this question, we explained that it is important that blood levels of immune suppressants remain constant. Currently, blood samples are taken every week or in intervals of up to three months, dependent on the amount of time that has passed since the transplantation. Our goal is to develop an easy method that enables patients to test their immune suppressants at home, at any given time. This would lead to a better follow-up, and would allow the doctors to react to unexpected changes in concentration that would otherwise remain undetected. This way, the risk of organ rejection will be reduced.</p>
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                                 <h3>Professor Chris Bervoets</h3>
                                 <h3>Question 3: In which way do you think this device could influence your quality of life?</h3>
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                                <p>Professor Chris Bervoets is a psychiatrist. He is responsible for the department of transcranial magnetic stimulation, the department of deep brain stimulation and the department of compulsive disorders within the UPC (University Psychiatric Center) of KU Leuven. Additionally, he conducts research on neuromodulatory treatments for various psychiatric disorders.</p>
 
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                                <p>While investigating different branches in medicine that could benefit from improved therapeutic drug monitoring, our attention was drawn to psychiatry. In this field, there are several drugs, for example lithium, that affect ion channels and could therefore be measured directly by our system. These aspects spiked our interest, and to learn more we contacted the specialist professor Chris Bervoets, who gave us some valuable insights in the difficult world of psychiatry.</p>
                            <p style="text-align:justify">Despite the fact that all patients agreed that our project could increase their quality of life, the opinions on how it would affect their lives differed among the patients. Some of them think it would influence their life in a positive way as it could offer them piece of mind. Risk of rejection by the body increases as more time passes, and by then, most patients only visit the doctor once every three months. Therefore, they think the possibility of checking the level of immune suppression on a daily basis would give them comfort and reduce their stress levels, and it would also enable the doctors to react quickly to changes that would otherwise remain undetected for three months. Others shared the opinion that, while our project would not influence their lives directly, they think that our device could be a general advance in the organ transplantation field. When the risk of rejection of an organ could be lowered, this would ease their mind indirectly. Hearing from patients that this device could have an impact on their lives motivated us even further to complete our project successfully.</p>
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                    <p>In order to do these daily measurements, a small device would be placed under the skin, containing living, genetically modified cells that respond to the concentration in the blood.</p>
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                                <h3>Question 4: Would you be willing to undergo this procedure if this could lower your risk of rejection? What is your opinion about the device containing genetically modified cells?</h3>
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                            <p style="text-align:justify">All responses of the patients were positive. They were indeed willing to undergo the procedure if this could lower the risk of rejection of the transplanted organ. A crucial consideration is that the device would be placed during the transplantation process. Most patients were tired of the various medical interventions, and would like to avoid undergoing surgeries that were not strictly necessary, as they inflict a lot of pain and are a cause of frustrations. </p>
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                            <p style="text-align:justify">When asked about the genetically manipulated cells in the device, all patients reacted positively. As long as they are given sufficient information and are made aware of all the consequences and risks that result from the genetic manipulation, they would be willing to use the device.</p>
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                                After explaining our project, professor Bervoets shared his enthusiasm about the possible advantages of our device. He mentioned three ways in which HEKcite could further shape the field of psychiatry. </p>
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                                <p>First of all, he described the current problems concerning treatments using dopamine antagonists. These dopamine antagonist are blockers of the so-called dopamine receptors, and are used for a wide range of psychologic disorders, among which are depression, psychosis, and many more. At present, researches lack detailed information about the correct dosage of these dopamine antagonists: The amount of receptors that have to be occupied to achieve a certain clinical effect is not yet known. In some cases, doctors see a more favourable clinical outcome when patients take dopamine antagonists irregularly, while for other patients, this is not the case. Therefore, a better understanding of how the correct dosage correlates with dopamine receptor occupancy could be extremely valuable.
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<p>Nowadays, this occupancy can only be measured using expensive PET scans. If we could find a way to insert the dopamine receptor in our HEKcite cells and genetically design a correlation of the electric rhythm and the occupancy of the receptors, it could generate valuable information concerning different drug concentrations and their corresponding receptor occupancies. Not only would this measurement be less expensive than a PET scan, it would also provide a more dynamic measurement of the receptor occupancy, which could result in additional insights in dopamine antagonist metabolism.</p>
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<p>Furthermore, Chris Bervoets told us about a novel way of clinical assessment, called the experience sampling method (ESM). Patients are asked to answer ten or more questions a day regarding their emotional status. The answers to these questions are then used to improve diagnosis or foresee psychotic episodes. Professor Bervoets suggests that our device could complement this method by combining the answers of the patients with the exact drug concentrations at a certain time. This could lead to a better comprehension of the connection between symptoms and drug dosage, and help further treatments. </p>
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<p>Finally, professor Bervoets mentioned safety monitoring, which was our original motivation to investigate the field of psychiatry. With our device, we could verify the concentration of certain drugs that only have a small therapeutic range in which they are effective. Furthermore, Professor Bervoets explained to us that lithium may cause side effects even in the right doses. As a result, many patients visit the hospital unnecessarily. Our device could prevent these avoidable hospital visits by reassuring the patient that the experienced symptoms  are due to a benign lithium intoxication. On the other hand, it could also warn the patients when their lithium concentrations are dangerously high and a hospital visit is required.</p>
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<p>After discussing these interesting possibilities for our project, we asked professor Bervoets if he thinks whether patients would accept to undergo the implantation of a small device. He suspects that our project would most likely only reach a select group of patients. For instance, patients who experience severe symptoms are often treated by transcranial magnetic stimulation and are used to medical interventions. This group of patients would not mind a minor subcutaneous implantation, if this would decrease their symptoms. Additionally, our device could help determine which drug is most suitable for a patient and optimise doses to reduce side effects.</p>
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<p>To conclude, professor Bervoets confirmed our speculations that therapeutic drug monitoring is important in psychiatry. Furthermore, he opened our eyes to other potential applications of HEKcite in this branch of medicine and research. We are very interested in investigating the correlation of ESM and drug concentrations and the possibilities of developing a system to analyse dopamine antagonists. However, due to time and resource constraints, we have to remain focussed on therapeutic drug monitoring. Thanks to professor Bervoets’ enthusiasm about the project and the possible applications, we have become even more motivated to investigate the possibilities of safety monitoring, and believe it could bring science and medicine a substantial step closer towards solving important problems in psychiatry.</p>
 
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                                 <h3>Question 5: Would you be willing to participate in a clinical study to assess this device during a case in which you do not know if this could lower the risk of rejection?</h3>
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                                 <h3>Professor Wim Van Paesschen</h3>
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                                <p>Professor doctor Wim Van Paesschen is a neurosurgeon specialized in epilepsy. He also is head of the epilepsy research laboratory, part-time teaches at the faculty of medicine and supervises thesis students.</p>
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                                <p>Professor Van Paesschen confirmed that therapeutic drug monitoring is necessary for anti-epileptics and mentioned the importance of verifying patient compliance. He also showed us that our project has more potential than even we imagined by giving some more examples of possible applications.</p>
 
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                            <p style="text-align:justify">The interviewed patients told us they would like to help scientific advances to improve the lives of future transplantation patients. Some of them mention that they have already participated in clinical studies in the past, and indicate that they are open to new developments. Therefore, two of the four patients would be willing to participate if a trusted transplantation doctor, such as professor Monbaliu, supported the study. The other two patients were more hesitant and they would only consider participating in case the risks were minimal and well known.</p>
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                                In light of our group focusing on drug monitoring as our target for human practices, anti-epileptic drugs seemed to be a quite interesting to research. Given that, we set a meeting with Doctor/Neurologist Wim Van Paesschen, a specialist in epilepsy. Prior to the meeting, our main interest was figuring out if drug monitoring was in fact needed for patients being treated from epilepsy, and it case it was, how could the concept of HEKcite come in handy for said patients. During the meeting, Prof. Van Paesschen showed a great deal of excitement and enthusiasm about the concept of HEKcite, assuring us that drug monitoring of anti-epileptics is indeed necessary, especially for patients suffering severe forms of epilepsy. There have been already various attempts to implement drug monitoring in epilepsy patients but none were quite successful. Since the concept of HEKcite mainly relies on different ion channels, his advice wasn’t to necessarily work with the most used anti-epileptics, but instead focus on those directly linked to the ion channels we are working with. Some of those include: Retigabine which opens potassium channels or ethosuximide which influences T-type calcium channels. Furthermore, some epileptics bind partially to albumin which hinders their activity. Nowadays laboratory tests can only measure the total concentration of anti-epileptics in the blood and not only the free, active concentration. Our system would be able to distinguish between the free, active versus the bound, non-active drug compounds. Another crucial point that was discussed during the meeting was what the patients would think/react to idea of an inserted monitoring device. He proceeded to say that field of “biosensors” is now a very interesting, growing field, and due to its simplicity and accuracy, it would be most welcome by patients. Prof. Van Paesschen was also so helpful, shedding light on a very important matter related to drug monitoring, that is, checking patients’ compliance. He mentioned how that is such a big problem especially with epilepsy patients, and that HEKcite could also be used to solve that problem. Last but not least, he gave a few suggestions for other useful applications that HEKcite could be used for. First of all he gave the idea of using our system as a form of personalized medicine. By using ion channels who contain the exact mutation of the patient, we could use our system to verify which drug is most effective specifically for the mutated channel of the patient. Next to this, he mentioned that epilepsy is often the result of multiple mutations in multiple channels. Our system could study the interactions between different ion channels and their mutation to further understand the mechanisms that can lead to epilepsy. These examples of the professor show again the diversity of our project and the great range of possible applications. All in all, the meeting was extremely helpful to us. We were able to leave the meeting with an answer to our original inquiry, that is, if the concept of HEKcite could be useful with patients with cases of epilepsy. We were also able to realize the full potential of the project and its various applications, giving us extra motivation and drive to move forward with our human practices.
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                                 <h3>Question 6: According to professor Monbaliu, patient compliance is a problem in the organ transplantation field, especially some years after the surgery. The device could alert you when you have not taken your drugs yet by sending out notifications. Do you think this could be a helpful reminder for you when you forget to take your medicine or be helpful for taking your medicine at the same time on a daily basis?</h3>
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                                 <h3>professor Iemand anders</h3>
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                             <p style="text-align:justify">The patients we talked to have received their transplants 2 to 7 years ago. However, they all told us that they have never forgotten to take their drugs, and this is no issue for them. However, the immune suppressants have to be taken at specific time points. The patients admitted that, as more time passed after the organ transplantation, they tended to take their drugs at less specific time points. These inaccuracies occur especially on holidays or special occasions, as it is difficult to take a medicine at the exact same time every day. Therefore, the patients see our device as a useful system, as it could give out a notification on their computer or smartphone.</p>
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Revision as of 09:14, 1 September 2017

Human practices

In HEKcite we create an oscillating HEK-cell, but for what purpose? Therapeutic drug monitoring is our answer. In the treatment of multiple severe diseases, a stable concentration of drugs is crucial. Steady blood levels determine therapeutic outcomes and increase survival rates. Currently, the most common therapeutic drug monitoring technique is blood sampling. For patients who need lifelong observation, the numerous hospital visits and frequent blood samplings can have a negative effect on the quality of life. Therefore, we develop a system that allows patients to determine the level of drugs at home. Furthermore, the ease of these measurements allows for daily or even continuous analysis.

Using this dynamic data collection instead of the static measurements performed in hospitals today, we might increase both therapeutic outcomes and quality of life of patients. In order to investigate the different views on our projects we talked to specialists in several fields where therapeutic drug monitoring is of great importance: transplantations, psychotics and epileptics. Three specialists have provided insights in how they expect our project will influence the lives of their patients and future treatments. We used this information to further shape our project.

Professor Diethard Monbaliu

Professor Monbaliu is a reputable abdominal transplant surgeon, at the department of microbiology and immunology at UZ Leuven. He is also responsible for a course on topographical and radiological anatomy and supervises several thesis students.

Professor Monbaliu confirmed our expectations that there is a need for a more dynamic measurement. In addition, he suspects that it could lead to a better evaluation of patients’ compliance. Together, these advances could result in fewer transplant rejections. He has also brought our attention to a novel and more prevalent immunosuppressant drug, tacrolimus. Finally, he mentioned that patient variability is an issue in his field, and that our device should take this into account. Want to learn more? Press for more details.

Professor Chris Bervoets

Professor Chris Bervoets is a psychiatrist. He is responsible for the department of transcranial magnetic stimulation, the department of deep brain stimulation and the department of compulsive disorders within the UPC (University Psychiatric Center) of KU Leuven. Additionally, he conducts research on neuromodulatory treatments for various psychiatric disorders.

While investigating different branches in medicine that could benefit from improved therapeutic drug monitoring, our attention was drawn to psychiatry. In this field, there are several drugs, for example lithium, that affect ion channels and could therefore be measured directly by our system. These aspects spiked our interest, and to learn more we contacted the specialist professor Chris Bervoets, who gave us some valuable insights in the difficult world of psychiatry.

Professor Wim Van Paesschen

Professor doctor Wim Van Paesschen is a neurosurgeon specialized in epilepsy. He also is head of the epilepsy research laboratory, part-time teaches at the faculty of medicine and supervises thesis students.

Professor Van Paesschen confirmed that therapeutic drug monitoring is necessary for anti-epileptics and mentioned the importance of verifying patient compliance. He also showed us that our project has more potential than even we imagined by giving some more examples of possible applications.

professor Iemand anders

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